A Study of the Effect of Tocilizumab on Markers of Atherogenic Risk in Patients With Moderate to Severe Rheumatoid Arthritis
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT00535782
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This 2 arm study will investigate the effects of tocilizumab on lipids, arterial stiffness, and markers of atherogenic risk in patients with moderate to severe active rheumatoid arthritis. In Part 1 of the study, patients will be randomized to receive either tocilizumab 8mg/kg intravenously or placebo every 4 weeks, in combination with methotrexate 7.5-25 mg weekly. In Part 2, all patients will receive open-label treatment with tocilizumab plus methotrexate.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 132
- adult patients, 18-75 years of age
- rheumatoid arthritis (RA) of >6 months duration
- able to receive outpatient treatment
- on methotrexate for at least 12 weeks before entering study, at a stable dose of 7.5-25 mg/week for the last 8 weeks
- oral corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDS) permitted, if at a stable dose for 4 weeks before study start
Exclusion Criteria
- major surgery (including joint surgery) within 8 weeks prior to screening, or planned surgery within 6 months after entering study
- history of, or current inflammatory joint disease or rheumatic autoimmune disease other than RA
- inadequate response to anti-tumor necrosis factor (TNF) agent during the 6 months prior to baseline, or inadequate response to >2 anti-TNF agents
- initiation of treatment with lipid lowering agents within 12 weeks prior to baseline
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + MTX Placebo Participants received placebo intravenous infusion (IV) every 4 weeks plus methotrexate (MTX) 7.5-25 mg (oral or parenteral) weekly for the first 24 weeks. From Week 24 to 104, participants received open-label tocilizumab (TCZ) 8 mg/kg every 4 weeks plus 7.5-25 mg MTX. TCZ + MTX Methotrexate Participants received 8 mg/kg tocilizumab (TCZ) by intravenous infusion (IV) every 4 weeks plus methotrexate (MTX) 7.5-25 mg (oral or parenteral) weekly for the first 24 weeks. From Week 24 to Week 104, participants received open-label TCZ 8 mg/kg every 4 weeks plus 7.5-25 mg MTX weekly. TCZ + MTX Tocilizumab Participants received 8 mg/kg tocilizumab (TCZ) by intravenous infusion (IV) every 4 weeks plus methotrexate (MTX) 7.5-25 mg (oral or parenteral) weekly for the first 24 weeks. From Week 24 to Week 104, participants received open-label TCZ 8 mg/kg every 4 weeks plus 7.5-25 mg MTX weekly. Placebo + MTX Tocilizumab Participants received placebo intravenous infusion (IV) every 4 weeks plus methotrexate (MTX) 7.5-25 mg (oral or parenteral) weekly for the first 24 weeks. From Week 24 to 104, participants received open-label tocilizumab (TCZ) 8 mg/kg every 4 weeks plus 7.5-25 mg MTX. Placebo + MTX Methotrexate Participants received placebo intravenous infusion (IV) every 4 weeks plus methotrexate (MTX) 7.5-25 mg (oral or parenteral) weekly for the first 24 weeks. From Week 24 to 104, participants received open-label tocilizumab (TCZ) 8 mg/kg every 4 weeks plus 7.5-25 mg MTX.
- Primary Outcome Measures
Name Time Method Change From Baseline in Small Low Density Lipoprotein (sLDL) Particle Numbers Baseline and Week 12 Small LDL particles are associated with an increased risk of cardiovascular disease: more of these small particles lead to a greater risk. The concentration of fasting small LDL particles was determined using the Nuclear Magnetic Resonance (NMR) methodology.
Change From Baseline to Week 12 in Aortic Pulse Wave Velocity (PWV) Baseline and Week 12 Aortic (central) arterial stiffness was assessed with Pulse Wave Analysis (PWA) of the radial artery and carotid-femoral PWV using applanation tonometry after the patient had rested in a supine position for at least 10 minutes.
- Secondary Outcome Measures
Name Time Method Number of Participants Experiencing Adverse Events (AEs) Up to Week 24 A severe AE is an event in which the intensity of the event results in an inability to work or perform normal daily activity.
A Serious AE is fatal, life-threatening, requires in-patient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant or requires intervention to prevent one of the above outcomes.
