Efficacy, Safety and Immunogenicity of Takeda's Tetravalent Dengue Vaccine (TDV) in Healthy Children (TIDES)

Phase III, Double-Blind, Randomized, Placebo-Controlled Trial to Investigate the Efficacy, Safety and Immunogenicity of a Tetravalent Dengue Vaccine (TDV) Administered Subcutaneously in Healthy Children Aged 4 - 16 Years Old

The main purpose of this study is to evaluate the efficacy of 2 doses of Tetravalent Dengue Vaccine Candidate (TDV) in preventing symptomatic dengue fever of any severity and due to any of the four dengue virus serotypes in 4 to 16 year old participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Biological: Tetravalent Dengue Vaccine (TDV)

Detailed Description

The vaccine being tested in this study is Takeda's Tetravalent Dengue Vaccine Candidate (TDV). TDV is being tested to protect people against dengue fever and to look at long-term safety results. This study will look at the success rate of TDV in preventing dengue fever (vaccine efficacy) and long-term side effects of the vaccine.

The study will be conducted in 5 parts. Part 1 will evaluate vaccine efficacy (VE) and will last a minimum of 15 months. Part 2 will be for an additional 6 months to evaluate VE. Part 3 will evaluate long-term safety by following participants for side effects and will last an additional 3 years. Part 4 will evaluate safety for 13 months post-booster vaccination. Part 5 will be the long-term safety follow-up for 1 year after completion of Part 4. Participants may be enrolled into a dry-run to commence and test febrile surveillance methodology; this dry-run part may be up to 10 months prior to receiving study injection, however, will not be applicable to all trials sites or participants.

Approximately 20,100 participants will be enrolled into the study and randomly assigned (by chance) to one of the two treatment groups-which will remain undisclosed to the participants and study doctors during the study (unless there is an urgent medical need):

• TDV 0.5 mL subcutaneous injection
• Placebo (dummy inactive subcutaneous injection) - this is a solution that looks like the study drug but has no active ingredient

All participants will receive a single injection of TDV or placebo on Day 1, Day 90. Participation in a booster phase will be offered to approximately 10,500 participants to receive (TDV or placebo) on Day 1b (Day 1 in booster phase). A subset of participants will be asked to record any local symptoms at the injection site (Pain, Erythema and Swelling) in a diary card for 7 days after each injection. The same subset of participants will also be asked to record any systemic symptoms (child <6 years: fever, irritability/fussiness, drowsiness, loss of appetite and child ≥6 years: fever, headache, asthenia, malaise and myalgia) in a diary card for 14 days after each injection.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 7 years excluding the dry-run. Participants will make multiple visits to the clinic and will be contacted at least every week for the entire study duration.

