A Comparison of the Safety and Immunogenicity of Various Schedules of Dengue Vaccine in Healthy Adult Volunteers

A Randomized, Phase 1b Study to Investigate the Safety and Immunogenicity of Various Schedules of Tetravalent Chimeric Dengue Vaccine in Healthy Adult Volunteers Between the Ages of 18 - 45 Years

A Phase 1 study to compare the safety, tolerability and immunogenicity of different dose schedules of subcutaneously (SC) administered dengue vaccine in healthy adults and to compare the immunogenicity of different dose schedules of the vaccine.

Blood samples were obtained for safety labs on Days 0, 7, 14, 90, 97, 104 and measurement of viremia at baseline [during the screening period or on day of vaccination (Day 0)], and then on Days 7, 9, 11, 14, 17, 21, 90, 97, and 104. Blood samples for measurement of dengue neutralizing antibodies in serum were obtained at baseline [during the screening period or on day of vaccination (Day 0)], then on Days 30, 90 and 120.

The entire duration for each individual subjects participation was approximately 5 months including recruitment and collection of data for primary outcomes (through Day 120).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV); Biological: TDV New Formulation; Drug: New Formulation Placebo

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Fort Collins, Colorado, United States, 80528
      • Heart Center of the Rockies
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch
  • Utah
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female at least 18 years and ≤ 45 years old at time of screening
2. In good health as determined by medical history, physical examination including height and weight
3. Normal clinical safety laboratory examinations [Sodium (Na), Potassium (K), Glucose, Blood Urea Nitrogen (BUN), creatinine, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), total bilirubin, White Blood Cell (WBC), neutrophil count, hemoglobin, platelets, Prothrombin Time (PT), Partial Thromboplastin Time (PTT), and urinalysis (by dipstick)].
4. Weight: Body Mass Index (BMI) ≤32
5. Blood tests negative for antibodies to Human Immuno-virus (HIV-1), Hepatitis C, and Hepatitis B surface antigen

Exclusion Criteria:

