Safety of and Immune Response to an HIV-1 Subtype C Vaccine (AVX101) in HIV Uninfected Adults

NCT ID: NCT00097838

Last Updated: 2012-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-31
• Study Completion Date: 2009-09-30

Brief Summary

The purpose of this study is to evaluate the safety of and immune response to an alphavirus replicon, HIV-1 subtype C gag vaccine, AVX101, in HIV uninfected adults in the United States, South Africa, and Botswana.

Detailed Description

HIV-1 subtype C is the prevailing subtype of HIV found in sub-Saharan Africa and is primarily responsible for the HIV/AIDS epidemic in southern Africa. Thus, development of a preventive subtype C vaccine is critically important in controlling the spread of HIV in this part of the world. This study will determine the safety and immunogenicity of an alphavirus replicon HIV-1 subtype C gag vaccine, AVX101, in HIV uninfected adults. This vaccine utilizes a propagation-defective replicon vector system derived from an attenuated strain of Venezuelan Equine Encephalitis (VEE) virus. The vaccine replicon expresses the gag gene from a South African subtype C isolate of HIV-1. Participants will be recruited in the United States, South Africa, and Botswana.

The study will last for 1 year. Participants will be enrolled sequentially, from lowest to highest dose of vaccine, into one of four groups. Groups will begin enrollment only following safety review of the previous group. Participants will be randomly assigned to receive active vaccine or placebo. During the study, participants will receive either 3 injections of one of four possible doses of the vaccine or 3 injections of placebo. Injections will be given at study entry and at Days 28 and 84. At screening, participants will undergo medical history assessment, a complete physical, HIV testing and counseling, and blood and urine collection; they will also be interviewed and asked to complete a questionnaire. After screening, there will be 8 study visits; the visits will occur at Days 14, 28, 42, 84, 98, 168, 273, and 364. Participants will be interviewed and asked to fill out a questionnaire at each study visit; participants will undergo a physical, additional HIV testing and counseling, and blood and urine collection at selected visits.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

1 x 10^5 IU dose

Vaccine dose of 1 x 10\^5 IU per injection

Group Type: EXPERIMENTAL

AVX101

Intervention Type: BIOLOGICAL

Alphavirus replicon particle vaccine expressing HIV Gag antigen

1 x 10^6 IU dose

Vaccine dose of 1 x 10\^6 IU per injection

Group Type: EXPERIMENTAL

AVX101

Intervention Type: BIOLOGICAL

Alphavirus replicon particle vaccine expressing HIV Gag antigen

1 x 10^7 IU dose

Vaccine dose of 1 x 10\^7 IU per injection

Group Type: EXPERIMENTAL

AVX101

Intervention Type: BIOLOGICAL

Alphavirus replicon particle vaccine expressing HIV Gag antigen

1 x 10^8 IU dose

Vaccine dose of 1 x 10\^8 IU per injection

Group Type: EXPERIMENTAL

AVX101

Intervention Type: BIOLOGICAL

Alphavirus replicon particle vaccine expressing HIV Gag antigen

Placebo

phosphate buffered saline, pH 7.2, HSA, sodium gluconate, and sucrose

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

phosphate buffered saline, pH 7.2, HSA, sodium gluconate, and sucrose

Interventions

AVX101

Alphavirus replicon particle vaccine expressing HIV Gag antigen

Intervention Type: BIOLOGICAL

placebo

phosphate buffered saline, pH 7.2, HSA, sodium gluconate, and sucrose

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• HIV uninfected
• At low risk for HIV infection
• Willing to receive HIV test results
• Good general health
• Acceptable methods of contraception for females of reproductive potential
• Hepatitis B surface antigen negative
• Anti-hepatitis C virus antibody (anti-HCV) negative or negative HCV PCR if anti-HCV is positive
• Meets educational requirements of the study

