HIV Infections Clinical Trial
Official title:
A Phase I, Dose Escalation, Safety, and Immunogenicity Trial of an Alphavirus Replicon HIV-1 Subtype C Gag Vaccine (AVX101) in Healthy HIV-1 Uninfected Adult Participants
Verified date | June 2012 |
Source | AlphaVax, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | United States: Food and Drug Administration |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 96 |
Est. completion date | September 2009 |
Est. primary completion date | September 2009 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Both |
Age group | 18 Years to 50 Years |
Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Country | Name | City | State |
---|---|---|---|
Botswana | Botswana HIV Vaccine Clinical Eval. Ctr, Princess | Gaborone | |
South Africa | Perinatal HIV Research Unit, Chris Hani Baragwanat | Bertsham | |
United States | Johns Hopkins University | Baltimore | Maryland |
United States | New York Blood Center - Bronx | Bronx | New York |
United States | Vanderbilt University | Nashville | Tennessee |
United States | Columbia University | New York | New York |
United States | New York Blood Center - Union Square | New York | New York |
United States | University of Rochester | Rochester | New York |
Lead Sponsor | Collaborator |
---|---|
AlphaVax, Inc. | HIV Vaccine Trials Network, National Institute of Allergy and Infectious Diseases (NIAID) |
United States, Botswana, South Africa,
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. Review. — View Citation
Schlesinger S. Alphavirus vectors: development and potential therapeutic applications. Expert Opin Biol Ther. 2001 Mar;1(2):177-91. Review. — View Citation
Williamson AL. The development of HIV-1 subtype C vaccines for Southern Africa. IUBMB Life. 2002 Apr-May;53(4-5):207-8. Review. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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%. | 1 year | Yes |
Secondary | 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). | 7 days after each dose | Yes |
Secondary | 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. | 1 year | No |
Secondary | 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. | 3 months | No |
Secondary | IFN-gamma ELISpot assay | Bulk T cell responses were assessed by IFN-? ELISpot, using cryopreserved PBMC collected at baseline and 2 weeks after the second and third vaccinations, and stimulated overnight with Gag peptide pools at 200,000 cells per well. | 3 months | No |
Secondary | Antibodies to VEE virus | Neutralizing antibodies to VEE virus were measured in serum obtained at baseline, 2 weeks after the second and third vaccinations and at the final visit. | 1 year | No |
Secondary | Replication-competent viral vector viremia | Any participant who reported a fever greater than 38oC, or other moderate symptoms consistent with a viral illness (e.g. headache or malaise) during the 7 days following vaccination, or neurological symptoms (e.g. nuchal rigidity, ataxia, convulsions, coma, paralysis) within the window of the 2-week post vaccination visit, provided a serum sample to confirm the absence of replication-competent VEE viremia. | 2 weeks after each vaccine dose | Yes |
Secondary | Intracellular cytokine staining (ICS) assay | Flow cytometry was used to examine HIV-specific CD4+ and CD8+ T cell responses using ICS, following stimulation with Gag peptides that span the protein sequence encoded by the vaccine construct. ICS assays were performed at baseline and 2 weeks after the second and third vaccinations. | 3 months | No |
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