A Randomized, Observer-Blind, Placebo-Controlled, Phase 3 Trial to Investigate the Immunogenicity and Safety of a Tetravalent Dengue Vaccine Candidate and a Yellow Fever YF-17D Vaccine Administered Concomitantly and Sequentially in Healthy Subjects Aged 18 to 60 Years in Non-Endemic Country(Ies)
Overview
- Phase
- Phase 3
- Intervention
- YF-17D
- Conditions
- Dengue
- Sponsor
- Takeda
- Enrollment
- 900
- Locations
- 10
- Primary Endpoint
- Percentage of Participants Who Are YF and Dengue Virus (DENV)-Naive at Baseline and Are Seroprotected Against YF on Day 30 as Measured by Plaque Reduction Neutralization Test (PRNT)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The main purpose of this study is to assess the immunogenicity and safety of the concomitant and sequential administration of yellow fever (YF) vaccine and tetravalent dengue vaccine (TDV) in healthy participants aged 18 to 60 years living in country non-endemic for both dengue and YF.
Detailed Description
The vaccine tested in this study is TDV also known as TAK-003 (DENVax). TDV with concomitant and sequential administration of yellow fever (YF-17D) vaccine will be tested to assess immunogenicity and safety in healthy adult participants in non-endemic area(s) for both dengue and YF. The study will enroll 900 healthy participants. Participants will be randomized to 3 groups in 1:1:1 ratio and will be administered concomitantly and sequentially. The 3 groups are: * Group 1: YF-17D vaccine + placebo concomitantly administered on Day 1, first dose of TDV administered on Day 90 and second dose of TDV administered on Day 180. * Group 2: first dose of TDV + placebo concomitantly administered on Day 1, second dose of TDV administered on Day 90 and YF-17D vaccine administered on Day 180. * Group 3: first dose of TDV + YF-17D vaccine concomitantly administered on Day 1, second dose of TDV administered on Day 90 and placebo administered on Day 180. This multi-center trial will be conducted in the United States. The overall time to participate in this study is 360 days. Participants will make multiple visits to the clinic with a 6-month follow up including a final visit at Day 360 for a follow-up assessment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Is aged 18 to 60 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 the clinical judgment of the Investigator.
Exclusion Criteria
- •Has an elevated oral temperature ≥ 38°C (100.4°F) within 3 days of the intended date of vaccination.
- •Has contraindications, warnings and/or precautions to vaccination with the YF-17D vaccine as specified within the product information (especially history of thymus dysfunction).
- •Female participant who are pregnant or breastfeeding
- •Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (e.g., Guillain-Barre syndrome) or suspected impairment/alteration of immune function.
- •Has body mass index (BMI) greater than or equal to 35 kg/m\^2 (=weight in kg/\[height in meters\^2\]).
- •Is intent to travel to dengue or YF endemic countries during the trial period.
- •Has received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial or who are planning to receive any non-trial vaccine within 28 days of trial vaccine administration.
- •Has previous and planned vaccination (during the trial conduct), against any flavivirus including dengue, YF, Japanese encephalitis (JE) or tick-borne encephalitis viruses.
- •Has previous participation in any clinical trial of a dengue or other flavivirus (e.g., West Nile \[WN\] virus) candidate vaccine, except for participants who received placebo in those trials.
- •Has a current or previous infection with a flavivirus such as dengue, Zika, YF, JE, WN fever, or Saint Louis encephalitis viruses and participants with a history of prolonged (≥1 year) habitation in a dengue endemic area.
Arms & Interventions
Group 1: YF-17D + Placebo/TDV/TDV
YF-17D vaccine, 0.5 mL injection, subcutaneously (SC) plus YF 17D + TDV placebo-matching 0.5 mL, injection, SC on Day 1, followed by TDV, 0.5 mL, injection, SC on Day 90 (first dose), followed by TDV, 0.5 mL, injection, SC on Day 180 (second dose).
Intervention: YF-17D
Group 1: YF-17D + Placebo/TDV/TDV
YF-17D vaccine, 0.5 mL injection, subcutaneously (SC) plus YF 17D + TDV placebo-matching 0.5 mL, injection, SC on Day 1, followed by TDV, 0.5 mL, injection, SC on Day 90 (first dose), followed by TDV, 0.5 mL, injection, SC on Day 180 (second dose).
Intervention: TDV
Group 1: YF-17D + Placebo/TDV/TDV
YF-17D vaccine, 0.5 mL injection, subcutaneously (SC) plus YF 17D + TDV placebo-matching 0.5 mL, injection, SC on Day 1, followed by TDV, 0.5 mL, injection, SC on Day 90 (first dose), followed by TDV, 0.5 mL, injection, SC on Day 180 (second dose).
Intervention: Placebo
Group 2: TDV + Placebo/TDV/YF-17D
TDV, 0.5 mL, injection, SC plus TDV placebo-matching, 0.5 mL injection, SC on Day 1 (first dose), followed by TDV, 0.5 mL, injection, SC on Day 90 (second dose), followed by YF-17D vaccine, 0.5 mL, injection, SC on Day 180.
