Safety and Immunogenicity Study to Assess TDV, a Live Attenuated Tetravalent Vaccine for Prevention of Dengue Fever

NCT01224639 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: INV-DEN-102U1111-1181-8290
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

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.

Conditions

Dengue Fever

Keywords

dengue fever; live attenuated tetravalent dengue vaccine; TDV; Drug therapy

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Local Injection Site Reaction by Severity

  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).

  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

  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.

  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 Solicited Local and Systemic AEs

  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 Unsolicited Local and Systemic AEs

  Baseline up to 30 days after second vaccination (Day 120)

Secondary Outcomes (8)

• Geometric Mean Neutralizing Antibody Titers (GMTs) of All Four Dengue Serotypes After First Vaccination

  Days 14, 30, 60 and 90 after first 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

• 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)

• Percentage of Participants With Durability of Immune Response

  Days 180 and 270

Study Arms (6)

Group 1: Low Dose; SC

EXPERIMENTAL

TDV-1: 8 x 10\^3 Plaque Forming Units (PFU), TDV-2: 5 x 10\^3 PFU, TDV-3: 1 x 10\^4 PFU, TDV-4: 2 x 10\^5 PFU or placebo administered subcutaneously on Days 0 and 90. Dose volume is 0.5 mL.

Biological: TDV - Low Dose

Group 2: Low Dose; ID

EXPERIMENTAL

TDV-1: 8 x 10\^3 PFU, TDV-2: 5 x 10\^3 PFU, TDV-3: 1 x 10\^4 PFU, TDV-4: 2 x 10\^5 PFU or placebo administered intradermally on Days 0 and 90. Dose volume is 0.1 mL.

Biological: TDV - Low Dose

Group 3: High Dose; SC

EXPERIMENTAL

TDV-1: 2 x 10\^4 PFU, TDV-2: 5 x 10\^4 PFU, TDV-3: 1 x 10\^5 PFU, TDV-4: 3 x 10\^5 PFU or placebo administered subcutaneously on Days 0 and 90. Dose volume is 0.5 mL.

Biological: TDV - High Dose

Group 4: High Dose; ID

EXPERIMENTAL

TDV-1: 2 x 10\^4 PFU, TDV-2: 5 x 10\^4 PFU, TDV-3: 1 x 10\^5 PFU, TDV-4: 3 x 10\^5 PFU or placebo administered intradermally on Days 0 and 90. Dose volume is 0.1 mL.

Biological: TDV - High Dose

Placebo (SC)

PLACEBO COMPARATOR

Phosphate buffered saline administered subcutaneously in a volume of 0.5 mL.

Biological: Placebo

Placebo (ID)

PLACEBO COMPARATOR

Phosphate buffered saline administered intradermally in a dose volume of 0.1 mL.

Biological: Placebo

Interventions

TDV - Low Dose BIOLOGICAL

TDV is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. Low dose contains: TDV-1: 8 x 10\^3 PFU, TDV-2: 5 x 10\^3 PFU, TDV-3: 1 x 10\^4 PFU, and TDV-4: 2 x 10\^5 PFU, total virus per dose 2.2 x 10\^5 PFU

Also known as: Live attenuated tetravalent dengue vaccine

Group 1: Low Dose; SC; Group 2: Low Dose; ID

TDV - High Dose BIOLOGICAL

TDV is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. High dose contains TDV-1: 2 x 10\^4 PFU, TDV-2: 5 x 10\^4 PFU, TDV-3: 1 x 10\^5 PFU, and TDV-4: 3 x 10\^5 PFU, total virus per dose : 4.7 x 10\^5 PFU. TDV administered intradermally.

Also known as: Live attenuated tetravalent dengue vaccine

Group 3: High Dose; SC; Group 4: High Dose; ID

Placebo BIOLOGICAL

Phosphate Buffered Saline (PBS)

Also known as: PBS

Placebo (ID); Placebo (SC)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Inviragen Inc.: lead

Study Sites (1)

Program For The Study and Control of Tropical Diseases

Medellín, Colombia

Location

Related Publications (1)

• 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.

  PMID: 25087476 DERIVED

MeSH Terms

Conditions

Dengue

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Ivan D Velez, MD, Ph.D.

  PECET, Universidad the Antioquia, Medellin, Colombia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2010
• First Posted: October 20, 2010
• Study Start: October 11, 2010
• Primary Completion: June 9, 2011
• Study Completion: November 9, 2011
• Last Updated: June 19, 2018
• Results First Posted: February 27, 2017

Record last verified: 2018-06

Locations

CO (1)