A Multicenter, Randomized, Placebo-Controlled, Double-Blinded, Phase I Trial to Evaluate the Safety and Immunogenicity of Live Recombinant Canarypox ALVAC-HIV vCP205 Combined With GM-CSF in Healthy, HIV-1 Uninfected Volunteers

NCT ID: NCT00001090

Last Updated: 2021-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 1999-10-31

Brief Summary

To evaluate the safety and immunogenicity of live recombinant canarypox ALVAC-HIV vCP205 in combination with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) at 80 microg and 250 microg. [AS PER AMENDMENT 4/30/99: To study the safety of following 4 ALVAC immunizations with a nucleic acid gag/pol HIV-1 immunogen (APL-400-047, Wyeth-Lederle). To assess the ability of this sequence of immunization to boost the LTL, T-helper cell, and antibody response.] ALVAC-HIV candidate vaccines have induced HIV-specific CTL responses in more than half of recipients in some protocols. Depending on the HIV-1 gene products expressed by the particular ALVAC-HIV candidate vaccine, volunteers have generated anti-Envelope (vCP125, vCP205, and vCP300), anti-Gag (vCP205 and vCP300), and anti-Nef (vCP300) CTL activity. Although 3 to 4 immunizations with the different ALVAC-HIV experimental vaccines induce anti-HIV-1 neutralizing antibodies in a portion, often the majority, of volunteers, the geometric mean titers of these antibodies are modest, usually less than 50. This study will determine whether there is an increase in the anti-HIV antibody titers when GM-CSF is used as an adjuvant with ALVAC-HIV vCP205 and will also examine the kinetics and magnitude of the HIV-specific CTL response.

Detailed Description

ALVAC-HIV candidate vaccines have induced HIV-specific CTL responses in more than half of recipients in some protocols. Depending on the HIV-1 gene products expressed by the particular ALVAC-HIV candidate vaccine, volunteers have generated anti-Envelope (vCP125, vCP205, and vCP300), anti-Gag (vCP205 and vCP300), and anti-Nef (vCP300) CTL activity. Although 3 to 4 immunizations with the different ALVAC-HIV experimental vaccines induce anti-HIV-1 neutralizing antibodies in a portion, often the majority, of volunteers, the geometric mean titers of these antibodies are modest, usually less than 50. This study will determine whether there is an increase in the anti-HIV antibody titers when GM-CSF is used as an adjuvant with ALVAC-HIV vCP205 and will also examine the kinetics and magnitude of the HIV-specific CTL response.

In this randomized, placebo-controlled, double-blinded study volunteers receive ALVAC-HIV vCP205 at 10^6.3 TCID50 or placebo and GM-CSF or placebo by intramuscular injection at Months 0, 1, 3, and 6 as follows:

Group A: vCP205 plus GM-CSF placebo (10 volunteers) Group B: vCP205 plus 80 microg GM-CSF (10 volunteers) Group C: vCP205 plus 250 microg GM-CSF (10 volunteers) Group D: vcP205 placebo plus GM-CSF placebo (6 volunteers). [AS PER AMENDMENT 04/30/99: Boosting with APL-400-047 HIV-1 gag/pol DNA is added for volunteers who have received all scheduled immunization in the original protocol. Volunteers in Groups A, B, and C will receive booster intramuscular injections of DNA vaccine at Months 0 and 1, those in Group D will receive DNA control (bupivacaine carrier alone) at Months 0 and 1].

Conditions

HIV Infections

Keywords

Reference Values; Granulocyte-Macrophage Colony-Stimulating Factor; AIDS Vaccines; HIV Seronegativity; Dose-Response Relationship, Immunologic; HIV Preventive Vaccine

Study Design

• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Interventions

APL 400-047

Intervention Type: BIOLOGICAL

ALVAC-HIV MN120TMG (vCP205)

Intervention Type: BIOLOGICAL

Sargramostim

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Volunteers must have:

• Negative ELISA for HIV within 8 weeks prior to immunization.
• CD4 count of 400 cells/mm3 or higher.
• Normal history and physical examination.
• Viable EBV line prior to initial immunization. [AS PER AMENDMENT 4/30/99:
• Negative anti-dsDNA antibodies (for volunteers receiving booster vaccine).]

Exclusion Criteria

Co-existing Condition:

Volunteers with the following conditions or symptoms are excluded:

• Medical or psychiatric condition or occupational responsibilities that preclude compliance with the protocol.
• Recent suicidal ideation or psychosis.
• Active syphilis. NOTE:
• If the serology is documented to be a false positive or due to a remote (greater than 6 months) treated infection, the volunteer is eligible.
• Active tuberculosis. NOTE:
• Volunteers who have a positive PPD and a normal chest x-ray showing no evidence of TB and who do not require INH therapy are eligible.
• Positive for hepatitis C antibody or hepatitis B surface antigen.
• Allergy to eggs, neomycin, or thimerosal. [AS PER AMENDMENT 4/30/99:
• Hypersensitivity to bupivacaine or other amide-type anesthetics (e.g., lidocaine, mepivacaine) for volunteers receiving booster vaccine).]

Concurrent Medication:

Excluded:

Lithium or cimetidine.

Volunteers with the following prior conditions are excluded:

• History of immunodeficiency, chronic illness, or autoimmune disease.
• History of cancer unless there has been surgical excision with reasonable assurance of cure.
• History of suicide attempts or past psychosis.
• History of anaphylaxis or other serious adverse reactions to vaccines.
• History of serious allergic reaction to any substance requiring hospitalization or emergent care (e.g., Stevens-Johnson syndrome, bronchospasm, or hypotension).

[AS PER AMENDMENT 11/13/97:

• History of cardiac disease or cardiac arrhythmias.]

Prior Medication:

Excluded:

• Live attenuated vaccines within 60 days of study. NOTE:
• Medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal) are not exclusionary, but should be given at least 2 weeks away from HIV immunizations.
• Experimental agents within 30 days prior to study.
• Blood products or immunoglobulin in the past 6 months.
• HIV-1 vaccines or placebo as part of a previous HIV vaccine trial.
• Immunosuppressive medications.

Risk Behavior:

Excluded:

Volunteers with an identifiable higher-risk behavior for HIV infection (i.e., AVEG Risk Group C or D), including a history of injection drug use within 12 months prior to enrollment or higher-risk sexual behavior as defined by the AVEG.

• Minimum Eligible Age: 18 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

T Evans

Role: STUDY_CHAIR

Locations

UAB AVEG

Birmingham, Alabama, United States

JHU AVEG

Baltimore, Maryland, United States

Univ. of Rochester AVEG

Rochester, New York, United States

Vanderbilt Univ. Hosp. AVEG

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

10582

Identifier Type: REGISTRY

Identifier Source: secondary_id

AVEG 033

Identifier Type: -

Identifier Source: org_study_id