Intervention: YF-17D
Group 2: TDV + Placebo/TDV/YF-17D
TDV, 0.5 mL, injection, SC plus TDV placebo-matching, 0.5 mL injection, SC on Day 1 (first dose), followed by TDV, 0.5 mL, injection, SC on Day 90 (second dose), followed by YF-17D vaccine, 0.5 mL, injection, SC on Day 180.
Intervention: TDV
Group 2: TDV + Placebo/TDV/YF-17D
TDV, 0.5 mL, injection, SC plus TDV placebo-matching, 0.5 mL injection, SC on Day 1 (first dose), followed by TDV, 0.5 mL, injection, SC on Day 90 (second dose), followed by YF-17D vaccine, 0.5 mL, injection, SC on Day 180.
Intervention: Placebo
Group 3: TDV + YF-17D/TDV/Placebo
TDV, 0.5 mL, injection, SC plus YF-17D vaccine, 0.5 mL, injection, SC on Day 1 (first dose), followed by TDV, 0.5 mL, injection, SC on day 90 (second dose), followed by TDV + YF 17D placebo-matching, 0.5 mL, injection, SC on Day 180.
Intervention: YF-17D
Group 3: TDV + YF-17D/TDV/Placebo
TDV, 0.5 mL, injection, SC plus YF-17D vaccine, 0.5 mL, injection, SC on Day 1 (first dose), followed by TDV, 0.5 mL, injection, SC on day 90 (second dose), followed by TDV + YF 17D placebo-matching, 0.5 mL, injection, SC on Day 180.
Intervention: TDV
Group 3: TDV + YF-17D/TDV/Placebo
TDV, 0.5 mL, injection, SC plus YF-17D vaccine, 0.5 mL, injection, SC on Day 1 (first dose), followed by TDV, 0.5 mL, injection, SC on day 90 (second dose), followed by TDV + YF 17D placebo-matching, 0.5 mL, injection, SC on Day 180.
Intervention: Placebo
Outcomes
Primary Outcomes
Percentage of Participants Who Are YF and Dengue Virus (DENV)-Naive at Baseline and Are Seroprotected Against YF on Day 30 as Measured by Plaque Reduction Neutralization Test (PRNT)
Time Frame: Day 30
Seroprotection was defined as reciprocal anti-YF neutralizing antibody titer ≥10. Immunological naivety to YF and DENV was defined as Baseline reciprocal neutralizing antibody titers \<10 for YF and for the 4 dengue serotypes. The 95% CI was calculated using exact Clopper-Pearson method.
Secondary Outcomes
- Geometric Mean Titers (GMTs) of Anti-YF Neutralizing Antibodies at Day 210 in Participants YF and DENV-Naive at Baseline(1-month post-third vaccination (Day 210))
- Geometric Mean Titers (GMTs) of Anti-YF Neutralizing Antibodies at Day 30 in Participants YF and DENV-Naive at Baseline(1-month post-first vaccination (Day 30))
- Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes on Days 30, 90, 120, 180 and 210 in Participants YF and DENV-naive at Baseline(Pre-second and -third vaccination (Days 90 and 180, respectively); and 1 month post -first, second, and third vaccination (Days 30, 120, and 210, respectively))
- Percentage of Participants Who Are Seropositive for Each of the 4 Dengue Serotypes on Days 30, 90, 120, 180 and 210 in Participants YF and DENV-naive at Baseline(Pre-second and -third vaccination (Days 90 and 180, respectively); and 1-month post -first, -second, and -third vaccination (Days 30, 120, and 210, respectively))
- Percentage of Participants Who Are Seropositive for Multiple (2, 3 or 4) Dengue Serotypes on Days 30, 90, 120, 180 and 210 in Participants YF and DENV-naive at Baseline(Pre-second and -third vaccination (Days 90 and 180, respectively); and 1-month post -first, second, and -third vaccination (Days 30, 120, and 210, respectively))
- Percentage of YF and DENV-naive Participants at Baseline Who Are Seroprotected Against YF on Day 210 as Measured by PRNT(1-month post third vaccination (Day 210))
- Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) Following Each Vaccination Dose by Severity(Within 7 Days of each Vaccination (day of vaccination + 6 days))
- Percentage of Participants With Solicited Systemic Adverse Events Following Each Vaccination Dose by Severity(Within 14 Days of each Vaccination (day of vaccination + 13 days))
- Percentage of Participants With Any Unsolicited Adverse Events (AEs)(Within 28 days (day of vaccination + 27 days) after each vaccination)
- Percentage of Participants With Medically Attended Adverse Events (MAAEs)(From first vaccination (Day 1) through end of study (Day 360))
- Percentage of Participants With Serious Adverse Events (SAEs)(From first vaccination (Day 1) through end of study (Day 360))