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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00001090

Collaborator

(none)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Biological: APL 400-047 Biological: ALVAC-HIV MN120TMG (vCP205) Drug: Sargramostim	Phase 1

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].

Study Design

Study Type:

Interventional

Masking:

Double

Primary Purpose:

Prevention

Official Title:

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 Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in Healthy, HIV-1 Uninfected Volunteers

Actual Study Completion Date :

Oct 1, 1999

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB AVEG	Birmingham	Alabama	United States	35294
2	JHU AVEG	Baltimore	Maryland	United States
3	Univ. of Rochester AVEG	Rochester	New York	United States	14642
4	Vanderbilt Univ. Hosp. AVEG	Nashville	Tennessee	United States	37232