Investigation of V520 in an HIV Vaccine Proof-of-Concept Study (V520-023)

Study Overview
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Brief Summary
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This study will test the safety and efficacy of an investigational Human Immunodeficiency Virus (HIV) vaccine. Efficacy will be measured by either prevention of HIV infection or control of HIV viral load in subjects who become HIV infected. On September 18, 2007 the Protocol V520-023 DSMB (Data & Safety Monitoring Board) reviewed data from a planned interim analysis. These data demonstrated that the investigational vaccine candidate was not effective, and all vaccinations in the study were halted. Participants were encouraged to continue to come to the clinic for scheduled visits and ongoing risk reduction counseling since the vaccine was not effective.

Detailed Description
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No further treatment was given in V520-023, however participants were followed. V520-023 protocol ended earlier than originally planned per protocol and participants (HIV infected and uninfected) had the option of participating in an observational long term follow up protocol called V520-030/HVTN 504, which served as an extension of V520-023 and would continue through the end of 2009.

Official Title
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A Multicenter, Double-Blind, Randomized, Placebo-Controlled Phase II Proof-of-Concept Study to Evaluate the Safety and Efficacy of a 3-Dose Regimen of the Merck Adenovirus Serotype 5 HIV-1 Gag/Pol/Nef Vaccine (MRK AD5 HIV-1 Gag/Pol/Nef) in Adults at High Risk of HIV-1 Infection

Conditions
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AIDS, HIV Infections

Intervention / Treatment
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* Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef (1.5x10^10 ad-vg/dose)
* Drug: Comparator: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, HIV seronegative adults at high risk of acquiring HIV infection Cannot have previously received an investigational vaccine Exclusion Criteria: In a monogamous relationship with an HIV-1 seronegative partner for > 1 year History of anaphylaxis and/or allergy to vaccine components, including Tris buffer, MgCl2, and polysorbate 80 (TWEEN) Received an immune globulin or blood derived products 3 months before injection with the first dose of vaccine/placebo or scheduled within 14 days after injection Previously vaccinated with a live virus vaccine within 30 days before injection with the first dose of vaccine or scheduled within 14 days after injection Previously vaccinated with an inactivated vaccine within 5 days before injection with the first dose of vaccine or scheduled within 14 days after injection Known history of immunodeficiency History of malignancy (with some exceptions) Contraindication to intramuscular (IM) injection such as anticoagulant therapy or thrombocytopenia Female subject who is pregnant or breast feeding, or expecting to conceive or donate eggs through Week 30 of the study Male subject who is planning to impregnate or provide sperm donation through Week 30 of the study Previously received an investigational HIV vaccine Has active drug or alcohol abuse or dependence that would interfere with adherence to study requirements, or endanger the subject's health while on the study Has a condition that might endanger the subject's health or interfere with the evaluation of the study objectives

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trivalent MRKAd5 HIV-1 gag/pol/nef<br>Participants randomized to receive three 1.0-ml intramuscular (IM) injections of Merck Trivalent Adenovirus Serotype 5 HIV-1 gag/pol/nef (MRKAd5 HIV-1 gag/pol/nef) Vaccine at a dose of 1.5x10^10 adenovirus genomes (Ad vg) per dose at Day 1, Week 4, and Week 26. | Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef (1.5x10^10 ad-vg/dose)<br>* Trivalent MRKAd5 HIV-1 gag/pol/nef (1.5x10^10 adenovirus genomes [ad-vg]/dose). This dose is equivalent to 3x10^10 vp/dose used in study V520-016.<br>* Other names: V520;|
| Placebo Comparator: Placebo<br>Participants randomized to receive three 1.0-ml intramuscular (IM) injections of placebo to MRKAd5 HIV-1 gag/pol/nef at Day 1, Week 4, and Week 26. | Drug: Comparator: placebo<br>* Placebo to Trivalent MRKAd5 HIV-1 gag/pol/nef in three 1 mL doses at Day 1, Week 4, and Week 26 administered intramuscularly.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Adverse Experiences | Number of participants with non-serious AEs with an incidence cut-off of 5% (>5% in at least one treatment group) and number of participants with >1 SAE following administration of study vaccine. AEs collected include serious and non-serious systemic AEs, and injection-site AEs. All systemic AEs were collected up to 14 days after any vaccine dose, and serious AEs were collected for the entire study period (up to Week 210). Injection-site AEs are any swelling, redness, pain or tenderness at the injection site. All injection site AEs were collected up to Day 4 after any vaccine dose. | Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) | 
| Number of Participants With Laboratory Adverse Experiences | Number of participants with laboratory adverse experiences with an incidence cut-off of 5% (events occurring > 5% in at least one treatment group) following administration of the first dose of study vaccine. 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 14 days after any vaccine dose. | Day 1 to Week 208 | 
| Number of Participants With HIV-1 Infections | The number of participants with HIV-1 infections was to be determined with a periodic HIV-1 screening test to detect antibodies to recombinant HIV-1 envelope protein in the participants' serum. | Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) | 
| HIV-1 Viral Load in Infected Participants | Plasma HIV-1 viral RNA was to be measured using a ribonucleic acid polymerase chain reaction (RNA PCR) on the last archived sample, and at Weeks 1, 2, 8, 12, and 26 post-HIV-1 infection, and subsequently every 6 months. | Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) |