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

This study has been completed.
Sponsor:
Collaborators:
HIV Vaccine Trials Network
Information provided by (Responsible Party):
AlphaVax, Inc.
ClinicalTrials.gov Identifier:
NCT00097838
First received: November 30, 2004
Last updated: June 27, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Biological: AVX101
Other: placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by AlphaVax, Inc.:

Primary Outcome Measures:
  • Grade IV adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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%.


Secondary Outcome Measures:
  • Local and systemic adverse events [ Time Frame: 7 days after each dose ] [ Designated as safety issue: Yes ]
    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).

  • Binding antibodies by ELISA [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • Chromium release CTL assay [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.

  • IFN-gamma ELISpot assay [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Bulk T cell responses were assessed by IFN-γ 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.

  • Antibodies to VEE virus [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • Replication-competent viral vector viremia [ Time Frame: 2 weeks after each vaccine dose ] [ Designated as safety issue: Yes ]
    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.

  • Intracellular cytokine staining (ICS) assay [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 96
Study Start Date: October 2004
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 x 10^5 IU dose
Vaccine dose of 1 x 10^5 IU per injection
Biological: AVX101
Alphavirus replicon particle vaccine expressing HIV Gag antigen
Experimental: 1 x 10^6 IU dose
Vaccine dose of 1 x 10^6 IU per injection
Biological: AVX101
Alphavirus replicon particle vaccine expressing HIV Gag antigen
Experimental: 1 x 10^7 IU dose
Vaccine dose of 1 x 10^7 IU per injection
Biological: AVX101
Alphavirus replicon particle vaccine expressing HIV Gag antigen
Experimental: 1 x 10^8 IU dose
Vaccine dose of 1 x 10^8 IU per injection
Biological: AVX101
Alphavirus replicon particle vaccine expressing HIV Gag antigen
Placebo Comparator: Placebo
phosphate buffered saline, pH 7.2, HSA, sodium gluconate, and sucrose
Other: placebo
phosphate buffered saline, pH 7.2, HSA, sodium gluconate, and sucrose

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00097838

Locations
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21205-1901
United States, New York
New York Blood Center - Bronx
Bronx, New York, United States, 10456
New York Blood Center - Union Square
New York, New York, United States, 10003
Columbia University
New York, New York, United States, 10032
University of Rochester
Rochester, New York, United States, 14642-0001
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Botswana
Botswana HIV Vaccine Clinical Eval. Ctr, Princess
Gaborone, Botswana
South Africa
Perinatal HIV Research Unit, Chris Hani Baragwanat
Bertsham, South Africa, 2013
Sponsors and Collaborators
AlphaVax, Inc.
HIV Vaccine Trials Network
Investigators
Study Chair: Donald S. Burke, MD Center for Immunization Research, Johns Hopkins School of Public Health
Study Chair: Salim Abdool Karim, MD, PhD University of KwaZulu
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AlphaVax, Inc.
ClinicalTrials.gov Identifier: NCT00097838     History of Changes
Other Study ID Numbers: HVTN 059
Study First Received: November 30, 2004
Last Updated: June 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by AlphaVax, Inc.:
HIV Seronegativity
HIV Preventive Vaccine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on July 23, 2014