A Study of Tocilizumab in Combination With DMARDs in Patients With Moderate to Severe Rheumatoid Arthritis - Full Text View

Sponsor:	Hoffmann-La Roche
Information provided by:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT00531817

Purpose

This 2-arm study assessed the safety and efficacy, with regard to reduction in signs and symptoms, of tocilizumab versus placebo, both in combination with DMARDs, in patients with moderate to severe active rheumatoid arthritis, with an inadequate response to DMARDs. Patients were randomized in a ratio of 2:1 to receive either tocilizumab 8 mg/kg intravenously (IV) or placebo IV every 4 weeks. All patients also received stable antirheumatic therapy, including permitted DMARDs. The anticipated time on study treatment was 3-12 months, and the target sample size was 500+ individuals.

Condition	Intervention	Phase
Rheumatoid Arthritis	Drug: tocilizumab Drug: Placebo Drug: Permitted DMARDs	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Randomized, Double-blind, Parallel-group Study to Evaluate the Safety and Efficacy of Tocilizumab (TCZ) Versus Placebo in Combination With Disease Modifying Antirheumatic Drugs (DMARDs) in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA)

Resource links provided by NLM:

MedlinePlus related topics: Rheumatoid Arthritis

Drug Information available for: Atlizumab

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Percentage of Patients With an ACR50 Response [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Percentage of patients with an ACR50 response (≥50% improvement from baseline) at Week 24.

Secondary Outcome Measures:

Percentage of Patients With ACR20 Response at Each Timepoint [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR20 Response at Each Timepoint [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR20 Response at Each Timepoint [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR20 Response at Each Timepoint [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR20 Response at Each Timepoint [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR20 Response at Each Timepoint [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR50 Response at Each Timepoint [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR50 Response at Each Timepoint [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR50 Response at Each Timepoint [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR50 Response at Each Timepoint [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR50 Response at Each Timepoint [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR70 Response at Each Timepoint [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR70 Response at Each Timepoint [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR70 Response at Each Timepoint [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR70 Response at Each Timepoint [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR70 Response at Each Timepoint [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Percentage of Patients With ACR70 Response at Each Timepoint [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Each Timepoint [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
The DAS28 index uses a 28 joint count. The scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of <2.6 represents clinical remission, a score of ≤3.2 represents low disease activity, and a score of >5.1 represents severe disease.
Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Each Timepoint [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
The DAS28 index uses a 28 joint count. The scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of <2.6 represents clinical remission, a score of ≤3.2 represents low disease activity, and a score of >5.1 represents severe disease.
Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Each Timepoint [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
The DAS28 index uses a 28 joint count. The scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of <2.6 represents clinical remission, a score of ≤3.2 represents low disease activity, and a score of >5.1 represents severe disease.
Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Each Timepoint [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
The DAS28 index uses a 28 joint count. The scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of <2.6 represents clinical remission, a score of ≤3.2 represents low disease activity, and a score of >5.1 represents severe disease.
Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Each Timepoint [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
The DAS28 index uses a 28 joint count. The scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of <2.6 represents clinical remission, a score of ≤3.2 represents low disease activity, and a score of >5.1 represents severe disease.
Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Each Timepoint [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
The DAS28 index uses a 28 joint count. The scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of <2.6 represents clinical remission, a score of ≤3.2 represents low disease activity, and a score of >5.1 represents severe disease.

Enrollment:	614
Study Start Date:	September 2007
Estimated Study Completion Date:	April 2011
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Tocilizumab 8 mg/kg + DMARDs	Drug: tocilizumab Tocilizumab intravenously at a dose of 8 mg/kg over a 1-hour infusion, every 4 weeks, for a total of 6 infusions. Other Names: Actemra RoActemra Drug: Permitted DMARDs As prescribed. The following DMARDs were permitted in this study: methotrexate (MTX), chloroquine, hydroxychloroquine, parenteral gold, sulfasalazine, azathioprine, and leflunomide. These DMARDs could be used alone or in combination, except for the combination of MTX and leflunomide, which was not allowed.
Placebo Comparator: Placebo + DMARDs	Drug: Placebo Placebo IV over a 1-hour infusion, every 4 weeks, for a total of 6 infusions. Drug: Permitted DMARDs As prescribed. The following DMARDs were permitted in this study: methotrexate (MTX), chloroquine, hydroxychloroquine, parenteral gold, sulfasalazine, azathioprine, and leflunomide. These DMARDs could be used alone or in combination, except for the combination of MTX and leflunomide, which was not allowed.

Arms

Assigned Interventions

Experimental: Tocilizumab 8 mg/kg + DMARDs

Drug: tocilizumab

Tocilizumab intravenously at a dose of 8 mg/kg over a 1-hour infusion, every 4 weeks, for a total of 6 infusions.

Other Names:

Actemra
RoActemra

Drug: Permitted DMARDs

As prescribed. The following DMARDs were permitted in this study: methotrexate (MTX), chloroquine, hydroxychloroquine, parenteral gold, sulfasalazine, azathioprine, and leflunomide. These DMARDs could be used alone or in combination, except for the combination of MTX and leflunomide, which was not allowed.

Placebo Comparator: Placebo + DMARDs

Drug: Placebo

Placebo IV over a 1-hour infusion, every 4 weeks, for a total of 6 infusions.

Drug: Permitted DMARDs

As prescribed. The following DMARDs were permitted in this study: methotrexate (MTX), chloroquine, hydroxychloroquine, parenteral gold, sulfasalazine, azathioprine, and leflunomide. These DMARDs could be used alone or in combination, except for the combination of MTX and leflunomide, which was not allowed.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adult patients, ≥18 years of age
Active rheumatoid arthritis of >6 months duration
Received permitted DMARDs each at a stable dose for at least 7 weeks prior to baseline

Exclusion Criteria:

Rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis
Major surgery within 8 weeks prior to screening or planned within 6 months following randomization
Unsuccessful treatment with a biologic agent, including an anti-TNF agent
Previous treatment with tocilizumab

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00531817

Show 157 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:

Clinical Trials

Hoffmann-La Roche

More Information

Additional Information:

Clinical Study Report Synopsis This link exits the ClinicalTrials.gov site

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Yazici Y, Curtis JR, Ince A, Baraf H, Malamet RL, Teng LL, Kavanaugh A. Efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis and a previous inadequate response to disease-modifying antirheumatic drugs: the ROSE study. Ann Rheum Dis. 2012 Feb;71(2):198-205. Epub 2011 Sep 26.

Responsible Party:	Disclosures Group, Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT00531817 History of Changes
Other Study ID Numbers:	ML21136
Study First Received:	September 18, 2007
Results First Received:	July 6, 2010
Last Updated:	August 3, 2010
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases

Autoimmune Diseases
Immune System Diseases
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012