Safety Study of a Vaccine (DENV-1 PIV) to Prevent Dengue Disease (DENV-1 PIV)

A Phase 1 Trial of the Walter Reed Army Institute of Research (WRAIR) Dengue Virus Serotype-1 Purified Inactivated Vaccine (DENV-1 PIV) in Flavivirus Antibody Naïve Adults

This is a phase 1 study to evaluate the safety of a vaccine (DENV-1 PIV) for the prevention of dengue fever.

Study Overview

• Status: Completed
• Conditions: Dengue Fever
• Intervention / Treatment: Biological: DENV-1 PIV, 5 µg; Biological: DENV-1 PIV, 2.5 µg

Detailed Description

DENV infections can cause self-limited but incapacitating acute illness lasting four to seven days. The illness is characterized by fever, headache, severe pain in muscles, joints, pain behind the eyes, and a rash. DENV infection can be complicated by the development of hemorrhagic fever (DHF) or shock syndrome (DSS), which is manifested by plasma leakage and a bleeding diathesis or frank hemorrhage. DHF is fatal in at least 0.5% of pediatric cases but rarely in adults. People, particularly children, living in hyper-endemic areas who have antibodies from an earlier dengue infection with one serotype are at increased risk for DHF if subsequently infected by another dengue virus serotype.

Currently, no specific anti-viral therapy exists. Therapy is largely supportive. Mosquito control has failed to prevent dengue transmission; therefore, prevention of dengue through vaccination is an important objective of the World Health Organization (WHO) and many national governments, including the United States.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • WRAIR, Clinical Trials Center (CTC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females 18 years of age or the legal age of consent (whichever is greater) to 50 (inclusive) years of age
• Negative screening laboratory test against dengue, Japanese Encephalitis, West Nile, and Yellow Fever viruses
• Healthy
• All subjects must agree to use contraception or to abstain from sex from enrollment through trial completion
• Able to provide informed consent and able to be followed throughout the trial period

Exclusion Criteria:

• History of Flavivirus infection or history of Flavivirus vaccine (experimental or licensed product) including Japanese encephalitis, West Nile virus, Yellow fever, and dengue
• Have a known or suspected hypersensitivity or adverse reaction to vaccines
• Have received a live-attenuated vaccine within 42 days prior to the initial injection on Day 0 or a subunit or killed vaccine within 30 days of the initial injection on Day 0
• Are pregnant or breastfeeding
• Known HIV, Hepatitis B and/or Hepatitis C infection
• Have any acute illness, including an oral body temperature greater than 100.4°F at the day of vaccination
• Have any occupational, social, or medical concerns that would impact subject safety, interfere with protocol adherence, or affect a subject's ability to give informed consent
• Have been using immunomodulatory therapy (use of systemic corticosteroids or chemotherapeutics that may influence antibody development) within the past 6 months; medications or nutritional supplements known to or which potentially could affect organ function within 30 days prior to the initial injection
• Have received an investigational drug or vaccine or participated in a drug product or vaccine study within a period of 30 days prior to Day 0
• Have received or donated blood or plasma within 90 days of Day 0 (or plan on receiving or donating blood or plasma during the study)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: DENV-1 PIV (high dose)	Biological: DENV-1 PIV, 5 µg; 5 µg Purified Inactivated Virus (PIV) in a volume of 0.5 mL administered via intramuscular injection on Study Days 0, and 28 (±4 days)
EXPERIMENTAL: DENV-1 PIV (low dose)	Biological: DENV-1 PIV, 2.5 µg; 2.5 µg Purified Inactivated Virus (PIV) in a volume of 0.5 mL administered via intramuscular injection on Study Days 0, and 28 (±4 days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with solicited adverse events (AEs) from study day 0 to 90	Up to 90 days
Number of subjects with unsolicited AEs from study day 0 to 90	Up to 90 days
Number of subjects who experience serious adverse events (SAEs) during the study period	Up to 360 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with a change in geometric mean titer of neutralizing antibody to DENV types 1,2,3, and 4	Up to Day 28
Number of subjects with a change in geometric mean titer of neutralizing antibody to DENV types 1,2,3, and 4	Up to Day 90

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Investigators: Principal Investigator: Stephen Thomas, MD, Walter Reed Army Institute of Research (WRAIR)

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ACTUAL): September 1, 2013

Study Registration Dates

• First Submitted: December 16, 2011
• First Submitted That Met QC Criteria: December 29, 2011
• First Posted (ESTIMATE): January 2, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): April 22, 2015
• Last Update Submitted That Met QC Criteria: April 21, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: dengue fever; dengue; monovalent 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: S-10-0003; WRAIR IRB Protocol # 1856 (OTHER: WRAIR); HSRRB Protocol #: A-17104 (OTHER: HSRRB); IND 14338 (OTHER: FDA)