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

AlphaVax, Inc.48 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

Conditions

HIV Infections

Interventions

AVX101BIOLOGICAL

Alphavirus replicon particle vaccine expressing HIV Gag antigen

placeboOTHER

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (7)

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

Outcomes

Primary Outcomes

Grade IV adverse events

The sample size at each vaccine dose level was selected such that the stopping rule for not escalating the dose (2 or more vaccine-related Grade IV adverse experiences) would be met with high probability if the true toxicity rate was above 15-20%, and such that dose escalation would occur with high probability if the true toxicity rate was less than 5%.

Time frame: 1 year

Secondary Outcomes

Local and systemic adverse events

Reactogenicity assessments were performed for all participants before and after each injection, beginning 25 to 45 minutes post injection and continuing daily for 7 days. Assessments performed included systemic reactogenicity (body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, nausea, vomiting) and local reactogenicity (injection site pain, tenderness, erythema or induration, and axillary lymph node tenderness or enlargement).

Time frame: 7 days after each dose

Binding antibodies by ELISA

Binding antibodies to commercially available Gag protein (P55 Gag; Quality Biologicals) were assessed by ELISA using single serum dilutions (1/50 or 1/100) on samples taken at baseline, two weeks after the second and third vaccinations and at the final visit. Samples that were positive in the initial ELISA were tested by endpoint titration ELISA using six 2- to 7-fold serial dilutions of serum beginning at a 1/50 or 1/100 dilution. Magnitude of responses is reported as the difference in optical density (OD) in antigen-containing and non-antigen containing wells at the 1:50 dilution.

Time frame: 1 year

Chromium release CTL assay

A standard 51Cr-release CTL assay was performed on fresh peripheral blood mononuclear cells (PBMC) at baseline and 2 weeks after the second and third vaccinations, using a 50:1 effector to target (E:T) ratio.

Time frame: 3 months

IFN-gamma ELISpot assay

Data from ClinicalTrials.gov

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