A Study of Dengue Vaccine in Healthy Children, Teenagers and Adults in India

Study Overview
=================
Brief Summary
-----------------
The main aims of the study are to learn about side effects and a participant's immune response to Takeda's Dengue Vaccine when given twice within 3 months. Participants will receive 2 doses of their randomized treatment (vaccine or placebo). Children, teenagers and adults will receive one dose of either the vaccine or placebo on Day 1 and the second dose of either the vaccine or placebo 3 months later. Up to 4 blood samples will be taken throughout the study. During the study, participants will visit their study clinic 6 times.

Detailed Description
-----------------
The vaccine being tested in this study is called TDV (Live, Attenuated). TDV is being tested to prevent dengue. This study will assess the safety and immunogenicity of TDV in healthy participants. The study will enroll approximately 480 patients. Participants will be randomly assigned (by chance, like flipping a coin) to receive either TDV or placebo- which will remain undisclosed to the participant, and investigator during the study: Cohort 1, ≥18 to ≤60 Age Group: TDV Cohort 1, ≥18 to ≤60 Age Group: Placebo Cohort 2, ≥4 to <18 Age Group: TDV Cohort 2, ≥4 to <18 Age Group: Placebo This multi-center trial will be conducted in India. The overall duration of the study is approximately 9 months.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Investigate the Safety and Immunogenicity of a Dengue Tetravalent Vaccine (Live, Attenuated) (TDV) Administered Subcutaneously to Healthy Subjects Aged 4 to 60 Years in India

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Biological: TDV
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: 1. Participants who can comply with trial procedures and are available for the duration of follow-up. Key Exclusion Criteria: At screening and at vaccination: A body mass index (BMI) ≥35 kg/m^2. Intent to participate in another clinical trial at any time during the conduct of this trial. Plans to receive any of the following: A licensed vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to TDV or placebo administration. A coronavirus vaccine within 14 days prior to TDV or placebo administration. A vaccine authorized for emergency use within 28 days of TDV or placebo administration. Known substance or alcohol abuse within the past 2 years that may interfere with his/her ability to comply with requirements for trial participation. Receipt of previous vaccination against dengue virus. Previous participation in any clinical trial of a dengue candidate vaccine. At Vaccination: Participants with febrile illness or moderate or severe acute illness, or infection, at the time of random assignment. Participants medicated with antipyretic and/or analgesic medication(s) within 24 hours prior to TDV or placebo administration. NOTE: Other protocol defined Inclusion/exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 4 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: ≥18 to ≤60 Age Group: TDV<br> | Biological: TDV<br>* TDV SC injection on Day 1 and Day 90 of the study<br>* Other names: TAK-003;|
| Placebo Comparator: Cohort 1: ≥18 to ≤60 Age Group: Placebo<br> | Biological: Placebo<br>* Normal Saline (0.9% NaCl) SC injection on Day 1 and Day 90 of the study<br>|
| Experimental: Cohort 2: ≥4 to <18 Age Group: TDV<br> | Biological: TDV<br>* TDV SC injection on Day 1 and Day 90 of the study<br>* Other names: TAK-003;|
| Placebo Comparator: Cohort 2: ≥4 to <18 Age Group: Placebo<br> | Biological: Placebo<br>* Normal Saline (0.9% NaCl) SC injection on Day 1 and Day 90 of the study<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Solicited Local (Injection Site) Adverse Events (AEs) by Severity Within 7 Days Post Vaccination at Day 1 | Solicited local AEs at injection site are defined as injection site pain, injection site erythema, and injection site swelling. The AEs will be graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe. | Within 7 days postvaccination at Day 1 | 
| Number of Participants with Solicited Local Injection Site AEs, by Severity Within 7 Days Post Vaccination at Day 90 | Solicited local AEs at injection site are defined as injection site pain, injection site erythema, and injection site swelling. The AEs will be graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe. | Within 7 days postvaccination at Day 90 | 
| Number of Participants with Solicited Systemic AEs by Severity Within 14 Days Post Vaccination at Day 1 | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. Solicited systemic AEs assessments for children <6 years old include: drowsiness, irritability/fussiness, loss of appetite and fever, and those for children ≥ 6 years old/adolescent/adult include: headache, asthenia, malaise, myalgia and fever. The AEs will be graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe. | Within 14 days postvaccination at Day 1 | 
| Number of Participants with Solicited Systemic AEs, by Severity Within 14 Days Post Vaccination at Day 90 | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. Solicited systemic AEs assessments for children <6 years old include: drowsiness, irritability/fussiness, loss of appetite and fever, and those for children ≥ 6 years old/adolescent/adult include: headache, asthenia, malaise, myalgia and fever. The AEs will be graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe. | Within 14 days postvaccination at Day 90 | 
| Percentage of Participants with Any Unsolicited AEs Within 28 Days Post Vaccination at Day 1 | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. | Within 28 days postvaccination at Day 1 | 
| Percentage of Participants with Any Unsolicited AEs Within 28 Days Post Vaccination at Day 90 | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. | Within 28 days postvaccination at Day 90 | 
| Percentage of Participants with an AE Leading to Participant Withdrawal from Trial | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. | From first vaccination on Day 1 through the end of trial (up to Day 270) | 
| Percentage of Participants with an AE Leading to TDV or Placebo Discontinuation. | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. | From first vaccination on Day 1 through the end of trial (up to Day 270) | 
| Percentage of Participants with a Medically-attended AE (MAAE) | 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. | From first vaccination on Day 1 through the end of trial (up to Day 270) | 
| Percentage of Participants with a Serious Adverse Event (SAE) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An SAE is 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. | From first vaccination on Day 1 through the end of trial (up to Day 270) | 
| Geometric Mean Titers (GMTs) of Neutralizing Antibodies by Microneutralization Test for Each of the 4 Dengue Virus Serotypes | GMTs of neutralizing antibodies will be measured by microneutralization test 50% [MNT50] for each of the 4 Dengue Serotypes for all participants. The 4 dengue virus serotypes are dengue virus (DENV)-1, DENV-2, DENV-3 and DENV-4. | Day 120 (Month 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers by Microneutralization Test for Each of the 4 Dengue Virus Serotypes | GMTs of neutralizing antibodies will be measured by MNT50 for each of the 4 Dengue Serotypes for all participants. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. | Day 1 and Day 270 | 
| Percentage of Participants With Seroconversion for Each of the 4 Dengue Virus Serotypes | Seroconversion rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositive is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. | Day 1, Day 120 and Day 270 | 
| Percentage of Participants With Seroconversion for Multiple (2, 3, or 4) Dengue Virus Serotypes | Seroconversion rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositive is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. | Day 1, Day 120 and Day 270 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug Therapy