• Study Type: Interventional
• Enrollment (Actual): 20099
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Espírito Santo
    • Vitória, Espírito Santo, Brazil, 29040-091
      • Universidade Federal Do Espirito Santo Hospital Universitario Cassiano Antonio de Moraes HUCAM
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 40415-000
      • Associacao Obras Sociais Irma Dulce Hospital Santo Antonio
  • Mato Grosso do Sul
    • Campo Grande, Mato Grosso do Sul, Brazil, 79070-900
      • Universidade Federal de Mato Grosso do Sul
  • Natal - RN
    • Cidade Alta, Natal - RN, Brazil, 59025-050
      • Centro de Estudos e Pesquisa em Molestias Infecciosas LTDA (CPCLIN)
• Colombia
  • Casanare Department
    • Aguazul, Casanare Department, Colombia
      • Centro de Atencion e Investigacion Medica S.A - CAIMED - Aguazul - PPDS-PV
    • Yopal, Casanare Department, Colombia
      • Centro de Atencion e Investigacion Medica S.A - CAIMED - Yopal - PPDS-PV
  • Meta Department
    • Acacías, Meta Department, Colombia, 507001
      • Centro de Atencion e Investigacion Medica S.A. - CAIMED - Acacias - PPDS-PV
  • San Fernando
    • Cali, San Fernando, Colombia
      • Centro de Estudios em Infectologia Pediatrica SAS (CEIP S.A.S)
• Dominican Republic
  • Distrito Nacional Santo Domingo
    • Santo Domingo, Distrito Nacional Santo Domingo, Dominican Republic, 10204
      • Hospital Maternidad Nuestra Senora de Altagracia
    • Santo Domingo, Distrito Nacional Santo Domingo, Dominican Republic, 10514
      • Calle Alexander Fleming No. 90 Esquina 37, Ensanche La Fe
• Nicaragua
  • León, Nicaragua
    • Universidad Nacional Autonoma de Nicaragua
• Panama
  • Panama City, Panama, 10662
    • Centro De Vacunacion Internacional, S.A. (Cevaxin)
  • Panama City, Panama
    • Centro De Vacunacion Internacional, S.A. (Cevaxin) Sede 24 de Diciembre
  • Panama City, Panama
    • Centro De Vacunacion Internacional, S.A. (Cevaxin) Sede Plaza Carolina
  • Panama City, Panama
    • Centro De Vacunacion Internacional, S.A.(Cevaxin) - La Chorrera
• Philippines
  • City of Muntinlupa, Philippines, 1781
    • Research Institute For Tropical Medicine
  • Ermita, Philippines, 1000
    • University of the Philippine Manila
  • Las Piñas, Philippines
    • Las Pinas Health Center A
  • Las Piñas, Philippines
    • Las Pinas Health Center D
  • Cavite
    • Dasmariñas, Cavite, Philippines, 4114
      • Dela Salle Health Sciences Institute
  • Cebu
    • Cebu City, Cebu, Philippines, 6000
      • Philippines-AFRIMS Virology Research Unit
• Sri Lanka
  • Colombo, Sri Lanka, 00800
    • Lady Ridgeway Hospital for Children
  • Dehiwala, Sri Lanka, 10250
    • Colombo South Teaching Hospital
  • Negombo, Sri Lanka, 11500
    • Negombo General Hospital
  • Ragama, Sri Lanka, 11010
    • Colombo North Teaching Hospital
• Thailand
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital
  • Bangkok
    • Bangkok, Bangkok, Thailand, 10270
      • The Hospital for Tropical Diseases
    • Bangkok, Bangkok, Thailand, 10400
      • Phramongkutklao Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 16 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Is aged 4 to 16 years, inclusive, at the time of randomization.
2. Is in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and clinical judgment of the Investigator.
3. The participant and/or the participant's parent/guardian signs and dates an assent/written informed consent form where applicable, 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.
4. Can comply with trial procedures and are available for the duration of follow-up.

Inclusion criteria for Booster Phase:

1. Is included in the per-protocol set (PPS) of the trial.
2. Was aged 4 to 11 years at the time of randomization in the study (Day 1 [Month 0]).

Exclusion Criteria:

1. Has febrile illness (temperature ≥38°C) or moderate or severe acute illness or infection at the time of randomization.
2. Has history of or any illness that, in the opinion of the Investigator, might interfere with the results of the trial or pose an additional risk to the participant due to participation in the trial.
3. Has received any other vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to Day 1 (Month 0) or planning to receive any vaccine within 28 days after Day 1 (Month 0).
4. Has participated in any clinical trial with another investigational product 30 days prior to Day 1 (Month 0) or intent to participate in another clinical trial at any time during the conduct of this trial.
5. Has previously participated in any clinical trial of a dengue candidate vaccine, or previous receipt of a dengue vaccine.
6. Is first degree relative of individuals involved in trial conduct.
7. Females of childbearing potential who are sexually active, and who have not used any of the acceptable contraceptive methods for at least 2 months prior to Day 1 (Month 0).
8. Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method up to 6 weeks post-second vaccination.
9. Deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized involuntarily.
10. Current alcohol abuse or drug addiction that may interfere with the participant's ability to comply with trial procedures.
11. Identified as an employee of the Investigator or trial center, with direct involvement in the proposed trial or other trials under the direction of that Investigator or trial center.

