A Phase II Clinical Trial to Evaluate the Immunogenicity and Reactogenicity of the Recombinant HIV-1 Envelope Vaccines SF-2 rgp120 (CHO) [Chiron Vaccines] in MF59 Adjuvant and MN rgp120/HIV-1 [VaxGen] in Alum Adjuvant in Healthy Adults

• ClinicalTrials.gov Identifier: NCT00001031
• Recruitment Status: Completed
• First Posted: August 31, 2001
• Last Update Posted: May 25, 2012
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Biocine; Genentech, Inc.
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

To evaluate the safety and immunogenicity of SF-2 rgp120 vaccine in MF59 versus MN rgp120 vaccine in alum in volunteers who are seronegative for HIV-1. AS PER AMENDMENT 07/02/97: To determine the ability of immunization with MN rgp120/HIV-1 in combination with alum or SF-2 rgp120 in combination with MF59 to induce an HIV-1 envelope-specific delayed-type hypersensitivity (DTH) response in volunteers who receive rsgp120/MN skin testing.

The amino acid sequence of HIV-1 gp120 can vary as much as 40 percent from isolate to isolate. Thus, the identification of an immunogen that can elicit broadly neutralizing antibodies to HIV-1 is a major challenge in AIDS vaccine development. Two candidate vaccines, recombinant envelope subunit proteins from the SF-2 and MN isolates of HIV-1, have shown immunogenicity and good tolerance in healthy immunocompetent adults. This study will expand testing into a larger population base, particularly targeting individuals at high risk for HIV infection.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Biological: rgp120/HIV-1MN; Biological: rgp120/HIV-1 SF-2	Phase 2

Detailed Description:

The amino acid sequence of HIV-1 gp120 can vary as much as 40 percent from isolate to isolate. Thus, the identification of an immunogen that can elicit broadly neutralizing antibodies to HIV-1 is a major challenge in AIDS vaccine development. Two candidate vaccines, recombinant envelope subunit proteins from the SF-2 and MN isolates of HIV-1, have shown immunogenicity and good tolerance in healthy immunocompetent adults. This study will expand testing into a larger population base, particularly targeting individuals at high risk for HIV infection.

HIV-seronegative volunteers (including four populations at higher risk for HIV infection and two populations at lower risk) receive one of four regimens. Two treatment groups receive 50 mcg SF-2 rgp 120 (BIOCINE) in MF59 adjuvant or 600 mcg MN rgp120 (Genentech) in alum. Two control groups receive vehicle (placebo) in MF59 adjuvant alone or alum adjuvant alone. Immunizations are given at months 0, 1, and 6. AS PER AMENDMENT 10/93: patients enrolled by June 15, 1993, receive a fourth immunization at month 12 or 18 (50 percent of patients for each schedule). Patients are followed until 2 years after the first injection. AS PER AMENDMENT 05/10/94: a special study of vaccine acceptability and HIV-related risk behavior will be conducted at some time between months 12 and 18. AS PER AMENDMENT 07/02/97: a special DTH study will be conducted in consenting volunteers who have received three or four immunizations. The injections will be given at the end of the study (on or after day 1, & 56). Followup is extended to 56 days after administration of the intradermal injection.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 296 participants
• Masking: Double
• Primary Purpose: Prevention
• Official Title: A Phase II Clinical Trial to Evaluate the Immunogenicity and Reactogenicity of the Recombinant HIV-1 Envelope Vaccines SF-2 rgp120 (CHO) [Chiron Vaccines] in MF59 Adjuvant and MN rgp120/HIV-1 [VaxGen] in Alum Adjuvant in Healthy Adults
• Actual Study Completion Date: December 1997

Arms and Interventions

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 60 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria

Subjects must have:

• Normal history and physical exam.
• HIV negativity by ELISA.
• CD4 count >= 400 cells/mm3.
• No clinically significant medical disease.
• No history of immunodeficiency, autoimmune disease, or use of immunosuppressive medication.
• No prior HIV vaccines.
• Classification in one of the eligible risk groups defined in the Disease Status field.

Eligible higher risk groups:

• Heterosexual teenagers and young adults (ages 16-28 permitted) who have attended a clinic for sexually transmitted diseases in the last 3 months or have higher risk sexual behavior.
• Homosexually active males who are practicing higher risk behavior (ages 18-60).
• Injection drug users active within the past 3 years (ages 18-60).
• Heterosexual partners of HIV seropositive individuals (ages 18-60).

