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Immunogenicity and Safety of Tetravalent Dengue Vaccine (TDV) Administered With a Yellow Fever Vaccine in Adults

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ClinicalTrials.gov Identifier: NCT03342898
Recruitment Status : Recruiting
First Posted : November 17, 2017
Last Update Posted : June 12, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda

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(ies) non-endemic for both dengue and YF.

Condition or disease Intervention/treatment Phase
Dengue Biological: Yellow Fever (YF-17D) Vaccine Biological: Tetravalent Dengue Vaccine (TDV) Biological: Placebo Phase 3

Detailed Description:

The vaccine tested in this study is TDV. TDV with concomitant administration of yellow fever (YF-17D) vaccine will be tested to assess immunogenicity and safety in healthy 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 (Month [M0]), first dose of TDV administered on Day 90 (M3) and second dose of TDV administered on Day 180 (M6).
  • Group 2: first dose of TDV+placebo concomitantly administered on Day 1 (M0), second dose of TDV administered on Day 90 (M3) and YF-17D vaccine administered on Day 180 (M6).
  • Group 3: first dose of TDV+YF-17D vaccine concomitantly administered on Day 1 (M0), second dose of TDV administered on Day 90 (M3) and placebo administered onDay 180 (M6).

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 months follow up including a final visit at Day 360 for a follow-up assessment.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 900 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
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)
Actual Study Start Date : February 28, 2018
Actual Primary Completion Date : May 29, 2018
Estimated Study Completion Date : May 17, 2019


Arm Intervention/treatment
Experimental: Group 1
YF-17D vaccine, 0.6 mL, injection, subcutaneously plus placebo, 0.5 mL, injection, subcutaneously on Day 1, followed by TDV, 0.5 mL, injection, subcutaneously (first dose) on Day 90, followed by TDV, 0.5 mL, injection, subcutaneously on Day 180 (second dose).
Biological: Yellow Fever (YF-17D) Vaccine
YF-17D subcutaneous injection

Biological: Tetravalent Dengue Vaccine (TDV)
TDV subcutaneous injection

Biological: Placebo
Normal Saline (0.9% NaCl) subcutaneous injection

Experimental: Group 2
TDV, 0.5 mL, injection, subcutaneously plus placebo, 0.5 mL injection, subcutaneously on Day 1 (first dose), followed by TDV, 0.5 mL, injection, subcutaneously on Day 90 (second dose), followed by YF-17D vaccine, 0.6 mL, injection, subcutaneously on Day 180.
Biological: Yellow Fever (YF-17D) Vaccine
YF-17D subcutaneous injection

Biological: Tetravalent Dengue Vaccine (TDV)
TDV subcutaneous injection

Biological: Placebo
Normal Saline (0.9% NaCl) subcutaneous injection

Experimental: Group 3
TDV, 0.5 mL, injection, subcutaneously plus YF-17D vaccine, 0.6 mL, injection, subcutaneously on Day 1 (first dose), followed by TDV, 0.5 mL, injection, subcutaneously on day 90 (second dose), followed by placebo, 0.5 mL, injection, subcutaneously on Day 180.
Biological: Yellow Fever (YF-17D) Vaccine
YF-17D subcutaneous injection

Biological: Tetravalent Dengue Vaccine (TDV)
TDV subcutaneous injection

Biological: Placebo
Normal Saline (0.9% NaCl) subcutaneous injection




Primary Outcome Measures :
  1. 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) in a Subset of 120 Participants in each Trial Group [ Time Frame: Day 30 ]
    Seroprotection is defined as reciprocal anti-YF neutralizing antibody titer ≥10. Immunological naivety to YF and DENV is defined as Baseline reciprocal neutralizing antibody titers <10 for YF and for the 4 dengue serotypes.


Secondary Outcome Measures :
  1. Geometric Mean Titers (GMTs) of Neutralizing Antibodies for each of the 4 Dengue Serotypes on Days 30, 90, 120, 180 and 210 in YF and DENV-naive Participants at Baseline [ 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) ]
    GMTs of neutralizing antibodies will be 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.

  2. Percentage of Participants with Seropositivity for each of the 4 Dengue Serotypes on Days 30, 90, 120, 180 and 210 in YF and DENV-naive Participants at Baseline [ 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) ]
    The percentage of seropositive participants is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10.

  3. Percentage of Participants with Seropositivity for Multiple (2, 3 or 4) Dengue Serotypes on Days 30, 90, 120, 180 and 210 in YF and DENV-naive Participants at Baseline [ 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) ]
    Seropositivity rate is defined as the percentage of seropositive participants, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10.

  4. Percentage of YF and DENV-naive Participants at Baseline who are Seroprotected against YF on Day 210 as Measured by PRNT [ Time Frame: 1 month post third vaccination (Day 210) ]
    Seroprotection is defined as reciprocal anti-YF neutralizing antibody titer ≥10.

  5. Geometric Mean Titers (GMTs) of Anti-YF Neutralizing Antibodies at Baseline in YF and DENV-Naive Participants on Days 30 and 210 [ Time Frame: 1 month post-first and -third vaccination (Days 30 and Day 210, respectively) ] in YF and DENV-Naive Participants at Baseline ]
    Geometric mean titers of YF neutralizing antibodies will be measured by plaque reduction neutralization test.

  6. Number of Participants with Solicited Local (Injection Site) Adverse Events (AEs) Following Either Vaccination Dose by Severity [ Time Frame: Within 7 Days of each Vaccination ]
    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 local injection site AEs recorded from participant's-diary. Severity grade for pain is 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). Severity grade for erythema at injection site is grade 0 (erythema <25 mm), 1 (erythema >25-≤50 mm), 2 (erythema >50-≤100 mm) and 3 (erythema >100 mm). Severity grade for swelling at injection site is grade 0 (erythema <25 mm), 1 (erythema >25-≤50 mm), 2 (erythema >50-≤100 mm) and 3 (erythema >100 mm).

  7. Number of Participants with Solicited Systemic Adverse Events Following Either Vaccination Dose by Severity [ Time Frame: Within 14 Days of each Vaccination ]
    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.

  8. Percentage of Participants with any Unsolicited Adverse Events (AEs) [ Time Frame: Within 28 days (day of vaccination+27 days) after each vaccination ]
    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.

  9. Percentage of Participants with Medically Attended Adverse Events (MAAEs) [ Time Frame: Baseline Up to Day 360 ]
    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.

  10. Percentage of Participants with Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Day 360 ]
    A SAE is defined as any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03342898


Contacts
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Contact: Takeda Study Registration Call Center +1-877-825-3327 medicalinformation@tpna.com

Locations
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United States, Alabama
Coastal Clinical Research Inc Recruiting
Mobile, Alabama, United States, 36608
United States, California
Empire Clinical Research Recruiting
Pomona, California, United States, 91767
United States, Idaho
Advanced Clinical Research Recruiting
Meridian, Idaho, United States, 83462
United States, Kansas
Johnson County Clin-Trials Recruiting
Lenexa, Kansas, United States, 66219
United States, Missouri
Center for Pharmaceutical Research Recruiting
Kansas City, Missouri, United States, 64114
United States, Nebraska
Meridian Clinical Research LLC Recruiting
Omaha, Nebraska, United States, 68134
United States, New York
Regional Clinical Research Inc. Recruiting
Endwell, New York, United States, 13760
United States, Ohio
Rapid Medical Research Inc Recruiting
Cleveland, Ohio, United States, 44122
United States, Texas
Tekton Research Recruiting
Austin, Texas, United States, 78745
United States, Utah
Advanced Clinical Research Not yet recruiting
West Jordan, Utah, United States, 84088
United States, Virginia
Clinical Research Associates of Tidewater Recruiting
Norfolk, Virginia, United States, 23507
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Medical Director Clinical Science Takeda

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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT03342898     History of Changes
Other Study ID Numbers: DEN-305
U1111-1201-5257 ( Registry Identifier: WHO )
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: June 12, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda:
Drug Therapy

Additional relevant MeSH terms:
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Dengue
Yellow Fever
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral
Vaccines
Immunologic Factors
Physiological Effects of Drugs