Exclusion criteria for Booster Phase:

1. Receipt of any other vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to Day 1b (Month 0b), or planning to receive any vaccine within 28 days after Day 1b (Month 0b).
2. Participation in any clinical trial with another investigational product at any time during participation in this trial or intent to participate in another clinical trial at any time during the conduct of the booster phase of this trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo-matching TDV, 0.5 milliliters (mL), subcutaneous (SC) injection on Day 1 (Month 0) and Day 90 (Month 3) in Part 1 of the study. Participants eligible for Booster Phase received placebo matching TDV, SC injection on Day 1 booster [b] (Month 0b) in Part 4 of the study based on the randomization code applied in Part 1 of the study.	Drug: Placebo; TDV placebo-matching SC injection.
Experimental: Tetravalent Dengue Vaccine (TDV) 0.5 mL; Participants received TDV, 0.5 mL, SC injection on Day 1 (Month 0) and Day 90 (Month 3) in Part 1 of the study. Participants eligible for Booster Phase received TDV, SC injection on Day 1b (Month 0b) in Part 4 of the study based on the randomization code applied in Part 1 of the study.	Biological: Tetravalent Dengue Vaccine (TDV); TDV SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaccine Efficacy (VE) of Two Doses of Tetravalent Dengue Vaccine Candidate (TDV) in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype	The VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific reverse transcriptase polymerase chain reaction (RT-PCR). The primary endpoint of VE was assessed using the number of virologically-confirmed dengue fever cases that occurred during Part 1.	30 days post-second vaccination (Day 120 [Month 4]) until the end of Part 1 (Month 15) when at least 120 cases of dengue fever were confirmed and minimum duration of participant follow-up was 12 months post-second vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VE of Two Doses of TDV in Preventing Hospitalization Due to Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of cases requiring hospitalization due to virologically-confirmed dengue fever that occurred during Part 1 and Part 2.	From 30 days post-second vaccination (Day 120 [Month 4]) until the end of Part 2 (Month 21)
VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Each Dengue Serotype	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases that occurred during Part 1 and Part 2.	From 30 days post-second vaccination (Day 120 [Month 4]) until the end of Part 2 (Month 21)
VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype in Participants Dengue Seronegative at Baseline	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases that occurred during Part 1 and Part 2.	From 30 days post-second vaccination (Day 120 [Month 4]) until the end of Part 2 (Month 21)
VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype in Participants Dengue Seropositive at Baseline	VE is defined as 1 - (λv/λC), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases that occurred during Part 1 and Part 2.	From 30 days post-second vaccination (Day 120 [Month 4]) until the end of Part 2 (Month 21)
VE of Two Doses of TDV in Preventing Virologically-Confirmed Severe Dengue Fever Induced by Any Dengue Serotype	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. Severe cases were determined by Adjudication Committee. VE was assessed using the number of severe cases due to virologically-confirmed dengue fever that occurred during Part 1 and Part 2.	From 30 days post-second vaccination (Day 120 [Month 4]) until the end of Part 2 (Month 21)
Percentage of Participants With Solicited Local Injection Site Adverse Events (AEs) by Severity in the Safety Set Immunogenicity Subset	Solicited local AEs at injection site are defined as pain, erythema and swelling that occurred within 7 days after each vaccination. The participant/legal guardian recorded the severity of each AE (except erythema and swelling) according to the diary card instruction as none, mild, moderate, or severe. Severity grades for erythema and swelling were derived from the recorded diameters. Percentages were rounded off to the nearest single decimal place except the data points where rounding-up may lead to data misinterpretation.	Days 1 through 7 after each vaccination
