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

January 21, 2015 updated by: Merck Sharp & Dohme LLC

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

317

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • V520

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Experiences
Time Frame: up to 260 weeks after first vaccination

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.
up to 260 weeks after first vaccination
Number of Participants With Laboratory Adverse Experiences
Time Frame: up to 260 weeks after first vaccination

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.
up to 260 weeks after first vaccination
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
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).
4 weeks after booster injection
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

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.
4 weeks after booster injection

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2003

Primary Completion (ACTUAL)

March 1, 2005

Study Completion (ACTUAL)

February 1, 2010

Study Registration Dates

First Submitted

February 20, 2009

First Submitted That Met QC Criteria

February 20, 2009

First Posted (ESTIMATE)

February 24, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

February 2, 2015

Last Update Submitted That Met QC Criteria

January 21, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • V520-016
  • 2009_548

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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