Clinical trial NCT03342898: Immunogenicity and Safety of Tetravalent Dengue Vaccine (TDV) Administered With a Yellow Fever Vaccine in Adults
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dengue
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-11-17
Enrollment: 900
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

1. Is aged 18 to 60 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 the clinical judgment of the Investigator.

Exclusion Criteria:

1. Has an elevated oral temperature ≥ 38°C (100.4°F) within 3 days of the intended date of vaccination.
2. Has contraindications, warnings and/or precautions to vaccination with the YF-17D vaccine as specified within the product information (especially history of thymus dysfunction).
3. Female participant who are pregnant or breastfeeding
4. 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.
5. Has body mass index (BMI) greater than or equal to 35 kg/m\^2 (=weight in kg/\[height in meters\^2\]).
6. Is intent to travel to dengue or YF endemic countries during the trial period.
7. 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.
8. Has previous and planned vaccination (during the trial conduct), against any flavivirus including dengue, YF, Japanese encephalitis (JE) or tick-borne encephalitis viruses.
9. 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.
10. 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.

Primary outcomes:
measure: 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)
timeFrame: Day 30
Secondary outcomes:
measure: 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
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Percentage of YF and DENV-naive Participants at Baseline Who Are Seroprotected Against YF on Day 210 as Measured by PRNT
timeFrame: 1-month post third vaccination (Day 210)
measure: Geometric Mean Titers (GMTs) of Anti-YF Neutralizing Antibodies at Day 30 in Participants YF and DENV-Naive at Baseline
timeFrame: 1-month post-first vaccination (Day 30)
measure: Geometric Mean Titers (GMTs) of Anti-YF Neutralizing Antibodies at Day 210 in Participants YF and DENV-Naive at Baseline
timeFrame: 1-month post-third vaccination (Day 210)
measure: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) Following Each Vaccination Dose by Severity
timeFrame: Within 7 Days of each Vaccination (day of vaccination + 6 days)
measure: Percentage of Participants With Solicited Systemic Adverse Events Following Each Vaccination Dose by Severity
timeFrame: Within 14 Days of each Vaccination (day of vaccination + 13 days)
measure: Percentage of Participants With Any Unsolicited Adverse Events (AEs)
timeFrame: Within 28 days (day of vaccination + 27 days) after each vaccination
measure: Percentage of Participants With Medically Attended Adverse Events (MAAEs)
timeFrame: From first vaccination (Day 1) through end of study (Day 360)
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: From first vaccination (Day 1) through end of study (Day 360)
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Coastal Clinical Research Inc
state: Alabama
city: Pomona
country: United States
facility: Empire Clinical Research
state: California
city: Meridian
country: United States
facility: Advanced Clinical Research
state: Idaho
city: Lenexa
country: United States
facility: Johnson County Clin-Trials
state: Kansas
city: Kansas City
country: United States
facility: Center for Pharmaceutical Research
state: Missouri
city: Omaha
country: United States
facility: Meridian Clinical Research LLC
state: Nebraska
city: Endwell
country: United States
facility: Regional Clinical Research Inc.
state: New York
city: Cleveland
country: United States
facility: Rapid Medical Research Inc
state: Ohio
city: Austin
country: United States
facility: Tekton Research
state: Texas
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
city: Norfolk
country: United States
facility: Clinical Research Associates of Tidewater
state: Virginia
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: