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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00063778
Recruitment Status : Completed
First Posted : July 8, 2003
Last Update Posted : July 2, 2012
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
HIV Infections Biological: AVX101 Other: placebo Phase 1

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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 Start Date : July 2003
Primary Completion Date : July 2005
Study Completion Date : July 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: 1 x 10^4 IU dose
Vaccine dose of 1 x 10^4 IU per injection
Biological: AVX101
Alphavirus replicon particle vaccine expressing HIV Gag antigen
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
Placebo Comparator: Placebo Other: placebo
phosphate buffered saline, pH 7.2, HSA, sodium gluconate, and sucrose

Outcome Measures

Primary Outcome Measures :
  1. Grade IV adverse events [ Time Frame: 1 year ]
    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 :
  1. Local and systemic adverse events [ Time Frame: 7 days after each dose ]
    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).

  2. Binding antibodies by ELISA [ Time Frame: 1 year ]
    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.

  3. Chromium release CTL assay [ Time Frame: 3 months ]
    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.

  4. IFN-gamma ELISpot assay [ Time Frame: 3 months ]
    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.

  5. Antibodies to VEE virus [ Time Frame: 1 year ]
    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.

  6. Replication-competent viral vector viremia [ Time Frame: 2 weeks after each vaccine dose ]
    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.

  7. Lymphoproliferation assay [ Time Frame: 1 year ]
    A lymphocyte proliferation assay in response to purified Gag protein and/or Gag peptides was performed on cryopreserved PBMC collected at baseline, 2 weeks after the second and third vaccinations, and at the final visit.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00063778

United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21205-1901
United States, New York
New York Blood Ctr- Union Square
Bronx, New York, United States, 10456
Columbia University
New York, New York, United States, 10032
University of Rochester Medical Center
Rochester, New York, United States, 14642-0002
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
South Africa
SAAVI Vaccine Research Unit
Durban, South Africa
Chris Hani Baragwanath Hospital
Soweto, South Africa
Sponsors and Collaborators
AlphaVax, Inc.
HIV Vaccine Trials Network
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Donald Burke, MD Johns Hopkins University
Study Chair: Salim Abdool Karim, MD, PhD University of Natal, Durban, South Africa
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AlphaVax, Inc.
ClinicalTrials.gov Identifier: NCT00063778     History of Changes
Other Study ID Numbers: HVTN 040
First Posted: July 8, 2003    Key Record Dates
Last Update Posted: July 2, 2012
Last Verified: June 2012

Keywords provided by AlphaVax, Inc.:
HIV Seronegativity
HIV Preventive Vaccine
AIDS Vaccines
Gene Products, gag
Dose-Response Relationship, Immunologic
Injections, Subcutaneous

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Immunologic Factors
Physiological Effects of Drugs