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
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Healthy Volunteers
- Sponsor
- Takeda
- Enrollment
- 20099
- Locations
- 28
- Primary Endpoint
- Vaccine Efficacy (VE) of Two Doses of Tetravalent Dengue Vaccine Candidate (TDV) in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief Summary
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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Is aged 4 to 16 years, inclusive, at the time of randomization.
- •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.
- •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.
- •Can comply with trial procedures and are available for the duration of follow-up.
- •Inclusion criteria for Booster Phase:
- •Is included in the per-protocol set (PPS) of the trial.
- •Was aged 4 to 11 years at the time of randomization in the study (Day 1 \[Month 0\]).
Exclusion Criteria
- •Has febrile illness (temperature ≥38°C) or moderate or severe acute illness or infection at the time of randomization.
- •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.
- •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).
- •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.
- •Has previously participated in any clinical trial of a dengue candidate vaccine, or previous receipt of a dengue vaccine.
- •Is first degree relative of individuals involved in trial conduct.
- •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).
- •Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method up to 6 weeks post-second vaccination.
- •Deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized involuntarily.
- •Current alcohol abuse or drug addiction that may interfere with the participant's ability to comply with trial procedures.
Arms & Interventions
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.
Intervention: Placebo
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.
Intervention: Tetravalent Dengue Vaccine (TDV)
Outcomes
Primary Outcomes
Vaccine Efficacy (VE) of Two Doses of Tetravalent Dengue Vaccine Candidate (TDV) in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype
Time Frame: 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
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.
Secondary Outcomes
- VE of Two Doses of TDV in Preventing Hospitalization Due to Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype(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(From 30 days post-second vaccination (Day 120 [Month 4]) until the end of Part 2 (Month 21))
- Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity in the Safety Set Immunogenicity Subset(Days 1 through 14 after each vaccination on Day 1 (Month 0) and Day 90 (Month 3))
- VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype in Participants Dengue Seronegative at Baseline(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(From 30 days post-second vaccination (Day 120 [Month 4]) until the end of Part 2 (Month 21))
- Percentage of Participants With Any Unsolicited Adverse Events (AEs) in the Safety Set Immunogenicity Subset(Days 1 through 28 after each vaccination on Day 1 (Month 0) and Day 90 (Month 3))
- VE of Two Doses of TDV in Preventing Virologically-Confirmed Severe Dengue Fever Induced by Any Dengue Serotype(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(Days 1 through 7 after each vaccination)
- Percentage of Participants With Serious Adverse Events (SAEs) During Parts 1 and 2(From Day 1 until the end of Parts 1 (Month 15) and 2 (Month 21))
- Seropositivity Rate for Each of the Four Dengue Serotypes in the Immunogenicity Subset(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(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))
- Percentage of Participants With Fatal SAEs and SAEs Related to Study Drug During the First and Second Half of Part 3(First and Second half (18 months each) of Part 3 (up to 3 years, beginning at Month 22))
- Seropositivity Rate for Multiple Dengue Serotypes in the Immunogenicity Subset(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))