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

Primary Purpose

HIV-1, HIV Infections

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Comparator: Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine
Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)
Comparator: Placebo to MRKAd5 HIV-1 gag vaccine
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV-1 focused on measuring HIV Seronegativity, Preventive Vaccine

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm 8

    Arm Type

    Placebo Comparator

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Placebo

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

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

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

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

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

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

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

    Arm 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.

    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.

    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.

    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.

    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.

    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.

    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)

    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.

    Outcomes

    Primary Outcome Measures

    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.
    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.
    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).
    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.

    Secondary Outcome Measures

    Full Information

    First Posted
    February 20, 2009
    Last Updated
    January 21, 2015
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00849680
    Brief Title
    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

    2. Study Status

    Record Verification Date
    January 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    April 2003 (undefined)
    Primary Completion Date
    March 2005 (Actual)
    Study Completion Date
    February 2010 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    HIV-1, HIV Infections
    Keywords
    HIV Seronegativity, Preventive Vaccine

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    317 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm 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.
    Arm Title
    Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)
    Arm Type
    Experimental
    Arm 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)
    Arm Title
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)
    Arm Type
    Experimental
    Arm 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.
    Intervention Type
    Other
    Intervention Name(s)
    Comparator: Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine
    Intervention Description
    Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine.
    Intervention Type
    Biological
    Intervention Name(s)
    Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)
    Other Intervention Name(s)
    V520
    Intervention Description
    Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)
    Intervention Type
    Biological
    Intervention Name(s)
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)
    Other Intervention Name(s)
    V520
    Intervention Description
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)
    Intervention Type
    Biological
    Intervention Name(s)
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)
    Other Intervention Name(s)
    V520
    Intervention Description
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)
    Intervention Type
    Biological
    Intervention Name(s)
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)
    Other Intervention Name(s)
    V520
    Intervention Description
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)
    Intervention Type
    Biological
    Intervention Name(s)
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)
    Other Intervention Name(s)
    V520
    Intervention Description
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)
    Intervention Type
    Biological
    Intervention Name(s)
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)
    Other Intervention Name(s)
    V520
    Intervention Description
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)
    Intervention Type
    Biological
    Intervention Name(s)
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)
    Other Intervention Name(s)
    V520
    Intervention Description
    Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)
    Intervention Type
    Biological
    Intervention Name(s)
    Comparator: Placebo to MRKAd5 HIV-1 gag vaccine
    Intervention Description
    Placebo to the MRKAd5 HIV-1 gag vaccine.
    Primary Outcome Measure Information:
    Title
    Number of Participants With Adverse Experiences
    Description
    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.
    Time Frame
    up to 260 weeks after first vaccination
    Title
    Number of Participants With Laboratory Adverse Experiences
    Description
    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.
    Time Frame
    up to 260 weeks after first vaccination
    Title
    Immune Response by Levels of Unfractionated Gag, Pol, and Nef-specific IFN-gamma Following a 3-dose Vaccine Regimen
    Description
    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).
    Time Frame
    4 weeks after booster injection
    Title
    Immune Response by Levels of Unfractionated Gag, Pol, and Nef-specific IFN-gamma Following a 2-dose Vaccine Regimen
    Description
    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.
    Time Frame
    4 weeks after booster injection

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    45 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Monitor
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    18433307
    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.
    Results Reference
    background
    PubMed Identifier
    21695251
    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.
    Results Reference
    derived
    PubMed Identifier
    21203546
    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.
    Results Reference
    derived

    Learn more about this trial

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

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