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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: HIV-1; HIV Infections

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT00849680

V520-016

2009_548

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 317 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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317 participants in 8 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Other: Comparator: Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine

Biological: Comparator: Placebo to MRKAd5 HIV-1 gag vaccine

Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)

Experimental group

Description:

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.

Treatment:

Biological: Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)

Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)

Experimental group

Description:

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.

Treatment:

Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)

Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)

Experimental group

Description:

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.

Treatment:

Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)

Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)

Experimental group

Description:

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.

Treatment:

Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)

Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)

Experimental group

Description:

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.

Treatment:

Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)

Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)

Experimental group

Description:

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)

Treatment:

Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)

Other: Comparator: Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine

Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)

Experimental group

Description:

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.

Treatment:

Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)