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity in the Safety Set Immunogenicity Subset	Solicited systemic AEs in children (< 6 years) are defined as fever, irritability/fussiness, drowsiness and loss of appetite that occurred within 14 days after each vaccination. Solicited systemic AEs in children (≥ 6 years) are defined as fever, headache, asthenia, malaise and myalgia that occurred within 14 days after each vaccination. The participant/legal guardian recorded the severity of each AE (except fever) according to the diary card instruction as none, mild, moderate, or severe. Severity grades for fever were derived from the recorded body temperature measurements and presented using the proposed temperature increments published by the Brighton Collaboration. Percentages were rounded off to the nearest single decimal place except the data points where rounding-up may lead to data misinterpretation.	Days 1 through 14 after each vaccination on Day 1 (Month 0) and Day 90 (Month 3)
Percentage of Participants With Any Unsolicited Adverse Events (AEs) in the Safety Set Immunogenicity Subset	An AE is 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. Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study. Percentages were rounded off to the nearest single decimal place.	Days 1 through 28 after each vaccination on Day 1 (Month 0) and Day 90 (Month 3)
Percentage of Participants With Serious Adverse Events (SAEs) During Parts 1 and 2	An AE is 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. A serious adverse event (SAE) is 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 due to other reasons than the above mentioned criteria. Percentages were rounded off to the nearest single decimal place. In the category 'Part 1 and 2 combined' participants are counted only once even if they experienced events in both Part 1 and Part 2 in order to yield total of unique participants who had SAEs.	From Day 1 until the end of Parts 1 (Month 15) and 2 (Month 21)
Percentage of Participants With Fatal SAEs and SAEs Related to Study Drug During the First and Second Half of Part 3	An AE is 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. A SAE is 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 due to other reasons than the above mentioned criteria. Percentages were rounded off to the nearest single decimal place except the data points where rounding-up may lead to data misinterpretation.	First and Second half (18 months each) of Part 3 (up to 3 years, beginning at Month 22)
Seropositivity Rate for Each of the Four Dengue Serotypes in the Immunogenicity Subset	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 four DENV serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Percentages were rounded off to the nearest single decimal place except the data points where rounding-up may lead to data misinterpretation.	Pre-vaccination on Day 1 (Baseline), post-first vaccination on Month 1, pre-vaccination on Month 3; post-second vaccination at Months 4, 9 and 15, and then annually (up to 3 years)
Seropositivity Rate for Multiple Dengue Serotypes in the Immunogenicity Subset	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for any one (monovalent), two (bivalent), three (trivalent), and four (tetravalent) dengue serotypes, as well as at least bivalent (seropositive for ≥2 dengue serotypes) and at least trivalent (seropositive for ≥3 dengue serotypes), is derived from the titers of dengue-neutralizing antibodies. Seropositive response is defined as a reciprocal neutralizing titer ≥ 10. The four DENV serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Percentages were rounded off to the nearest single decimal place except the data points where rounding-up may lead to data misinterpretation.	Pre-vaccination on Day 1 (Baseline), post-first vaccination on Month 1, pre-vaccination on Month 3; post-second vaccination at Months 4, 9 and 15, and then annually (up to 3 years)
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the Four Dengue Serotypes in the Immunogenicity Subset	GMTs of neutralizing antibodies were measured via microneutralization test 50% (MNT50). The four DENV serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Pre-vaccination on Day 1 (Baseline), post-first vaccination on Month 1, pre-vaccination on Month 3; post-second vaccination at Months 4, 9 and 15, and then annually (up to 3 years)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of cases due to virologically-confirmed dengue fever that occurred during the first half of Part 3.	First half of Part 3 (18 months beginning at Month 22)
VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of cases due to virologically-confirmed dengue fever that occurred during the second half of Part 3.	Second half of Part 3 (18 months beginning at Month 40)
