Back to resultsImmunogenicity and Safety of Tetravalent Dengue Vaccine (TDV) Administered With a Yellow Fever Vaccine in Adults
Primary Purpose
Dengue
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
YF-17D
TDV
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Dengue focused on measuring Drug Therapy
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.
Sites / Locations
- Coastal Clinical Research Inc
- Empire Clinical Research
- Advanced Clinical Research
- Johnson County Clin-Trials
- Center for Pharmaceutical Research
- Meridian Clinical Research LLC
- Regional Clinical Research Inc.
- Rapid Medical Research Inc
- Tekton Research
- Advanced Clinical Research
- Clinical Research Associates of Tidewater
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Group 1: YF-17D + Placebo/TDV/TDV
Group 2: TDV + Placebo/TDV/YF-17D
Group 3: TDV + YF-17D/TDV/Placebo
Arm Description
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).
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.
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.
Outcomes
Primary Outcome Measures
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)
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 Outcome Measures
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
GMTs of neutralizing antibodies was measured by microneutralization test 50% [MNT50] for each of the 4 dengue serotypes. The 4 DENV serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.
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
Seropositivity rate was defined as the percentage of seropositive participants as derived from the titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10. Seropositivity for each dengue serotype were analyzed and was summarized as: DENV-1, DENV-2, DENV-3, and DENV-4.
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
Seropositivity rate was defined as the percentage of seropositive participants, as derived from the titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10. Seropositivity for multiple dengue serotypes were summarized in the following categories: at least bivalent, at least trivalent and tetravalent.
Percentage of YF and DENV-naive Participants at Baseline Who Are Seroprotected Against YF on Day 210 as Measured by PRNT
Seroprotection was defined as reciprocal anti-YF neutralizing antibody titer ≥10.
Geometric Mean Titers (GMTs) of Anti-YF Neutralizing Antibodies at Day 30 in Participants YF and DENV-Naive at Baseline
Geometric mean titers of YF neutralizing antibodies was measured by plaque reduction neutralization test.
Geometric Mean Titers (GMTs) of Anti-YF Neutralizing Antibodies at Day 210 in Participants YF and DENV-Naive at Baseline
Geometric mean titers of YF neutralizing antibodies was measured by plaque reduction neutralization test.
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) Following Each Vaccination Dose by Severity
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. Solicited local injection site AEs recorded from participant's-diary. Severity grade at injection site for pain: Grade 0 (No Pain), 1 (did not interfere with daily activity), 2 (interference with daily activity with or without treatment) and 3 (prevents daily activity with or without treatment). For erythema: grade 0 (<25 mm), 1 (>25-≤50 mm), 2 (>50-≤100 mm) and 3 (>100 mm). For swelling: grade 0 (<25 mm), 1 (>25-≤50 mm), 2 (>50-≤100 mm) and 3 (>100 mm). Percentages were rounded off for each category. For the first vaccination (Vac.) YF is given in Arm 1 (A1) and TDV is given in Arm 2 (A2). A1 = YF for Group 1, Placebo for Group 2, and YF for Group 3; A2 = Placebo for Group 1, TDV for Group 2, and TDV for Group 3.
Percentage of Participants With Solicited Systemic Adverse Events Following Each Vaccination Dose by Severity
Solicited systemic AEs (fever, headache, asthenia, malaise, and myalgia) recorded from participant's-diary. Severity grades for headache are grade 0 (none), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity with or without treatment) and 3 (severe: prevents normal activity with or without treatment). Severity grades for asthenia, malaise and myalgia is grade 0 (none), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity), 3 (severe: prevents daily activity). Fever is defined as greater than or equal to 38º C or 100.4º C. Fever was excluded from the overall count as no severity grading was applied for it. Percentages were rounded off for each category.
Percentage of Participants With Any Unsolicited Adverse Events (AEs)
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.
Percentage of Participants With Medically Attended Adverse Events (MAAEs)
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.
Percentage of Participants With Serious Adverse Events (SAEs)
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 that may require intervention to prevent any of the above mentioned criteria and/or may expose the subject to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03342898
Brief Title
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
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
February 28, 2018 (Actual)
Primary Completion Date
May 9, 2018 (Actual)
Study Completion Date
May 22, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue
Keywords
Drug Therapy
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
900 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1: YF-17D + Placebo/TDV/TDV
Arm Type
Experimental
Arm Description
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).
Arm Title
Group 2: TDV + Placebo/TDV/YF-17D
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 3: TDV + YF-17D/TDV/Placebo
Arm Type
Experimental
Arm Description
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 Type
Biological
Intervention Name(s)
YF-17D
Intervention Description
YF-17D SC injection.
Intervention Type
Biological
Intervention Name(s)
TDV
Other Intervention Name(s)
TAK-003, DENVax
Intervention Description
TDV SC injection.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Normal Saline (0.9% NaCl) SC injection.
Primary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
Day 30
Secondary Outcome Measure Information:
Title
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
Description
GMTs of neutralizing antibodies was measured by microneutralization test 50% [MNT50] for each of the 4 dengue serotypes. The 4 DENV serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.
