Clinical trial NCT01224639: Safety and Immunogenicity Study to Assess TDV, a Live Attenuated Tetravalent Vaccine for Prevention of Dengue Fever
Official title: Phase I, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study to Assess the Safety and Immunogenicity of DENVax Vaccine in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dengue Fever
Keywords: dengue fever
live attenuated tetravalent dengue vaccine
TDV
Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-10-20
Enrollment: 96
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 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).

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.
* Has receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
* Planned receipt of any vaccine in the 4 weeks following each of the vaccinations in this study.
* Travel to dengue-endemic areas in the two months prior to study start or planned travel to dengue-endemic areas during the study period, including low altitude regions of Colombia where dengue is endemic.
* Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months prior to the first vaccination, or long- term (at least 2 weeks within the previous 3 months) systemic corticosteroids therapy (at a dose of at least 0.5 milligram per kilogram per day \[mg/kg/day\]) prior to the first vaccination.
* Has a history of recurring migraines or on prescription medication for treatment of recurring headaches or migraines.
* Use of any non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen or antihistamines for the 3 days immediately prior to each vaccination.
* Use of prescription or over the counter medications 7 days before the first vaccination (Day 0), excluding contraceptives and painkillers containing NSAIDs or acetaminophen, cold remedies, hormone replacement and antihistamines.
* Positive urine screen for cocaine, amphetamines, opiates, or cannabinoids.
* Receipt of any other investigational product or participation in any other clinical trial in the month before the first vaccination (Day 0) or during the conduct of this study.
* Receipt of blood products or immunoglobulins 8 weeks before the first vaccination (Day 0) or planned use during the study period.
* Donation of blood 6 weeks before the first vaccination (Day 0) or at any time during the study.
* Females who are pregnant or lactating.

Primary outcomes:
measure: Number of Participants With Local Injection Site Reaction by Severity
timeFrame: Within 14 days after either of the vaccination given on Day 1 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
measure: Number of Participants With Systemic Adverse Events (AEs) by Severity
timeFrame: Within 14 days after either of the vaccination given on Day 1 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
measure: Number of Participants With Solicited Local and Systemic AEs
timeFrame: Within 14 days after either of the vaccination given on Day 1 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
measure: Number of Participants With Unsolicited Local and Systemic AEs
timeFrame: Baseline up to 30 days after second vaccination (Day 120)
Secondary outcomes:
measure: Geometric Mean Neutralizing Antibody Titers (GMTs) of All Four Dengue Serotypes After First Vaccination
timeFrame: Days 14, 30, 60 and 90 after first vaccination
measure: GMTs of All Four Dengue Serotypes After Second Vaccination
timeFrame: Days 14 and 30 after second vaccination (Day 104 and 120 respectively)
measure: Rate of Seroconversion to Each of Four Dengue Serotypes After the First Vaccination
timeFrame: Days 14, 30, 60 and 90 after first vaccination
measure: Rate of Seroconversion to Each of Four Dengue Serotypes After the Second Vaccination
timeFrame: Days 14 and 30 after second vaccination (Days 104 and 120 respectively)
measure: Percentage of Participants With Durability of Immune Response
timeFrame: Days 180 and 270
measure: Number of Participants Positive for Vaccine Viremia for Each of the Four Vaccine Strain Serotypes After the First and Second Vaccination
timeFrame: Baseline and at multiple time points up to Day 14 after each vaccination
measure: Duration of Vaccine Viremia
timeFrame: 14 Days after each vaccination
measure: Titers of Vaccine Viremia
timeFrame: 14 Days after each vaccination
Other outcomes:
Locations:
city: Medellin
country: Colombia
facility: Program For The Study and Control of Tropical Diseases
Study officials:
affiliation: PECET, Universidad the Antioquia, Medellin, Colombia
name: Ivan D Velez, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Osorio JE, Velez ID, Thomson C, Lopez L, Jimenez A, Haller AA, Silengo S, Scott J, Boroughs KL, Stovall JL, Luy BE, Arguello J, Beatty ME, Santangelo J, Gordon GS, Huang CY, Stinchcomb DT. Safety and immunogenicity of a recombinant live attenuated tetravalent dengue vaccine (DENVax) in flavivirus-naive healthy adults in Colombia: a randomised, placebo-controlled, phase 1 study. Lancet Infect Dis. 2014 Sep;14(9):830-8. doi: 10.1016/S1473-3099(14)70811-4. Epub 2014 Jul 23.