Back to resultsA Study of the Effect of Tocilizumab on Markers of Atherogenic Risk in Patients With Moderate to Severe Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Tocilizumab
Placebo
Methotrexate
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
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
Sites / Locations
- Pinnacle Research Group; Llc, Central
- Rheumatology Associates of North Alabama
- Advanced Arthritis Care & Research
- Catalina Pointe Clinical Research, Inc.
- Pacific Arthritis Care Center
- Arthritis & Rheumatism; Disease Specialities
- Science and Research Institute, Inc.
- Arthritis Center Palm Harbor
- Arthritis Rsrch of Florida, Inc.
- Sarasota Arthritis Center; Research Dept
- Burnette & Silverfield, MDS
- Arthritis & Rheumatology of Georgia
- Deerbrook Medical Associates
- Johns Hopkins Uni
- Borgess Research Institute
- Jackson Arthritis Clinic
- Physicians Group, LC DBA Rheumatology & Internal Medicine Associates
- NJP Clinical Research
- Asheville Arthritis & Osteoporosis Center, PA
- Health Research of Oklahoma, Llc
- Lehigh Valley Hospital; Dept of Medicine
- Altoona Center For Clinical Research
- Clinical Research Center of Reading
- Houston Inst. For Clinical Research
- Texas Research Center
- South Puget Sound Clinical Research
- The Governors of the Uni of Alberta; Heritage Medical Research Centre
- Laurel Medical Clinic
- Manitoba Clinic
- Nexus Clinical Research Centre
- Dr. William G. Bensen Medicine Professional Corporation
- Credit Valley, Rheumatology
- Rheumatology Research Associates
- Private Practice
- Chus Hopital Fleurimont
- Centre Re Recherche Saint-Louis
- Ponce School of Medicine; Caimed Center
- Glasgow Royal Infirmary; Centre For Rheumatic Diseases
- Trafford General Hospital; Rheumatology
- Royal Victoria Infirmary; Clinical Research Facility
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
TCZ + MTX
Placebo + MTX
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Change From Baseline to Week 24 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.
Change From Baseline to Week 24 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.
Number of Participants Experiencing Adverse Events (AEs)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00535782
Brief Title
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
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
October 31, 2007 (Actual)
Primary Completion Date
September 30, 2008 (Actual)
Study Completion Date
January 31, 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
132 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TCZ + MTX
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo + MTX
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
RoActemra, Actemra
Intervention Description
Administered by intravenous infusion, 8 mg/kg every 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to tocilizumab administered by intravenous infusion every 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Administered orally or parenterally, 7.5-25 mg weekly.
Primary Outcome Measure Information:
Title
Change From Baseline in Small Low Density Lipoprotein (sLDL) Particle Numbers
Description
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.
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in Aortic Pulse Wave Velocity (PWV)
Description
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.
Time Frame
Baseline and Week 12
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 24 in Small Low Density Lipoprotein (sLDL) Particle Numbers
Description
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.
Time Frame
Baseline and Week 24
Title
Change From Baseline to Week 24 in Aortic Pulse Wave Velocity (PWV)
Description
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.
Time Frame
Baseline and Week 24
Title
Number of Participants Experiencing Adverse Events (AEs)
Description
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.
Time Frame
Up to Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Pinnacle Research Group; Llc, Central
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
Facility Name
Rheumatology Associates of North Alabama
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35801
Country
United States
Facility Name
Advanced Arthritis Care & Research
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Catalina Pointe Clinical Research, Inc.
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
Pacific Arthritis Care Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90045
Country
United States
Facility Name
Arthritis & Rheumatism; Disease Specialities
City
Aventura
State/Province
Florida
ZIP/Postal Code
33180
Country
United States
Facility Name
Science and Research Institute, Inc.
City
Jupiter
State/Province
Florida
ZIP/Postal Code
33458
Country
United States
Facility Name
Arthritis Center Palm Harbor
City
Palm Harbor
State/Province
Florida
ZIP/Postal Code
34684
Country
United States
Facility Name
Arthritis Rsrch of Florida, Inc.
