Safety of and Immune Response to DEN4 Vaccine Component Candidate for Dengue Virus

NCT00919178 | Completed Phase 1 DMC

• 1 other identifier: CIR 256
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 2

Brief Summary

Infection with dengue viruses is one of the leading causes of hospitalization and death in children in several tropical Asian counties. The World Health Organization (WHO) estimates that these viruses are responsible for more than 50 million cases of dengue fever (DF) and approximately 0.5 million cases of the more severe disease, dengue hemorrhagic fever/ shock syndrome (DHF/DSS) annually. Because dengue viruses are endemic in most tropical and subtropical regions, keeping more than 2 billion persons at risk for acquiring dengue, the WHO has made development of a dengue vaccine a top priority. The purpose of this study is to evaluate the safety and effectiveness of a candidate DEN4 vaccine aimed at preventing infection with dengue virus serotype 4.

Conditions

Dengue Shock Syndrome; Dengue Hemorrhagic Fever

Keywords

Dengue virus; Vaccine; DEN4; Dengue

Outcome Measures

Primary Outcomes (2)

• Immunogenicity of vaccine candidate, as assessed by neutralizing antibody titers to DEN4

  At Weeks 4 and 6 following vaccination

• Safety of vaccine candidate, as assessed by the frequency of vaccine-related adverse events, graded by severity

  Throughout study

Secondary Outcomes (7)

• Frequency, quantity, and duration of viremia following vaccination

  Throughout study

• Number of vaccinees infected with vaccine virus

  Throughout study

• Infectivity rates, safety, and immunogenicity of a single dose of candidate vaccine compared with previous rates from a previous lot of similar vaccine

  Throughout study

• Durability of antibody response

  At 26 Weeks following vaccination

• Phenotype of peripheral blood mononuclear cells at primary infection with the rDEN4delta30 vaccine

  Throughout study

Study Arms (2)

1

EXPERIMENTAL

Participants will receive a single immunization for Dengue virus serotype 4 (DEN4)

Biological: DEN4 Vaccine Candidate

2

PLACEBO COMPARATOR

Participants will receive a single immunization in the form of placebo resembling vaccine for DEN 4

Biological: DEN4 Vaccine Placebo

Interventions

DEN4 Vaccine Candidate BIOLOGICAL

DEN4 Vaccine Candidate Participants will receive a single immunization on Study Day 0. Vaccine will be delivered by subcutaneous injection in the upper arm, at a volume of 0.5 mL.

1

DEN4 Vaccine Placebo BIOLOGICAL

DEN4 Vaccine Placebo Participants will receive a single immunization on Study Day 0. Placebo will be delivered by subcutaneous injection in the upper arm, at a volume of 0.5 mL.

2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to provide informed consent
• Good general health as determined by physical examination, laboratory screening, and review of medical history
• Available for the duration of the study, approximately 26 weeks postvaccination
• Willing to use acceptable forms of birth control. More information on this criterion can be found in the study protocol.

You may not qualify if:

• Currently breast-feeding, or pregnant
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies
• Behavioral, cognitive, or psychiatric disease that in the opinion of the Investigator affects the ability of the volunteer to understand and cooperate with the requirements of the study protocol
• Screening laboratory values of Grade 1 or above for absolute neutrophil count(ANC), ALT, and serum creatinine, as defined in this protocol
• Any other condition that in the opinion of the Investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the volunteer unable to comply with the protocol
• Any significant alcohol or drug abuse in the past 12 months which has caused medical, occupational, or family problems, as indicated by volunteer history
• History of a severe allergic reaction or anaphylaxis
• Severe asthma (emergency room visit or hospitalization within the last 6 months)
• Positive HIV-1 serology by screening and confirmatory assays
• Positive for hepatitis C virus (HCV) by screening and confirmatory assays
• Positive for hepatitis B virus (HBV) by hepatitis B surface antigen (HBsAg) screening
• Any known immunodeficiency syndrome
• Use of anticoagulant medications
• Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 42 days prior to or following vaccination. Immunosuppressive dose of corticosteroids is defined as 10 mg or more prednisone equivalent per day for 14 or more days.
• Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to vaccination or anticipated receipt of any vaccine during the 42 days following vaccination

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

Center for Immunization Research, Johns Hopkins School of Public Health

Baltimore, Maryland, United States

Location

University of Vermont Vaccine Testing Center

Burlington, Vermont, United States

Location

Related Publications (3)

• Swaminathan S, Khanna N. Dengue: recent advances in biology and current status of translational research. Curr Mol Med. 2009 Mar;9(2):152-73. doi: 10.2174/156652409787581592.

  PMID: 19275624 BACKGROUND

• Tan GK, Alonso S. Pathogenesis and prevention of dengue virus infection: state-of-the-art. Curr Opin Infect Dis. 2009 Jun;22(3):302-8. doi: 10.1097/QCO.0b013e328329ae32.

  PMID: 19262377 BACKGROUND

• Wiwanitkit V. Dengue vaccines: a new hope? Hum Vaccin. 2009 Aug;5(8):566-7. doi: 10.4161/hv.5.8.8481. Epub 2009 Aug 18.

  PMID: 19337028 BACKGROUND

MeSH Terms

Conditions

Severe Dengue; 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

Study Officials

• Anna Durbin, MD

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

• Beth Kirkpatrick, MD

  University of Vermont Vaccine Testing Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 11, 2009
• First Posted: June 12, 2009
• Study Start: July 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: January 3, 2013

Record last verified: 2012-12

Locations

US (2)