A Study of the Effect of Tocilizumab on Markers of Atherogenic Risk in Patients With Moderate to Severe Rheumatoid Arthritis
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).
2 other identifiers
interventional
132
4 countries
40
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3 rheumatoid-arthritis
Started Oct 2007
Typical duration for phase_3 rheumatoid-arthritis
40 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 24, 2007
CompletedFirst Posted
Study publicly available on registry
September 26, 2007
CompletedStudy Start
First participant enrolled
October 31, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
January 31, 2011
CompletedResults Posted
Study results publicly available
November 14, 2012
CompletedJuly 26, 2017
June 1, 2017
11 months
September 24, 2007
August 8, 2012
June 28, 2017
Conditions
Outcome Measures
Primary Outcomes (2)
Change From Baseline in Small Low Density Lipoprotein (sLDL) Particle Numbers
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.
Baseline and Week 12
Change From Baseline to Week 12 in Aortic Pulse Wave Velocity (PWV)
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.
Baseline and Week 12
Secondary Outcomes (3)
Change From Baseline to Week 24 in Small Low Density Lipoprotein (sLDL) Particle Numbers
Baseline and Week 24
Change From Baseline to Week 24 in Aortic Pulse Wave Velocity (PWV)
Baseline and Week 24
Number of Participants Experiencing Adverse Events (AEs)
Up to Week 24
Study Arms (2)
TCZ + MTX
EXPERIMENTALParticipants 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
PLACEBO COMPARATORParticipants 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.
Interventions
Administered by intravenous infusion, 8 mg/kg every 4 weeks.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (40)
Pinnacle Research Group; Llc, Central
Anniston, Alabama, 36207, United States
Rheumatology Associates of North Alabama
Huntsville, Alabama, 35801, United States
Advanced Arthritis Care & Research
Scottsdale, Arizona, 85258, United States
Catalina Pointe Clinical Research, Inc.
Tucson, Arizona, 85704, United States
Pacific Arthritis Care Center
Los Angeles, California, 90045, United States
Arthritis & Rheumatism; Disease Specialities
Aventura, Florida, 33180, United States
Science and Research Institute, Inc.
Jupiter, Florida, 33458, United States
Arthritis Center Palm Harbor
Palm Harbor, Florida, 34684, United States
Arthritis Rsrch of Florida, Inc.
Palm Harbor, Florida, 34684, United States
Sarasota Arthritis Center; Research Dept
Sarasota, Florida, 34239, United States
Burnette & Silverfield, MDS
Tampa, Florida, 33614, United States
Arthritis & Rheumatology of Georgia
Atlanta, Georgia, 30342, United States
Deerbrook Medical Associates
Vernon Hills, Illinois, 60061, United States
Johns Hopkins Uni
Baltimore, Maryland, 21224, United States
Borgess Research Institute
Kalamazoo, Michigan, 49048, United States
Jackson Arthritis Clinic
Flowood, Mississippi, 39232, United States
Physicians Group, LC DBA Rheumatology & Internal Medicine Associates
St Louis, Missouri, 63131, United States
NJP Clinical Research
Clifton, New Jersey, 07012, United States
Asheville Arthritis & Osteoporosis Center, PA
Asheville, North Carolina, 28803, United States
Health Research of Oklahoma, Llc
Oklahoma City, Oklahoma, 73103, United States
Lehigh Valley Hospital; Dept of Medicine
Allentown, Pennsylvania, 18103, United States
Altoona Center For Clinical Research
Duncansville, Pennsylvania, 16635, United States
Clinical Research Center of Reading
Wyomissing, Pennsylvania, 19610, United States
Houston Inst. For Clinical Research
Houston, Texas, 77074, United States
Texas Research Center
Sugar Land, Texas, 77479, United States
South Puget Sound Clinical Research
Olympia, Washington, 98502, United States
The Governors of the Uni of Alberta; Heritage Medical Research Centre
Edmonton, Alberta, T6G 2S2, Canada
Laurel Medical Clinic
Vancouver, British Columbia, V5Z 3Y1, Canada
Manitoba Clinic
Winnipeg, Manitoba, R3A 1M3, Canada
Nexus Clinical Research Centre
St. John's, Newfoundland and Labrador, A1A 5E8, Canada
Dr. William G. Bensen Medicine Professional Corporation
Hamilton, Ontario, L8N 1Y2, Canada
Credit Valley, Rheumatology
Mississauga, Ontario, L5M 2V8, Canada
Rheumatology Research Associates
Ottawa, Ontario, K1H 1A2, Canada
Private Practice
Toronto, Ontario, M4K 1N2, Canada
Chus Hopital Fleurimont
Sherbrooke, Quebec, J1H 5N4, Canada
Centre Re Recherche Saint-Louis
Québec, G1W 4R4, Canada
Ponce School of Medicine; Caimed Center
Ponce, 00716, Puerto Rico
Glasgow Royal Infirmary; Centre For Rheumatic Diseases
Glasgow, G4 0SF, United Kingdom
Trafford General Hospital; Rheumatology
Manchester, M41 5SL, United Kingdom
Royal Victoria Infirmary; Clinical Research Facility
Newcastle upon Tyne, NE1 4LP, United Kingdom
Related Publications (1)
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.
PMID: 22491018DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffman-LaRoche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 24, 2007
First Posted
September 26, 2007
Study Start
October 31, 2007
Primary Completion
September 30, 2008
Study Completion
January 31, 2011
Last Updated
July 26, 2017
Results First Posted
November 14, 2012
Record last verified: 2017-06