ALVAC-HIV vCP1452 Alone and Combined With MN rgp120

Study Overview
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Brief Summary
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The purpose of this study is to test how the body's immune system responds to the vaccine ALVAC-HIV vCP1452 and to determine if the vaccine is safe when given alone and with MN rgp120. HIV infection and AIDS have no cure, in spite of recent advances in anti-HIV drugs. Many worldwide populations cannot afford the antiviral treatments for infected people. HIV vaccines offer hope for disease prevention. In this trial, 2 experimental HIV vaccines called ALVAC vCP1452 and MN rgp120 will be given to volunteers in Haiti, Brazil, Peru, and Trinidad and Tobago. The study will determine how volunteers' immune systems respond to the vaccines. (This protocol has been changed by adding new international sites.)

Detailed Description
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There is no cure for HIV infection or AIDS in spite of recent advances in antiviral therapy. Furthermore, drug therapy is too expensive for most affected populations. For this reason, there is a commitment to the development of safe, effective vaccines to prevent HIV infection and AIDS worldwide. This study evaluates the immunogenicity and safety of candidate HIV-1 vaccines, based on the canarypox vector termed ALVAC, alone and combined with an MN rgp120 product, at 3 [AS PER AMENDMENT 7/19/01: 5] international sites. [AS PER AMENDMENT 7/19/01: Volunteers in Rio de Janeiro, Haiti, and Trinidad and Tobago comprise Part I; volunteers in Sao Paulo and Peru comprise Part II.] Volunteers from Haiti, Brazil, [AS PER AMENDMENT 7/19/01: Peru] and Trinidad and Tobago are enrolled into 1 of 3 arms and followed for 18 months. Arm 1 volunteers receive ALVAC-HIV vCP1452 at 0, 1, 3, and 6 months. Arm 2 volunteers receive ALVAC-HIV vCP1452 on the same schedule as Arm 1 and receive HIV-1 MN rgp120 subunit simultaneously with the 3-month and 6-month vaccine doses. Arm 3 volunteers receive a placebo. Blood and urine samples are collected for immunologic assays, virologic determinations, pregnancy testing, and safety assessments. Risk behavior and social harms are assessed every 6 months during follow-up [AS PER AMENDMENT 7/19/01: Social harms are assessed every 3 months during follow-up and risk behavior every 6 months]. At all clinic visits volunteers receive counseling on avoidance of HIV infection and pregnancy. Participants are tested for HIV-1 every 3 [AS PER AMENDMENT 7/19/01: the following text has been deleted: to 6] months. Counseling and follow-up for any needed medical care are provided.

Official Title
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A Multisite Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of ALVAC-HIV vCP1452 Alone and Combined With MN rgp120

Conditions
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HIV Infections, HIV Seronegativity

Intervention / Treatment
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* Biological: ALVAC(2)120(B,MN)GNP (vCP1452)
* Biological: MN rgp120/HIV-1
* Biological: ALVAC(2)120(B,MN)GNP (vCP1452) placebo
* Biological: MN rgp120/HIV-1 placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Volunteers may be eligible for this study if they: Are from Brazil (Rio de Janeiro), Haiti, Peru, or Trinidad and Tobago. Are 18 to 60 years old. Are HIV-negative. Have not developed a sexually transmitted disease in the last 6 months. Have had no more than 2 sexual partners in the last 6 months. Have not injected drugs or used crack cocaine in the last 6 months. Have not exchanged sex for money or drugs in the last 6 months. Have used an adequate birth control method for 1 month prior to study injections and intend to continue for the injection period (7 months). Are available for 18 months of follow-up. Have a normal history and physical examination. (The criteria for inclusion have been changed from the original.) Exclusion Criteria Volunteers will not be eligible for this study if they: Have had immune diseases, chronic illness, or cancer (unless cured by surgical removal), or have used medications affecting the immune system. Have a medical or mental condition, or job that interferes with the study requirements. Have a sexual partner who is HIV-infected, unless practicing abstinence or have always used condoms for the last 6 months. Have a sexual partner at high risk of HIV infection. Have received live vaccines or experimental agents within 30 days prior to planned vaccination. Have received blood products or immunoglobulin in the past 6 months. Have active tuberculosis. Have had a severe allergic reaction, including 1 requiring hospitalization or medical care, or a serious reaction to vaccines. Have received HIV-1 vaccines or placebo in a previous HIV vaccine trial. Are pregnant or breast-feeding. Are allergic to egg products, thimerosal, or neomycin.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will receive ALVAC-HIV vCP1452 at 0, 1, 3, and 6 months and MN rgp120 and Months 3 and 6 | Biological: ALVAC(2)120(B,MN)GNP (vCP1452)<br>* 1 x 10^ 7 TCID50 administered intramuscularly<br>Biological: MN rgp120/HIV-1<br>* 0.6 mg administered intramuscularly<br>|
| Experimental: 2<br>Participants will receive ALVAC-HIV vCP1452 at 0, 1, 3, and 6 months and MN rgp120 placebo and Months 3 and 6 | Biological: ALVAC(2)120(B,MN)GNP (vCP1452)<br>* 1 x 10^ 7 TCID50 administered intramuscularly<br>Biological: MN rgp120/HIV-1 placebo<br>* Alum placebo administered intramuscularly<br>|
| Placebo Comparator: 3<br>Participants will receive ALVAC-HIV vCP1452 placebo at 0, 1, 3, and 6 months and MN rgp120 placebo and Months 3 and 6 | Biological: ALVAC(2)120(B,MN)GNP (vCP1452) placebo<br>* ALVAC placebo administered intramuscularly<br>Biological: MN rgp120/HIV-1 placebo<br>* Alum placebo administered intramuscularly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity and safety of two vaccine regimens |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD8-Positive T-Lymphocytes, Haiti, HIV Antibodies, HIV Antigens, HIV Envelope Protein gp120, AIDS Vaccines, CD4-Positive T-Lymphocytes, Neutralization Tests, Brazil, Cytotoxicity, Immunologic, Epitopes, Viral Proteins, Trinidad and Tobago, Peru, HIV Preventive Vaccine, HIV Seronegativity