Clinical trial NCT00000958: A Placebo-Controlled, Phase I, Pilot Clinical Trial to Evaluate the Safety and Immunogenicity of ENV 2-3, a Yeast-Derived Recombinant Envelope Protein of Human Immunodeficiency Virus-1, in Combination With MTP-PE/MF59 in Individuals With HIV Infection (Placebo Patients Receive MF59 Emulsion Only)
Official title: A Placebo-Controlled, Phase I, Pilot Clinical Trial to Evaluate the Safety and Immunogenicity of ENV 2-3, a Yeast-Derived Recombinant Envelope Protein of Human Immunodeficiency Virus-1, in Combination With MTP-PE/MF59 in Individuals With HIV Infection (Placebo Patients Receive MF59 Emulsion Only)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Vaccines, Synthetic
Recombinant Proteins
Adjuvants, Immunologic
Acquired Immunodeficiency Syndrome
HIV Envelope Protein gp120
AIDS Vaccines
HIV Therapeutic Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Biocine
First posted: 2001-08-31
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To determine the safety and immunogenicity of Env 2-3 in combination with MTP-PE/MF59 adjuvant in adult volunteers with HIV infection.

By vaccinating those who have HIV infection, perhaps the replication (reproduction) of existing viral strains can be suppressed and the asymptomatic period early in the infectious process can be prolonged. One potential way to do this is to boost HIV antigen-specific CD4 responses, which may in turn increase the effectiveness of CD8 killing of HIV infected cells.

Detailed description: By vaccinating those who have HIV infection, perhaps the replication (reproduction) of existing viral strains can be suppressed and the asymptomatic period early in the infectious process can be prolonged. One potential way to do this is to boost HIV antigen-specific CD4 responses, which may in turn increase the effectiveness of CD8 killing of HIV infected cells.

Eight patients are entered in the pilot portion of the study, thirty patients are entered on Part A and fifteen patients are entered on Part B. In the pilot study, patients receive 30 mcg Env 2-3 vaccine plus 0 - 10 mcg MTP-PE/MF59 adjuvant. Patients on Part A receive one of the following: MF59 emulsion only; 100 mcg MTP-PE/MF59 only; 30 mcg Env 2-3 with MF59 emulsion only; or 30 mcg Env 2-3 vaccine with 100 mcg MTP-PE/MF59. Patients on Part B receive either 100 mcg MTP-PE/MF59 only or 30 mcg Env 2-3 vaccine plus 100 mcg MTP-PE/MF59. Treatment is administered on days 0, 28, and 112, and patients are followed for up to 10 months. Per amendment, patients may receive two additional doses of 30 mcg Env 2-3 or placebo in MTP-PE/MF59 at 7 and 10 months (Parts A and B) or 9 and 12 months (Pilot study) after their initial inoculation.

Eligibility criteria: Inclusion Criteria

Patients must be:

* Healthy HIV-seropositive adults (generalized lymphadenopathy, seborrheic dermatitis acceptable).
* Negative for HIV plasma culture.
* Available for 6 months follow-up (patients in Pilot study) or 10 months follow-up (patients in Parts A and B).

Prior Medication: Required:

* Part B: Zidovudine (AZT), tolerating a dose of 500 - 600 mg/day for at least 4 months prior to entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

* Evidence of psychological disorder during the past year that would impair adherence to the protocol.
* Evidence of an AIDS defining opportunistic infection.

Prior Medication:

Excluded:

* Any potential immunomodulating agents (e.g., isoprinosine, imuthiol, lithium) within 90 days of screening.
* Immunosuppressive medications during the past 3 months.
* Part A: Use of zidovudine (AZT) for more than 30 days in the preceding 6 months, or any AZT within the last 30 days.
* Parts A and B: Any non-AZT antiretroviral drug.
* Any other investigational agent within the past 30 days.
* Immunoglobulins within the past 60 days.

Patients may not have the following prior conditions:

* Evidence of psychological disorder during the past year that would impair adherence to the protocol.
* History of an AIDS-defining opportunistic infection.

Use of illicit drugs or significant amounts of alcohol that, in the opinion of the principal investigator, would interfere with compliance with the study.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Univ. of Rochester AVEG
state: New York
Study officials:
name: Corey L
role: STUDY_CHAIR
References:
citation: Keefer MC, Graham BS, McElrath MJ, Matthews TJ, Stablein DM, Corey L, Wright PF, Lawrence D, Fast PE, Weinhold K, Hsieh RH, Chernoff D, Dekker C, Dolin R. Safety and immunogenicity of Env 2-3, a human immunodeficiency virus type 1 candidate vaccine, in combination with a novel adjuvant, MTP-PE/MF59. NIAID AIDS Vaccine Evaluation Group. AIDS Res Hum Retroviruses. 1996 May 20;12(8):683-93. doi: 10.1089/aid.1996.12.683.
citation: Mohamed OA, Ashley R, Goldstein A, McElrath J, Dalessio J, Corey L. Detection of rectal antibodies to HIV-1 by a sensitive chemiluminescent western blot immunodetection method. J Acquir Immune Defic Syndr (1988). 1994 Apr;7(4):375-80.