VE of Two Doses of TDV in Preventing Hospitalization Due to Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of cases requiring hospitalization due to virologically-confirmed dengue fever that occurred during the first half of Part 3.	First half of Part 3 (18 months beginning at Month 22)
VE of Two Doses of TDV in Preventing Hospitalization Due to Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of cases requiring hospitalization due to virologically-confirmed dengue fever that occurred during the second half of Part 3.	Second half of Part 3 (18 months beginning at Month 40)
VE of a TDV Booster Dose in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype From 30 Days Post-Booster Vaccination (Day 30 Booster [b] (Month 1b)) Until the End of Part 4	The VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases.	From 30 days post-booster vaccination (Day 30 booster [b] (Month 1b)) until the end of Part 4 (Month 13b)
VE of a TDV Booster Dose in Preventing Virologically Confirmed Dengue Fever Induced by Each Dengue Serotype From 30 Days Post-Booster Vaccination (Day 30b [Month 1b]) Until the End of Part 4	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases.	From 30 days post-booster vaccination (Day 30b [Month 1b]) until the end of Part 4 (Month 13b)
VE of a TDV Booster Dose in Preventing Virologically Confirmed Dengue Fever Induced by Any And Each Dengue Serotype in Dengue Seronegative Participants at Baseline From 30 Days Post-Booster Vaccination (Day 30b [Month 1b]) Until the End of Part 4	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases. Participants are counted only once for the "Any Dengue Serotype" category but counted separately for each dengue serotype they belong to.	From 30 days post-booster vaccination (Day 30b [Month 1b]) until the end of Part 4 (Month 13b)
VE of a TDV Booster Dose in Preventing Virologically Confirmed Dengue Fever Induced by Any and Each Dengue Serotype in Dengue Seropositive Participants at Baseline From 30 Days Post-Booster Vaccination (Day 30b [Month 1b]) Until the End of Part 4	VE is defined as 1 - (λv/λC), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases. Participants are counted only once for the "Any Dengue Serotype" category but counted separately for each dengue serotype they belong to.	From 30 days post-booster vaccination (Day 30b [Month 1b]) until the end of Part 4 (Month 13b)
VE of a TDV Booster Dose in Preventing Hospitalization Due to Virologically Confirmed Dengue Fever Induced by Any Dengue Serotype From 30 Days Post-Booster Vaccination (Day 30b [Month 1b]) Until the End of Part 4	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of cases requiring hospitalization due to virologically-confirmed dengue fever.	From 30 days post-booster vaccination (Day 30b [Month 1b]) until the end of Part 4 (Month 13b)
VE of a TDV Booster Dose in Preventing Virologically Confirmed Severe Dengue Fever Induced by Any Dengue Serotype From 30 Days Post-Booster Vaccination (Day 30b [Month 1b]) Until the End of Part 4	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. Severe cases were determined by Adjudication Committee. VE was assessed using the number of severe cases due to virologically-confirmed dengue fever.	From 30 days post-booster vaccination (Day 30b [Month 1b]) until the end of Part 4 (Month 13b)
VE of a TDV Booster Dose in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype During Part 5	The VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases. Participants are counted only once for the any dengue serotype.	From Month 14b until the end of Part 5 (Month 25b)
VE of a TDV Booster Dose in Preventing Virologically Confirmed Dengue Fever Induced by Each Dengue Serotype During Part 5	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases. Participants are counted separately for each dengue serotype.	From Month 14b until the end of Part 5 (Month 25b)
VE of a TDV Booster Dose in Preventing Virologically Confirmed Dengue Fever Induced by Any And Each Dengue Serotype in Dengue Seronegative Participants at Baseline During Part 5	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases. Participants are counted only once for the "Any Dengue Serotype" category but counted separately for each dengue serotype they belong to.	From Month 14b until the end of Part 5 (Month 25b)
VE of a TDV Booster Dose in Preventing Virologically Confirmed Dengue Fever Induced by Any and Each Dengue Serotype in Dengue Seropositive Participants at Baseline During Part 5	VE is defined as 1 - (λv/λC), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases. Participants are counted only once for the "Any Dengue Serotype" category but counted separately for each dengue serotype they belong to.	From Month 14b until the end of Part 5 (Month 25b)
