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Maraviroc in Rheumatoid Arthritis

2014年10月30日 更新者：Pfizer

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

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.

研究概览

地位

终止

条件

干预/治疗

详细说明

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.

研究类型

介入性

注册 (实际的)

128

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 乌克兰
      • Dnipropetrovsk、乌克兰、49005
        • Pfizer Investigational Site
      • Kharkiv、乌克兰、61000
        • Pfizer Investigational Site
      • Simferopol、乌克兰、95017
        • Pfizer Investigational Site
  • 印度
    • Andhra Pradesh
      • Hyderabad、Andhra Pradesh、印度、500 082
        • Pfizer Investigational Site
    • Karnataka
      • Bangalore、Karnataka、印度、560 034
        • Pfizer Investigational Site
      • Bangalore、Karnataka、印度、560003
        • Pfizer Investigational Site
  • 墨西哥
    • Jalisco
      • Guadalajara、Jalisco、墨西哥、44690
        • Pfizer Investigational Site
      • Guadalajara、Jalisco、墨西哥、CP 44340
        • Pfizer Investigational Site
  • 德国
      • Berlin、德国、10117
        • Pfizer Investigational Site
      • Berlin、德国、14059
        • Pfizer Investigational Site
      • Leipzig、德国、04103
        • Pfizer Investigational Site
  • 意大利
      • Genova、意大利、16132
        • Pfizer Investigational Site
      • Pavia、意大利、27100
        • Pfizer Investigational Site
  • 澳大利亚
    • Queensland
      • Maroochydore、Queensland、澳大利亚、4558
        • Pfizer Investigational Site
    • South Australia
      • Woodville、South Australia、澳大利亚、5011
        • Pfizer Investigational Site
    • Tasmania
      • Hobart、Tasmania、澳大利亚、7001
        • Pfizer Investigational Site
  • 美国
    • California
      • Huntington Beach、California、美国、92646
        • Pfizer Investigational Site
      • San Francisco、California、美国、94115
        • Pfizer Investigational Site
    • Connecticut
      • Hamden、Connecticut、美国、06518
        • Pfizer Investigational Site
      • Meriden、Connecticut、美国、06450
        • Pfizer Investigational Site
      • New Haven、Connecticut、美国、06511-5473
        • Pfizer Investigational Site
      • New Haven、Connecticut、美国、06510-2716
        • Pfizer Investigational Site
    • Florida
      • Daytona Beach、Florida、美国、32114
        • Pfizer Investigational Site
      • Port Orange、Florida、美国、32127
        • Pfizer Investigational Site
    • Georgia
      • Savannah、Georgia、美国、31405
        • Pfizer Investigational Site
      • Savannah、Georgia、美国、31406
        • Pfizer Investigational Site
    • Illinois
      • Moline、Illinois、美国、61265
        • Pfizer Investigational Site
    • Kentucky
      • Madisonville、Kentucky、美国、42431
        • Pfizer Investigational Site
    • Michigan
      • Kalamazoo、Michigan、美国、49007
        • Pfizer Investigational Site
      • Kalamazoo、Michigan、美国、49048
        • Pfizer Investigational Site
    • Nebraska
      • Omaha、Nebraska、美国、68154
        • Pfizer Investigational Site
    • Nevada
      • Las Vegas、Nevada、美国、89128
        • Pfizer Investigational Site
    • New York
      • Syracuse、New York、美国、13210
        • Pfizer Investigational Site
    • North Carolina
      • Hickory、North Carolina、美国、28601
        • Pfizer Investigational Site
      • Hickory、North Carolina、美国、28602
        • Pfizer Investigational Site
    • North Dakota
      • Minot、North Dakota、美国、58701
        • Pfizer Investigational Site
    • Pennsylvania
      • Duncansville、Pennsylvania、美国、16635
        • Pfizer Investigational Site
  • 葡萄牙
      • Coimbra、葡萄牙、3000-075
        • Pfizer Investigational Site
      • Lisboa、葡萄牙、1600-035
        • Pfizer Investigational Site
      • Lisbon、葡萄牙、1000-247
        • Pfizer Investigational Site
  • 西班牙
      • Barcelona、西班牙、08035
        • Pfizer Investigational Site
      • Madrid、西班牙、28007
        • Pfizer Investigational Site
      • Sevilla、西班牙、41014
        • Pfizer Investigational Site
    • A Coruña
      • Santiago de Compostela、A Coruña、西班牙、15705
        • Pfizer Investigational Site

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：双倍的

武器和干预

参与者组/臂
干预/治疗
安慰剂比较：2个
药品：Maraviroc Placebo
Placebo tablets to match active drug. Two tablets are administered by mouth twice a day (BID) for 12 weeks.
实验性的：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.
药品：Maraviroc
300 mg (2- 150 mg tablets) are administered by mouth twice a day (BID) for 12 weeks.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
American College of Rheumatology (ACR) 20% Responders at Week 12
大体时间：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).
Week 12

