Clinical trial NCT00849680: A Study of Safety, Tolerability, and Immunogenicity of the MRKAd5 Gag/Pol/Nef Vaccine in Healthy Adults (V520-016)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-1
HIV Infections
Keywords: HIV Seronegativity
Preventive Vaccine
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-02-24
Enrollment: 317
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Adverse Experiences
timeFrame: up to 260 weeks after first vaccination
measure: Number of Participants With Laboratory Adverse Experiences
timeFrame: up to 260 weeks after first vaccination
measure: Immune Response by Levels of Unfractionated Gag, Pol, and Nef-specific IFN-gamma Following a 3-dose Vaccine Regimen
timeFrame: 4 weeks after booster injection
measure: Immune Response by Levels of Unfractionated Gag, Pol, and Nef-specific IFN-gamma Following a 2-dose Vaccine Regimen
timeFrame: 4 weeks after booster injection
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Priddy FH, Brown D, Kublin J, Monahan K, Wright DP, Lalezari J, Santiago S, Marmor M, Lally M, Novak RM, Brown SJ, Kulkarni P, Dubey SA, Kierstead LS, Casimiro DR, Mogg R, DiNubile MJ, Shiver JW, Leavitt RY, Robertson MN, Mehrotra DV, Quirk E; Merck V520-016 Study Group. Safety and immunogenicity of a replication-incompetent adenovirus type 5 HIV-1 clade B gag/pol/nef vaccine in healthy adults. Clin Infect Dis. 2008 Jun 1;46(11):1769-81. doi: 10.1086/587993.
citation: Li F, Finnefrock AC, Dubey SA, Korber BT, Szinger J, Cole S, McElrath MJ, Shiver JW, Casimiro DR, Corey L, Self SG. Mapping HIV-1 vaccine induced T-cell responses: bias towards less-conserved regions and potential impact on vaccine efficacy in the Step study. PLoS One. 2011;6(6):e20479. doi: 10.1371/journal.pone.0020479. Epub 2011 Jun 10.
citation: Hutnick NA, Carnathan DG, Dubey SA, Cox KS, Kierstead L, Makadonas G, Ratcliffe SJ, Lasaro MO, Robertson MN, Casimiro DR, Ertl HC, Betts MR. Vaccination with Ad5 vectors expands Ad5-specific CD8 T cells without altering memory phenotype or functionality. PLoS One. 2010 Dec 22;5(12):e14385. doi: 10.1371/journal.pone.0014385.