VE of a TDV Booster Dose in Preventing Hospitalization Due to Virologically Confirmed Dengue Fever Induced by Any Dengue Serotype During Part 5	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of cases requiring hospitalization due to virologically-confirmed dengue fever.	From Month 14b until the end of Part 5 (Month 25b)
VE of a TDV Booster Dose in Preventing Virologically Confirmed Severe Dengue Fever Induced by Any Dengue Serotype During Part 5	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. Severe cases were determined by Adjudication Committee. VE was assessed using the number of severe cases due to virologically-confirmed dengue fever.	From Month 14b until the end of Part 5 (Month 25b)
VE of a TDV Booster Dose in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype for Parts 4 And 5 Combined	The VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases.	From 30 days post-booster vaccination (Day 30b [Month 1b) until the end of Part 5 (Month 25b)
VE of a TDV Booster Dose in Preventing Virologically Confirmed Dengue Fever Induced by Each Dengue Serotype for Parts 4 And 5 Combined	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases.	From 30 days post-booster vaccination (Day 30b [Month 1b]) until the end of Part 5 (Month 25b)
VE of a TDV Booster Dose in Preventing Virologically Confirmed Dengue Fever Induced by Any And Each Dengue Serotype in Dengue Seronegative Participants at Baseline for Parts 4 And 5 Combined	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases. Participants are counted only once for the "Any Dengue Serotype" category but counted separately for each dengue serotype they belong to.	From 30 days post-booster vaccination (Day 30b [Month 1b]) until the end of Part 5 (Month 25b)
VE of a TDV Booster Dose in Preventing Virologically Confirmed Dengue Fever Induced by Any and Each Dengue Serotype in Dengue Seropositive Participants at Baseline for Parts 4 And 5 Combined	VE is defined as 1 - (λv/λC), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of virologically-confirmed dengue fever cases. Participants are counted only once for the "Any Dengue Serotype" category but counted separately for each dengue serotype they belong to.	From 30 days post-booster vaccination (Day 30b [Month 1b]) until the end of Part 5 (Month 25b)
VE of a TDV Booster Dose in Preventing Hospitalization Due to Virologically Confirmed Dengue Fever Induced by Any Dengue Serotype for Parts 4 And 5 Combined	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. VE was assessed using the number of cases requiring hospitalization due to virologically-confirmed dengue fever.	From 30 days post-booster vaccination (Day 30b [Month 1b]) until the end of Part 5 (Month 25b)
VE of a TDV Booster Dose in Preventing Virologically Confirmed Severe Dengue Fever Induced by Any Dengue Serotype for Parts 4 And 5 Combined	VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific RT-PCR. Severe cases were determined by Adjudication Committee. VE was assessed using the number of severe cases due to virologically-confirmed dengue fever.	From 30 days post-booster vaccination (Day 30b [Month 1b]) until the end of Part 5 (Month 25b)
Percentage of Participants With Solicited Local Injection Site Adverse Events (AEs) by Severity in the Safety Set-Booster-Immunogenicity Subset During Part 4	Solicited local AEs at injection site are defined as pain, erythema and swelling that occurred within 7 days after each vaccination. The participant/legal guardian recorded the severity of each AE (except erythema and swelling) according to the diary card instruction as none, mild, moderate, or severe. Severity grades for erythema and swelling were derived from the recorded diameters. Percentages were rounded off to the nearest single decimal place.	Days 1b through 7b after booster vaccination in Part 4
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity in the Safety Set-Booster-Immunogenicity Subset During Part 4	Solicited systemic AEs are defined as fever, headache, asthenia, malaise and myalgia that occurred within 14 days after each vaccination. The participant/legal guardian recorded the severity of each AE (except fever) according to the diary card instruction as none, mild, moderate, or severe. Severity grades for fever were derived from the recorded body temperature measurements and presented using the proposed temperature increments published by the Brighton Collaboration. Percentages were rounded off to the nearest single decimal place except the data point where rounding-up may lead to data misinterpretation.	Days 1b through 14b after booster vaccination in Part 4
