Clinical trial NCT00427934: Maraviroc in Rheumatoid Arthritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Arthritis, Rheumatoid
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-01-29
Enrollment: 128
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: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: American College of Rheumatology (ACR) 20% Responders at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: ACR 20% Responders at Weeks 1, 2, 4, and 8
timeFrame: Weeks 1, 2, 4, and 8
measure: ACR 50% Responders at Weeks 1, 2, 4, 8, and 12
timeFrame: Weeks 1, 2, 4, 8, and 12
measure: ACR 70% Responders at Weeks 1, 2, 4, 8, and 12
timeFrame: Weeks 1, 2, 4, 8, and 12
measure: Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12
timeFrame: Baseline, Weeks 1, 2, 4, 8, and 12
measure: Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12
timeFrame: Baseline, Weeks 1, 2, 4, 8, and 12
measure: Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12
timeFrame: Baseline, Weeks 1, 2, 4, 8, and 12
measure: Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12
timeFrame: Baseline, Weeks 1, 2, 4, 8, and 12
measure: Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12
timeFrame: Baseline, Weeks 1, 2, 4, 8, and 12
measure: Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12
timeFrame: Baseline, Weeks 1, 2, 4, 8, and 12
measure: Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12
timeFrame: Baseline, Weeks 1, 2, 4, 8, and 12
measure: Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12
timeFrame: Baseline, Weeks 1, 2, 4, 8, and 12
measure: Change From Baseline in Mean Orthostatic Blood Pressure (BP)
timeFrame: Baseline, 16 weeks
measure: Change From Baseline in Mean Heart Rate
timeFrame: Baseline, 16 weeks
measure: Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline
timeFrame: Baseline, 16 weeks
measure: 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]).
timeFrame: Baseline, 16 weeks
measure: Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate).
timeFrame: Baseline, 16 weeks
measure: Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline
timeFrame: Baseline, 16 weeks
measure: Change From Baseline in Short Form-36 (SF-36) Physical Component Summary at Weeks 4 and 12
timeFrame: Baseline, Weeks 4 and 12
measure: Change From Baseline in SF-36 Mental Component Summary at Weeks 4 and 12
timeFrame: Baseline, Weeks 4 and 12
measure: Number of Subjects With Withdrawal From Study Due to Lack of Efficacy
timeFrame: 16 weeks
measure: Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy.
timeFrame: Weeks 1 to 12
measure: 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
timeFrame: Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)
measure: Maximum Observed Concentration (Cmax) During the Dosing Interval for MTX at Screening and Week 1 and Maraviroc at Week 1
timeFrame: Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)
measure: Time for Cmax (Tmax) for MTX at Screening and Week 1 and Maraviroc at Week 1
timeFrame: Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)
Other outcomes:
Locations:
city: Huntington Beach
country: United States
facility: Pfizer Investigational Site
state: California
city: San Francisco
country: United States
facility: Pfizer Investigational Site
state: California
city: Hamden
country: United States
facility: Pfizer Investigational Site
state: Connecticut
city: Meriden
country: United States
facility: Pfizer Investigational Site
state: Connecticut
city: New Haven
country: United States
facility: Pfizer Investigational Site
state: Connecticut
city: New Haven
country: United States
facility: Pfizer Investigational Site
state: Connecticut
city: Daytona Beach
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Port Orange
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Savannah
country: United States
facility: Pfizer Investigational Site
state: Georgia
city: Savannah
country: United States
facility: Pfizer Investigational Site
state: Georgia
city: Moline
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Madisonville
country: United States
facility: Pfizer Investigational Site
state: Kentucky
city: Kalamazoo
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: Kalamazoo
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: Omaha
country: United States
facility: Pfizer Investigational Site
state: Nebraska
city: Las Vegas
country: United States
facility: Pfizer Investigational Site
state: Nevada
city: Syracuse
country: United States
facility: Pfizer Investigational Site
state: New York
city: Hickory
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Hickory
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Minot
country: United States
facility: Pfizer Investigational Site
state: North Dakota
city: Duncansville
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Maroochydore
country: Australia
facility: Pfizer Investigational Site
state: Queensland
city: Woodville
country: Australia
facility: Pfizer Investigational Site
state: South Australia
city: Hobart
country: Australia
facility: Pfizer Investigational Site
state: Tasmania
city: Berlin
country: Germany
facility: Pfizer Investigational Site
city: Berlin
country: Germany
facility: Pfizer Investigational Site
city: Leipzig
country: Germany
facility: Pfizer Investigational Site
city: Hyderabad
country: India
facility: Pfizer Investigational Site
state: Andhra Pradesh
city: Bangalore
country: India
facility: Pfizer Investigational Site
state: Karnataka
city: Bangalore
country: India
facility: Pfizer Investigational Site
state: Karnataka
city: Genova
country: Italy
facility: Pfizer Investigational Site
city: Pavia
country: Italy
facility: Pfizer Investigational Site
city: Guadalajara
country: Mexico
facility: Pfizer Investigational Site
state: Jalisco
city: Guadalajara
country: Mexico
facility: Pfizer Investigational Site
state: Jalisco
city: Coimbra
country: Portugal
facility: Pfizer Investigational Site
city: Lisboa
country: Portugal
facility: Pfizer Investigational Site
city: Lisbon
country: Portugal
facility: Pfizer Investigational Site
city: Santiago de Compostela
country: Spain
facility: Pfizer Investigational Site
state: A Coruña
city: Barcelona
country: Spain
facility: Pfizer Investigational Site
city: Madrid
country: Spain
facility: Pfizer Investigational Site
city: Sevilla
country: Spain
facility: Pfizer Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: Pfizer Investigational Site
city: Kharkiv
country: Ukraine
facility: Pfizer Investigational Site
city: Simferopol
country: Ukraine
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Fleishaker DL, Garcia Meijide JA, Petrov A, Kohen MD, Wang X, Menon S, Stock TC, Mebus CA, Goodrich JM, Mayer HB, Zeiher BG. Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatment of patients with rheumatoid arthritis in a randomized, double-blind placebo-controlled trial. Arthritis Res Ther. 2012 Jan 17;14(1):R11. doi: 10.1186/ar3685.