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 - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00000871

Purpose

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	Intervention	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 II

MedlinePlus related topics: AIDS

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Double-Blind, Safety Study
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

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

Estimated Enrollment:	420
Study Start Date:	May 1997
Study Completion Date:	January 2000
Primary Completion Date:	January 2000 (Final data collection date for primary outcome measure)

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.]

Eligibility

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

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000871

Locations

United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
San Francisco Dept of Hlth / AIDS Office
San Francisco, California, United States, 94102
United States, Colorado
Univ Hosp / Univ of Colorado Health Sci Ctr
Denver, Colorado, United States, 80262
Univ of Colorado Health Ctr / Denver Gen Hosp
Denver, Colorado, United States, 80262
Denver Dept of Public Health / HIVNET
Denver, Colorado, United States, 80204
United States, Illinois
Howard Brown Health Ctr / HIVNET
Chicago, Illinois, United States, 60657
United States, Maryland
Johns Hopkins Univ / School of Hygiene & Public Health
Baltimore, Maryland, United States, 212051901
Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, United States, 02215
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
Boston Med Ctr
Boston, Massachusetts, United States, 02118
Fenway Community Health Ctr / HIVNET
Boston, Massachusetts, United States, 02115
United States, Missouri
St Louis Univ School of Medicine
St Louis, Missouri, United States, 63104
Saint Louis Univ Health Sciences Ctr
Saint Louis, Missouri, United States, 63110
United States, New York
Univ of Rochester Med Ctr
Rochester, New York, United States, 14642
New York Univ Med Ctr
New York, New York, United States, 100163240
United States, Pennsylvania
Univ of Pennsylvania / HIVNET
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbilt Univ Hosp
Nashville, Tennessee, United States, 37232
United States, Washington
Univ of Washington / Fred Hutchinson Cancer Rsch Cntr
Seattle, Washington, United States, 98104
Univ of Washington
Seattle, Washington, United States, 98104

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	Belshe R
Study Chair:	Gorse G

More Information

Publications:

Belshe RB, Stevens C, Gorse G, Buchbinder S, Sridhara R, Self S, Weinhold K, Sheppard H, Duliege AM, Meignier B, McNamara J, Flores J (NIAID AVEG, HIVNET Vaccine Development Groups). Phase II evaluation of a live recombinant canarypox (ALVAC) vector HIV-1 vaccine with or without gp120 subunit HIV-1 vaccine. 13th Meeting, International Society for Sexually Transmitted Diseases Research, 1999 Jul 11-14 [227].

Gorse GJ, Patel GB, Mandava MD, Arbuckle JA, Doyle TM, Belshe RB. Cytokine responses to human immunodeficiency virus type 1 (HIV-1) induced by immunization with live recombinant canarypox virus vaccine expressing HIV-1 genes boosted by HIV-1(SF-2) recombinant GP120. Vaccine. 2001 Feb 8;19(13-14):1806-19.

Belshe RB, Stevens C, Gorse GJ, Buchbinder S, Weinhold K, Sheppard H, Stablein D, Self S, McNamara J, Frey S, Flores J, Excler JL, Klein M, Habib RE, Duliege AM, Harro C, Corey L, Keefer M, Mulligan M, Wright P, Celum C, Judson F, Mayer K, McKirnan D, Marmor M, Woody G. Safety and immunogenicity of a canarypox-vectored human immunodeficiency virus Type 1 vaccine with or without gp120: a phase 2 study in higher- and lower-risk volunteers. J Infect Dis. 2001 May 1;183(9):1343-52.

Worku S, Gorse GJ, Belshe RB, Hoft DF. Canarypox vaccines induce antigen-specific human gammadelta T cells capable of interferon-gamma production. J Infect Dis. 2001 Sep 1;184(5):525-32.

Gorse GJ, Patel GB, Belshe RB. HIV type 1 vaccine-induced T cell memory and cytotoxic T lymphocyte responses in HIV type 1-uninfected volunteers. AIDS Res Hum Retroviruses. 2001 Aug 10;17(12):1175-89.

Study ID Numbers:	AVEG 202, HIVNET 014
Study First Received:	November 2, 1999
Last Updated:	December 19, 2008
ClinicalTrials.gov Identifier:	NCT00000871
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Vaccines, Synthetic
AIDS Vaccines
HIV Seronegativity
Avipoxvirus
HIV Preventive Vaccine

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Sexually Transmitted Diseases

Acquired Immunodeficiency Syndrome
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
Lentivirus Infections
Infection

ClinicalTrials.gov processed this record on January 15, 2009