Exclusion Criteria

• HIV vaccines or placebos in prior HIV vaccine trial
• Immunosuppressive medications within 168 days prior to first study vaccine administration
• Blood products within 120 days prior to first study vaccine administration
• Immunoglobulin within 60 days prior to first study vaccine administration
• Live attenuated vaccines within 30 days prior to first study vaccine administration
• Investigational research agents within 30 days prior to first study vaccine administration
• Subunit or killed vaccines within 14 days prior to first study vaccine administration
• Allergy treatment with antigen injections within 30 days prior to first vaccine administration
• Current tuberculosis prophylaxis or therapy
• Serious adverse reaction to a vaccine. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
• Autoimmune disease or immunodeficiency
• Active syphilis
• Unstable asthma
• Type 1 or type 2 diabetes mellitus
• Thyroid disease requiring treatment in the past 12 months
• Serious angioedema within the past 3 years
• Uncontrolled hypertension
• Bleeding disorder
• Malignancy unless it has been surgically removed and, in the opinion of the investigator, is not likely to recur during the study period
• Seizure disorder requiring medication within the past 3 years
• Asplenia
• Mental illness that would interfere with compliance with the protocol
• Other conditions that, in the judgment of the investigator, would interfere with the study
• Pregnant or breastfeeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

HIV Vaccine Trials Network

NETWORK

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

AlphaVax, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donald S. Burke, MD

Role: STUDY_CHAIR

Center for Immunization Research, Johns Hopkins School of Public Health

Salim Abdool Karim, MD, PhD

Role: STUDY_CHAIR

University of KwaZulu

Locations

Johns Hopkins University

Baltimore, Maryland, United States

New York Blood Center - Union Square

New York, New York, United States

Columbia University

New York, New York, United States

University of Rochester

Rochester, New York, United States

New York Blood Center - Bronx

The Bronx, New York, United States

Vanderbilt University

Nashville, Tennessee, United States

Botswana HIV Vaccine Clinical Eval. Ctr, Princess

Gaborone, , Botswana

Perinatal HIV Research Unit, Chris Hani Baragwanat

Bertsham, , South Africa

Countries

United States; Botswana; South Africa

References

Davis NL, West A, Reap E, MacDonald G, Collier M, Dryga S, Maughan M, Connell M, Walker C, McGrath K, Cecil C, Ping LH, Frelinger J, Olmsted R, Keith P, Swanstrom R, Williamson C, Johnson P, Montefiori D, Johnston RE. Alphavirus replicon particles as candidate HIV vaccines. IUBMB Life. 2002 Apr-May;53(4-5):209-11. doi: 10.1080/15216540212657.

Reference Type: BACKGROUND

PMID: 12120997 (View on PubMed)

Williamson AL. The development of HIV-1 subtype C vaccines for Southern Africa. IUBMB Life. 2002 Apr-May;53(4-5):207-8. doi: 10.1080/15216540212648.

Reference Type: BACKGROUND

PMID: 12120996 (View on PubMed)

Williamson C, Morris L, Maughan MF, Ping LH, Dryga SA, Thomas R, Reap EA, Cilliers T, van Harmelen J, Pascual A, Ramjee G, Gray G, Johnston R, Karim SA, Swanstrom R. Characterization and selection of HIV-1 subtype C isolates for use in vaccine development. AIDS Res Hum Retroviruses. 2003 Feb;19(2):133-44. doi: 10.1089/088922203762688649.

Reference Type: BACKGROUND

PMID: 12639249 (View on PubMed)

Schlesinger S. Alphavirus vectors: development and potential therapeutic applications. Expert Opin Biol Ther. 2001 Mar;1(2):177-91. doi: 10.1517/14712598.1.2.177.

Reference Type: BACKGROUND

PMID: 11727528 (View on PubMed)

Wecker M, Gilbert P, Russell N, Hural J, Allen M, Pensiero M, Chulay J, Chiu YL, Abdool Karim SS, Burke DS; HVTN 040/059 Protocol Team; NIAID HIV Vaccine Trials Network. Phase I safety and immunogenicity evaluations of an alphavirus replicon HIV-1 subtype C gag vaccine in healthy HIV-1-uninfected adults. Clin Vaccine Immunol. 2012 Oct;19(10):1651-60. doi: 10.1128/CVI.00258-12. Epub 2012 Aug 22.

Reference Type: DERIVED

PMID: 22914365 (View on PubMed)

Other Identifiers

HVTN 059

Identifier Type: -

Identifier Source: org_study_id