A Phase I, Multicenter, Randomized, Double-Blind, Placebo-Controlled HIV-1 Vaccine Trial to Evaluate the Safety and Immunogenicity of rgp120/HIV-1MN (Genentech) in Combination With QS21 Adjuvant and/or Alum in Healthy Adults.

NCT ID: NCT00001044

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 1995-05-31

Brief Summary

PRIMARY: To examine the safety and potential improvement in immune responses elicited by combining rsgp120/HIV-1MN with the adjuvant QS-21. SECONDARY: To examine the role of alum in the vaccine/adjuvant formulation; to determine the optimal dose ratio of vaccine to adjuvant; and to obtain initial information on the optimal schedule of administration. AS PER AMENDMENT 07/02/97: To determine the ability of immunization with rsgp120/HV-1MN in combination with QS21 with or without alum to induce an HIV-1 envelope-specific delayed-type hypersensitivity (DTH) response in volunteers who undergo rsgp120/MN skin testing.

Immune responses in HIV-uninfected individuals receiving subunit envelope vaccines formulated with alum adjuvant suggest that functional antibodies capable of neutralizing HIV-1 in vitro may be induced, but the titers are relatively low in comparison to those measured in individuals with natural HIV-1 infection. These limitations might be overcome by the addition or substitution of a more suitable adjuvant such as QS-21.

Detailed Description

Immune responses in HIV-uninfected individuals receiving subunit envelope vaccines formulated with alum adjuvant suggest that functional antibodies capable of neutralizing HIV-1 in vitro may be induced, but the titers are relatively low in comparison to those measured in individuals with natural HIV-1 infection. These limitations might be overcome by the addition or substitution of a more suitable adjuvant such as QS-21.

Volunteers are randomized to 20 treatment arms containing four patients each. rsgp120/HIV-1MN is administered at four dose levels: 0, 100, 300, and 600 mcg, and QS-21 adjuvant is administered at three dose levels: 0, 50, and 100 mcg. Some subject cohorts receive alum in the vaccine formulation. Sixty volunteers receive injections at months 0, 1, and 10, and 20 volunteers receive injections at months 0, 1, and 6. AS PER AMENDMENT 07/02/97: All consenting volunteers who have received three immunizations will be tested for DTH response to HIV-1 envelope with use of intradermal MN rsgp120. Follow-up is extended to 56 days after administration of the intradermal injections.

Conditions

HIV Infections

Keywords

Vaccines, Synthetic; Drug Therapy, Combination; Adjuvants, Immunologic; HIV Envelope Protein gp120; AIDS Vaccines; HIV Seronegativity; HIV Preventive Vaccine

Study Design

• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Interventions

Aluminum hydroxide

Intervention Type: BIOLOGICAL

QS-21

Intervention Type: BIOLOGICAL

rgp120/HIV-1MN

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

Subjects must have:

• Normal history and physical exam.
• HIV negativity by ELISA within 6 weeks of immunization.
• CD4 count >= 400 cells/mm3.
• Normal urine dipstick with esterase and nitrite.

Exclusion Criteria

Co-existing Condition:

Subjects with the following symptoms or conditions are excluded:

• Hepatitis B surface antigen.
• Medical or psychiatric condition or occupational responsibilities that preclude compliance.
• Active syphilis. NOTE: Subjects with serology documented to be false positive or due to a remote (> 6 months) treated infection are eligible.
• Active tuberculosis. NOTE: Subjects with a positive PPD and normal chest x-ray showing no evidence of TB and not requiring isoniazid therapy are eligible.

Subjects with the following prior conditions are excluded:

• History of immunodeficiency, autoimmune disease, or use of immunosuppressive medications.
• History of anaphylaxis or other serious adverse reactions to vaccines.
• History of allergy to thimerosal.
• AS PER AMENDMENT 07/02/97: History of eczema or allergic-type reactions to rsgp120/HIV-1MN vaccine (for volunteers undergoing DTH testing).

Prior Medication:

Excluded:

• Live attenuated vaccines within 60 days prior to study entry. (NOTE: Medically indicated subunit or killed vaccines, such as influenza or pneumococcal, are allowed but should be given at least 2 weeks prior to HIV immunizations.)
• Experimental agents within 30 days prior to study entry.
• Prior HIV vaccines.
• AS PER AMENDMENT 07/02/97: Use of systemic steroids in the past month (for volunteers undergoing DTH testing).

Prior Treatment:

Excluded:

• Receipt of blood products or immunoglobulin within the past 6 months.

Identifiable high-risk behavior for HIV infection as determined by screening questionnaire, including history of injection drug use within the past year and higher or intermediate risk sexual behavior.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

McElrath J

Role: STUDY_CHAIR

Locations

St. Louis Univ. School of Medicine AVEG

St Louis, Missouri, United States

Univ. of Rochester AVEG

Rochester, New York, United States

JHU AVEG

Pittsburgh, Pennsylvania, United States

UW - Seattle AVEG

Seattle, Washington, United States

Countries

United States

References

Evans TG, McElrath MJ, Matthews T, Montefiori D, Weinhold K, Wolff M, Keefer MC, Kallas EG, Corey L, Gorse GJ, Belshe R, Graham BS, Spearman PW, Schwartz D, Mulligan MJ, Goepfert P, Fast P, Berman P, Powell M, Francis D; NIAID AIDS Vaccine Evaluation Group. QS-21 promotes an adjuvant effect allowing for reduced antigen dose during HIV-1 envelope subunit immunization in humans. Vaccine. 2001 Feb 28;19(15-16):2080-91. doi: 10.1016/s0264-410x(00)00415-1.

Reference Type: BACKGROUND

PMID: 11228380 (View on PubMed)

Zolla-Pazner S, Alving C, Belshe R, Berman P, Burda S, Chigurupati P, Clements ML, Duliege AM, Excler JL, Hioe C, Kahn J, McElrath MJ, Sharpe S, Sinangil F, Steimer K, Walker MC, Wassef N, Xu S. Neutralization of a clade B primary isolate by sera from human immunodeficiency virus-uninfected recipients of candidate AIDS vaccines. J Infect Dis. 1997 Apr;175(4):764-74. doi: 10.1086/513969.

Reference Type: BACKGROUND

PMID: 9086128 (View on PubMed)

Other Identifiers

10564

Identifier Type: REGISTRY

Identifier Source: secondary_id

AVEG 016

Identifier Type: -

Identifier Source: org_study_id