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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Inviragen Inc.
ClinicalTrials.gov Identifier:
NCT01224639
First received: October 9, 2010
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to assess the safety of 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.


Condition Intervention Phase
Dengue Fever
Biological: DENVax - Low Dose
Biological: DENVax - High Dose
Biological: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase I, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study to Assess the Safety and Immunogenicity of DENVax Vaccine in Healthy Adults

Resource links provided by NLM:


Further study details as provided by Inviragen Inc.:

Primary Outcome Measures:
  • Number of subjects with adverse events as a measure of safety and tolerability of DENVax [ Time Frame: From the time the first dose of vaccine is administered on Day 0 to Day120. ] [ Designated as safety issue: Yes ]
    Frequency and severity of local (injection site) reactions and vaccine-associated systemic adverse events.


Secondary Outcome Measures:
  • Geometric Mean Titers (GMTs) [ Time Frame: At 14, 30, 60, and 90 days after the prime vaccination and at 14, 30, 90 and 180 days after the boost vaccination on Day 90 ] [ Designated as safety issue: No ]
    GMTs of neutralizing antibodies to all four dengue serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) for all Groups.

  • Number of subjects with neutralizing antibody titer ≥ 1:10 to each four dengue serotypes. [ Time Frame: At 14, 30, 60, and 90 days after the prime vaccination and 14 and 30 days after the boost vaccination on Day 90. ] [ Designated as safety issue: No ]
    Seroconversion rate (%) to each of four dengue serotypes, where seroconversion is defined as Plaque Reduction Neutralization Titer (PRNT50) titer of ≥ 1:10.

  • Number of subjects with viremia [ Time Frame: From Day 0 to Day 14/15 after each vaccination. ] [ Designated as safety issue: No ]
    Incidence of viremia for each of the four DENVax vaccine components (DENVax-1, DENVax-2, DENVax-3 or DENVax-4) after each vaccination.

  • Duration of viremia [ Time Frame: From Day 0 to Day 14/15 after each vaccination. ] [ Designated as safety issue: No ]
    The duration of viremia in each subject for each of the DENVax (DENVax-1, DENVax-2, DENVax-3 or DENVax-4) vaccine components.

  • Titers of viremia [ Time Frame: From Day 0 to Day 14/15 after each vaccination ] [ Designated as safety issue: No ]
    The titers for viremia for each of the four DENVax (DENVax-1, DENVax-2, DENVax-3 or DENVax-4) vaccine components.


Enrollment: 96
Study Start Date: October 2010
Study Completion Date: September 2013
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1: Low Dose; SC
DENVax-1: 8 x 10^3 Plaque Forming Units (PFU), DENVax-2: 5 x 10^3 PFU, DENVax-3: 1 x 10^4 PFU, DENVax-4: 2 x 10^5 PFU or placebo administered subcutaneously on Days 0 and 90. Dose volume is 0.5 mL.
Biological: DENVax - Low Dose
DENVax is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: DENVax-1, DENVax-2, DENVax-3 and DENVax-4. Low dose contains: DENVax-1: 8 x 10^3 PFU, DENVax-2: 5 x 10^3 PFU, DENVax-3: 1 x 10^4 PFU, and DENVax-4: 2 x 10^5 PFU, total virus per dose 2.2 x 10^5 PFU
Other Name: Live attenuated tetravalent dengue vaccine
Experimental: Group 2: Low Dose; ID
DENVax-1: 8 x 10^3 PFU, DENVax-2: 5 x 10^3 PFU, DENVax-3: 1 x 10^4 PFU, DENVax-4: 2 x 10^5 PFU or placebo administered intradermally on Days 0 and 90. Dose volume is 0.1 mL.
Biological: DENVax - Low Dose
DENVax is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: DENVax-1, DENVax-2, DENVax-3 and DENVax-4. Low dose contains: DENVax-1: 8 x 10^3 PFU, DENVax-2: 5 x 10^3 PFU, DENVax-3: 1 x 10^4 PFU, and DENVax-4: 2 x 10^5 PFU, total virus per dose 2.2 x 10^5 PFU
Other Name: Live attenuated tetravalent dengue vaccine
Experimental: Group 3: High Dose; SC
DENVax-1: 2 x 10^4 PFU, DENVax-2: 5 x 10^4 PFU, DENVax-3: 1 x 10^5 PFU, DENVax-4: 3 x 10^5 PFU or placebo administered subcutaneously on Days 0 and 90. Dose volume is 0.5 mL.
Biological: DENVax - High Dose
DENVax is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: DENVax-1, DENVax-2, DENVax-3 and DENVax-4. High dose contains DENVax-1: 2 x 10^4 PFU, DENVax-2: 5 x 10^4 PFU, DENVax-3: 1 x 10^5 PFU, and DENVax-4: 3 x 10^5 PFU, total virus per dose : 4.7 x 10^5 PFU. DENVax administered intradermally.
Other Name: Live attenuated tetravalent dengue vaccine
Experimental: Group 4: High Dose; ID
DENVax-1: 2 x 10^4 PFU, DENVax-2: 5 x 10^4 PFU, DENVax-3: 1 x 10^5 PFU, DENVax-4: 3 x 10^5 PFU or placebo administered intradermally on Days 0 and 90. Dose volume is 0.1 mL.
Biological: DENVax - High Dose
DENVax is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: DENVax-1, DENVax-2, DENVax-3 and DENVax-4. High dose contains DENVax-1: 2 x 10^4 PFU, DENVax-2: 5 x 10^4 PFU, DENVax-3: 1 x 10^5 PFU, and DENVax-4: 3 x 10^5 PFU, total virus per dose : 4.7 x 10^5 PFU. DENVax administered intradermally.
Other Name: Live attenuated tetravalent dengue vaccine
Placebo Comparator: Placebo (SC)
Phosphate buffered saline administered subcutaneously in a volume of 0.5 mL.
Biological: Placebo
Phosphate Buffered Saline (PBS)
Other Name: PBS
Placebo Comparator: Placebo (ID)
Phosphate buffered saline administered intradermally in a dose volume of 0.1 mL.
Biological: Placebo
Phosphate Buffered Saline (PBS)
Other Name: PBS

