A Study of Tocilizumab in Combination With Disease-Modifying Anti-Rheumatic Drugs (DMARDs) in Participants With Moderate to Severe Active Rheumatoid Arthritis With an Inadequate Response to DMARDs
Open Label, Multicentric Phase IIIb Study to Evaluate the Effect of Tocilizumab in Combination With DMARDs in the Inhibition of Progression of Synovitis, Bone Marrow Edema, and Erosions Evaluated by Dedicated Magnetic Resonance Imaging (MRI) in the Hand of Patients With Rheumatoid Arthritis (RA)
2 other identifiers
interventional
58
1 country
11
Brief Summary
This open-label, single-arm study will evaluate the efficacy and safety of tocilizumab in combination with DMARDs in participants with moderate to severe active rheumatoid arthritis who have an inadequate response to DMARDs. Participants will receive tocilizumab as 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 4 weeks in addition to their current DMARD therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3 rheumatoid-arthritis
Started Oct 2009
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2009
CompletedFirst Submitted
Initial submission to the registry
October 15, 2009
CompletedFirst Posted
Study publicly available on registry
October 16, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2012
CompletedResults Posted
Study results publicly available
November 9, 2016
CompletedJune 19, 2017
May 1, 2017
2.5 years
October 15, 2009
September 20, 2016
May 25, 2017
Conditions
Outcome Measures
Primary Outcomes (3)
Change From Baseline to Week 4 in Synovitis of the Wrist According to Rheumatoid Arthritis Magnetic Resonance Imaging (RAMRIS) Score
Synovitis of the wrist was assessed at three sites including the radioulnar joint (RUJ), the radiocarpal joint (RCJ), and the intercarpal-carpometacarpal joints (IC-CMCJ). Global RAMRIS scores were assigned on a scale of 0 to 3 at each site, where 0 represented normal appearance with no synovial enhancement and each 1-point increase reflected one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. The scores for all three sites were added to give an aggregated score of 0 to 9. Baseline absolute value (AV) and change from Baseline to Week 4 were averaged among all participants, where negative changes indicated improvement in synovitis.
Baseline and Week 4
Change From Baseline to Week 4 in Synovitis of the Wrist According to Relative Enhancement (RE) Before and After Contrast Injection
RE was calculated as \[S0 minus (-) S55\] divided by (÷) S0, multiplied by (×) 100 percent (%), where S0 was defined as the signal noise ratio before contrast injection, and S55 was defined as the signal noise ratio 55 seconds after injection. Signal noise ratios were measured as the ratio between the signal in the region of interest and the standard deviation of background noise. Baseline AV and change from Baseline to Week 4 were averaged among all participants, where negative changes indicated improvement in synovitis.
Baseline and Week 4
Change From Baseline to Week 4 in Synovitis of the Wrist According to Rate of Early Enhancement (REE) Per Second Before and After Contrast Injection
REE per second was calculated as \[S55 - S0\] ÷ \[S0 × 55 seconds\] × 100%, where S0 was defined as the signal noise ratio before contrast injection, and S55 was defined as the signal noise ratio 55 seconds after injection. Signal noise ratios were measured as the ratio between the signal in the region of interest and the standard deviation of background noise. Baseline AV and change from Baseline to Week 4 were averaged among all participants, where negative changes indicated improvement in synovitis.
Baseline and Week 4
Secondary Outcomes (88)
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to RAMRIS Score
Baseline and Weeks 2, 12, 24, 48
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to RE Before and After Contrast Injection
Baseline and Weeks 2, 12, 24, 48
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to REE Per Second Before and After Contrast Injection
Baseline and Weeks 2, 12, 24, 48
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score
Baseline and Weeks 2, 4, 12, 24, 48
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Erosion in the Wrist and MCP Joints
Baseline and Weeks 2, 4, 12, 24, 48
- +83 more secondary outcomes
Study Arms (1)
Tocilizumab in Active RA
EXPERIMENTALParticipants with active RA will receive tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions will be given from Baseline to Week 44, and participants will be assessed through Week 48.
Interventions
Participants may continue on a stable dose of their current DMARD therapy as prescribed. The choice of DMARD is at the discretion of the treating physician and is not specified by the protocol.
Tocilizumab will be given as 8 mg/kg via IV infusion every 4 weeks for a total of 12 infusions. The maximum allowed dose is 800 mg.
Eligibility Criteria
You may qualify if:
- Moderate to severe active RA of ≥6 months duration
- DAS28 \>3.2
- Inadequate response to a stable dose of non-biologic DMARD for ≥2 months
- Those receiving oral corticosteroids must have been at stable dose for ≥25 days in the 28 days prior to first study treatment
You may not qualify if:
- Rheumatic autoimmune disease other than RA
- History of or current inflammatory joint disease other than RA
- Previous treatment with alkylating agents or total lymphoid irradiation
- Intra-articular or parenteral corticosteroids within 6 weeks prior to Baseline
- Previous treatment with any cell-depleting therapies
- American College of Rheumatology (ACR) Functional Class IV
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
Unknown Facility
Coppito, Abruzzo, 67100, Italy
Unknown Facility
Napoli, Campania, 80131, Italy
Unknown Facility
Rome, Lazio, 00161, Italy
Unknown Facility
Genoa, Liguria, 16132, Italy
Unknown Facility
Milan, Lombardy, 20122, Italy
Unknown Facility
Milan, Lombardy, 20157, Italy
Unknown Facility
Pavia, Lombardy, 27100, Italy
Unknown Facility
Palermo, Sicily, 90127, Italy
Unknown Facility
Pisa, Tuscany, 56100, Italy
Unknown Facility
Cona (Ferrara), Veneto, 44124, Italy
Unknown Facility
Padua, Veneto, 35128, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
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
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 15, 2009
First Posted
October 16, 2009
Study Start
October 1, 2009
Primary Completion
April 1, 2012
Study Completion
April 1, 2012
Last Updated
June 19, 2017
Results First Posted
November 9, 2016
Record last verified: 2017-05