Phase I, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study to Assess the Safety and Immunogenicity of DENVax Vaccine in Healthy Adults
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Dengue Fever
- Sponsor
- Inviragen Inc.
- Enrollment
- 96
- Locations
- 1
- Primary Endpoint
- Number of Participants With Local Injection Site Reaction by Severity
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The purpose of this study is to assess the safety of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) (previously DENVax) in healthy adults when given as either a subcutaneous (SC) or intradermal (ID) injection at two dose levels (low and high). The vaccine will be given as two doses 90 days apart. Safety assessments include injection site evaluation and adverse events. The immune response generated after vaccination will be assessed up to 9 months after the first vaccination.
Detailed Description
This is a single center, placebo-controlled, randomized study assessing the safety and tolerability of two dose levels (low and high) of TDV administered subcutaneously or intradermally in two doses separated by an interval of 90 days. Initial dosing of low dose cohort will be performed and Day 21 safety assessed prior to administration of second dose to low dose cohort on Day 90 and initial dosing of high dose cohort. Day 21 safety for the high dose cohort will be assessed prior to administration of second dose for this cohort. Safety (local injection site reactions and solicited and unsolicited adverse events) will be assessed through Day 120 post-first (1 month after the second dose). Immunogenicity will be assessed at specified time points up to Day 120 post-prime (1 month after the second dose) and again on Days 180 and 270 (6 and 9 months post-first).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Is male or female aged 18 to 45 years, inclusive, at time of screening.
- •Is in good health as determined by medical history, physical examination, and clinical safety laboratory examinations.
- •Has body mass index (BMI) in the range 18-27 kilogram per square meter (kg/m\^2).
- •Has negative serology for Human Immunodeficiency Virus (HIV), Hepatitis C antibody, and Hepatitis B surface antigen.
- •Females of child bearing potential must have a negative urine pregnancy test result during screening and a negative urine pregnancy test immediately prior to vaccination and be willing to use oral, implantable, transdermal or injectable contraceptives or another reliable means of contraception approved by the Investigator (intrauterine device, female condom, diaphragm with spermicidal, cervical cap, use of condom by the sexual partner or a sterile sexual partner, or abstinence) from screening until after the last blood sample (at Day 270).
- •Is willing and able to give written informed consent to participate.
- •Is willing and able to communicate with the Investigator and understand the requirements of the study.
Exclusion Criteria
- •Has any condition which would limit the participant's ability to complete the study.
- •Clinically significant hematological, renal, hepatic, pulmonary, central nervous system, cardiovascular or gastrointestinal disorders.
- •Has abnormal electrocardiogram (ECG).
- •Has febrile illness (temperature greater than or equal to (\>=) 38 degree Celsius (°C) or 100.4 degree Fahrenheit (°F) or moderate or severe acute illness or infection within three days of vaccination.
- •Diabetes mellitus.
- •Has allergy to penicillin, neomycin, streptomycin or gentamicin.
- •Hypersensitivity to any vaccine.
- •Seropositivity to any of the four dengue serotypes (TDV-1, TDV-2, TDV-3 or TDV-4), yellow fever (YF) virus or West Nile (WN) virus.
- •Has previous vaccination (in a clinical trial or with an approved product) against flaviviruses including dengue, YF or WN.
- •Has planned vaccination against YF throughout the duration of this study.
Outcomes
Primary Outcomes
Number of Participants With Local Injection Site Reaction by Severity
Time Frame: Within 14 days after either of the vaccination given on Day 1 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
Solicited local reactions were reported using a participant diary. Pain was categorized as Mild (aware of pain but it does not interfere with daily activity and no pain medication is taken); Moderate (aware of pain; there is interference with daily activity or it requires use of pain medication); Severe (aware of pain and it prevents daily activity), redness was categorized as Mild (greater than \[\>\] 15 millimeter \[mm\]); Moderate as (15-30 mm); Severe (\>30 mm), swelling was categorized as Mild (\<15 mm); Moderate (15-30 mm); Severe (\>30 mm), and itching was categorized as Mild (slight itching at injection site); Moderate (moderate itching at injection extremity); Severe (itching over entire body).
Number of Participants With Solicited Local and Systemic AEs
Time Frame: Within 14 days after either of the vaccination given on Day 1 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
Number of Participants With Systemic Adverse Events (AEs) by Severity
Time Frame: Within 14 days after either of the vaccination given on Day 1 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
Solicited systemic AEs were reported using a participant diary. Solicited systemic AEs included fever (\>= 37.8°C), headache, muscle pain, joint pain, eye pain, photophobia, fatigue, body rash, nausea, vomiting and other (any other symptom not listed in the diary) and were categorized as Mild: transient symptoms, discomfort noticed but easily tolerated, no interference to normal daily activities; Moderate: marked symptoms, moderate interference with daily activities; Severe: considerable interference with daily activities.
Number of Participants With Unsolicited Local and Systemic AEs
Time Frame: Baseline up to 30 days after second vaccination (Day 120)
Secondary Outcomes
- Rate of Seroconversion to Each of Four Dengue Serotypes After the Second Vaccination(Days 14 and 30 after second vaccination (Days 104 and 120 respectively))
- Titers of Vaccine Viremia(14 Days after each vaccination)
- Number of Participants Positive for Vaccine Viremia for Each of the Four Vaccine Strain Serotypes After the First and Second Vaccination(Baseline and at multiple time points up to Day 14 after each vaccination)
- Duration of Vaccine Viremia(14 Days after each vaccination)
- GMTs of All Four Dengue Serotypes After Second Vaccination(Days 14 and 30 after second vaccination (Day 104 and 120 respectively))
- Rate of Seroconversion to Each of Four Dengue Serotypes After the First Vaccination(Days 14, 30, 60 and 90 after first vaccination)
- Percentage of Participants With Durability of Immune Response(Days 180 and 270)
- Geometric Mean Neutralizing Antibody Titers (GMTs) of All Four Dengue Serotypes After First Vaccination(Days 14, 30, 60 and 90 after first vaccination)