Long-Term Safety and Antibody Persistence of TDV and the Impact of a Booster Dose

A Phase 3, Follow-Up Trial to Evaluate Long-Term Safety and Antibody Persistence, and the Impact of a Booster Dose of a Tetravalent Dengue Vaccine Candidate in Healthy Adolescents and Adults in Areas Non-Endemic for Dengue

The purpose of this study is to describe antibody persistence for each of the 4 dengue serotypes for up to 63 months after the first vaccination in the primary vaccination series for participants from parent trial DEN-315 (NCT03341637) (Mexico) and for up to 36 months after the first vaccination in the primary vaccination series for participants from parent trial DEN-304 (NCT03423173) (United States [US]) and to describe the impact of a tetravalent dengue vaccine (TDV) booster dose vs placebo on antibody response for each of the 4 dengue serotypes at 1 month and 6 months post administration of the TDV booster or placebo.

Study Overview

• Status: Completed
• Conditions: Dengue Fever
• Intervention / Treatment: Biological: Placebo; Biological: Takeda's Dengue Tetravalent Vaccine (Live, Attenuated) (TDV)

Detailed Description

The vaccine tested in this study is Takeda's Dengue Tetravalent Vaccine (Live, Attenuated) (TDV). This study will look at the long-term antibody persistence and safety of Takeda's TDV in healthy adolescents and adults and will assess the impact of a booster dose.

The study has enrolled 365 healthy participants. Participants who previously received TDV in two parent trials (DEN-304 [NCT03423173] and DEN-315 [NCT03341637]), will be invited to participate in this follow-up trial. Participants will be assessed for antibody persistence and safety from Baseline (Month 0) through Month 15 (for participants from parent trial DEN-304 [US]) or Month 42 (for participants from parent trial DEN-315 [Mexico]). At Month 15 (for participants from parent trial DEN-304 [US]) or at Month 42 (for participants from parent trial DEN-315 [Mexico]), eligible participants will be randomized in 1:1 ratio to one of two trial groups to receive TDV or placebo:

A. Group 1- TDV 0.5 mL subcutaneous (SC) injection at Month 15 for participants from parent trial DEN-304 (US) or at Month 42 for participants from parent trial DEN-315 (Mexico]).

B. Group 2- Takeda's tetravalent dengue placebo (dummy SC injection - this is a liquid that looks like the study drug but has no active ingredient), 0.5 mL, subcutaneous injection at Month 15 for participants from parent trial DEN-304 (US) or at Month 42 for participants from parent trial DEN-315 (Mexico).

This multi-centre trial will be conducted in US and Mexico. The overall time to participate in this study is up to 21 months for parent trial DEN-304 (US) and up to 48 months for parent trial DEN-315 (Mexico). Participants from parent trial DEN-304 (US) and participants from parent trial DEN-315 (Mexico) will come for 5 visits to the clinic which includes a final visit (Visit 5) 6 months after the booster dose for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 365
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Ciudad De Mexico, Mexico, 04530
    • Instituto Nacional de Pediatría
  • Ciudad de Mexico, Mexico, 06760
    • CAIMED Investigacion en salud S.A de C.V.
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35802
      • AES - DRS - Optimal Research Alabama - Huntsville
  • Illinois
    • Peoria, Illinois, United States, 61614
      • AES - DRS - Optimal Research Illinois - Peoria
  • Kansas
    • Newton, Kansas, United States, 67114
      • Alliance for Multispecialty Research, LLC - Newton - PPDS
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Optima Research
  • Minnesota
    • Richfield, Minnesota, United States, 55423-2590
      • AES - DRS - Synexus Clinical Research US, Inc. Minneapolis
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • AES - DRS - Synexus Clinical Research US, Inc. - St. Louis
  • Nebraska
    • Papillion, Nebraska, United States, 68046
      • AES - DRS - Synexus Clinical Research US, Inc. - Omaha
  • Utah
    • West Jordan, Utah, United States, 84088-8865
      • Advanced Clinical Research/Velocity Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 63 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male or female participants (irrespective of serostatus at baseline in the parent trials (DEN-304 [(NCT03423173)] and DEN-315 [NCT03341637]) who received at least one dose of Takeda's tetravalent dengue vaccine candidate (TDV) in the parent trials and have data from at least one blood draw post-vaccination.