Percentage of Participants With Any Unsolicited Adverse Events (AEs) in the Safety Set-Booster-Immunogenicity Subset During Part 4	An AE is 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. Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study. Percentages were rounded off to the nearest single decimal place.	Days 1b through 28b after booster vaccination in Part 4
Percentage of Participants With Serious Adverse Events (SAEs) During Parts 4 and 5	An AE is 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. A serious adverse event (SAE) is 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 due to other reasons than the above mentioned criteria. Percentages were rounded off to the nearest single decimal place. In the category 'Part 4 and 5 combined' participants are counted only once even if they experienced events in both Part 4 and Part 5 in order to yield total of unique participants who had SAEs.	From Day 1b until the end of Part 4 (Month 13b) and Part 5 (Month 25b)
Percentage of Participants With Fatal SAEs and SAEs Related to Study Drug During Parts 4 and 5	An AE is 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. A SAE is 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 due to other reasons than the above mentioned criteria. Percentages were rounded off to the nearest single decimal place except the data points where rounding-up may lead to data misinterpretation. In the category 'Part 4 and 5 combined' participants are counted only once even if they experienced events in both Part 4 and Part 5 in order to yield total of unique participants who had SAEs.	From Day 1b until the end of Part 4 (Month 13b) and Part 5 (Month 25b)
Seropositivity Rate for Each of The 4 Dengue Serotypes During Parts 4 and 5	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 four DENV serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Percentages were rounded off to the nearest single decimal place except the data points where rounding-up may lead to data misinterpretation.	Pre-booster Vaccination on Day 1b (Month 0b) and post-booster vaccination on Day 30b (Month 1b), Day 180b (Month 6b), Day 395b (Month 13b) and Day 760b (Month 25b) in Parts 4 and 5
Seropositivity Rate for Multiple Dengue Serotypes During Parts 4 and 5	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for any one (monovalent), two (bivalent), three (trivalent), and four (tetravalent) dengue serotypes, as well as at least bivalent (seropositive for ≥2 dengue serotypes) and at least trivalent (seropositive for ≥3 dengue serotypes), is derived from the titers of dengue-neutralizing antibodies. Seropositive response is defined as a reciprocal neutralizing titer ≥ 10. The four DENV serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Percentages were rounded off to the nearest single decimal place except the data points where rounding-up may lead to data misinterpretation.	Pre-booster vaccination on Day 1b (Month 0b) and post-booster vaccination on Day 30b (Month 1b), Day 180b (Month 6b), Day 395b (Month 13b) and Day 760b (Month 25b) in Parts 4 and 5
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the Four Dengue Serotypes During Parts 4 And 5	GMTs of neutralizing antibodies were measured via MNT50. The four DENV serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Pre-booster Vaccination on Day 1b (Month 0b) and post-booster vaccination on Day 30b (Month 1b), Day 180b (Month 6b), Day 395b (Month 13b) and Day 760b (Month 25b) in Parts 4 and 5
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each Dengue Serotype	The GMR is the geometric mean of the ratio of the two visits being compared.	Pre-booster Vaccination on Day 1b (Month 0b) versus post-booster vaccination on Day 30b (Month 1b) in Part 4
GMR of Neutralizing Antibodies for Each Dengue Serotype	The GMR is the geometric mean of the ratio of the two visits being compared.	Pre-booster Vaccination on Day 1b (Month 0b) versus post-booster vaccination on Day 180b (Month 6b) in Part 4
GMR of Neutralizing Antibodies for Each Dengue Serotype	The geometric mean ratio is the geometric mean of the ratio of the two visits being compared.	Pre-booster Vaccination on Day 1b (Month 0b) versus post-booster vaccination on Day 395b (Month 13b) in Part 4
GMR of Neutralizing Antibodies for Each Dengue Serotype	The geometric mean ratio is the geometric mean of the ratio of the two visits being compared.	Pre-booster Vaccination on Day 1b (Month 0b) versus post-booster vaccination on Day 720b (Month 25b) in Part 5

