A Phase II Safety and Immunogenicity Trial of Live Recombinant Canarypox ALVAC-HIV vCP205 With or Without HIV-1 SF-2 RGP120 in HIV-1 Uninfected Adult Volunteers

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT00000871

Collaborator

(none)

420

Enrollment

Locations

23.3

Patients Per Site

Study Details

Study Description

Brief Summary

To expand the available data regarding the safety and immunogenicity of 2 HIV-1 vaccine strategies: canarypox vector vCP205, or vCP205 with SF-2 rgp120. [AS PER AMENDMENT 7/2/98: To obtain immunogenicity and safety data on gp120 subunits that may induce enhanced neutralizing antibody response to primary isolates of HIV-1 in the context of previous immunization with a canarypox vector expressing HIV antigens (vCP205). To evaluate cytotoxic T lymphocyte responses at 1 and 2 years after initial vaccination with vCP205 plus rgp120 SF-2 or vCP205 alone.] In previous ALVAC vCP205/SF-2 rgp 120 studies, patients have developed antibodies that neutralize homologous laboratory strains; over 50% of patients have developed CD8+ cytotoxic T-lymphocyte responses to HIV env and gag epitopes at some point in the study. This Phase II study seeks to confirm these results among persons at lower or higher risk for HIV infection with a new lot of ALVAC vCP205, at a dose that is suitable for potential large-scale trials. [AS PER AMENDMENT 7/2/98: Addition of AIDSVAX B/B or AIDSVAX B/E boosts starting at least 12 months after receiving rgp120 or ALVAC vaccines may induce enhanced neutralizing antibody response as deemed from prior studies and thus is planned as "follow-up" therapy.]

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Biological: MN rgp120/HIV-1 and GNE8 rgp120/HIV-1 Biological: MN rgp120/HIV-1 and A244 rgp120/HIV-1 Biological: ALVAC-HIV MN120TMG (vCP205) Biological: rgp120/HIV-1 SF-2	Phase 2

Detailed Description

In previous ALVAC vCP205/SF-2 rgp 120 studies, patients have developed antibodies that neutralize homologous laboratory strains; over 50% of patients have developed CD8+ cytotoxic T-lymphocyte responses to HIV env and gag epitopes at some point in the study. This Phase II study seeks to confirm these results among persons at lower or higher risk for HIV infection with a new lot of ALVAC vCP205, at a dose that is suitable for potential large-scale trials. [AS PER AMENDMENT 7/2/98: Addition of AIDSVAX B/B or AIDSVAX B/E boosts starting at least 12 months after receiving rgp120 or ALVAC vaccines may induce enhanced neutralizing antibody response as deemed from prior studies and thus is planned as "follow-up" therapy.]

Volunteers are recruited and screened; those who are enrolled are then stratified by their risk status into 2 groups: individuals having lower-risk behavior for HIV and individuals having higher-risk behavior for HIV. Volunteers are then randomly assigned to arm A, B, or C and receive immunizations at months 0, 1, 3, and 6 as follows:

Group A- ALVAC vCP205 plus SF-2 rgp120 in MF59. Group B- ALVAC vCP205 plus saline placebo. Group C- Placebo-ALVAC plus saline placebo. [AS PER AMENDMENT 7/2/98: Beginning 12-18 months after initial vaccination, then 2, 6, and 12 months later, 10 volunteers from group A receive saline placebo, while 50 volunteers each from groups B and C are rerandomized within their respective groups, and are treated as follows.

Group B (subgroup 1) - AIDSVAX B/B. Group B (subgroup 2) - AIDSVAX B/E. Group B (subgroup 3)

alum placebo. Group C (subgroup 1) - AIDSVAX B/B. Group C (subgroup 2) - AIDSVAX B/E. Group C (subgroup 3) - alum placebo.] Volunteers are followed for 2 years and are tested for humoral immune response to HIV-1. Neutralizing activity to HIV-1 is performed on a subset of volunteers monitored for CTL response. [AS PER AMENDMENT 7/2/98: Volunteers receiving AIDSVAX B/B and AIDSVAX B/E will additionally be studied for formation of various neutralizing antibodies and parameters of cellular immunity.] [AS PER AMENDMENT 4/30/99: Because the subunit boosts that were added in version 3.0 are not available, the subunit boost portion of version 3.0 is cancelled.]