Exclusion Criteria:

1. Participants with a prolonged period of habitation (≥1 year) in a dengue endemic area within the 2 years prior to Visit 1 Day 1 (Month 0).
2. Previous and planned vaccination (during the trial conduct), against any flavivirus including dengue (other than Takeda's TDV), yellow fever (YF), Japanese encephalitis (JE) viruses or tick-borne encephalitis.

Booster Exclusion Criteria:

1. Participants for whom baseline serostatus is not defined in the parent trials (DEN-304 [(NCT03423173)] and DEN-315 [NCT03341637]).
2. Participants with any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (eg, Guillain-Barré syndrome).

3. Known or suspected impairment/alteration of immune function, including:

   1. Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Month 42 for participants from parent trial DEN-315 (Mexico)/ Month 15 for participants from parent trial DEN-304 (US); use of inhaled, intranasal, or topical corticosteroids is allowed.
   2. Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Month 42 for participants from parent trial DEN-315 (Mexico)/ Month 15 for participants from parent trial DEN-304 (US).
   3. Administration of immunoglobulins and/or any blood products within the 3 months prior to administration of the TDV booster or placebo at Month 42 for participants from parent trial DEN-315 (Mexico)/ Month 15 for participants from parent trial DEN-304 (US); consider whether applicable as an exclusion criterion or criterion for delay.
   4. Receipt of immunostimulants within 60 days prior to Month 42 for participants from parent trial DEN-315 (Mexico)/ Month 15 for participants from parent trial DEN-304 (US).
   5. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Month 42 for participants from parent trial DEN-315 (Mexico) / Month 15 for participants from parent trial DEN-304 (US).
   6. Known human immunodeficiency virus (HIV) infection or HIV-related disease.
   7. Hepatitis C virus infection.
   8. Genetic immunodeficiency.
4. Abnormalities of splenic or thymic function.
5. Participants with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
6. Participants with history of current or previous infection with a flavivirus such as dengue, Zika, YF, JE, West Nile fever, tick-borne encephalitis or Murray Valley encephalitis and participants with a prolonged period of habitation (≥1 year) in a dengue endemic area during trial conduct.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prior to Booster: DEN-304; Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Month 15.	Biological: Takeda's Dengue Tetravalent Vaccine (Live, Attenuated) (TDV); TDV subcutaneous injection
Experimental: Prior to Booster: DEN-315; Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Month 42.	Biological: Takeda's Dengue Tetravalent Vaccine (Live, Attenuated) (TDV); TDV subcutaneous injection
Placebo Comparator: Booster Phase: Placebo; Participants received TDV placebo-matching 0.5 milliliters (ml) injection, subcutaneous (SC), once at Month 15 for participants from parent trial DEN-304 (US) or once at Month 42 for participants from parent trial DEN-315 (Mexico).	Biological: Placebo; Normal Saline (0.9% NaCl) subcutaneous injection
Experimental: Booster Phase: TDV; Participants received TDV 0.5 ml, injection, SC, once at Month 15 for participants from parent trial DEN-304 (US) or once at Month 42 for participants from parent trial DEN-315 (Mexico).	Biological: Takeda's Dengue Tetravalent Vaccine (Live, Attenuated) (TDV); TDV subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1])	GMTs of neutralizing antibodies were measured by microneutralization test 50% (MNT50) for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 1 at Month 0 for participants from both parent trials (DEN-304 and DEN-315).	Month 0 (Day 1)
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 2 at Month 12 for participants from both parent trials (DEN-304 and DEN-315).	Month 12
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 3 at Month 15 for participants from parent trial DEN-304.	Month 15 (DEN-304)
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 3 at Month 42 for participants from parent trial DEN-315.	Month 42 (DEN-315)
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1])	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 1 at Month 0 for participants from both parent trials (DEN-304 and DEN-315).	Month 0 [Day 1)
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 2 at Month 12 for participants from both parent trials (DEN-304 and DEN-315).	Month 12
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 3 at Month 15 for participants from parent trial DEN-304.	Month 15 (DEN-304)
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 3 at Month 42 for participants from parent trial DEN-315.	Month 42 (DEN-315)
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1])	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 1 at Month 0 for participants from both parent trials (DEN-304 and DEN-315).	Month 0 (Day 1)
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 2 at Month 12 for participants from both parent trials (DEN-304 and DEN-315).	Month 12
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304)	Seropositivity Rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 15 for participants from parent trial DEN-304.	Month 15 (DEN-304)
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 42 for parent trial DEN-315.	Month 42 (DEN-315)
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 [Month 0 (Day 1])	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 1 at Month 0 for participants from both parent trials (DEN-304 and DEN-315).	Month 0 (Day 1)
