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
2 other identifiers
interventional
317
0 countries
N/A
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2003
Longer than P75 for phase_1
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2005
CompletedFirst Submitted
Initial submission to the registry
February 20, 2009
CompletedFirst Posted
Study publicly available on registry
February 24, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2010
CompletedResults Posted
Study results publicly available
July 7, 2011
CompletedFebruary 2, 2015
January 1, 2015
1.9 years
February 20, 2009
June 9, 2011
January 21, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
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.
up to 260 weeks after first vaccination
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.
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
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
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
Study Arms (8)
Placebo
PLACEBO COMPARATORParticipants 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.
Monovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)
EXPERIMENTALParticipants 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.
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)
EXPERIMENTALParticipants 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.
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)
EXPERIMENTALParticipants 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.
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)
EXPERIMENTALParticipants 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.
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)
EXPERIMENTALParticipants 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.
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)
EXPERIMENTALParticipants 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)
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)
EXPERIMENTALParticipants 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.
Interventions
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)
Placebo to the MRKAd5 HIV-1 gag vaccine.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Publications (3)
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.
PMID: 18433307BACKGROUNDLi 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.
PMID: 21695251DERIVEDHutnick 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.
PMID: 21203546DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Limitations and Caveats
An interim analysis of a related study, V520 Protocol 023 (NCT00095576), showed that the MRKAd5 vaccine used in Protocol 016 (NCT00849680) was not efficacious; therefore, only a high level summary of the safety data was performed.
Results Point of Contact
- Title
- Senior Vice President, Global Clinical Development
- Organization
- Merck Sharp & Dohme Corp.
Study Officials
- STUDY DIRECTOR
Medical Monitor
Merck Sharp & Dohme LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 20, 2009
First Posted
February 24, 2009
Study Start
April 1, 2003
Primary Completion
March 1, 2005
Study Completion
February 1, 2010
Last Updated
February 2, 2015
Results First Posted
July 7, 2011
Record last verified: 2015-01