Eligible lower risk groups:

• Homosexually active males who are practicing lower risk behavior (ages 18-60).
• Adult women and heterosexual adult men practicing lower risk sexual behavior (ages 18-60).

Exclusion Criteria

Prior Medication:

Excluded:

• Prior HIV vaccines.
• Prior immunosuppressive medications.
• Experimental agents within the past 30 days.
• AS PER AMENDMENT 07/02/97: Use of systemic steroids in the past month (for volunteers undergoing DTH testing).

AS PER AMENDMENT 07/02/97:

• History of eczema or allergic-type reactions to vaccines used in protocol 201 (for volunteers undergoing DTH testing).

Contacts and Locations

Locations

United States, Alabama

UAB AVEG

Birmingham, Alabama, United States

United States, Missouri

St. Louis Univ. School of Medicine AVEG

St. Louis, Missouri, United States, 63104

United States, New York

Univ. of Rochester AVEG

Rochester, New York, United States, 02115

Univ. of Rochester ACTG CRS

Rochester, New York, United States, 14642

United States, Pennsylvania

JHU AVEG

Pittsburgh, Pennsylvania, United States

United States, Tennessee

Vanderbilt Univ. Hosp. AVEG

Nashville, Tennessee, United States, 37232

United States, Washington

UW - Seattle AVEG

Seattle, Washington, United States, 98195

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Biocine

Genentech, Inc.

Investigators

• Study Chair: Corey L
• Study Chair: McElrath J

More Information

Publications:

McElrath MJ, Corey L, Clements ML, Belshe R, Keefer M, Graham B, Fast P, Matthews T, Duliege AM, Francis D. A phase II HIV vaccine trial in seronegative subjects: safety, immunogenicity, and future directions. Int Conf AIDS. 1994 Aug 7-12;10(1):91 (abstract no 317A)

McElrath MJ, Montefiori DM, Clements ML, Belshe RB, Dolin R, Graham BS, Duliege A-M, Francis D, Bolognesi DP, Matthews TJ, Wolff M, Fast P, Corey L. Longitudinal vaccine-induced immunity and risk behavior of study participants of AVEG phase II protocol 201. Conf Adv AIDS Vaccine Dev. 1996 Feb 11-15;216 [Poster 96]

McElrath MJ, Corey L, Montefiori D, Wolff M, Schwartz D, Keefer M, Belshe R, Graham BS, Matthews T, Wright P, Gorse G, Dolin R, Berman P, Francis D, Duliege AM, Bolognesi D, Stablein D, Ketter N, Fast P. A phase II study of two HIV type 1 envelope vaccines, comparing their immunogenicity in populations at risk for acquiring HIV type 1 infection. AIDS Vaccine Evaluation Group. AIDS Res Hum Retroviruses. 2000 Jun 10;16(9):907-19.

Harrison K, Vlahov D, Jones K, Charron K, Clements ML. Medical eligibility, comprehension of the consent process, and retention of injection drug users recruited for an HIV vaccine trial. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Nov 1;10(3):386-90.

McElrath MJ, Montefiori D, Wolff M, Clements M, Gorse G, Keefer M, Graham B, Duliege AM, Francis D, Matthews T, Fast P, Corey L. Safety, immunity, and risk behavior in HIV-1-uninfected volunteers representing diverse risk populations following recombinant envelope vaccinations: a three-year followup. Int Conf AIDS. 1996 Jul 7-12;11(1):10 (abstract no MoA284)

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00001031 History of Changes
• Other Study ID Numbers: AVEG 201; 10588 ( Registry Identifier: DAIDS ES Registry Number )
• First Posted: August 31, 2001
• Last Update Posted: May 25, 2012
• Last Verified: May 2012

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Vaccines, Synthetic; HIV-1; HIV Envelope Protein gp120; AIDS Vaccines; HIV Seronegativity; HIV Preventive Vaccine

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; Aluminum Hydroxide; Vaccines; Aluminum sulfate; Immunologic Factors; Physiological Effects of Drugs; Adjuvants, Immunologic; Antacids; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents