Clinical trial NCT00063778: Safety of an HIV Vaccine (AVX101) in HIV Uninfected Volunteers in the United States and South Africa
Official title: A Phase I Safety and Immunogenicity Trial of an Alphavirus Replicon HIV Subtype C Gag Vaccine (AVX101, Alphavax, Inc.) in Healthy HIV-1 Uninfected Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: HIV Seronegativity
HIV Preventive Vaccine
AIDS Vaccines
Gene Products, gag
HIV-1
Dose-Response Relationship, Immunologic
Injections, Subcutaneous
Lead sponsor: AlphaVax, Inc.
Sponsor class: INDUSTRY
Collaborators: name: HIV Vaccine Trials Network
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2003-07-08
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Grade IV adverse events
timeFrame: 1 year
Secondary outcomes:
measure: Local and systemic adverse events
timeFrame: 7 days after each dose
measure: Binding antibodies by ELISA
timeFrame: 1 year
measure: Chromium release CTL assay
timeFrame: 3 months
measure: IFN-gamma ELISpot assay
timeFrame: 3 months
measure: Antibodies to VEE virus
timeFrame: 1 year
measure: Replication-competent viral vector viremia
timeFrame: 2 weeks after each vaccine dose
measure: Lymphoproliferation assay
timeFrame: 1 year
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Bronx
country: United States
facility: New York Blood Ctr- Union Square
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Durban
country: South Africa
facility: SAAVI Vaccine Research Unit
city: Soweto
country: South Africa
facility: Chris Hani Baragwanath Hospital
Study officials:
affiliation: Johns Hopkins University
name: Donald Burke, MD
role: STUDY_CHAIR
affiliation: University of Natal, Durban, South Africa
name: Salim Abdool Karim, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.