Clinical trial NCT01765426: Phase 1b Study Investigating Safety & Immunogenicity of TDV Given Intradermally by Needle or Needle-Free PharmaJet Injector
Official title: Phase 1b, Partial-Blind, Parallel Group, Randomized Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine (DENVax) Administered Intradermally Using Needle or a Needle-Free PharmaJet® Injector in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Prophylactic vaccination
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: National Institutes of Health (NIH)
First posted: 2013-01-10
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to compare the safety, tolerability and immunogenicity of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) \[previously DENVax\] when administered intradermally in varied dosing schedules and via different methods of administration (conventional needle/syringe versus needle-free PharmaJet® injector).

Detailed description: This is an exploratory trial to assess the safety, tolerability and immunogenicity of vaccination with a tetravalent dengue vaccine (TDV) in healthy adults delivered intradermally using the conventional needle/syringe or a needle-free PharmaJet® injector.

Two (2) intradermal injections of either vaccine or placebo will be administered to qualified participants (one in each arm) on Day 0 of the study. A subsequent injection will also be given on Day 90 with either vaccine or placebo (in one arm only).

Participants will be evaluated for safety and dengue neutralizing antibody to all four serotypes. All participants will also be evaluated for injection site reactions and have blood drawn for viremia, neutralizing antibodies, cell mediated immunity and innate immunity.

Participants will be required to participate for approximately 10 months from recruitment and collection of data for primary outcomes (through Day 120) including collection of additional samples for measurement of longer term antibody titers (through Day 270).

This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272201000034C.

Eligibility criteria: Inclusion Criteria:

* In good health as determined by medical history and physical examination (including blood pressure and heart rate).
* Negative for human immunodeficiency virus-1 (HIV-1) antibodies, Hepatitis C antibodies \& Hepatitis B surface antigen.
* Females negative by urine pregnancy test at screening and immediately prior to injection, and were willing to use reliable means of contraception.
* Body Mass Index (BMI) ≤ 35 kg/m\^2.

Exclusion Criteria:

* Any Grade 2 or above abnormality in the screening laboratory tests.
* History of Dengue Fever, Japanese Encephalitis, West Nile or Yellow Fever disease.
* Seropositivity to dengue or West Nile virus.
* Extensive scarring or tattoo (\> 50%) on arms, shoulders, neck face and head.
* History of significant dermatologic disease in the last 6 months.
* Receipt or planned receipt of any vaccine in the 4 weeks preceding or following the Day 0 or 90 vaccinations.
* Any planned travel to dengue endemic areas including the Caribbean, Mexico, Central America, South America or Southeast Asia, during the study period and during the month prior to screening.
* Use of systemic corticosteroids therapy within the previous 6 months (at a dose of 0.5 mg/kg/day). Topical prednisone is not permitted if currently in use or used within the last month prior to the first vaccination.
* Use of any prescribed medication 7 days before the first injection.
* Previous vaccination in a clinical study or with an approved product against Dengue Fever, Yellow Fever and or Japanese Encephalitis.
* Known or suspected congenital or acquired immunodeficiency or receipt of immunosuppressive therapy in the last 6 months.
* Planned donation of blood during the period of the study.

Primary outcomes:
measure: Percentage of Participants With Local (Injection Site) Adverse Events (AEs) After Either Vaccine Dose by Maximum Severity as Assessed by the Clinical Staff
timeFrame: 28 Days after each dose
measure: Percentage of Participants With Unsolicited Adverse Events (AE) by Maximum Severity
timeFrame: 28 Days after each dose
measure: Percentage of Participants With Solicited Systemic AEs as Reported by the Participant Using a Memory Aid 14 Days After Either Vaccine Dose by Maximum Severity
timeFrame: 14 days after each dose
measure: Percentage of Participants With Solicited Local AEs as Reported by the Participant Using a Memory Aid 14 Days After Either Vaccine Dose by Maximum Severity
timeFrame: 14 days after each dose
measure: Percentage of Participants With Unsolicited Vaccine-Related AEs Within 28 Days After Either Vaccine Dose by Maximum Severity
timeFrame: 28 Days after each dose
measure: Percentage of Participants With Abnormal Laboratory Values Reported as Adverse Events (AEs)
timeFrame: 118 Days
measure: Seroconversion Rates (SCR) for Each of the Four Dengue Serotypes After First Injection
timeFrame: Day 28
measure: Seroconversion Rates (SCR) for Each of the Four Dengue Serotypes After Second Injection
timeFrame: Day 118
measure: Percentage of Participants With Unsolicited Vaccine-Related SAEs
timeFrame: Dose 1 until 28 days after Dose 2 (Up to Day 118)
Secondary outcomes:
measure: Geometric Mean Titers of Neutralizing Antibody Titers Against Each of the Four Dengue Serotypes
timeFrame: Days 0, 28, 90, 118 and 270
measure: Seroconversion Rates (SCR) for Each of the Four Dengue Serotypes at Days 90 and 270
timeFrame: Days 90 and 270
measure: Percentage of Participants With Serotype-Specific DENVax RNA Detected Due to Each of the Four Dengue Vaccine Components After Each Vaccination
timeFrame: Day 0 to Day 104
Other outcomes:
Locations:
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Seattle
country: United States
facility: Group Health Research Institute
state: Washington
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Jackson LA, Rupp R, Papadimitriou A, Wallace D, Raanan M, Moss KJ. A phase 1 study of safety and immunogenicity following intradermal administration of a tetravalent dengue vaccine candidate. Vaccine. 2018 Jun 22;36(27):3976-3983. doi: 10.1016/j.vaccine.2018.05.028. Epub 2018 May 19.