Clinical trial NCT03423173: Lot-to-lot Consistency of 3 Lots of Tetravalent Dengue Vaccine (TDV) in Non-endemic Country(Ies) for Dengue
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Demonstrate Lot-to-Lot Consistency of 3 Lots of a Tetravalent Dengue Vaccine Candidate in Healthy Adults in Non-Endemic Country(Ies) for Dengue
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dengue Fever
Keywords: Vaccine
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-02-06
Enrollment: 923
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 purpose of this study is to investigate lot-to-lot consistency in terms of equivalence of the immune responses induced by 3 consecutive TDV lots in healthy participants aged 18 to 60 years in non-endemic country(ies) for dengue.

Detailed description: The vaccine tested in this study is Takeda's Tetravalent Dengue Vaccine Candidate (TDV). The primary objective of this trial is to investigate lot-to-lot consistency in terms of equivalence of the immune responses induced by 3 consecutive lots of TDV in healthy participants in non-endemic country(ies) for dengue.

The study will enroll approximately 924 healthy participants. Participants will be randomized in 2:2:2:1 to one of 4 trial groups to receive TDV (Lots 1, 2 or 3) or placebo:

* TDV 0.5 mL subcutaneous injection OR
* Placebo normal saline solution (0.9% NaCl) for injection.

In each trial group, all participants will receive 2 doses of TDV or placebo by subcutaneous injection on Days 1 (Month 0) and 90 (Month 3). Immunogenicity will be assessed in participants included in the immunogenicity subset (TDV groups: 176 participants each and placebo group: 88 participants) and safety will be assessed in all participants in each group.

This multi-center trial will be conducted in the United States. The overall time to participate in this study is 270 days. Participants will make multiple visits to the clinic including a final visit at Day 270.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Signs and dates a written informed consent form 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.

Exclusion Criteria:

1. Has an elevated oral temperature (≥38°C or 100.4°F) within 3 days of the intended date of vaccination.
2. Known hypersensitivity or allergy to any of the vaccine components (including excipients of the investigational vaccine or placebo).
3. Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (e.g., Guillain-Barré syndrome).
4. Known or suspected impairment/alteration of immune function, including:

   1. Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (M0) (use of inhaled, intranasal, or topical corticosteroids is allowed)
   2. Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥ 2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (M0).
   3. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (M0) or planned administration during the trial.
   4. Receipt of immunostimulants within 60 days prior to Day 1 (M0).
   5. Hepatitis C virus infection.
   6. Genetic immunodeficiency.
5. Has abnormalities of splenic or thymic function.
6. Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
7. Has any serious chronic or progressive disease according to judgment of the Investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
8. Has body mass index (BMI) greater than or equal to 35 kg/m\^2 (= weight in kg/\[height in meters\^2\]).
9. Has history of substance or alcohol abuse within the past 2 years.
10. Had previous and planned vaccination (during the trial conduct) against any flavivirus including dengue, yellow fever (YF), Japanese encephalitis (JE) viruses or tick-borne encephalitis.
11. Has a current or previous infection with a flavivirus such as dengue, Zika, YF, JE, West Nile (WN) fever, tick-borne encephalitis or Murray Valley encephalitis and participants with a history of prolonged (≥1 year) habitation in a dengue endemic area.

Primary outcomes:
measure: Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 120 in the Immunogenicity Subset
timeFrame: 1 month post second dose (Day 120)
Secondary outcomes:
measure: Percentage of Participants Who Are Seropositive for Each of the 4 Dengue Serotypes at Days 120 and 270 in the Immunogenicity Subset
timeFrame: 1 month post second dose (Day 120) and 6 months post second dose (Day 270)
measure: GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270 in the Immunogenicity Subset
timeFrame: 6 months post second dose (Day 270)
measure: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination
timeFrame: Within 7 Days of each Vaccination (day of vaccination + 6 days)
measure: Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination
timeFrame: Within 14 Days of each Vaccination (day of vaccination + 13 days)
measure: Percentage of Participants With Any Unsolicited Adverse Events (AEs) After Each Vaccination
timeFrame: Within 28 days (day of vaccination + 27 days) after each vaccination
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: From the first vaccination on Day 1 until the end of the trial (Day 270)
measure: Percentage of Participants With Medically Attended Adverse Events (MAAEs)
timeFrame: From the first vaccination on Day 1 until the end of the trial (Day 270)
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Optimal Research
state: Alabama
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Boise
country: United States
facility: Advanced Clinical Research
state: Idaho
city: Peoria
country: United States
facility: Optimal Research
state: Illinois
city: Council Bluffs
country: United States
facility: Synexus Limited- Council Bluffs
state: Iowa
city: Augusta
country: United States
facility: Heartland Research Associates LLC - Augusta
state: Kansas
city: Park City
country: United States
facility: Heartland Research Associates LLC
state: Kansas
city: Rockville
country: United States
facility: Optimal Research
state: Maryland
city: Edina
country: United States
facility: Synexus Limited - Minneapolis
state: Minnesota
city: Saint Louis
country: United States
facility: Synexus Limited - St. Louis
state: Missouri
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada
state: Nevada
city: Columbus
country: United States
facility: Synexus Limited - Columbus
state: Ohio
city: Salt Lake City
country: United States
facility: Advanced Clinical Research
state: Utah
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: