Vicriviroc (SCH 417690) in Combination Treatment With Optimized ART Regimen in Experienced Subjects (VICTOR-E1)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 116
- 主要终点
- Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
There were Double-blind and an Open Label extension period.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Double-Blind - Vicriviroc 30 mg
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.
干预措施: Vicriviroc 30 mg (Drug)
Double-Blind - Vicriviroc 30 mg
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.
干预措施: Background ART Regimen (Drug)
Double-Blind - Vicriviroc 20 mg
Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
干预措施: Vicriviroc 20 mg (Drug)
Double-Blind - Vicriviroc 20 mg
Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
干预措施: Placebo (Drug)
Double-Blind - Vicriviroc 20 mg
Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
干预措施: Background ART Regimen (Drug)
Double-Blind - Placebo
Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
干预措施: Placebo (Drug)
Double-Blind - Placebo
Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
干预措施: Background ART Regimen (Drug)
Open-label - Vicriviroc 30 mg
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.
干预措施: Vicriviroc 30 mg (Drug)
Open-label - Vicriviroc 30 mg
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.
干预措施: Background ART Regimen (Drug)
结局指标
主要结局
Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period
时间窗: Baseline and Week 48 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 copies/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero. Analysis was performed with a variance (ANOVA) model that adjusted for the treatment and stratification factors (intended enfuvirtide (T20) use in current newly-optimized background regimen (OBT) (Y/N) and HIV RNA at Screening (\> or ≤100,000 copies/mL)).
次要结局
- Participants With <400 Copies/mL HIV RNA at Week 24 of the Double-blind Period(Week 24 of the Double-blind Period)
- Change From Baseline in Log10 HIV RNA at Week 12 of the Double-blind Period(Baseline and Week 12 of the Double-blind Period)
- Participants With ≥1.0 log10 Change From Baseline HIV RNA at Week 48 of the Double-blind Period(Baseline and 48 Weeks of the Double-blind Period)
- Change From Baseline CD4 Count at Week 24 of the Double-blind Period(Baseline and Week 24 of the Double-blind Period)
- Participants With HIV RNA <400 Copies/mL at Week 48 of the Double-blind Period(Week 48 of the Double-blind Period)
- Change From Baseline in Log10 HIV RNA at Week 24 of the Double-blind Period(Baseline and Week 24 of the Double-blind Period)
- Change From Baseline CD4 Count at Month 42 of the Open Label Extension(Baseline and Month 42 of the Open Label Period)
- Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period(Up to 48 weeks of the Double-blind Period)
- Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension(Up to 45 months of the Open Label Extension)
- Participants With <50 Copies/mL HIV RNA at Week 24 of the Double-blind Period(Week 24 of the Double-blind Period)
- Participants With <50 Copies/mL HIV RNA at Week 48 of the Double-blind Period(Week 48 of the Double-blind Period)
- Observed Minimum Serum Concentration of Vicriviroc (Cmin) of the Double-blind Period(Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period)
- Observed Maximum (Peak) Plasma Concentration of Vicriviroc (Cmax) of the Double-blind Period(Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period)
- Area Under the Plasma Concentration Versus Time Curve of Vicriviroc (AUC) of the Double-blind Period(Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period)
- Change From Baseline CD4 Cells Count at Week 12 of the Double-blind Period(Baseline and Week 12 of the Double-blind Period)
- Participants With <400 Copies/mL HIV RNA at Week 12 of the Double-blind Period(Week 12 of the Double-blind Period)
- Participants With <50 Copies/mL HIV RNA at Week 12 of the Double-blind Period(Week 12 of the Double-blind Period)
- Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Events of the Double-blind Period(Up to 48 weeks of the Double-blind Period)
- Participants With AIDS-defining Events of the Open Label Extension(Up to 45 months of the Open Label Extension)
- Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period(Up to 48 weeks of the Double-blind Period)
- Change From Baseline CD4 Count at Week 48 of the Double-blind Period(Baseline and Week 48 of the Double-blind Period)
- Time to Occurrence of an AIDS-defining Event of the Double-blind Period(Up to 48 weeks of the Double-blind Period)
- Participants With Detectable CXCR4-Tropic Virus and Immune Decline (≥50% Fall in CD4 Count From Baseline) of the Double-blind Period(Up to 48 weeks of the Double-blind Period)
- Participants With Detectable Vicriviroc Resistance of the Double-blind Period(Up to 48 weeks of the Double-blind Period)