Clinical trial NCT00243230: Vicriviroc (SCH 417690) in Combination Treatment With Optimized ART Regimen in Experienced Participants (VICTOR-E1) (MK-7690-020/P03672)
Official title: Vicriviroc (SCH 417690) in Combination Treatment With Optimized ART Regimen in Experienced Subjects (VICTOR-E1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2005-10-21
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period
timeFrame: Baseline and Week 48 of the Double-blind Period
Secondary outcomes:
measure: Participants With ≥1.0 log10 Change From Baseline HIV RNA at Week 48 of the Double-blind Period
timeFrame: Baseline and 48 Weeks of the Double-blind Period
measure: Participants With HIV RNA <400 Copies/mL at Week 48 of the Double-blind Period
timeFrame: Week 48 of the Double-blind Period
measure: Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period
timeFrame: Up to 48 weeks of the Double-blind Period
measure: Change From Baseline in Log10 HIV RNA at Week 12 of the Double-blind Period
timeFrame: Baseline and Week 12 of the Double-blind Period
measure: Change From Baseline in Log10 HIV RNA at Week 24 of the Double-blind Period
timeFrame: Baseline and Week 24 of the Double-blind Period
measure: Change From Baseline CD4 Cells Count at Week 12 of the Double-blind Period
timeFrame: Baseline and Week 12 of the Double-blind Period
measure: Change From Baseline CD4 Count at Week 24 of the Double-blind Period
timeFrame: Baseline and Week 24 of the Double-blind Period
measure: Change From Baseline CD4 Count at Week 48 of the Double-blind Period
timeFrame: Baseline and Week 48 of the Double-blind Period
measure: Change From Baseline CD4 Count at Month 42 of the Open Label Extension
timeFrame: Baseline and Month 42 of the Open Label Period
measure: Participants With <400 Copies/mL HIV RNA at Week 12 of the Double-blind Period
timeFrame: Week 12 of the Double-blind Period
measure: Participants With <400 Copies/mL HIV RNA at Week 24 of the Double-blind Period
timeFrame: Week 24 of the Double-blind Period
measure: Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension
timeFrame: Up to 45 months of the Open Label Extension
measure: Participants With <50 Copies/mL HIV RNA at Week 12 of the Double-blind Period
timeFrame: Week 12 of the Double-blind Period
measure: Participants With <50 Copies/mL HIV RNA at Week 24 of the Double-blind Period
timeFrame: Week 24 of the Double-blind Period
measure: Participants With <50 Copies/mL HIV RNA at Week 48 of the Double-blind Period
timeFrame: Week 48 of the Double-blind Period
measure: Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Events of the Double-blind Period
timeFrame: Up to 48 weeks of the Double-blind Period
measure: Participants With AIDS-defining Events of the Open Label Extension
timeFrame: Up to 45 months of the Open Label Extension
measure: Time to Occurrence of an AIDS-defining Event of the Double-blind Period
timeFrame: Up to 48 weeks of the Double-blind Period
measure: Observed Minimum Serum Concentration of Vicriviroc (Cmin) of the Double-blind Period
timeFrame: Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period
measure: Observed Maximum (Peak) Plasma Concentration of Vicriviroc (Cmax) of the Double-blind Period
timeFrame: Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period
measure: Area Under the Plasma Concentration Versus Time Curve of Vicriviroc (AUC) of the Double-blind Period
timeFrame: Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period
measure: Participants With Detectable Vicriviroc Resistance of the Double-blind Period
timeFrame: Up to 48 weeks of the Double-blind Period
measure: Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period
timeFrame: Up to 48 weeks of the Double-blind Period
measure: Participants With Detectable CXCR4-Tropic Virus and Immune Decline (≥50% Fall in CD4 Count From Baseline) of the Double-blind Period
timeFrame: Up to 48 weeks of the Double-blind Period
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Suleiman J, Zingman BS, Diaz RS, Madruga JV, DeJesus E, Slim J, Mak C, Lee E, McCarthy MC, Dunkle LM, Walmsley S. Vicriviroc in combination therapy with an optimized regimen for treatment-experienced subjects: 48-week results of the VICTOR-E1 phase 2 trial. J Infect Dis. 2010 Feb 15;201(4):590-9. doi: 10.1086/650342.