Clinical trial NCT01511250: Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine in Healthy Volunteers Between the Ages of 1.5 - 45 Years
Official title: A Double-Blind, Randomized, Placebo-Controlled, Age Descending and Expansion Phase 2 Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine in Healthy Volunteers Between the Ages of 1.5 - 45 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Healthy
Keywords: Normal healthy adults and children
Safety and tolerability
Active vaccine
Placebo
Dengue virus vaccine
Immune response
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2012-01-18
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: CHILD
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 (TDV) (previously DENVax) administered subcutaneously in healthy adults and children. In addition the antibody response to the four dengue virus serotypes will be evaluated.

Detailed description: The vaccine tested in this study was tetravalent dengue vaccine (TDV). TDV was tested to assess safety and immunogenicity in healthy adults and children living in dengue endemic countries.

The study enrolled 360 healthy participants. The study was conducted in 2 parts, Part 1 - age descending and and Part 2 - expansion - ages 1.5-11 years. Participants were allocated to one of the four age cohorts in Part 1 (21 to 45 years, 12 to 20 years, 6 to 11 years, and 1.5 to 5 years) and expansion age cohort 1.5-11 years in Part 2. Participants were randomized in 2:1 ratio and in 3: 1 ratio in Part 1 and 2 respectively to receive:

* TDV 0.5 mL SC injection
* Placebo (inactive solution) - this is a solution that looks like the study drug but has no active ingredient

This multi-center trial was conducted worldwide. The overall time to participate in this study was up to 37 months (including screening period). Participants made multiple visits to the clinic including a final visit at Day 1080.

Eligibility criteria: Inclusion Criteria:

* In good health as determined by medical history, physical examination including height and weight
* Normal safety laboratory values at screening
* 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
* Weight: Within 1.3 times of the upper limit of local normal age-adjusted body mass index (BMI)

Exclusion Criteria:

* For participants ≥12 years, clinically significant electrocardiogram (ECG) findings
* History of significant dermatologic (skin) disease within last 6 months
* History of diabetes mellitus
* History of thymic pathology, thymectomy, myasthenia or any immunodeficiency
* History of recurring headaches or migraines
* Hypersensitivity to any vaccine
* For participants ≥12 years, positive urine screen for cocaine, amphetamines, opiates, or cannabinoids
* History of alcohol abuse
* Pregnant or lactating female

Primary outcomes:
measure: Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity
timeFrame: Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
measure: Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (In Clinic Assessment) Following Either Vaccination Dose by Severity
timeFrame: Within 28 days after either of the vaccination given on Day 0 or 90 (Day 28 for first vaccination, Day 118 for second vaccination)
measure: Number of Participants With Solicited Systemic Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity
timeFrame: Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
measure: Number of Participants With Any Solicited AE Following Either Vaccination Dose
timeFrame: Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
measure: Number of Participants With at Least One Unsolicited AE Following Either Vaccination Dose by Severity
timeFrame: Unsolicited AEs were collected within 28 days of all vaccinations. Serious AEs were collected throughout the study up to Day 1080
measure: Seropositivity Rate to Each of the Four Dengue Serotypes at Day 120
timeFrame: 30 days after second vaccination (Day 120)
Secondary outcomes:
measure: Part I: Number of Participants Positive for Vaccine Viremia for Each of Four Vaccine Strain Serotypes After the Each Vaccination
timeFrame: Days 0, 7, 14, 90, 97, and 104
measure: Part I: Duration of Vaccine Viremia
timeFrame: Days 0, 7, 14, 90, 97, and 104
measure: Part I: Titers of Vaccine Viremia
timeFrame: Days 0, 7, 14, 90, 97, and 104
measure: Seropositivity Rate to Each of the Four Dengue Serotypes
timeFrame: Day 28 and Day 90 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1
measure: Seroconversion Rate to Each of the Four Dengue Serotypes
timeFrame: Day 28, 90 and 120 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1
measure: Geometric Mean Neutralizing Antibody Titers (GMTs) of All Four Dengue Serotypes
timeFrame: Day 28, 90 and 120 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1
measure: Geometric Mean Fold Rise (GMFR) of Dengue Neutralizing Antibody Titers for Each of the 4 Dengue Serotypes
timeFrame: Day 28 and Day 90 (Parts 1 and 2) and Days 120, 180, 360, 720 and 1080 in Part 1
measure: Number of Participants With Confirmed Dengue Fever
timeFrame: Day 1 to Day 1080
Other outcomes:
Locations:
city: Medellin
country: Colombia
facility: Program For The Study and Control of Tropical Diseases
city: Ponce
country: Puerto Rico
facility: Ponce School of Medicine, CAIMED Center
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico School of Medicine
city: San Juan
country: Puerto Rico
facility: Latin Clinical Trial Center
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Changi General Hospital
city: Bangkok
country: Thailand
facility: Faculty of Tropical Medicine, Mahidol University
state: Krung Thep Maha Nakhon
city: Bangkok
country: Thailand
facility: Phramongkutklao Hospital
state: Krung Thep Maha Nakhon
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Tsuji I, Dominguez D, Egan MA, Dean HJ. Development of a Novel Assay to Assess the Avidity of Dengue Virus-Specific Antibodies Elicited in Response to a Tetravalent Dengue Vaccine. J Infect Dis. 2022 May 4;225(9):1533-1544. doi: 10.1093/infdis/jiab064.
citation: Sirivichayakul C, Barranco-Santana EA, Rivera IE, Kilbury J, Raanan M, Borkowski A, Papadimitriou A, Wallace D. Long-term Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Children and Adults: A Randomized, Placebo-Controlled, Phase 2 Study. J Infect Dis. 2022 May 4;225(9):1513-1520. doi: 10.1093/infdis/jiaa406.
citation: Sharma M, Glasner DR, Watkins H, Puerta-Guardo H, Kassa Y, Egan MA, Dean H, Harris E. Magnitude and Functionality of the NS1-Specific Antibody Response Elicited by a Live-Attenuated Tetravalent Dengue Vaccine Candidate. J Infect Dis. 2020 Mar 2;221(6):867-877. doi: 10.1093/infdis/jiz081.
citation: Rupp R, Luckasen GJ, Kirstein JL, Osorio JE, Santangelo JD, Raanan M, Smith MK, Wallace D, Gordon GS, Stinchcomb DT. Safety and immunogenicity of different doses and schedules of a live attenuated tetravalent dengue vaccine (TDV) in healthy adults: A Phase 1b randomized study. Vaccine. 2015 Nov 17;33(46):6351-9. doi: 10.1016/j.vaccine.2015.09.008. Epub 2015 Sep 15.