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 2 at Month 12 for participants from both parent trials (DEN-304 and DEN-315).	Month 12
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 15 for participants from parent trial DEN-304.	Month 15 (DEN-304)
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) ((DEN-315)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 42 for parent trial DEN-315.	Month 42 (DEN-315)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1])	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 1 at Month 0 for both parent trials (DEN-304 and DEN-315).	Month 0 (Day 1)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 2 at Month 12 for both parent trials (DEN-304 and DEN-315).	Month 12
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 15 for parent trial DEN-304.	Month 15 (DEN-304)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 42 for parent trial DEN-315.	Month 42 (DEN-315)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1])	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 1 at Month 0 for both parent trials (DEN-304 and DEN-315).	Month 0 (Day 1)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 2 at Month 12 for both parent trials (DEN-304 and DEN-315).	Month 12
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. (DEN-304). All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 15 for parent trial DEN-304.	Month 15 (DEN-304)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 42 for parent trial DEN-315.	Month 42 (DEN-315)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).	1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 15 (DEN-304)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.	1 month post-booster dose at Month 16 (DEN-304)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 42 (DEN-315)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.	1 month post-booster dose at Month 43 (DEN-315)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).	1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 15 (DEN-304)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.	1 month post-booster dose at Month 16 (DEN-304)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 42 (DEN-315)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.	1 month post-booster dose at Month 43 (DEN-315)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 5, 6 months post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).	6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.	6 months post-booster dose at Month 21 (DEN-304)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.	6 months post-booster dose at Month 48 (DEN-315)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).	6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.	6 months post-booster dose at Month 21 (DEN-304)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315)	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.	6 months post-booster dose at Month 48 (DEN-315)
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).	1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 15 (DEN-304)
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.	1 month post-booster dose at Month 16 (DEN-304)
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 42 (DEN-315)
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.	1 month post-booster dose at Month 43 (DEN-315)
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).	1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 15 (DEN-304)
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.	1 month post-booster dose at Month 16 (DEN-304)
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 42 (DEN-315)
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.	1 month post-booster dose at Month 43 (DEN-315)
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).	6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.	6 months post-booster dose at Month 21 (DEN-304)
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.	6 months post-booster dose at Month 48 (DEN-315)
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).	6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.	6 months post-booster dose at Month 21 (DEN-304)
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.	6 months post-booster dose at Month 48 (DEN-315)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).	1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 15 (DEN-304)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.	1 month post-booster dose at Month 16 (DEN-304.)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 42 (DEN-315)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.	1 month post-booster dose at Month 43 (DEN-315)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), \ any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), \ any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).	1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), \ any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 15 (DEN-304)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), \any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.	1 month post-booster dose at Month 16 (DEN-304)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.	Pre-booster dose at Month 42 (DEN-315)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.	1 month post-booster dose at Month 43 (DEN-315)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).	6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.	6 months post-booster dose at Month 21 (DEN-304)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-booster Dose at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.	6 months post-Booster dose at Month 48 (DEN-315)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).	6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.	6 months post-booster dose at Month 21 (DEN-304)
