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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001096
First received: November 2, 1999
Last updated: May 16, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Biological: MN rgp120/HIV-1 and A244 rgp120/HIV-1
Biological: QS-21
Biological: rgp120/HIV-1MN
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 60
Study Completion Date: March 2000
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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  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: NCT00001096

Locations
United States, Maryland
JHU AVEG
Baltimore, Maryland, United States, 21205
United States, New York
Univ. of Rochester AVEG
Rochester, New York, United States, 14642
United States, Tennessee
Vanderbilt Univ. Hosp. AVEG
Nashville, Tennessee, United States, 37232
United States, Washington
UW - Seattle AVEG
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Investigators
Study Chair: Tom Evans
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001096     History of Changes
Other Study ID Numbers: AVEG 036, 10585
Study First Received: November 2, 1999
Last Updated: May 16, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Vaccines, Synthetic
HIV Antibodies
HIV Antigens
HIV-1
Adjuvants, Immunologic
AIDS Vaccines
T-Lymphocytes, Cytotoxic
HIV Seronegativity
HIV Envelope Protein gp120
Alum Compounds
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
Adjuvants, Immunologic
QS 21
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014