The purpose of this study is to see if the experimental vaccine, ALVAC-HIV (vCP1452) is safe and to study how the immune system responds to the vaccine. This trial is designed to determine whether a higher vaccine dose (6 times the usual dose) will elicit a higher immune response. As of May 2001, over 200 people received the ALVAC-HIV (vCP1452) vaccine at the lower dose. The higher dose of the vaccine to be used in this study has not been given to humans previously. High doses of a similar vaccine have been given to a few people without serious side effects. In a recent study done in mice, higher doses of ALVAC-HIV produced stronger immune responses. It is possible that the doses of ALVAC-HIV given to humans are below the amount needed for the maximum immune response. Because the exact relationship between an increased immune response and its effectiveness in preventing HIV infection is uncertain, the HVTN will use the highest dose that can be manufactured.

Condition	Treatment or Intervention	Phase
HIV Infections HIV Seronegativity	Vaccine: ALVAC(2)120(B,MN)GNP (vCP1452)	Phase I

Further Study Details: 

Expected Total Enrollment:  110

To date, adverse reactions to immunization with the various ALVAC-HIV candidate vaccines, including ALVAC-HIV (vCP1452), have been similar to those observed in healthy adults who have received other licensed vaccines of similar types. In a previous trial, even high doses of recombinant ALVAC vaccine were well tolerated in a group of participants that were significantly immunocompromised. In a recent study done in mice concerning dose escalation using the ALVAC-HIV vectors, the data demonstrated more robust immune responses with higher doses of ALVAC-HIV (vCP1452) in mice. It is certainly possible that the doses of ALVAC-HIV given to humans are well below the amount needed for a maximal cytotoxic T lymphocyte (CTL) response. As the predictive value of a CTL response is at present unknown with respect to its efficacy in preventing or ameliorating HIV acquisition or infection, the HVTN will utilize the highest dose that can be currently manufactured.

All study products are to be administered intramuscularly. Participants will receive 1 of 3 injections. Group A will receive a high dose of vaccine, group B will receive a low dose of vaccine, and group C will receive a placebo. Participants are inoculated at 4 time points. Assessment of product safety includes clinical observation, monitoring of hematological, chemical, and immunologic parameters, and a social harms questionnaire. Safety will be evaluated by monitoring of participants for local and systemic adverse reactions during the course of the trial. Participants will be monitored longitudinally for HIV-specific serologic and cellular immune responses.

Ages Eligible for Study:  18 Years   -   60 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Inclusion Criteria

Participants may be eligible for this study if they:

• Are between the ages of 18 and 60.
• Are in good general health.
• Have a CD4 count of 400 or more cells/mm3.
• Do not have hepatitis C or active hepatitis B.
• Have had a negative HIV blood test within 8 weeks prior to enrollment.
• Use approved methods of contraception.
• Have access to a participating site and are available for follow-up for 18 months.
• Complete a questionnaire evaluating the participant's understanding of the study prior to enrollment.
• Give written informed consent.

Exclusion Criteria

Participants may not be eligible for this study if they:

• Are pregnant or breast-feeding.
• Have received a live vaccine within 30 days prior to enrollment.
• Have received a killed vaccine or allergy treatment with injections within 14 days prior to study vaccine.
• Have used experimental research agents within 30 days prior to enrollment.
• Have received HIV-1 vaccines or placebo in a previous HIV vaccine trial.
• Have received blood products 120 days before HIV screening.
• Have received immunoglobulin 60 days before HIV screening.
• Have a history of serious harmful reactions to vaccines.
• Have a history of disease of the immune system.
• Have a history of cancer, unless it has been surgically removed and in the estimate of the investigator is not likely to happen again during the study period.
• Are using or have used (within past 6 months) drugs that interfere with the immune system.
• Have a history of type I or type II diabetes.
• Have thyroid disease.
• Have unstable asthma.
• Are currently taking preventive anti-TB therapy.
• Have a seizure disorder.
• Have a bleeding disorder that was diagnosed by a physician.
• Have had their spleen removed.
• Have angioedema with serious episodes.
• Have active syphilis.
• Have hypertension.
• Have mental problems that would interfere with the protocol.
• Have any other problems that, in the judgment of the investigator, would interfere with the study.
• Have a body mass index less than 20.
• Are allergic or sensitive to egg products.
• Have active tuberculosis.

Alabama
      Univ of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States
California
      San Francisco Dept of Hlth / AIDS Office, San Francisco,  California,  94102,  United States
District of Columbia
      Johns Hopkins Bloomberg School of Public Health, Washington,  District of Columbia,  20037,  United States
Maryland
      Johns Hopkins Bloomberg School of Public Health, Baltimore,  Maryland,  21205,  United States
      Univ of Maryland Institute of Human Virology, Baltimore,  Maryland,  212011192,  United States
Massachusetts
      Harvard University / Brigham and Women's Hospital, Boston,  Massachusetts,  02115,  United States
      Fenway Community Health, Boston,  Massachusetts,  02115,  United States
Missouri
      Saint Louis Univ Health Sciences Ctr, Saint Louis,  Missouri,  63110,  United States
New York
      Columbia Univ, New York,  New York,  10032,  United States
      Univ of Rochester Med Ctr, Rochester,  New York,  14642,  United States
      New York Blood Center, New York,  New York,  10021,  United States
Rhode Island
      Miriam Hosp, Providence,  Rhode Island,  02906,  United States
Tennessee
      Vanderbilt Univ Hosp, Nashville,  Tennessee,  37232,  United States
Virginia
      Univ of Marlyand / Infectious Diseases Physicians, Fairfax,  Virginia,  United States
Washington
      Fred Hutchinson Cancer Research Ctr, Seattle,  Washington,  98109,  United States

Study chairs or principal investigators

Paul Goepfert,  Study Chair

Study ID Numbers:  HVTN 039
Record last reviewed:  August 2004
Last Updated:  April 7, 2005
Record first received:  November 29, 2001
ClinicalTrials.gov Identifier:  NCT00027261
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08