A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Safety and Efficacy of Maraviroc in the Treatment of Rheumatoid Arthritis in Subjects Receiving Methotrexate
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 128
- 试验地点
- 1
- 主要终点
- American College of Rheumatology (ACR) 20% Responders at Week 12
研究概览
简要总结
The purpose of this study is to evaluate whether maraviroc, an investigational drug given with methotrexate (MTX) is safe and effective in the treatment of rheumatoid arthritis in adult patients.
详细描述
Following a planned interim analysis in the POC component on 21 August 2008 by the internal DMC (Data Monitoring Committee) of study A4001056, the trial was discontinued due to lack of efficacy. All participating investigators/country offices and monitors were notified on 22 August 2008 to cease patient enrollment. The DMC indicated that maraviroc was well tolerated in the Rheumatoid Arthritis patients and there were no safety concerns in the study. The termination date of this trial was 07 October 2008 when the last patient last visit occurred.
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
- Double (Participant, Investigator)
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
- •Must be legal age of consent
- •Must have active rheumatoid arthritis based upon the American College of Rheumatology (ACR) 1987 (Revised Criteria); minimum disease criteria required for entry into the efficacy component of the study
- •Must meet ACR 1991 Revised Criteria for Global Functional Status in RA, Class I, II, or III
- •Must be receiving methotrexate for at least 12 weeks duration and on a stable dose for 4 weeks.
排除标准
- •Diagnosed with any other inflammatory arthritis or a secondary non-inflammatory arthritis that would interfere with disease activity assessments.
- •Subject receiving prior treatment with certain medications for rheumatoid arthritis
- •Tuberculosis and/or a positive tuberculin reaction
- •Significant trauma or major surgery within 2 months
- •History of alcohol and/or drug abuse outside of a defined period of abstinence
- •History of or a finding at screening of postural hypotension
- •Any condition that would affect the oral absorption of the drug
- •History of cancer and in remission less than 3 years or Grade III-IV congestive heart failure
- •Having an infection of human immunodeficiency virus (HIV), Hepatitis B or C or evidence of any active infection
- •Abnormalities of clinical or laboratory assessments completed at the screening visit such as elevated liver enzymes, decreased hemoglobin or an abnormal ECG
- •Having a positive chemokine receptor 5 (CCR5) delta 32 mutation
- •Requiring the use of certain medications
- •Lactating or pregnant women or subjects have reproductive potential unwilling to use an adequate method of birth control
- •Chronic or recent serious or life-threatening infection; severe , progressive and/or uncontrollable renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological disease within 12 weeks of the first dose.
研究组 & 干预措施
2
干预措施: Maraviroc Placebo (Drug)
1
This study was divided into two components: safety/pharmacokinetic (PK) and proof-of-concept (POC). In the safety/PK component either 150 mg or 300 mg tablets of maraviroc was administered twice a day (BID) to 16 rheumatoid arthritis subjects for 4 weeks.
干预措施: Maraviroc (Drug)
结局指标
主要结局
American College of Rheumatology (ACR) 20% Responders at Week 12
时间窗: Week 12
A subject was an ACR 20 responder if: the counts for both tender and swollen joints had reduced by 20% or more from baseline; and 3 out of the following 5 assessments showed reduction of 20% or more from baseline assessment: Patient's Assessment of Arthritis Pain (Visual Analogue Scale \[VAS\]), Patient's Global Assessment of Arthritis (VAS), Physician's Global Assessment of Arthritis (Categorical), Health Assessment Questionnaire - Disability Index (HAQ-DI), and C-Reactive Protein (CRP).
次要结局
- ACR 50% Responders at Weeks 1, 2, 4, 8, and 12(Weeks 1, 2, 4, 8, and 12)
- ACR 70% Responders at Weeks 1, 2, 4, 8, and 12(Weeks 1, 2, 4, 8, and 12)
- Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12(Baseline, Weeks 1, 2, 4, 8, and 12)
- Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12(Baseline, Weeks 1, 2, 4, 8, and 12)
- Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12(Baseline, Weeks 1, 2, 4, 8, and 12)
- Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12(Baseline, Weeks 1, 2, 4, 8, and 12)
- Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12(Baseline, Weeks 1, 2, 4, 8, and 12)
- Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline(Baseline, 16 weeks)
- Change From Baseline in SF-36 Mental Component Summary at Weeks 4 and 12(Baseline, Weeks 4 and 12)
- Number of Subjects With Withdrawal From Study Due to Lack of Efficacy(16 weeks)
- Maximum Observed Concentration (Cmax) During the Dosing Interval for MTX at Screening and Week 1 and Maraviroc at Week 1(Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose))
- ACR 20% Responders at Weeks 1, 2, 4, and 8(Weeks 1, 2, 4, and 8)
- Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12(Baseline, Weeks 1, 2, 4, 8, and 12)
- Change From Baseline in Mean Orthostatic Blood Pressure (BP)(Baseline, 16 weeks)
- Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate).(Baseline, 16 weeks)
- Change From Baseline in Short Form-36 (SF-36) Physical Component Summary at Weeks 4 and 12(Baseline, Weeks 4 and 12)
- Time for Cmax (Tmax) for MTX at Screening and Week 1 and Maraviroc at Week 1(Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose))
- Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12(Baseline, Weeks 1, 2, 4, 8, and 12)
- Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline(Baseline, 16 weeks)
- Area Under the Plasma Concentration-Time Profile From Time Zero to Four Hours Postdose (AUC 0-4) for MTX at Screening and Week 1 and Maraviroc at Week 1(Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose))
- Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12(Baseline, Weeks 1, 2, 4, 8, and 12)
- Change From Baseline in Mean Heart Rate(Baseline, 16 weeks)
- Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy.(Weeks 1 to 12)
- Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (RR Interval, PR Interval, QRS Complex, QT Interval, Corrected QT [QTc] Interval, QTcB Interval [Bazett's Correction], QTcF Interval [Fridericia's Correction]).(Baseline, 16 weeks)