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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.

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Aluminum hydroxide
QS-21
rgp120/HIV-1MN
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring Vaccines, Synthetic, Drug Therapy, Combination, Adjuvants, Immunologic, HIV Envelope Protein gp120, AIDS Vaccines, HIV Seronegativity, HIV Preventive Vaccine

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • St. Louis Univ. School of Medicine AVEG
  • Univ. of Rochester AVEG
  • JHU AVEG
  • UW - Seattle AVEG

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00001044
Brief Title
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.
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
May 1995 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Vaccines, Synthetic, Drug Therapy, Combination, Adjuvants, Immunologic, HIV Envelope Protein gp120, AIDS Vaccines, HIV Seronegativity, HIV Preventive Vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Masking
Double
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
Aluminum hydroxide
Intervention Type
Biological
Intervention Name(s)
QS-21
Intervention Type
Biological
Intervention Name(s)
rgp120/HIV-1MN

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
McElrath J
Official's Role
Study Chair
Facility Information:
Facility Name
St. Louis Univ. School of Medicine AVEG
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104-1004
Country
United States
Facility Name
Univ. of Rochester AVEG
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
JHU AVEG
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261
Country
United States
Facility Name
UW - Seattle AVEG
City
Seattle
State/Province
Washington
ZIP/Postal Code
98144
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
11228380
Citation
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.
Results Reference
background
PubMed Identifier
9086128
Citation
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.
Results Reference
background

Learn more about this trial

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.

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