Trial record 17 of 38 for:    " February 11, 2009":" March 13, 2009"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

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
  Purpose

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.


Condition Intervention Phase
HIV-1
HIV Infections
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
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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.



Enrollment: 317
Study Start Date: April 2003
Study Completion Date: February 2010
Primary Completion Date: March 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other: Comparator: Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine
Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine.
Biological: Comparator: Placebo to MRKAd5 HIV-1 gag vaccine
Placebo to the 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.
Biological: Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)
Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)
Other Name: V520
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.
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
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.
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
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.
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
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.
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
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)
Other: Comparator: Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine
Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine.
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
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.
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

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

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00849680

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00849680     History of Changes
Other Study ID Numbers: V520-016, 2009_548
Study First Received: February 20, 2009
Results First Received: June 9, 2011
Last Updated: July 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
HIV Seronegativity
Preventive Vaccine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on August 18, 2014