Clinical trial NCT00095576: Investigation of V520 in an HIV Vaccine Proof-of-Concept Study (V520-023)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: AIDS
HIV Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: HIV Vaccine Trials Network
First posted: 2004-11-08
Enrollment: 3000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Clinical Adverse Experiences
timeFrame: Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants)
measure: Number of Participants With Laboratory Adverse Experiences
timeFrame: Day 1 to Week 208
measure: Number of Participants With HIV-1 Infections
timeFrame: Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants)
measure: HIV-1 Viral Load in Infected Participants
timeFrame: Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants)
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, Gilbert PB, Lama JR, Marmor M, Del Rio C, McElrath MJ, Casimiro DR, Gottesdiener KM, Chodakewitz JA, Corey L, Robertson MN; Step Study Protocol Team. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008 Nov 29;372(9653):1881-1893. doi: 10.1016/S0140-6736(08)61591-3. Epub 2008 Nov 13.
citation: Janes H, Friedrich DP, Krambrink A, Smith RJ, Kallas EG, Horton H, Casimiro DR, Carrington M, Geraghty DE, Gilbert PB, McElrath MJ, Frahm N. Vaccine-induced gag-specific T cells are associated with reduced viremia after HIV-1 infection. J Infect Dis. 2013 Oct 15;208(8):1231-9. doi: 10.1093/infdis/jit322. Epub 2013 Jul 21.
citation: Duerr A, Huang Y, Buchbinder S, Coombs RW, Sanchez J, del Rio C, Casapia M, Santiago S, Gilbert P, Corey L, Robertson MN; Step/HVTN 504 Study Team. Extended follow-up confirms early vaccine-enhanced risk of HIV acquisition and demonstrates waning effect over time among participants in a randomized trial of recombinant adenovirus HIV vaccine (Step Study). J Infect Dis. 2012 Jul 15;206(2):258-66. doi: 10.1093/infdis/jis342. Epub 2012 May 4.
citation: Barnabas RV, Wasserheit JN, Huang Y, Janes H, Morrow R, Fuchs J, Mark KE, Casapia M, Mehrotra DV, Buchbinder SP, Corey L; NIAID HIV Vaccine Trials Network. Impact of herpes simplex virus type 2 on HIV-1 acquisition and progression in an HIV vaccine trial (the Step study). J Acquir Immune Defic Syndr. 2011 Jul 1;57(3):238-44. doi: 10.1097/QAI.0b013e31821acb5.
citation: Fitzgerald DW, Janes H, Robertson M, Coombs R, Frank I, Gilbert P, Loufty M, Mehrotra D, Duerr A; Step Study Protocol Team. An Ad5-vectored HIV-1 vaccine elicits cell-mediated immunity but does not affect disease progression in HIV-1-infected male subjects: results from a randomized placebo-controlled trial (the Step study). J Infect Dis. 2011 Mar 15;203(6):765-72. doi: 10.1093/infdis/jiq114.