Vicriviroc (SCH 417690) in Combination Treatment With Optimized ART Regimen in Experienced Participants (VICTOR-E1) (MK-7690-020/P03672)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: HIV Infections

Treatments: Drug: Vicriviroc 30 mg; Drug: Vicriviroc 20 mg; Drug: Background ART Regimen; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00243230

P03672 (Other Identifier)

2005-001057-21 (EudraCT Number)

MK-7690-020 (Other Identifier)

Details and patient eligibility

About

Vicriviroc (vye-kri-VYE-rock) is an investigational drug that belongs to a new class of drugs, called C-C chemokine receptor type 5 (CCR5) receptor blockers. This group of drugs blocks one of the ways human immunodeficiency virus (HIV) enters T-cells (the cells that fight infection). The purpose of this 48-week study is to evaluate 2 dose levels of vicriviroc in participants with HIV who have not responded adequately to standard HIV treatments. This study was designed to evaluate the safety and efficacy of doses of vicriviroc, when taken in combination with other HIV drugs, in terms of ability to decrease the level of HIV (viral load) in the blood. The primary objective of the study was to evaluate antiviral efficacy of two doses of Vicriviroc maleate compared to placebo in combination with a protease inhibitor (PI)-containing optimized antiretroviral therapy (ART) regimen in CCR5-tropic HIV infected individuals failing a standard ART regimen.

Full description

This is a randomized, double-blind, placebo controlled, parallel-group, multi-center study of vicriviroc maleate in participants with HIV infected with CCR5-tropic virus only for whom standard antiretroviral treatment (ART) has failed. The study will evaluate the antiviral efficacy of two doses of vicriviroc (20 mg once daily (QD) and 30 mg QD) compared with placebo when added to optimized ART therapy. The optimized background regimen will be chosen by the investigator based on results of drug susceptibility tests, history of prior antiretroviral drug use by the participant, and drug toxicity. The background regimen must include at least 3 antiretroviral drugs (not including study drug), one of which must be a ritonavir-boosted protease inhibitor (≥100 mg ritonavir). There will be two interim analyses: when all participants have completed 12 weeks and 24 weeks of treatment, respectively. Based on the balance of safety and efficacy determined in these analyses, a dosage or dosages will be selected for further study in additional registrational trials. The primary efficacy analysis will be conducted when all participants have completed 48 weeks of treatment. After Week 48, participants who meet applicable criteria will be offered open label vicriviroc 30 mg QD, if appropriate, until the sponsor terminates the clinical development of vicriviroc. Additionally, participants who discontinue early from the study prior to Week 48 will be offered re-screening for the open label segment of the study.

Enrollment: 116 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult participants with documented HIV infection with no detectable C-X-C Motif Chemokine Receptor 4 (CXCR4)
• Prior therapy for ≥3 months with ≥3 classes of currently marketed (US FDA-approved) antiretroviral agents (nucleoside reverse transcriptase inhibitor, NRTIs, non-nucleoside reverse transcriptase inhibitor (NNRTIs), protease inhibitor (PIs), or fusion inhibitors) at any time prior to screening
• HIV ribonucleic acid (RNA) ≥1000 copies/mL on a stable ART regimen for ≥6 weeks prior to Screening and ≥8 weeks prior to randomization
• ≥1 genotypically documented resistance mutation to a reverse transcriptase (RT) inhibitor and ≥1 primary resistance mutation to a PI
• Acceptable hematologic, renal and hepatic laboratory parameters

Exclusion criteria

• No history of previous malignancy (with the exceptions of cutaneous Kaposi's Sarcoma without visceral or mucosal involvement that resolved with highly active antiretroviral therapy (HAART) but without systemic anti-cancer treatment, and basal-cell carcinoma of skin surgically resected with disease-free margins on pathology exam)
• Treatment with cytotoxic cancer chemotherapy,
• Recurrent seizure, or central nervous system (CNS) condition or drug use predisposing to seizure in the opinion of the investigator
• No active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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116 participants in 4 patient groups, including a placebo group

Double-Blind - Vicriviroc 30 mg

Experimental group

Description:

Vicriviroc 30 mg once daily (QD), orally (PO), plus an open-label optimized antiretroviral therapy (ART) regimen containing a ritonavir-boosted protease inhibitor (PI/r) for 48 weeks.

Treatment:

Drug: Background ART Regimen

Drug: Vicriviroc 30 mg

Double-Blind - Vicriviroc 20 mg

Experimental group

Description:

Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.

Treatment:

Drug: Background ART Regimen

Drug: Placebo

Drug: Vicriviroc 20 mg

Drug: Placebo

Double-Blind - Placebo

Placebo Comparator group

Description:

Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.

Treatment:

Drug: Background ART Regimen

Drug: Placebo

Drug: Placebo

Open-label - Vicriviroc 30 mg

Experimental group

Description:

Vicriviroc 30 mg once daily (QD), orally (PO), plus an open-label optimized ART regimen containing a ritonavir-boosted protease inhibitor (PI/r) for up to 45 months.

Treatment:

Drug: Background ART Regimen

Drug: Vicriviroc 30 mg