1. Any condition which would limit the subject's ability to complete the study in the opinion of the Investigator
2. Clinically significant ECG findings
3. History of any significant dermatologic disease in the last 6 months,
4. History of diabetes mellitus
5. History of recurring headaches or migraines (more frequent than once per week) or on prescription medication for treatment of recurring headaches or migraines
6. Hypersensitivity to any vaccine
7. Receipt of any vaccine in the 4 weeks preceding the first vaccination
8. Planned receipt of any vaccine in the 4 weeks following each of the vaccinations in this study
9. Known history of Japanese Encephalitis Virus (JEV) and/or Yellow Fever (YF)
10. Previous vaccination (in a clinical trial or with an approved product) against flaviviruses including dengue, yellow fever (YF) and Japanese Encephalitis (JE)
11. Seropositivity to dengue or West Nile (WN) virus
12. Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months
13. Use within the previous 6 months of systemic corticosteroids therapy (at a dose of at least 0.5 mg/kg/day). Topical prednisone is not permitted if currently in use or within the last 3 months. Note, inhaled prednisone (or equivalent) is allowed
14. Use of any non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen or antihistamines for the 3 days immediately prior to each vaccination
15. Use of any prescription or over the counter medications (besides those specifically mentioned above or those required for medical management of concurrent diseases) 7 days before the first vaccination (Day 0)
16. Positive urine screen for cocaine, amphetamines, opiates, or cannabinoids
17. Donation of blood 6 weeks before the first dose(s) (Day 0) until 30 days after the dose on day 90
18. Females who are pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1; Takeda's Tetravalent Dengue Vaccine Candidate (TDV), 0.5 mL, subcutaneous injection in one arm and placebo, 0.5 mL, subcutaneous injection in the other arm on Day 0. TDV, 0.5 mL, subcutaneous injection on Day 90.	Drug: Placebo; Placebo subcutaneous injection; Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV); TDV subcutaneous injection
EXPERIMENTAL: Group 2; TDV, 0.5 mL, subcutaneous injection in one arm and TDV 0.5 mL, subcutaneous injection in the other arm on Day 0. Placebo, 0.5 mL, subcutaneous injection on Day 90.	Drug: Placebo; Placebo subcutaneous injection; Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV); TDV subcutaneous injection
EXPERIMENTAL: Group 3; TDV, 0.5 mL, subcutaneous injection in one arm and TDV, 0.5 mL, subcutaneous injection in the other arm on Day 0. TDV, 0.5 mL, subcutaneous injection on Day 90.	Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV); TDV subcutaneous injection
EXPERIMENTAL: Group 4; TDV new formulation, 0.5 mL, subcutaneous injection in one arm and new formulation placebo, 0.5 mL, subcutaneous injection in the other arm on Days 0 and 90.	Biological: TDV New Formulation; TDV New Formulation subcutaneous injection; Drug: New Formulation Placebo; New Formulation placebo subcutaneous injection
EXPERIMENTAL: Group 5; TDV new formulation, 0.5 mL, subcutaneous injection in one arm and TDV new formulation, 0.5 mL, subcutaneous injection in the other arm on Days 0 and 90.	Biological: TDV New Formulation; TDV New Formulation subcutaneous injection; Drug: New Formulation Placebo; New Formulation placebo subcutaneous injection
EXPERIMENTAL: Group 6; 1/10 TDV, 0.5 mL, subcutaneous injection on Days 1 and 90.	Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV); TDV subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Injection Site Reactions Following Either Vaccine Dose Worst Severity Reported	Erythema and Edema Were Graded Per The FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Where Grade 0=none to Grade 4=Severe. Pain and Itching were graded using Common Terminology Criteria for Adverse Events (CTCAE) 4.03 where Grade 0=no pain or itching to Grade 4= Life-threatening/severe. Only those score categories for which there was at least 1 participant are reported.	Day 0 to Day 104
Number of Participants With at Least 1 Adverse Event Following Either Vaccine Dose	An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.	For 30 days after each dose (Up to Day 120)
Number of Participants With at Least 1 Adverse Events Related to TDV Following Either Vaccine Dose	An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. Some AEs are automatically considered related because of temporal relationship to vaccination.	For 30 days after each dose (Up to Day 120)
Rate of Seroconversion to Each of Four Dengue Serotypes	Rate of seroconversion was defined as the percentage of participants with Plaque Reduction Neutralization Test titer resulting in 50 % reduction in Plagues (PRNT50) titer ≥ 10 for participants seronegative at Baseline or a greater than four-fold increase in PRNT50 for participants seropositive at Baseline.	Up to 30 days after the last immunization (Up to Day 120)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Serotype-Specific TDV Viral RNA Detected After First and Second Vaccinations	Serotype-Specific TDV Viral RNA was assessed for the four dengue serotypes: Dengue-1, Dengue-2, Dengue-3 and Dengue-4 . Only those serotypes and time-points where at least 1 participant had Serotype-Specific TDV Viral RNA Detected is reported.	various timepoints up to 30 days after each dose (Up to Day 120)
Geometric Mean Neutralizing Antibody Titers (GMTs) of All Four Dengue Serotypes		Days 30, 90 and 120 after 1st vaccination

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Gilad Gordon, MD, Inviragen Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2012
• Primary Completion (ACTUAL): January 1, 2014
• Study Completion (ACTUAL): January 10, 2014

Study Registration Dates

• First Submitted: February 27, 2012
• First Submitted That Met QC Criteria: March 1, 2012
• First Posted (ESTIMATE): March 2, 2012

Study Record Updates

• Last Update Posted (ACTUAL): July 18, 2019
• Last Update Submitted That Met QC Criteria: July 16, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: safety and immunogenicity of dengue vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Dengue
• Other Study ID Numbers: INV-DEN-104; U1111-1177-8166 (REGISTRY: WHO)