City
Palm Harbor
State/Province
Florida
ZIP/Postal Code
34684
Country
United States
Facility Name
Sarasota Arthritis Center; Research Dept
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34239
Country
United States
Facility Name
Burnette & Silverfield, MDS
City
Tampa
State/Province
Florida
ZIP/Postal Code
33614
Country
United States
Facility Name
Arthritis & Rheumatology of Georgia
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Deerbrook Medical Associates
City
Vernon Hills
State/Province
Illinois
ZIP/Postal Code
60061
Country
United States
Facility Name
Johns Hopkins Uni
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Borgess Research Institute
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49048
Country
United States
Facility Name
Jackson Arthritis Clinic
City
Flowood
State/Province
Mississippi
ZIP/Postal Code
39232
Country
United States
Facility Name
Physicians Group, LC DBA Rheumatology & Internal Medicine Associates
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63131
Country
United States
Facility Name
NJP Clinical Research
City
Clifton
State/Province
New Jersey
ZIP/Postal Code
07012
Country
United States
Facility Name
Asheville Arthritis & Osteoporosis Center, PA
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28803
Country
United States
Facility Name
Health Research of Oklahoma, Llc
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
Facility Name
Lehigh Valley Hospital; Dept of Medicine
City
Allentown
State/Province
Pennsylvania
ZIP/Postal Code
18103
Country
United States
Facility Name
Altoona Center For Clinical Research
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Clinical Research Center of Reading
City
Wyomissing
State/Province
Pennsylvania
ZIP/Postal Code
19610
Country
United States
Facility Name
Houston Inst. For Clinical Research
City
Houston
State/Province
Texas
ZIP/Postal Code
77074
Country
United States
Facility Name
Texas Research Center
City
Sugar Land
State/Province
Texas
ZIP/Postal Code
77479
Country
United States
Facility Name
South Puget Sound Clinical Research
City
Olympia
State/Province
Washington
ZIP/Postal Code
98502
Country
United States
Facility Name
The Governors of the Uni of Alberta; Heritage Medical Research Centre
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2S2
Country
Canada
Facility Name
Laurel Medical Clinic
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 3Y1
Country
Canada
Facility Name
Manitoba Clinic
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3A 1M3
Country
Canada
Facility Name
Nexus Clinical Research Centre
City
St John's
State/Province
Newfoundland and Labrador
ZIP/Postal Code
A1A 5E8
Country
Canada
Facility Name
Dr. William G. Bensen Medicine Professional Corporation
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 1Y2
Country
Canada
Facility Name
Credit Valley, Rheumatology
City
Mississauga
State/Province
Ontario
ZIP/Postal Code
L5M 2V8
Country
Canada
Facility Name
Rheumatology Research Associates
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 1A2
Country
Canada
Facility Name
Private Practice
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4K 1N2
Country
Canada
Facility Name
Chus Hopital Fleurimont
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
Facility Name
Centre Re Recherche Saint-Louis
City
Quebec
ZIP/Postal Code
G1W 4R4
Country
Canada
Facility Name
Ponce School of Medicine; Caimed Center
City
Ponce
ZIP/Postal Code
00716
Country
Puerto Rico
Facility Name
Glasgow Royal Infirmary; Centre For Rheumatic Diseases
City
Glasgow
ZIP/Postal Code
G4 0SF
Country
United Kingdom
Facility Name
Trafford General Hospital; Rheumatology
City
Manchester
ZIP/Postal Code
M41 5SL
Country
United Kingdom
Facility Name
Royal Victoria Infirmary; Clinical Research Facility
City
Newcastle Upon Tyne
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
22491018
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.
Results Reference
derived
Learn more about this trial
A Study of the Effect of Tocilizumab on Markers of Atherogenic Risk in Patients With Moderate to Severe Rheumatoid Arthritis
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