A Study of Safety, Tolerability, and Immunogenicity of the MRKAd5 Gag/Pol/Nef Vaccine in Healthy Adults (V520-016)

Study Overview
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Brief Summary
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The goal of this study is to understand the safety, tolerability and immunogenicity of the Merck Trivalent Adenovirus Serotype 5 HIV-1 gag/pol/nef Vaccine (MRKAd 5 HIV-1 gag/pol/nef) vaccine in healthy human volunteers compared to placebo. The study will also evaluate a number of dose levels and the necessity for and timing of booster injections.

Detailed Description
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The study will proceed in four stages. Following stages I, II and III, all subjects will have the Postdose 1 (PD1) clinical and laboratory safety data reviewed by the Safety Evaluation Committee (SEC). If these data are acceptable, the next stage will be initiated. In Stage I, participants will be randomized to receive 3 doses of the 3x10^9vp/dose level Trivalent vaccine or placebo. In Stage II, participants will be randomized to receive 2 or 3 doses of the 3x10^10vp/dose level Trivalent vaccine or placebo. In Stage III, participants will be randomized to receive 3 doses of the Trivalent vaccine with titers of 1x10^11vp/dose, 3x10^6vp/dose, 3x10^7vp/dose, or 3x10^8vp/dose or placebo. In Stage IV, participants will be randomized to all treatment groups. In addition, some participants will be randomized to an MRKAd 5 HIV-1 gag Monovalent vaccine. In this stage, participants will be pre-stratified by baseline Ad5 titers (=<200, and >200), to ensure an even distribution of participants with high and low Ad5 titers across the various treatment groups.

Official Title
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A Phase I Dose-Ranging Study of the Safety, Tolerability, and Immunogenicity of the Merck Trivalent Adenovirus Serotype 5 HIV-1 Gag/Pol/Nef Vaccine (MRKAd5 HIV-1 Gag/Pol/Nef) in a Prime-Boost Regimen in Healthy Adults

Conditions
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HIV-1, HIV Infections

Intervention / Treatment
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* Other: Comparator: Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine
* Biological: Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)
* Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)
* Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)
* Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)
* Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)
* Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)
* Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)
* Biological: Comparator: Placebo to MRKAd5 HIV-1 gag vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects 18 Years to 45 Years in Stages I-III and 18 Years to 50 Years in Stage IV. Subject is in good general health Subjects of reproductive potential agree to use acceptable method of birth control through study Subject tests negative for Hepatitis B, Hepatitis C, and HIV Exclusion Criteria: Subject has a recent history of fever at time of vaccination Subject has received immune globulin or blood product 3 months prior to injection Subject has been vaccinated with live virus vaccine 30 days prior to receipt of first dose Subject has been vaccinated with inactivated vaccine with 14 days prior to receipt of first dose Subject has a chronic medical condition that is considered progressive Subject has history of malignancy Subject weighs less than 105 lb. Female subject is pregnant or breast feeding, Male subject is planning to impregnate during the first year of study Subject has contraindication to intramuscular injection Subject has a tattoo on the deltoid region of the arm or the injection of Depo-Provera Subject is unlikely or unwilling to adhere to lower risk sex practices during the course of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants receiving 1.0 ml of placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine or the placebo to the MRKAd5 HIV-1 gag vaccine injected intramuscularly in a 3-dose regimen at Day 1, Week 4 and Week 26 or a 2-dose regimen at Day 1 and Week 26 or Day 1 and Week 4. | Other: Comparator: Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine<br>* Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine.<br>Biological: Comparator: Placebo to MRKAd5 HIV-1 gag vaccine<br>* Placebo to the MRKAd5 HIV-1 gag vaccine.<br>|
| Experimental: Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)<br>Participants receiving 1.0 ml of the Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose) injected intramuscularly in a 3-dose regimen at Day 1, Week 4 and Week 26. | Biological: Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)<br>* Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)<br>* Other names: V520;|
| Experimental: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)<br>Participants receiving 1.0 ml of Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose) injected intramuscularly in a 3-dose regimen at Day 1, Week 4 and Week 26. | Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)<br>* Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)<br>* Other names: V520;|
| Experimental: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)<br>Participants receiving 1.0 ml of Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose) injected intramuscularly in a 3-dose regimen at Day 1, Week 4 and Week 26. | Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)<br>* Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)<br>* Other names: V520;|
| Experimental: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)<br>Participants receiving 1.0 ml of Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose) injected intramuscularly in a 3-dose regimen at Day 1, Week 4 and Week 26. | Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)<br>* Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)<br>* Other names: V520;|
| Experimental: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)<br>Participants receiving 1.0 ml of Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose) injected intramuscularly in a 3-dose regimen at Day 1, Week 4 and Week 26. | Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)<br>* Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)<br>* Other names: V520;|
| Experimental: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)<br>Participants receiving 1.0 ml of Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose) injected intramuscularly in a 3-dose regimen at Day 1, Week 4 and Week 26, or in a 2-dose regimen at Day 1 and Week 4 (with no vaccine administered at Week 26) or Day 1 and Week 26 (with placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine administered at Week 4) | Other: Comparator: Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine<br>* Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine.<br>Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)<br>* Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)<br>* Other names: V520;|
| Experimental: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)<br>Participants receiving 1.0 ml of Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose) injected intramuscularly in a 3-dose regimen at Day 1, Week 4 and Week 26. | Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)<br>* Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)<br>* Other names: V520;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Experiences | Adverse experiences (AE) collected include serious and non serious systemic AEs, and injection-site AEs. Systemic and Laboratory AEs include any unfavorable & unintended change in the structure, function, or chemistry of the body. Injection-site AEs include any swelling, redness, pain or tenderness at the injection site. All injection site AEs were collected up to 5 days after any vaccine dose. | up to 260 weeks after first vaccination | 
| Number of Participants With Laboratory Adverse Experiences | Laboratory AEs were based on a grading system considering the severity of abnormal laboratory values in participants and reflect any unfavorable and unintentional change in function, or chemistry of the body. All laboratory AEs were collected up to 29 days after any vaccine dose. | up to 260 weeks after first vaccination | 
| Immune Response by Levels of Unfractionated Gag, Pol, and Nef-specific IFN-gamma Following a 3-dose Vaccine Regimen | Participants expressing HIV antigens (gag, pol and nef) secrete antigen specific interferon-gamma (IFN-gamma). Levels of unfractionated gag, pol, and nef-specific IFN-gamma were to be measured using an Enzyme Linked Immunospot Assay (ELISPOT), which measures spot forming cells per 10^6 peripheral blood mononuclear cells (SFC per million PBMCs). | 4 weeks after booster injection | 
| Immune Response by Levels of Unfractionated Gag, Pol, and Nef-specific IFN-gamma Following a 2-dose Vaccine Regimen | Participants expressing HIV antigens (gag, pol and nef) secrete antigen specific interferon-gamma (IFN-gamma). Levels of unfractionated gag, pol, and nef-specific IFN-gamma were to be measured using an Enzyme Linked Immunospot Assay (ELISPOT), which measures spot forming cells per 10^6 peripheral blood mononuclear cells (SFC per million PBMCs). No immunogenicity analyses were performed because the results from a previous study, V520-023 (NCT00095576), which used the same vaccine as the one used in this study (NCT00849680) proved it was not efficacious. | 4 weeks after booster injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV Seronegativity, Preventive Vaccine