次要结果测量

结果测量
措施说明
大体时间
ACR 20% Responders at Weeks 1, 2, 4, and 8
大体时间：Weeks 1, 2, 4, and 8
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, Patient's Global Assessment of Arthritis, Physician's Global Assessment of Arthritis, HAQ-DI, and CRP. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 ACR 20% data were collected, but not analyzed.
Weeks 1, 2, 4, and 8
ACR 50% Responders at Weeks 1, 2, 4, 8, and 12
大体时间：Weeks 1, 2, 4, 8, and 12
A subject was an ACR 50 responder if: the counts for both tender and swollen joints had reduced by 50% or more from baseline; and 3 out of the following 5 assessments showed reduction of 50% or more from baseline assessment: Patient's Assessment of Arthritis Pain, Patient's Global Assessment of Arthritis, Physician's Global Assessment of Arthritis, HAQ-DI, and CRP. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 ACR 50% data were collected, but not analyzed.
Weeks 1, 2, 4, 8, and 12
ACR 70% Responders at Weeks 1, 2, 4, 8, and 12
大体时间：Weeks 1, 2, 4, 8, and 12
A subject was an ACR 70 responder if: the counts for both tender and swollen joints had reduced by 70% or more from baseline; and 3 out of the following 5 assessments showed reduction of 70% or more from baseline assessment: Patient's Assessment of Arthritis Pain, Patient's Global Assessment of Arthritis, Physician's Global Assessment of Arthritis, HAQ-DI, and CRP. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 ACR 70% data were collected, but not analyzed.
Weeks 1, 2, 4, 8, and 12
Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12
大体时间：Baseline, Weeks 1, 2, 4, 8, and 12
Change from baseline at each visit was analyzed for tender/painful joint count. Twenty-eight tender and swollen joint scores included the same joints: shoulders, elbows, wrists, metacarpophalangeal joints (MCP), proximal interphalangeal joints (PIP), and the knees. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 tender/painful joint count data were collected, but not analyzed.
Baseline, Weeks 1, 2, 4, 8, and 12
Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12
大体时间：Baseline, Weeks 1, 2, 4, 8, and 12
Change from baseline at each visit was analyzed for swollen joint count. Twenty-eight tender and swollen joint scores included the same joints: shoulders, elbows, wrists, MCP joints, PIP joints, and the knees. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 swollen joint count data were collected, but not analyzed.
Baseline, 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
大体时间：Baseline, Weeks 1, 2, 4, 8, and 12
The severity of arthritis was scored by the subject between 0 (no pain) and 100 (most severe pain) on a 100 mm VAS. Change from baseline at each visit was analyzed for Patient's Assessment of Arthritis Pain. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 Patient's Assessment of Arthritis Pain data were collected, but not analyzed.
Baseline, Weeks 1, 2, 4, 8, and 12
Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12
大体时间：Baseline, Weeks 1, 2, 4, 8, and 12
Subjects answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Subjects responded by using a 0 - 100 mm VAS where 0=very well and 100=very poorly. Change from baseline at each visit was analyzed for Patient's Global Assessment. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 Patient's Global Assessment of Arthritis Pain data were collected, but not analyzed.
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
大体时间：Baseline, Weeks 1, 2, 4, 8, and 12
Physician's evaluation based on subject's disease signs, functional capacity and physical exam. Response recorded using 5-point scale: 1=Very Good, 2=Good, 3=Fair, 4=Poor and 5=Very Poor. Change from baseline at each visit was analyzed for Physician's Global Assessment. The Week 16 visit (follow-up) was designed for safety rather than efficacy thus Week 16 Physician's Global Assessment of Arthritis Pain data were collected but not analyzed.
Baseline, Weeks 1, 2, 4, 8, and 12
Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12
大体时间：Baseline, Weeks 1, 2, 4, 8, and 12
HAQ-DI assesses degree of difficulty experienced in daily activity categories (dressing/grooming, arising, eating, walking, hygiene, reach, grip and other activities) over the past week. There are 20 questions and difficulty is scored from 0 (none), 1 (some), 2 (much) and 3 (unable to do). Scores were then averaged to give the disability index (scale of 0 to 3). Change from baseline at each visit was analyzed. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 HAQ-DI data were collected but not analyzed.
Baseline, Weeks 1, 2, 4, 8, and 12
Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12
大体时间：Baseline, Weeks 1, 2, 4, 8, and 12
Change from baseline at each visit were analyzed for CRP. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 CRP data were collected, but not analyzed.
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
大体时间：Baseline, Weeks 1, 2, 4, 8, and 12

DAS28-4 (CRP) was calculated using the following formula:

DAS28- 4(CRP) = 0.56 √28 Tender Joint Count + 0.28 √28 Swollen Joint Count + 0.36*natural logarithm(CRP + 1) + 0.014*Patient Global Assessment + 0.96. DAS28 provides a number on a scale (0 to 10) indicating current disease activity. A score above 5.1 means high disease activity and a score below 3.2 indicates low disease activity. Change from baseline at each visit was analyzed for DAS28-4 (CRP). The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 DAS28-4 (CRP) data were collected, but not analyzed.
Baseline, Weeks 1, 2, 4, 8, and 12
Change From Baseline in Mean Orthostatic Blood Pressure (BP)
大体时间：Baseline, 16 weeks
Supine BP was recorded after 5 minutes lying down; subjects then sat for 2 minutes then stood for 2 minutes and standing BP was recorded. Orthostatic BP = either a systolic BP drop > 20 mmHg, or diastolic BP drop > 10 mmHg and/or drop in systolic BP < 90 mmHg. If a subject met the orthostatic criteria, they were required to complete 2 additional readings to provide a triplicate reading. The means of replicate BP values were used in the analysis. Baseline = the latest non-missing value from a range of pre-treatment visits. Change from baseline to Week 16 was analyzed for orthostatic BP.
Baseline, 16 weeks
Change From Baseline in Mean Heart Rate
大体时间：Baseline, 16 weeks
Heart rate = standing and supine at the same time the orthostatic BP measurements were obtained. Baseline was defined to be the latest non-missing value from a range of pre-treatment visits. Means of replicate values were not used.
Baseline, 16 weeks
Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline
大体时间：Baseline, 16 weeks
Baseline was defined to be the latest non-missing value from a range of pre-treatment visits. Maximum increase from baseline in supine and standing systolic BP was > = 30 mmHg, and maximum increase from baseline in supine and standing diastolic BP was > = 20 mmHg.
Baseline, 16 weeks
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]).
大体时间：Baseline, 16 weeks
Baseline was defined to be the latest non-missing value from a range of pre-treatment visits. Means of replicate values were used. QTc interval was not measured for the PK populations.
Baseline, 16 weeks
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate).
大体时间：Baseline, 16 weeks
Baseline was defined to be the latest non-missing value from a range of pre-treatment visits. Means of replicate values were used.
Baseline, 16 weeks
Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline
大体时间：Baseline, 16 weeks
Maximum QTcB, QTcF, and QTc intervals were defined as 450 to < 480 msec, 480 to < 500 msec, or > = 500 msec.
Baseline, 16 weeks
Change From Baseline in Short Form-36 (SF-36) Physical Component Summary at Weeks 4 and 12
大体时间：Baseline, Weeks 4 and 12
The SF-36 v.2 (Acute version) is a 36-item generic health status measure that measures 8 general health concepts: Physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain of the eight domains and the summary concept (physical component score) are scored to yield values between 0 (worst) and 100 (best). Change from baseline at Weeks 4 and 12 were analyzed for SF-36. Due to the termination of the study, SF-36 results for the PK component group were not analyzed.
Baseline, Weeks 4 and 12
Change From Baseline in SF-36 Mental Component Summary at Weeks 4 and 12
大体时间：Baseline, Weeks 4 and 12
The SF-36 v.2 (Acute version) [12] is a 36-item generic health status measure that measures 8 general health concepts: Physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain of the eight domains and the summary concept (mental component score) are scored to yield values between 0 (worst) and 100 (best). Change from baseline at Weeks 4 and 12 were analyzed for SF-36. Due to the termination of the study, SF-36 results for the PK component group were not analyzed.
Baseline, Weeks 4 and 12
Number of Subjects With Withdrawal From Study Due to Lack of Efficacy
大体时间：16 weeks
Withdrawal is the total number of withdrawals from the study. Withdrawal due to lack of efficacy was collected based on the investigator's judgement.
16 weeks
Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy.
大体时间：Weeks 1 to 12
Withdrawal due to lack of efficacy was collected based on the investigator's judgement. Time to withdrawal was measured by the probability that a subject did not withdraw due to lack of efficacy by a particular visit. This was a statistical estimate (Kaplan-Meier Survival Analysis) of the probability that a participant would not withdraw due to lack of efficacy.
Weeks 1 to 12
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
大体时间：Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)
Effect of maraviroc on the PK of MTX (comparison of AUC0-4 of MTX at screening versus at Week 1 after coadministration with 150 mg or 300 mg of maraviroc). PK was assessed at screening (MTX) and at Week 1 (maraviroc and MTX).
Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)
Maximum Observed Concentration (Cmax) During the Dosing Interval for MTX at Screening and Week 1 and Maraviroc at Week 1
大体时间：Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)
Effect of maraviroc on the PK of MTX (comparison of Cmax of MTX at screening versus at Week 1 after coadministration with 150 mg or 300 mg of maraviroc). PK was assessed at screening (MTX) and at Week 1 (maraviroc and MTX).
Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)
Time for Cmax (Tmax) for MTX at Screening and Week 1 and Maraviroc at Week 1
大体时间：Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)
PK was assessed at screening (MTX) and at Week 1 (maraviroc and MTX).
Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Pfizer

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2007年2月1日

初级完成 (实际的)

2008年10月1日

研究完成 (实际的)

2008年10月1日

研究注册日期

首次提交

2007年1月25日

首先提交符合 QC 标准的

2007年1月25日

首次发布 (估计)

2007年1月29日

研究记录更新

最后更新发布 (估计)

2014年11月5日

上次提交的符合 QC 标准的更新

2014年10月30日

最后验证

2014年10月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • A4001056

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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条件

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药物干预

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赞助者/合作者

地点

3
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