Detailed Description:

This is a single center, placebo-controlled, randomized study assessing the safety and tolerability of two dose levels (low and high) of DENVax 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 booster 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 booster dose for this cohort. Safety (local injection site reactions and solicited and unsolicited adverse events) will be assessed through Day 120 post-prime (1 month after the booster dose). Immunogenicity will be assessed at specified time points up to Day 120 post-prime (1 month after the booster dose) and again on Days 180 and 270 (6 and 9 months post-prime).

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or female aged 18 to 45 years, inclusive, at time of screening.
  • In good health as determined by medical history, physical examination, and clinical safety laboratory examinations.
  • Body mass index (BMI) in the range 18-27 kg/m2
  • 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).
  • Willing and able to give written informed consent to participate.
  • Willing and able to communicate with the Investigator and understand the requirements of the study.

Exclusion Criteria:

  • Any condition which would limit the subject's ability to complete the study.
  • Clinically significant hematological, renal, hepatic, pulmonary, central nervous system, cardiovascular or gastrointestinal disorders.
  • Abnormal electrocardiogram (ECG).
  • Febrile illness (temperature ≥ 38°C or 100.4°F) or moderate or severe acute illness or infection within three days of vaccination.
  • Diabetes mellitus.
  • Allergy to penicillin, neomycin, streptomycin or gentamicin.
  • Hypersensitivity to any vaccine.
  • Seropositivity to any of the four dengue serotypes (DEN-1, DEN-2, DEN-3 or DEN-4), yellow fever (YF) virus or West Nile (WN) virus.
  • Previous vaccination (in a clinical trial or with an approved product) against flaviviruses including dengue, YF or WN.
  • Planned vaccination against YF throughout the duration of this study.
  • 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 mg/kg/day) prior to the first vaccination.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01224639

Sponsors and Collaborators
Inviragen Inc.
Investigators
Principal Investigator: Ivan D Velez, MD, Ph.D. PECET, Universidad the Antioquia, Medellin, Colombia
  More Information

No publications provided

Responsible Party: Inviragen Inc.
ClinicalTrials.gov Identifier: NCT01224639     History of Changes
Other Study ID Numbers: INV-DEN-102
Study First Received: October 9, 2010
Last Updated: October 14, 2013
Health Authority: United States: Food and Drug Administration
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Colombia: Institutional Review Board

Keywords provided by Inviragen Inc.:
dengue fever
live attenuated tetravalent dengue vaccine
DENVax

Additional relevant MeSH terms:
Dengue
Fever
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral
Body Temperature Changes
Signs and Symptoms

ClinicalTrials.gov processed this record on September 15, 2014