A Phase I, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Immunogenicity of HIV-1 MN rsgp120 and Bivalent AIDSVAX B/E (HIV-1 MN rgp120/A244 rgp120) in Combination With QS-21 With or Without Alum in Healthy HIV-1 Uninfected Adults

October 28, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To assess the safety and immune response to two experimental vaccines when formulated with QS-21 or QS-21 plus alum. To determine whether the new preparation of QS-21 in polysorbate 80 is less reactogenic than the QS-21 formulation used in AVEG Protocols 016, 016A, and 016B. To examine whether QS-21 is immunologically equivalent to that used in 16B. To determine if QS-21, when given with low doses of antigen, induces measurable HIV-1-specific CTL activity. To evaluate if the QS-21 dose-sparing effect extends to an antigen dose of 0.5 micrograms. To determine if the bivalent vaccine gives responses equivalent to the monovalent product or if a broadening of the HIV-1-specific binding and neutralizing antibody responses occurs.

An effective vaccine to prevent HIV-1 infection may need to generate diverse and multifaceted immunologic responses. Required parts of the immune response may include: humoral antibodies, which broadly neutralize non-syncytium-inducing strains of HIV-1; T cell help provided by both CD4 and CD8 positive subsets; and a class I-restricted cytotoxic lymphocyte response. Other effector responses, such as the generation of antibody-dependent cellular cytotoxicity, cytokines, chemokines, or other antiviral factors may also be critical in mounting protective immunity. Given the lack of a surrogate immunologic marker, the most practical approach for possible efficacy trials would be to evaluate a candidate vaccine that elicits as many of these responses as possible.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

An effective vaccine to prevent HIV-1 infection may need to generate diverse and multifaceted immunologic responses. Required parts of the immune response may include: humoral antibodies, which broadly neutralize non-syncytium-inducing strains of HIV-1; T cell help provided by both CD4 and CD8 positive subsets; and a class I-restricted cytotoxic lymphocyte response. Other effector responses, such as the generation of antibody-dependent cellular cytotoxicity, cytokines, chemokines, or other antiviral factors may also be critical in mounting protective immunity. Given the lack of a surrogate immunologic marker, the most practical approach for possible efficacy trials would be to evaluate a candidate vaccine that elicits as many of these responses as possible.

Volunteers in each of 5 groups receive vaccine or placebo by intramuscular injection at Months 0, 1, and 6. All patients receive one of two doses of QS-21 along with vaccine or placebo and some groups receive alum as follows:

Group 1: low-dose MN rsgp120/HIV-1 plus QS-21 (13 volunteers). Group 2: high-dose MN rsgp120/HIV-1 plus QS-21 (13 volunteers). Group 3: AIDSVAX B/E (injection contains each of the two vaccine components, HIV-1 MN rgp120 and A244 rgp120/HIV-1) plus QS-21 plus alum (13 volunteers).

Group 4: high-dose MN rgp120/HIV-1 plus QS-21 plus alum (13 volunteers). Group 5: placebo plus QS-21 (8 volunteers). Volunteers will be closely monitored after each immunization and followed for a minimum of 12 months after the initial immunization.

Study Type

Interventional

Enrollment

60

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • JHU AVEG
    • New York
      • Rochester, New York, United States, 14642
        • Univ. of Rochester AVEG
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Univ. Hosp. AVEG
    • Washington
      • Seattle, Washington, United States, 98104
        • UW - Seattle AVEG

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria

Volunteers must have:

  • Negative ELISA for HIV within 8 weeks prior to immunization.
  • CD4 count greater than or equal to 400 cells/mm3.
  • Normal history and physical examination. [Refer to Laboratory values for additional requirements.]

Exclusion Criteria

Co-existing Condition:

Volunteers with the following conditions or symptoms are excluded:

  • Medical or psychiatric conditions or occupational responsibilities which preclude subject compliance with the protocol.
  • Recent suicidal ideation or psychosis.
  • Active syphilis. NOTE: If the serology is documented to be a false positive or due to a remote (greater than 6 months) treated infection, the volunteer is eligible.
  • Active tuberculosis. NOTE: Volunteers with a positive PPD and a normal chest x-ray showing no evidence of TB and not requiring INH therapy are eligible.
  • Positive for hepatitis B surface antigen.

Volunteers with the following prior conditions are excluded:

  • History of immunodeficiency, chronic illness, or autoimmune disease.
  • History of cancer unless there has been surgical excision followed by a sufficient observation period to give a reasonable assurance of cure.
  • History of suicide attempts, recent suicidal ideation, or past or present psychosis.
  • History of anaphylaxis or other serious adverse reactions to vaccines.
  • History of serious allergic reaction to any substance requiring hospitalization or emergency medical care (e.g., Stevens-Johnson syndrome, bronchospasm, or hypotension).
  • History of reaction to thimerosal.

Prior Medication:

Excluded:

  • Live attenuated vaccine within 60 days of study. NOTE: Medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal) are not exclusionary, but should be given at least 2 weeks away from HIV immunizations.
  • Experimental agents within 30 days prior to study.
  • HIV-1 vaccines or placebo as part of a previous HIV vaccine trial.

Prior Treatment:

Excluded:

  • Blood products or immunoglobulin in the past 6 months.
  • Experimental agents within 30 days prior to study.

Risk Behavior:

Excluded:

  • Volunteers with an identifiable higher- or intermediate-risk sexual behavior for HIV infection (i.e., AVEG Risk Groups C or D ).
  • History of intravenous drug use within 12 months prior to enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Masking: DOUBLE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

March 1, 2000

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

November 4, 2021

Last Update Submitted That Met QC Criteria

October 28, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AVEG 036
  • 10585 (Registry Identifier: DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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