AEs of special interest include infection, gastrointestinal, infusion reaction (occurring during or within 24 hours of infusion), hepatic disorder, myocardial infarction and stroke.Change From Baseline to Week 24 in Small Low Density Lipoprotein (sLDL) Particle Numbers Baseline and Week 24 Small LDL particles are associated with an increased risk of cardiovascular disease: more of these small particles lead to a greater risk. The concentration of fasting small LDL particles was determined using the Nuclear Magnetic Resonance (NMR) methodology.
Change From Baseline to Week 24 in Aortic Pulse Wave Velocity (PWV) Baseline and Week 24 Aortic (central) arterial stiffness was assessed with Pulse Wave Analysis (PWA) of the radial artery and carotid-femoral PWV using applanation tonometry after the patient had rested in a supine position for at least 10 minutes.
Trial Locations
- Locations (40)
Rheumatology Associates of North Alabama
🇺🇸Huntsville, Alabama, United States
Pinnacle Research Group; Llc, Central
🇺🇸Anniston, Alabama, United States
Arthritis & Rheumatism; Disease Specialities
🇺🇸Aventura, Florida, United States
Pacific Arthritis Care Center
🇺🇸Los Angeles, California, United States
Arthritis Center Palm Harbor
🇺🇸Palm Harbor, Florida, United States
Sarasota Arthritis Center; Research Dept
🇺🇸Sarasota, Florida, United States
Science and Research Institute, Inc.
🇺🇸Jupiter, Florida, United States
Arthritis & Rheumatology of Georgia
🇺🇸Atlanta, Georgia, United States
Arthritis Rsrch of Florida, Inc.
🇺🇸Palm Harbor, Florida, United States
Johns Hopkins Uni
🇺🇸Baltimore, Maryland, United States
Jackson Arthritis Clinic
🇺🇸Flowood, Mississippi, United States
Physicians Group, LC DBA Rheumatology & Internal Medicine Associates
🇺🇸Saint Louis, Missouri, United States
Asheville Arthritis & Osteoporosis Center, PA
🇺🇸Asheville, North Carolina, United States
Lehigh Valley Hospital; Dept of Medicine
🇺🇸Allentown, Pennsylvania, United States
Altoona Center For Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
Clinical Research Center of Reading
🇺🇸Wyomissing, Pennsylvania, United States
Houston Inst. For Clinical Research
🇺🇸Houston, Texas, United States
Texas Research Center
🇺🇸Sugar Land, Texas, United States
Laurel Medical Clinic
🇨🇦Vancouver, British Columbia, Canada
South Puget Sound Clinical Research
🇺🇸Olympia, Washington, United States
Credit Valley, Rheumatology
🇨🇦Mississauga, Ontario, Canada
Dr. William G. Bensen Medicine Professional Corporation
🇨🇦Hamilton, Ontario, Canada
Rheumatology Research Associates
🇨🇦Ottawa, Ontario, Canada
Private Practice
🇨🇦Toronto, Ontario, Canada
Centre Re Recherche Saint-Louis
🇨🇦Quebec, Canada
Ponce School of Medicine; Caimed Center
🇵🇷Ponce, Puerto Rico
Trafford General Hospital; Rheumatology
🇬🇧Manchester, United Kingdom
Glasgow Royal Infirmary; Centre For Rheumatic Diseases
🇬🇧Glasgow, United Kingdom
Royal Victoria Infirmary; Clinical Research Facility
🇬🇧Newcastle Upon Tyne, United Kingdom
Manitoba Clinic
🇨🇦Winnipeg, Manitoba, Canada
Borgess Research Institute
🇺🇸Kalamazoo, Michigan, United States
Nexus Clinical Research Centre
🇨🇦St John's, Newfoundland and Labrador, Canada
Advanced Arthritis Care & Research
🇺🇸Scottsdale, Arizona, United States
Chus Hopital Fleurimont
🇨🇦Sherbrooke, Quebec, Canada
The Governors of the Uni of Alberta; Heritage Medical Research Centre
🇨🇦Edmonton, Alberta, Canada
Catalina Pointe Clinical Research, Inc.
🇺🇸Tucson, Arizona, United States
NJP Clinical Research
🇺🇸Clifton, New Jersey, United States
Health Research of Oklahoma, Llc
🇺🇸Oklahoma City, Oklahoma, United States
Deerbrook Medical Associates
🇺🇸Vernon Hills, Illinois, United States
Burnette & Silverfield, MDS
🇺🇸Tampa, Florida, United States