A Phase I, Randomized, Double-Blind, Placebo-Controlled, Clinical Trial to Compare the Safety and Immunogenicity of Recombinant Envelope Protein rgp120/HIV-1SF2 (BIOCINE) Combined With Seven Adjuvants in Healthy HIV-1 Uninfected Individuals

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001042
First received: November 2, 1999
Last updated: May 22, 2012
Last verified: May 2012
  Purpose

To determine in healthy HIV-negative volunteers the safety and immunogenicity of rgp120/HIV-1SF2 (BIOCINE) formulated with each of seven adjuvants.

PER AMENDMENT 3/6/96: Purpose of the extension study - To determine the ability of immunization with rgp 120/SF-2 to induce an HIV-1 envelope-specific delayed-type hypersensitivity (DTH) response in volunteers who receive rsgp 120/MN skin testing.

One approach to improve the immunogenicity of an HIV-1 subunit protein vaccine is to combine the immunogen with an adjuvant. Adjuvants may augment vaccine immunogenicity by several mechanisms, and as a result induce a more favorable antibody response with high titers, which appear earlier in the course of immunization and persist over time.


Condition Intervention Phase
HIV Infections
Biological: Aluminum hydroxide
Biological: Lipid A, Monophosphoryl
Biological: Lipid A, Liposome-encapsulated monophosphoryl
Biological: Syntex adjuvant formulation
Biological: MF59
Biological: Threonyl Muramyl Dipeptide
Biological: rgp120/HIV-1 SF-2
Biological: MTP-PE/MF59
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: A Phase I, Randomized, Double-Blind, Placebo-Controlled, Clinical Trial to Compare the Safety and Immunogenicity of Recombinant Envelope Protein rgp120/HIV-1SF2 (BIOCINE) Combined With Seven Adjuvants in Healthy HIV-1 Uninfected Individuals

Resource links provided by NLM:


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

Enrollment: 112
Study Completion Date: March 1996
Detailed Description:

One approach to improve the immunogenicity of an HIV-1 subunit protein vaccine is to combine the immunogen with an adjuvant. Adjuvants may augment vaccine immunogenicity by several mechanisms, and as a result induce a more favorable antibody response with high titers, which appear earlier in the course of immunization and persist over time.

Volunteers are randomized to receive 50 mcg rgp120/HIV-1SF2 in combination with one of seven different adjuvants: aluminum hydroxide (alum), monophosphoryl lipid A, liposome-encapsulated monophosphoryl lipid A, MF59, MTP-PE/MF59, Syntex adjuvant formulation (SAF/2), and SAF/2 plus threonyl muramyl dipeptide (threonyl MDP). An additional placebo control arm of volunteers receive alum only. Doses are administered at 0, 2, and 6 months. Volunteers are followed for 1 year after the last immunization. Per 8/5/94 amendment, eligible volunteers except those who received monophosphoryl lipid A for the first three immunizations may receive a fourth dose at month 15.

PER AMENDMENT 3/6/96: Extension Study- Protocol 015 has been modified to add a special DTH study. At the end of the study, on day 784, intradermal injections of MN rsgp 120 will be administered to consenting volunteers who have received 4 immunizations as part of protocol 015. Follow up will be extended to 56 days after administration of the intradermal injections.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

Subjects must have:

  • HIV negativity by ELISA.
  • Normal history and physical exam.
  • CD4 count >= 400 cells/mm3.
  • Lower risk sexual behavior.
  • Normal urine dipstick with esterase and nitrite.

PER AMENDMENT 3/6/96:

  • Extension study -
  • Consenting Protocol 015 volunteers who have received four immunizations.

Exclusion Criteria

Co-existing Condition:

Subjects with the following symptoms or conditions are excluded:

  • Hepatitis B surface antigen.
  • Active syphilis. NOTE:Subjects for whom serology is documented to be a 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.
  • Medical or psychiatric condition or occupational responsibilities that would preclude compliance.

Subjects with the following prior conditions are excluded:

  • History of immunodeficiency, chronic illness, or autoimmune disease.
  • History of anaphylaxis or other serious adverse reactions to vaccines.

PER AMENDMENT 3/6/96: Extension study -

  • History of eczema or allergic-type reactions to vaccine in Protocol 015.

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.

PER AMENDMENT 3/6/96: Extension study -

  • Use of systemic steroids in the past month.

Prior Treatment:

Excluded:

  • Blood products or immunoglobulin within 6 months prior to study entry. Higher risk behavior for HIV infection (as determined by screening questionnaire), including history of injection drug use within the last 12 months and higher or intermediate risk sexual behavior.
  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: NCT00001042

Locations
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, 14642
United States, Washington
UW - Seattle AVEG
Seattle, Washington, United States, 98144
Sponsors and Collaborators
Investigators
Study Chair: McElrath J
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001042     History of Changes
Other Study ID Numbers: AVEG 015, 10563
Study First Received: November 2, 1999
Last Updated: May 22, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Vaccines, Synthetic
Drug Therapy, Combination
Adjuvants, Immunologic
HIV Envelope Protein gp120
Acetylmuramyl-Alanyl-Isoglutamine
monophosphoryl lipid A
AIDS Vaccines
HIV Seronegativity
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
Acetylmuramyl-Alanyl-Isoglutamine
Adjuvants, Immunologic
Aluminum Hydroxide
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014