Safety of an HIV Vaccine (AVX101) in HIV Uninfected Volunteers in the United States and South Africa

NCT ID: NCT00063778

Last Updated: 2012-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31
• Study Completion Date: 2005-07-31

Brief Summary

The purpose of this study is to see if different doses of an experimental HIV vaccine are safe and to study how the immune system responds to the vaccine. The vaccine will be tested in healthy, HIV uninfected volunteers. AVX101 contains only one of the many substances that HIV needs to make more copies of itself; therefore, the vaccine cannot cause HIV or AIDS.

Detailed Description

This study was designed to evaluate the safety and immunogenicity of an alphavirus replicon HIV subtype C gag vaccine. 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.

This study evaluated the AVX101 vaccine in healthy, HIV uninfected volunteers in both the United States and South Africa. Participants will be randomized to receive either vaccine or placebo at study entry and again at Months 1 and 3. The study was originally designed to enroll four groups of participants in both the US and South Africa, with successive groups receiving increasing doses of the vaccine, but was later amended to enroll only two groups. Twelve US participants (US Group 1) were randomized to receive either vaccine or placebo. After a review of initial safety data from this group, 12 South African participants (SA Group 1) were randomized to receive the same vaccine dose as US Group 1 or placebo, while 12 US participants (US Group 2) were randomized to receive the next higher vaccine dose or placebo. Review of safety data from SA Group 1 and US Group 2 was used to inform the decision to begin enrollment into SA Group 2 .

Participants had nine study visits over 12 months. Study visits included clinical evaluation, urine and blood tests, and HIV tests. After each injection, participants were asked to record their temperature and any symptoms each day for 7 days and report them to the clinic staff.

Conditions

HIV Infections

Study Design

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

Study Groups

1 x 10^4 IU dose

Vaccine dose of 1 x 10\^4 IU per injection

Group Type: EXPERIMENTAL

AVX101

Intervention Type: BIOLOGICAL

Alphavirus replicon particle vaccine expressing HIV Gag antigen

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

Placebo

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 negative
• 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
• Access to participating site and available for follow-up during the 12 month study

Exclusion Criteria

• HIV vaccines or placebos in prior HIV vaccine trial
• Measurable anti-VEE antibody
• High risk for HIV infection according to HVTN Risk Criteria
• 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
• Current tuberculosis prophylaxis or therapy
• Active syphilis
• Serious adverse reaction to vaccines. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
• Autoimmune disease or immunodeficiency
• Unstable asthma
• Type 1 or Type 2 Diabetes Mellitus
• Thyroid disease requiring treatment
• 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 judgement of the investigator, would interfere with the study
• Pregnant or breast-feeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 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 Burke, MD

Role: STUDY_CHAIR

Johns Hopkins University

Salim Abdool Karim, MD, PhD

Role: STUDY_CHAIR

University of Natal, Durban, South Africa

Locations

Johns Hopkins University

Baltimore, Maryland, United States

Columbia University

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

New York Blood Ctr- Union Square

The Bronx, New York, United States

Vanderbilt University

Nashville, Tennessee, United States

SAAVI Vaccine Research Unit

Durban, , South Africa

Chris Hani Baragwanath Hospital

Soweto, , South Africa

Countries

United States; South Africa

References

Pushko P, Parker M, Ludwig GV, Davis NL, Johnston RE, Smith JF. Replicon-helper systems from attenuated Venezuelan equine encephalitis virus: expression of heterologous genes in vitro and immunization against heterologous pathogens in vivo. Virology. 1997 Dec 22;239(2):389-401. doi: 10.1006/viro.1997.8878.

Reference Type: BACKGROUND

PMID: 9434729 (View on PubMed)

Pushko P, Bray M, Ludwig GV, Parker M, Schmaljohn A, Sanchez A, Jahrling PB, Smith JF. Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus. Vaccine. 2000 Aug 15;19(1):142-53. doi: 10.1016/s0264-410x(00)00113-4.

Reference Type: BACKGROUND

PMID: 10924796 (View on PubMed)

Davis NL, Caley IJ, Brown KW, Betts MR, Irlbeck DM, McGrath KM, Connell MJ, Montefiori DC, Frelinger JA, Swanstrom R, Johnson PR, Johnston RE. Vaccination of macaques against pathogenic simian immunodeficiency virus with Venezuelan equine encephalitis virus replicon particles. J Virol. 2000 Jan;74(1):371-8. doi: 10.1128/jvi.74.1.371-378.2000.

Reference Type: BACKGROUND

PMID: 10590126 (View on PubMed)

Strauss JH, Strauss EG. The alphaviruses: gene expression, replication, and evolution. Microbiol Rev. 1994 Sep;58(3):491-562. doi: 10.1128/mr.58.3.491-562.1994.

Reference Type: BACKGROUND

PMID: 7968923 (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 040

Identifier Type: -

Identifier Source: org_study_id