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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00849680
First received: February 20, 2009
Last updated: July 25, 2014
Last verified: July 2014

February 20, 2009
July 25, 2014
April 2003
March 2005   (final data collection date for primary outcome measure)
  • Number of Participants With Adverse Experiences [ Time Frame: up to 260 weeks after first vaccination ] [ Designated as safety issue: Yes ]

    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.

  • Number of Participants With Laboratory Adverse Experiences [ Time Frame: up to 260 weeks after first vaccination ] [ Designated as safety issue: Yes ]

    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.

  • Immune Response by Levels of Unfractionated Gag, Pol, and Nef-specific IFN-gamma Following a 3-dose Vaccine Regimen [ Time Frame: 4 weeks after booster injection ] [ Designated as safety issue: No ]
    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).
  • Immune Response by Levels of Unfractionated Gag, Pol, and Nef-specific IFN-gamma Following a 2-dose Vaccine Regimen [ Time Frame: 4 weeks after booster injection ] [ Designated as safety issue: No ]

    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.

Safety and Tolerability of 3-dose prime boost regimen of MRKAd5 HIV-1 gag/pol/nef vaccine [ Time Frame: 4 weeks after booster injection ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00849680 on ClinicalTrials.gov Archive Site
Not Provided
the breadth of the immune response in each vaccine dose group, measured by various assays [ Time Frame: 4 weeks after booster injection ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of Safety, Tolerability, and Immunogenicity of the MRKAd5 Gag/Pol/Nef Vaccine in Healthy Adults (V520-016)
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

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.

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.
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
  • HIV-1
  • HIV Infections
  • Other: Comparator: Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine
    Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine.
  • Biological: Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)
    Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)
    Other Name: V520
  • Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)
    Other Name: V520
  • Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)
    Other Name: V520
  • Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)
    Other Name: V520
  • Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)
    Other Name: V520
  • Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)
    Other Name: V520
  • Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)
    Other Name: V520
  • Biological: Comparator: Placebo to MRKAd5 HIV-1 gag vaccine
    Placebo to the MRKAd5 HIV-1 gag vaccine.
  • Placebo Comparator: Placebo
    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.
    Interventions:
    • Other: Comparator: Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine
    • Biological: Comparator: Placebo to MRKAd5 HIV-1 gag vaccine
  • Experimental: Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)
    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.
    Intervention: Biological: Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)
  • Experimental: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)
    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.
    Intervention: Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)
  • Experimental: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)
    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.
    Intervention: Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)
  • Experimental: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)
    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.
    Intervention: Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)
  • Experimental: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)
    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.
    Intervention: Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)
  • Experimental: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)
    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)
    Interventions:
    • Other: Comparator: Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine
    • Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)
  • Experimental: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)
    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.
    Intervention: Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
317
February 2010
March 2005   (final data collection date for primary outcome measure)

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
Both
18 Years to 45 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00849680
V520-016, 2009_548
No
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP