Vicriviroc in HIV-Treatment Experienced Subjects (Study P04889AM8)(COMPLETED)

• ClinicalTrials.gov Identifier: NCT00474370
• Recruitment Status: Completed
• First Posted: May 16, 2007
• Last Update Posted: August 30, 2022
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

Brief Summary:

Vicriviroc (vye-kri-VYE-rock) is an investigational drug (not yet approved by Government Regulatory Authorities for commercial use) that belongs to a new class of drugs, called CCR5 receptor blockers. This group of drugs blocks one of the ways HIV enters T-cells (the cells that fight infection). Previous smaller studies in HIV treatment-experienced patients, have shown that vicriviroc is safe and effective. The purpose of this study is to confirm the previous findings in a larger phase 3 study over a 48-week period, and show that when taken in combination with other appropriate HIV drugs, vicriviroc can decrease the level of HIV (viral load) in the blood and that it is well tolerated.

Condition or disease	Intervention/treatment	Phase
HIV Infections; Acquired Immunodeficiency Syndrome	Drug: Vicriviroc; Drug: Placebo	Phase 3

Detailed Description:

This is a randomized, double-blind, placebo-controlled, parallel-group, multi-center study of vicriviroc maleate in HIV subjects infected with CCR5-tropic virus only and who have documented resistance to at least 2 of the 3 antiretroviral drug classes (NRTI, NNRTI or PI) or at least 6 months experience with at

least 2 of the following: one NRTI, one NNRTI, or two PIs (excluding low-dose ritonavir)and failed at least one standard triple-drug regimen. The study will compare the virologic benefit of adding vicriviroc to an optimized background regimen to a control group receiving placebo plus the new optimized background therapy. The optimized background regimen will be chosen by the investigator based on results of drug susceptibility tests performed at Screening, history of prior antiretroviral drug use by the patient, and drug toxicity. OBT must include a PI boosted by ritonavir (>=100 mg of ritonavir), and at least 2 active drugs (ie, to which HIV isolate is fully susceptible). Primary efficacy analysis will be conducted when all subjects have completed 48 weeks of treatment. An interim analysis will be performed when all subjects have completed 24 weeks of treatment. After completing Week 48 of the study, subjects will be offered open-label vicriviroc 30 mg QD, if appropriate, until the drug is commercially available or until the sponsor terminates the clinical development of vicriviroc. Additionally, subjects who discontinued early from the study prior to Week 48 may be eligible for the open-label segment of the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 400 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Vicriviroc in Combination Treatment With an Optimized ART Regimen in HIV-Infected Treatment-Experienced Subjects (VICTOR-E4)
• Actual Study Start Date: May 15, 2007
• Actual Primary Completion Date: August 24, 2009
• Actual Study Completion Date: October 26, 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Test Arm; Vicriviroc 30 mg QD	Drug: Vicriviroc; One tablet of vicriviroc 30 mg once daily.; Other Name: SCH 417690
Placebo Comparator: Placebo Control Arm; Placebo	Drug: Placebo; One tablet of placebo once daily.

Outcome Measures

Primary Outcome Measures :

1. Proportion of subjects with undetectable plasma HIV-1 RNA (<50 copies/mL) [ Time Frame: 48 weeks ]

Secondary Outcome Measures :

1. Mean change from baseline in plasma HIV-1 RNA (log10 copies/mL); Proportion of subjects with <400 copies/mL of plasma HIV-1 RNA; Proportion of subjects with at least 2log10 reduction from baseline in plasma HIV-1 RNA [ Time Frame: 48 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subject must be infected with HIV-1 virus.

• Subject must have documented plasma HIV-1 RNA >1000 copies/mL within 60 days of Visit 1/Day 1 (randomization) and must be either

  • on a stable regimen of 3 or more antiretrovirals (ART) for at least 4

weeks prior to the screening visit

OR

• on no ART agents for at least 4 weeks prior to

the screening visit.

• Subject must be ART experienced and have documented resistance to at least 2 of the following 3 drug classes: nucleoside reverse transcriptase inhibitor (NRTI); non-nucleoside reverse transcriptase inhibitor (NNRTI); or protease inhibitor (PI)

OR

Subject must have ART class experience for at least 6 months with at least two of the following: one NRTI; one NNRTI; two PIs (excluding low-dose ritonavir).

• Women of child-bearing potential must agree to use a medically accepted method of contraceptive as defined by the protocol.
• Subject must be willing to initiate CD4+ cell count-guided chemoprophylaxis to prevent opportunistic infection as defined in protocol.

Exclusion Criteria:

• Subjects with detectable CXCR4-tropic or dual/mixed CCR5/CXCR4-tropic HIV isolates at Screening.
• Subjects with prior history of malignancy (with exceptions of cutaneous Kaposi's sarcoma without visceral or mucosal involvement that resolved with HAART but without systemic anti-cancer treatment, and basal-cell carcinoma of skin); or prior receipt of cytotoxic cancer chemotherapy that may increase the risk of malignancy.
• Subjects with seizure disorder requiring anti-seizure therapy or with any condition that is likely to increase risk of seizure (CNS malignancy or toxoplasmosis).

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Caseiro MM, Nelson M, Diaz RS, Gathe J, de Andrade Neto JL, Slim J, Solano A, Netto EM, Mak C, Shen J, Greaves W, Dunkle LM, Vilchez RA, Zeinecker J. Vicriviroc plus optimized background therapy for treatment-experienced subjects with CCR5 HIV-1 infection: final results of two randomized phase III trials. J Infect. 2012 Oct;65(4):326-35. doi: 10.1016/j.jinf.2012.05.008. Epub 2012 May 24.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00474370
• Other Study ID Numbers: P04889; 3547030; 2006-006417-32 ( EudraCT Number )
• First Posted: May 16, 2007
• Last Update Posted: August 30, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Keywords provided by Merck Sharp & Dohme LLC:

Acquired Immunodeficiency Syndrome

Additional relevant MeSH terms:

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