Clinical trial NCT00535782: A Study of the Effect of Tocilizumab on Markers of Atherogenic Risk in Patients With Moderate to Severe Rheumatoid Arthritis
Official title: A Mechanism of Action Study to Evaluate the Effects of IL-6 Receptor Blockade With Tocilizumab (TCZ) on Lipids, Arterial Stiffness, and Markers of Atherogenic Risk in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2007-09-26
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Primary outcomes:
measure: Change From Baseline in Small Low Density Lipoprotein (sLDL) Particle Numbers
timeFrame: Baseline and Week 12
measure: Change From Baseline to Week 12 in Aortic Pulse Wave Velocity (PWV)
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change From Baseline to Week 24 in Small Low Density Lipoprotein (sLDL) Particle Numbers
timeFrame: Baseline and Week 24
measure: Change From Baseline to Week 24 in Aortic Pulse Wave Velocity (PWV)
timeFrame: Baseline and Week 24
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group; Llc, Central
state: Alabama
city: Huntsville
country: United States
facility: Rheumatology Associates of North Alabama
state: Alabama
city: Scottsdale
country: United States
facility: Advanced Arthritis Care & Research
state: Arizona
city: Tucson
country: United States
facility: Catalina Pointe Clinical Research, Inc.
state: Arizona
city: Los Angeles
country: United States
facility: Pacific Arthritis Care Center
state: California
city: Aventura
country: United States
facility: Arthritis & Rheumatism; Disease Specialities
state: Florida
city: Jupiter
country: United States
facility: Science and Research Institute, Inc.
state: Florida
city: Palm Harbor
country: United States
facility: Arthritis Center Palm Harbor
state: Florida
city: Palm Harbor
country: United States
facility: Arthritis Rsrch of Florida, Inc.
state: Florida
city: Sarasota
country: United States
facility: Sarasota Arthritis Center; Research Dept
state: Florida
city: Tampa
country: United States
facility: Burnette & Silverfield, MDS
state: Florida
city: Atlanta
country: United States
facility: Arthritis & Rheumatology of Georgia
state: Georgia
city: Vernon Hills
country: United States
facility: Deerbrook Medical Associates
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Uni
state: Maryland
city: Kalamazoo
country: United States
facility: Borgess Research Institute
state: Michigan
city: Flowood
country: United States
facility: Jackson Arthritis Clinic
state: Mississippi
city: Saint Louis
country: United States
facility: Physicians Group, LC DBA Rheumatology & Internal Medicine Associates
state: Missouri
city: Clifton
country: United States
facility: NJP Clinical Research
state: New Jersey
city: Asheville
country: United States
facility: Asheville Arthritis & Osteoporosis Center, PA
state: North Carolina
city: Oklahoma City
country: United States
facility: Health Research of Oklahoma, Llc
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Valley Hospital; Dept of Medicine
state: Pennsylvania
city: Duncansville
country: United States
facility: Altoona Center For Clinical Research
state: Pennsylvania
city: Wyomissing
country: United States
facility: Clinical Research Center of Reading
state: Pennsylvania
city: Houston
country: United States
facility: Houston Inst. For Clinical Research
state: Texas
city: Sugar Land
country: United States
facility: Texas Research Center
state: Texas
city: Olympia
country: United States
facility: South Puget Sound Clinical Research
state: Washington
city: Edmonton
country: Canada
facility: The Governors of the Uni of Alberta; Heritage Medical Research Centre
state: Alberta
city: Vancouver
country: Canada
facility: Laurel Medical Clinic
state: British Columbia
city: Winnipeg
country: Canada
facility: Manitoba Clinic
state: Manitoba
city: St John's
country: Canada
facility: Nexus Clinical Research Centre
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: Dr. William G. Bensen Medicine Professional Corporation
state: Ontario
city: Mississauga
country: Canada
facility: Credit Valley, Rheumatology
state: Ontario
city: Ottawa
country: Canada
facility: Rheumatology Research Associates
state: Ontario
city: Toronto
country: Canada
facility: Private Practice
state: Ontario
city: Sherbrooke
country: Canada
facility: Chus Hopital Fleurimont
state: Quebec
city: Quebec
country: Canada
facility: Centre Re Recherche Saint-Louis
city: Ponce
country: Puerto Rico
facility: Ponce School of Medicine; Caimed Center
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary; Centre For Rheumatic Diseases
city: Manchester
country: United Kingdom
facility: Trafford General Hospital; Rheumatology
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary; Clinical Research Facility
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Wang J, Bansal AT, Martin M, Germer S, Benayed R, Essioux L, Lee JS, Begovich A, Hemmings A, Kenwright A, Taylor KE, Upmanyu R, Cutler P, Harari O, Marchini J, Criswell LA, Platt A. Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis. Pharmacogenomics J. 2013 Jun;13(3):235-41. doi: 10.1038/tpj.2012.8. Epub 2012 Apr 10.