Time Frame
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)
Title
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
Description
Seropositivity rate was defined as the percentage of seropositive participants as derived from the titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10. Seropositivity for each dengue serotype were analyzed and was summarized as: DENV-1, DENV-2, DENV-3, and DENV-4.
Time Frame
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)
Title
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
Description
Seropositivity rate was defined as the percentage of seropositive participants, as derived from the titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10. Seropositivity for multiple dengue serotypes were summarized in the following categories: at least bivalent, at least trivalent and tetravalent.
Time Frame
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)
Title
Percentage of YF and DENV-naive Participants at Baseline Who Are Seroprotected Against YF on Day 210 as Measured by PRNT
Description
Seroprotection was defined as reciprocal anti-YF neutralizing antibody titer ≥10.
Time Frame
1-month post third vaccination (Day 210)
Title
Geometric Mean Titers (GMTs) of Anti-YF Neutralizing Antibodies at Day 30 in Participants YF and DENV-Naive at Baseline
Description
Geometric mean titers of YF neutralizing antibodies was measured by plaque reduction neutralization test.
Time Frame
1-month post-first vaccination (Day 30)
Title
Geometric Mean Titers (GMTs) of Anti-YF Neutralizing Antibodies at Day 210 in Participants YF and DENV-Naive at Baseline
Description
Geometric mean titers of YF neutralizing antibodies was measured by plaque reduction neutralization test.
Time Frame
1-month post-third vaccination (Day 210)
Title
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) Following Each Vaccination Dose by Severity
Description
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. Solicited local injection site AEs recorded from participant's-diary. Severity grade at injection site for pain: Grade 0 (No Pain), 1 (did not interfere with daily activity), 2 (interference with daily activity with or without treatment) and 3 (prevents daily activity with or without treatment). For erythema: grade 0 (<25 mm), 1 (>25-≤50 mm), 2 (>50-≤100 mm) and 3 (>100 mm). For swelling: grade 0 (<25 mm), 1 (>25-≤50 mm), 2 (>50-≤100 mm) and 3 (>100 mm). Percentages were rounded off for each category. For the first vaccination (Vac.) YF is given in Arm 1 (A1) and TDV is given in Arm 2 (A2). A1 = YF for Group 1, Placebo for Group 2, and YF for Group 3; A2 = Placebo for Group 1, TDV for Group 2, and TDV for Group 3.
Time Frame
Within 7 Days of each Vaccination (day of vaccination + 6 days)
Title
Percentage of Participants With Solicited Systemic Adverse Events Following Each Vaccination Dose by Severity
Description
Solicited systemic AEs (fever, headache, asthenia, malaise, and myalgia) recorded from participant's-diary. Severity grades for headache are grade 0 (none), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity with or without treatment) and 3 (severe: prevents normal activity with or without treatment). Severity grades for asthenia, malaise and myalgia is grade 0 (none), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity), 3 (severe: prevents daily activity). Fever is defined as greater than or equal to 38º C or 100.4º C. Fever was excluded from the overall count as no severity grading was applied for it. Percentages were rounded off for each category.
Time Frame
Within 14 Days of each Vaccination (day of vaccination + 13 days)
Title
Percentage of Participants With Any Unsolicited Adverse Events (AEs)
Description
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.
Time Frame
Within 28 days (day of vaccination + 27 days) after each vaccination
Title
Percentage of Participants With Medically Attended Adverse Events (MAAEs)
Description
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.
Time Frame
From first vaccination (Day 1) through end of study (Day 360)
Title
Percentage of Participants With Serious Adverse Events (SAEs)
Description
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 that may require intervention to prevent any of the above mentioned criteria and/or may expose the subject to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization.
Time Frame
From first vaccination (Day 1) through end of study (Day 360)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director Clinical Science
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Coastal Clinical Research Inc
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36608
Country
United States
Facility Name
Empire Clinical Research
City
Pomona
State/Province
California
ZIP/Postal Code
91767
Country
United States
Facility Name
Advanced Clinical Research
City
Meridian
State/Province
Idaho
ZIP/Postal Code
83462
Country
United States
Facility Name
Johnson County Clin-Trials
City
Lenexa
State/Province
Kansas
ZIP/Postal Code
66219
Country
United States
Facility Name
Center for Pharmaceutical Research
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64114
Country
United States
Facility Name
Meridian Clinical Research LLC
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68134
Country
United States
Facility Name
Regional Clinical Research Inc.
City
Endwell
State/Province
New York
ZIP/Postal Code
13760
Country
United States
Facility Name
Rapid Medical Research Inc
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44122
Country
United States
Facility Name
Tekton Research
City
Austin
State/Province
Texas
ZIP/Postal Code
78745
Country
United States
Facility Name
Advanced Clinical Research
City
West Jordan
State/Province
Utah
ZIP/Postal Code
84088
Country
United States
Facility Name
Clinical Research Associates of Tidewater
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
Learn more about this trial
Immunogenicity and Safety of Tetravalent Dengue Vaccine (TDV) Administered With a Yellow Fever Vaccine in Adults
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