Study Design

Study Type:

Interventional

Masking:

Double

Primary Purpose:

Prevention

Official Title:

A Phase II Safety and Immunogenicity Trial of Live Recombinant Canarypox ALVAC-HIV vCP205 With or Without HIV-1 SF-2 RGP120 in HIV-1 Uninfected Adult Volunteers

Actual Study Completion Date :

Jan 1, 2000

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria

Participants must have:

Negative ELISA for HIV within 8 weeks of immunization.
Normal history and physical examination.
Availability for follow-up for planned duration of at least 24 months and willing to have 2 brief evaluations at 36 and 48 months.

Exclusion Criteria

Co-existing Condition:

Participants with the following symptoms or conditions are excluded:

Active syphilis.

NOTE:

AS PER AMENDMENT 6/25/97:
Participant eligible if the serology is documented to be a false positive or due to adequately treated infection.
Active tuberculosis (TB).

NOTE:

Participant eligible if positive purified protein derivative and normal chest x-ray shows no evidence of TB and does not require isoniazid therapy.

Participants with the following prior conditions are excluded:

History of immunodeficiency, chronic illness, malignancy, idiopathic anaphylaxis (AS PER AMENDMENT 6/25/97) or autoimmune disease. Participants with a history of cancer are excluded unless they have undergone surgery followed by a sufficient observation period to give a reasonable assurance of cure.
Any history of anaphylaxis or history of other serious adverse reactions to vaccines.
Immediate-type hypersensitivity reaction to egg products or neomycin (used to prepare ALVAC vaccines).

Prior Medication:

Excluded:

Immunosuppressive medications.
Live attenuated vaccines within 60 days of study.
Use of investigational agents within 30 days prior to study.
Prior receipt of HIV-1 vaccines or placebo recipient in a previous HIV vaccine trial.

Prior Treatment:

Excluded:

Receipt of blood products or immunoglobulin within past 6 months.

Risk Behavior:

Excluded:

Medical or psychiatric condition or occupational responsibilities that preclude participant compliance with the protocol. Specifically excluded are persons with a history of suicide attempts within 3 years, recent suicidal ideation or who have past or present psychosis.
Medically indicated subunit or killed vaccines, e.g., influenza, pneumococcal, hepatitis A and B allowed provided administered more than 2 weeks from HIV study immunizations.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB AVEG	Birmingham	Alabama	United States	35294
2	Public Health Enterprises Foundation, Inc. HIVNET	San Francisco	California	United States
3	Denver Dept. of Health HIVNET	Denver	Colorado	United States
4	Denver Public Health CRS	Denver	Colorado	United States
5	Cook County Hospital HIVNET	Chicago	Illinois	United States	60612
6	Univ. of Illinois at Chicago HIVNET	Chicago	Illinois	United States
7	JHU AVEG	Baltimore	Maryland	United States	21205
8	Fenway Community Health Center HIVNET	Boston	Massachusetts	United States	02115
9	St. Louis Univ. School of Medicine AVEG	Saint Louis	Missouri	United States
10	NY Blood Ctr. HIVNET	New York	New York	United States	10016
11	NY Univ. Med. Ctr. HIVNET	New York	New York	United States	10016
12	Univ. of Rochester AVEG	Rochester	New York	United States	14642
13	Univ. of Pennsylvania HIVNET	Philadelphia	Pennsylvania	United States	19104
14	Memorial Hosp. of Rhode Island HIVNET	Providence	Rhode Island	United States	02906
15	The Miriam Hosp. HIVNET	Providence	Rhode Island	United States	02906
16	Vanderbilt Univ. Hosp. AVEG	Nashville	Tennessee	United States	37232
17	UW - Seattle AVEG	Seattle	Washington	United States
18	Uw Hivnet	Seattle	Washington	United States