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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00849680
• Other study ID #: V520-016
• Secondary ID: 2009_548
• Status: Completed
• Phase: Phase 1
• First received: February 20, 2009
• Last updated: January 21, 2015
• Start date: April 2003
• Est. completion date: February 2010

Study information

• Verified date: January 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 317
• Est. completion date: February 2010
• Est. primary completion date: March 2005
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• HIV Infections
• HIV-1

Intervention

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)
• Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 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 (3x10^7 vp/dose)
• Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 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 (3x10^9 vp/dose)
• Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 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)
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)
• Comparator: Placebo to MRKAd5 HIV-1 gag vaccine
Placebo to the MRKAd5 HIV-1 gag vaccine.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Primary	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	No
Primary	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	No