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

NCT00095576 | Terminated Phase 2 Results DMC

• 2 other identifiers: V520-0232004_091
• Study Type: interventional
• Target: 3,000
• Locations: 0 countries
• Sites: N/A

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.

Conditions

AIDS; HIV Infections

Outcome Measures

Primary Outcomes (4)

• 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)

Study Arms (2)

Trivalent MRKAd5 HIV-1 gag/pol/nef

EXPERIMENTAL

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)

Placebo

PLACEBO COMPARATOR

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

Interventions

Trivalent MRKAd5 HIV-1 gag/pol/nef (1.5x10^10 ad-vg/dose) BIOLOGICAL

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.

Also known as: V520

Trivalent MRKAd5 HIV-1 gag/pol/nef

Comparator: placebo DRUG

Placebo to Trivalent MRKAd5 HIV-1 gag/pol/nef in three 1 mL doses at Day 1, Week 4, and Week 26 administered intramuscularly.

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, HIV seronegative adults at high risk of acquiring HIV infection
• Cannot have previously received an investigational vaccine

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• HIV Vaccine Trials Network: collaborator

Related Publications (5)

• 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.

  PMID: 19012954 BACKGROUND

• 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.

  PMID: 23878319 DERIVED

• 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.

  PMID: 22561365 DERIVED

• 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.

  PMID: 21860356 DERIVED

• 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.

  PMID: 21343146 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Limitations and Caveats

The DSMB (Data \& Safety Monitoring Board) reviewed interim data which demonstrated that the investigational vaccine was not effective, and all vaccinations were halted. Long term follow up was available for participants in V520-030.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck, Sharp & Dohme

ClinicalTrialsDisclosure@merck.com

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2004
• First Posted: November 8, 2004
• Study Start: November 1, 2004
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2009
• Last Updated: October 6, 2015
• Results First Posted: August 15, 2011

Record last verified: 2015-10