Lot-to-lot Consistency of 3 Lots of Tetravalent Dengue Vaccine (TDV) in Non-endemic Country(Ies) for Dengue

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Demonstrate Lot-to-Lot Consistency of 3 Lots of a Tetravalent Dengue Vaccine Candidate in Healthy Adults in Non-Endemic Country(Ies) for Dengue

The purpose of this study is to investigate lot-to-lot consistency in terms of equivalence of the immune responses induced by 3 consecutive TDV lots in healthy participants aged 18 to 60 years in non-endemic country(ies) for dengue.

Study Overview

• Status: Completed
• Conditions: Dengue Fever
• Intervention / Treatment: Biological: Placebo; Biological: TAK-003

Detailed Description

The vaccine tested in this study is Takeda's Tetravalent Dengue Vaccine Candidate (TDV). The primary objective of this trial is to investigate lot-to-lot consistency in terms of equivalence of the immune responses induced by 3 consecutive lots of TDV in healthy participants in non-endemic country(ies) for dengue.

The study will enroll approximately 924 healthy participants. Participants will be randomized in 2:2:2:1 to one of 4 trial groups to receive TDV (Lots 1, 2 or 3) or placebo:

• TDV 0.5 mL subcutaneous injection OR
• Placebo normal saline solution (0.9% NaCl) for injection.

In each trial group, all participants will receive 2 doses of TDV or placebo by subcutaneous injection on Days 1 (Month 0) and 90 (Month 3). Immunogenicity will be assessed in participants included in the immunogenicity subset (TDV groups: 176 participants each and placebo group: 88 participants) and safety will be assessed in all participants in each group.

This multi-center trial will be conducted in the United States. The overall time to participate in this study is 270 days. Participants will make multiple visits to the clinic including a final visit at Day 270.

• Study Type: Interventional
• Enrollment (Actual): 923
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35802
      • Optimal Research
  • California
    • Anaheim, California, United States, 92805
      • Anaheim Clinical Trials, LLC
  • Idaho
    • Boise, Idaho, United States, 83704
      • Advanced Clinical Research
  • Illinois
    • Peoria, Illinois, United States, 61614
      • Optimal Research
  • Iowa
    • Council Bluffs, Iowa, United States, 51503
      • Synexus Limited- Council Bluffs
  • Kansas
    • Augusta, Kansas, United States, 67010
      • Heartland Research Associates LLC - Augusta
    • Park City, Kansas, United States, 67219
      • Heartland Research Associates LLC
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Optimal Research
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Synexus Limited - Minneapolis
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Synexus Limited - St. Louis
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Clinical Research Center Of Nevada
  • Ohio
    • Columbus, Ohio, United States, 43212
      • Synexus Limited - Columbus
  • Utah
    • Salt Lake City, Utah, United States, 84123
      • Advanced Clinical Research
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Is in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and the clinical judgment of the Investigator.
2. Signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any trial procedures, after the nature of the trial has been explained according to local regulatory requirements.

Exclusion Criteria:

1. Has an elevated oral temperature (≥38°C or 100.4°F) within 3 days of the intended date of vaccination.
2. Known hypersensitivity or allergy to any of the vaccine components (including excipients of the investigational vaccine or placebo).
3. Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (e.g., Guillain-Barré syndrome).

4. 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 Day 1 (M0) (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 Day 1 (M0).
   3. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (M0) or planned administration during the trial.
   4. Receipt of immunostimulants within 60 days prior to Day 1 (M0).
   5. Hepatitis C virus infection.
   6. Genetic immunodeficiency.
5. Has abnormalities of splenic or thymic function.
6. Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
7. Has any serious chronic or progressive disease according to judgment of the Investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
8. Has body mass index (BMI) greater than or equal to 35 kg/m^2 (= weight in kg/[height in meters^2]).
9. Has history of substance or alcohol abuse within the past 2 years.
10. Had previous and planned vaccination (during the trial conduct) against any flavivirus including dengue, yellow fever (YF), Japanese encephalitis (JE) viruses or tick-borne encephalitis.
11. Has a current or previous infection with a flavivirus such as dengue, Zika, YF, JE, West Nile (WN) fever, tick-borne encephalitis or Murray Valley encephalitis and participants with a history of prolonged (≥1 year) habitation in a dengue endemic area.

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
Placebo Comparator: Placebo; TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.	Biological: Placebo; TDV Placebo-matching normal saline (0.9% NaCl) subcutaneous injection
Experimental: TDV Lot 1; Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	Biological: TAK-003; TDV subcutaneous injection; Other Names: TDV
Experimental: TDV Lot 2; Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	Biological: TAK-003; TDV subcutaneous injection; Other Names: TDV
Experimental: TDV Lot 3; Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.	Biological: TAK-003; TDV subcutaneous injection; Other Names: TDV

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 at Day 120 in the Immunogenicity Subset	GMTs of neutralizing antibodies for each of the 4 Dengue Serotypes was measured by microneutralization test 50% [MNT50]. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.	1 month post second dose (Day 120)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Are Seropositive for Each of the 4 Dengue Serotypes at Days 120 and 270 in the Immunogenicity Subset	Seropositivity was defined as a reciprocal neutralizing titer ≥ 10. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.	1 month post second dose (Day 120) and 6 months post second dose (Day 270)
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270 in the Immunogenicity Subset	GMTs of neutralizing antibodies for each of the 4 Dengue Serotypes was measured by microneutralization test 50% [MNT50]. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.	6 months post second dose (Day 270)
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination	Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included pain (none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment and severe: prevents daily activity with or without treatment), redness (erythema) (<25 mm, mild: >25 - ≤50 mm, moderate: >50 - ≤100 mm, severe: >100 mm) and swelling (edema/induration) (<25 mm, mild: >25 - ≤50 mm, moderate: >50 - ≤100 mm, severe: >100 mm ). The percentages were rounded off to the first decimal place.	Within 7 Days of each Vaccination (day of vaccination + 6 days)
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination	Solicited systemic AEs include fever, headache, asthenia, malaise and myalgia that occurred within 14 days after each vaccination. Solicited systemic AEs (headache, asthenia, malaise and myalgia) was graded from 0 to 3 by severity; where 0=None, 1=Mild: No interference with daily activity, 2=Moderate: Interference with daily activity, 3=Severe: Prevents daily activity; A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 14 days after vaccination. Fever was excluded from the overall count as no severity grading was applied for it. The percentages were rounded off to the first decimal place.	Within 14 Days of each Vaccination (day of vaccination + 13 days)
Percentage of Participants With Any Unsolicited Adverse Events (AEs) After Each Vaccination	An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine; it does not necessarily have to have a causal relationship with trial vaccine administration.	Within 28 days (day of vaccination + 27 days) after each vaccination
Percentage of Participants With Serious Adverse Events (SAEs)	An SAE was defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, is an important medical event that may require intervention to prevent any of the above mentioned criteria and/or may expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization. The percentages were rounded off to the first decimal place.	From the first vaccination on Day 1 until the end of the trial (Day 270)
Percentage of Participants With Medically Attended Adverse Events (MAAEs)	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. The percentages were rounded off to the first decimal place.	From the first vaccination on Day 1 until the end of the trial (Day 270)

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2018
• Primary Completion (Actual): August 3, 2018
• Study Completion (Actual): January 14, 2019

Study Registration Dates

• First Submitted: January 31, 2018
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (Actual): February 6, 2018

Study Record Updates

• Last Update Posted (Actual): October 20, 2020
• Last Update Submitted That Met QC Criteria: October 15, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Dengue
• Other Study ID Numbers: DEN-304

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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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