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.	6 months post-Booster dose at Month 48 (DEN-315)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose	The geometric mean ratio is the geometric mean of the ratio of the two visits being compared.	Month 12 vs Month 0, Month 15 (DEN-304) vs parent trial Month 4, Mont 42 (DEN315) vs parent trial Month 4, Month 0 vs parent trial Month 9, Month 12 vs parent trial Month 9
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose	The geometric mean ratio is the geometric mean of the ratio of the two visits being compared. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial.	Month 12 vs Month 0, Month 15 (DEN-304) vs parent trial Month 4, Month 42 (DEN315) vs parent trial Month 4, Month 0 vs parent trial Month 9, Month 12 vs parent trial Month 9
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase	The geometric mean ratio is the geometric mean of the ratio of the two visits being compared.	Months (M) 1&6 post-booster dose in current trial vs M 4 in parent trials; post-booster M 6 vs post-booster M 1; post-booster M 1 vs pre-booster (M 15 for DEN-304/M 42 for DEN-315); post-booster M 6 vs pre-booster (M 15 for DEN-304/M 42 for DEN-315)
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase	The geometric mean ratio is the geometric mean of the ratio of the two visits being compared. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial.	Months (M) 1&6 post-booster dose in current trial vs M 4 in parent trials; post-booster M 1 vs pre-booster (M 15 for DEN-304/M 42 for DEN-315); post-booster M 6 vs pre-booster (M 15 for DEN-304/M 42 for DEN-315); post-booster M 6 vs post-booster M 1
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) Within 7 Days Post-Booster Vaccination	Solicited local AEs at injection site are defined as pain, erythema and swelling that occurred within 7 days post-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315). AEs were graded by the investigator in the following manner: Mild: Grade 1: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities. Relieved with or without symptomatic treatment; Moderate: Grade 2: Sufficient discomfort is present to cause interference with normal activity. Only partially relieved with symptomatic treatment; Severe: Grade 3: Extreme distress, causing significant impairment of functioning or incapacitation. Prevents normal everyday activities. Not relieved with symptomatic treatment.	Days 1 through 7 post-booster dose at Visit 3 (Month 15 [DEN-304]) and (Month 42 [DEN-315])
Percentage of Participants With Solicited Systemic Adverse Events Within 14 Days Post-Booster Vaccination by Severity	Solicited systemic AEs are defined as fever, headache, asthenia, malaise and myalgia that occurred within 14 days post-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315). AEs were graded by the investigator in the following manner: Mild: Grade 1: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities. Relieved with or without symptomatic treatment; Moderate: Grade 2: Sufficient discomfort is present to cause interference with normal activity. Only partially relieved with symptomatic treatment; Severe: Grade 3: Extreme distress, causing significant impairment of functioning or incapacitation. Prevents normal everyday activities. Not relieved with symptomatic treatment.	Days 1 through 14 post-booster dose at Visit 3 (Month 15 [DEN-304]) and (Month 42 [DEN-315])
Percentage of Participants With Any Unsolicited AEs in the Booster Phase	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine or placebo; it does not necessarily have to have a causal relationship with this treatment.	Days 1 through 28 post-booster dose at Visit 3 (Month 15 [DEN-304]) and (Month 42 [DEN-315])
Percentage of Participants With Any Medically Attended AEs (MAAEs) in the Booster Phase	MAAEs are defined as AEs leading to an unscheduled visit to or by a healthcare professional including visits to an emergency department, but not fulfilling seriousness criteria.	Month 15 post-booster dose through Month 21 (DEN-304); Month 42 post-booster dose through Month 48 (DEN-315)
Percentage of Participants With Any Serious Adverse Events (SAEs) Prior to the Booster Dose	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine or placebo; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically important event.	Month 0 through Month 15 (DEN-304) and Month 42 (DEN-315)
Percentage of Participants With Any SAEs in the Booster Phase	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine or placebo; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically important event.	Month 15 post-booster dose after vaccination through Month 21 (DEN-304); Month 42 post-booster dose after vaccination through Month 48 (DEN-315)

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Medical Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information about this study, click this link.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2019
• Primary Completion (Actual): May 25, 2024
• Study Completion (Actual): May 25, 2024

Study Registration Dates

• First Submitted: June 25, 2019
• First Submitted That Met QC Criteria: June 25, 2019
• First Posted (Actual): June 27, 2019

Study Record Updates

• Last Update Posted (Actual): June 12, 2025
• Last Update Submitted That Met QC Criteria: May 23, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Vaccine
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; RNA Virus Infections; Virus Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Dengue
• Other Study ID Numbers: DEN-303; 2023-000027-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No