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Rivera L, Biswal S, Saez-Llorens X, Reynales H, Lopez-Medina E, Borja-Tabora C, Bravo L, Sirivichayakul C, Kosalaraksa P, Martinez Vargas L, Yu D, Watanaveeradej V, Espinoza F, Dietze R, Fernando L, Wickramasinghe P, Duarte MoreiraJr E, Fernando AD, Gunasekera D, Luz K, Venancioda Cunha R, Rauscher M, Zent O, Liu M, Hoffman E, LeFevre I, Tricou V, Wallace D, Alera M, Borkowski A. Three-year Efficacy and Safety of Takeda's Dengue Vaccine Candidate (TAK-003). Clin Infect Dis. 2022 Aug 24;75(1):107-117. doi: 10.1093/cid/ciab864.
• Biswal S, Reynales H, Saez-Llorens X, Lopez P, Borja-Tabora C, Kosalaraksa P, Sirivichayakul C, Watanaveeradej V, Rivera L, Espinoza F, Fernando L, Dietze R, Luz K, Venancio da Cunha R, Jimeno J, Lopez-Medina E, Borkowski A, Brose M, Rauscher M, LeFevre I, Bizjajeva S, Bravo L, Wallace D; TIDES Study Group. Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents. N Engl J Med. 2019 Nov 21;381(21):2009-2019. doi: 10.1056/NEJMoa1903869. Epub 2019 Nov 6.
• Rauscher M, Youard Z, Faccin A, Patel SS, Pang H, Zent O. Pregnancy outcomes following unintentional exposure to TAK-003, a live-attenuated tetravalent dengue vaccine. Expert Rev Vaccines. 2025 Dec;24(1):221-229. doi: 10.1080/14760584.2025.2480297. Epub 2025 Mar 27.
• Borja-Tabora C, Fernando L, Lopez Medina E, Reynales H, Rivera L, Saez-Llorens X, Sirivichayakul C, Yu D, Folschweiller N, Moss KJ, Rauscher M, Tricou V, Zhao Y, Biswal S. Immunogenicity, Safety, and Efficacy of a Tetravalent Dengue Vaccine in Children and Adolescents: An Analysis by Age Group. Clin Infect Dis. 2025 Feb 5;80(1):199-206. doi: 10.1093/cid/ciae369.
• Sirivichayakul C, Biswal S, Saez-Llorens X, Lopez-Medina E, Borja-Tabora C, Bravo L, Kosalaraksa P, Alera MT, Reynales H, Rivera L, Watanaveeradej V, Yu D, Espinoza F, Dietze R, Fernando L, Wickramasinghe VP, Moreira ED Jr, Fernando AD, Gunasekera D, Luz K, Venancio da Cunha R, Oliveira AL, Rauscher M, Fan H, Borkowski A, Escudero I, Tuboi S, Lloyd E, Tricou V, Folschweiller N, LeFevre I, Vargas LM, Wallace D; TIDES Study Group. Efficacy and Safety of a Tetravalent Dengue Vaccine (TAK-003) in Children With Prior Japanese Encephalitis or Yellow Fever Vaccination. J Infect Dis. 2024 Dec 16;230(6):e1214-e1225. doi: 10.1093/infdis/jiae222.
• Tricou V, Yu D, Reynales H, Biswal S, Saez-Llorens X, Sirivichayakul C, Lopez P, Borja-Tabora C, Bravo L, Kosalaraksa P, Vargas LM, Alera MT, Rivera L, Watanaveeradej V, Dietze R, Fernando L, Wickramasinghe VP, Moreira ED Jr, Fernando AD, Gunasekera D, Luz K, Oliveira AL, Tuboi S, Escudero I, Hutagalung Y, Lloyd E, Rauscher M, Zent O, Folschweiller N, LeFevre I, Espinoza F, Wallace D. Long-term efficacy and safety of a tetravalent dengue vaccine (TAK-003): 4.5-year results from a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Glob Health. 2024 Feb;12(2):e257-e270. doi: 10.1016/S2214-109X(23)00522-3.
• Saez-Llorens X, Biswal S, Borja-Tabora C, Fernando L, Liu M, Wallace D, Folschweiller N, Reynales H, LeFevre I; TIDES Study Group. Effect of the Tetravalent Dengue Vaccine TAK-003 on Sequential Episodes of Symptomatic Dengue. Am J Trop Med Hyg. 2023 Mar 6;108(4):722-726. doi: 10.4269/ajtmh.22-0673. Print 2023 Apr 5.
• Biswal S, Borja-Tabora C, Martinez Vargas L, Velasquez H, Theresa Alera M, Sierra V, Johana Rodriguez-Arenales E, Yu D, Wickramasinghe VP, Duarte Moreira E Jr, Fernando AD, Gunasekera D, Kosalaraksa P, Espinoza F, Lopez-Medina E, Bravo L, Tuboi S, Hutagalung Y, Garbes P, Escudero I, Rauscher M, Bizjajeva S, LeFevre I, Borkowski A, Saez-Llorens X, Wallace D; TIDES study group. Efficacy of a tetravalent dengue vaccine in healthy children aged 4-16 years: a randomised, placebo-controlled, phase 3 trial. Lancet. 2020 May 2;395(10234):1423-1433. doi: 10.1016/S0140-6736(20)30414-1. Epub 2020 Mar 17.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2016
• Primary Completion (Actual): July 11, 2018
• Study Completion (Actual): June 28, 2024

Study Registration Dates

• First Submitted: April 14, 2016
• First Submitted That Met QC Criteria: April 19, 2016
• First Posted (Estimated): April 22, 2016

Study Record Updates

• Last Update Posted (Estimated): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 6, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Mosquito-Borne Diseases; Dengue; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; Dengue Vaccines
• Other Study ID Numbers: DEN-301; U1111-1166-8401 (Registry Identifier: WHO); PHRR150522-001010 (Registry Identifier: PHRR); 2018-003979-34 (Registry Identifier: EudraCT)

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