Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Study of Combination Treatment With MabThera (Rituximab) and RoActemra (Tocilizumab) Versus RoActemra in Patients With Rheumatoid Arthritis With an Incomplete Response to Methotrexate

This study has been completed.
Information provided by (Responsible Party):
Hoffmann-La Roche Identifier:
First received: February 17, 2009
Last updated: March 3, 2014
Last verified: March 2014

This 2 part study will investigate the safety, tolerability and efficacy of MabThera in combination with RoActemra in patients with active rheumatoid arthritis despite a stable dose of methotrexate. In Part 1 of the study, patients will be randomized to receive either MabThera 0.5g iv or placebo on days 1 and 15, followed by RoActemra at one of the ascending doses between 2mg/kg and 8mg/kg at weeks 4, 8 and 12 (MabThera arm) or 8mg/kg (placebo arm). In Part 2, additional patients will be randomized to one of 2 groups to receive MabThera 0.5g on days 1 and 15 followed by the selected dose (from Part 1)of RoActemra at weeks 4, 8 and 12, or placebo on days 1 and 15 followed by RoActemra 8mg/kg at weeks 4,8 and 12.All patients will then be eligible to receive extension treatment withRoActemra every 4 weeks. The anticipated time on study treatment is 12 months, and the target sample size is <100 individuals.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: tocilizumab [RoActemra/Actemra]
Drug: rituximab [MabThera/Rituxan]
Drug: Placebo
Phase 2

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, Active Controlled, Double-blind, Study to Compare the Safety and Reduction in Disease Activity With the Combination of Rituximab (MabThera®)and Tocilizumab (RoActemra®) Versus Tocilizumab in Patients With Active Rheumatoid Arthritis With an Incomplete Response to Methotrexate

Resource links provided by NLM:

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Proportion of patients with DAS<=3.2 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients in DAS-remission(<2.6) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
  • Proportion of patients with a EULAR good or moderate response [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
  • Change in DAS-ESR [ Time Frame: From baseline to week 48 ] [ Designated as safety issue: No ]
  • Change in CDAI, SDAI, SJC28, TJC28, HAQ, CRP, ESR [ Time Frame: From baseline to week 48 ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: March 2009
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: tocilizumab [RoActemra/Actemra]
2mg/kg-8mg/kg iv in Part 1 and selected dose in Part 2, on weeks 4, 8 and 12---Arm 1\n8mg/kg iv on weeks 4,8 and 12 (Parts 1 and 2)--- Arm 2
Drug: rituximab [MabThera/Rituxan]
0.5g iv on days 1 and 15 (Parts 1 and 2)
Active Comparator: 2 Drug: tocilizumab [RoActemra/Actemra]
2mg/kg-8mg/kg iv in Part 1 and selected dose in Part 2, on weeks 4, 8 and 12---Arm 1\n8mg/kg iv on weeks 4,8 and 12 (Parts 1 and 2)--- Arm 2
Drug: Placebo
iv on days 1 and 15 (Parts 1 and 2)


Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • adult patients, 18-65 years of age;
  • rheumatoid arthritis, functional status I-III;
  • SJC>=4 (28 joint count) and TJC>=4 (28 joint count) at screening and baseline;
  • RF and/or anti-CCP positive;
  • may have failed up to 1 approved anti-TNF agent (infliximab, etanercept or adalimumab);
  • inadequate response to methotrexate, at a dose of 7.5-25mg weekly for at least 12 weeks, at a stable dose for past 4 weeks.

Exclusion Criteria:

  • rheumatic autoimmune disease other than rheumatoid arthritis, or significant systemic involvement secondary to rheumatoid arthritis;
  • history of, or current, inflammatory joint disease other than rheumatoid arthritis;
  • diagnosis of juvenile idiopathic arthritis and/or rheumatoid arthritis before age 16;
  • significant cardiac or pulmonary disease;
  • previous treatment with any biologic agent for rheumatoid arthritis (other than infliximab, etanercept or adalimumab).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00845832

Le Kremlin Bicetre, France, 94275
Montpellier, France, 34295
Paris, France, 75679
Strasbourg, France, 67098
Berlin, Germany, 10117
Berlin, Germany, 14059
Heidelberg, Germany, 69120
Köln, Germany, 50924
Wuerzburg, Germany, 97080
Athens, Greece, 15121
Thessaloniki, Greece, 54636
Amsterdam, Netherlands, 1105 AZ
Leiden, Netherlands, 2333 ZA
Bytom, Poland, 41-902
Lublin, Poland, 20-607
Poznan, Poland, 60-218
Santander, Cantabria, Spain, 39008
Santiago de Compostela, La Coruña, Spain, 15706
Madrid, Spain, 28007
Sevilla, Spain, 41009
Bern, Switzerland, 3010
Lausanne, Switzerland, 1011
United Kingdom
Newcastle Upon Tyne, United Kingdom, NE1 4LP
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Hoffmann-La Roche
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche Identifier: NCT00845832     History of Changes
Other Study ID Numbers: WX21956, 2008-005525-11
Study First Received: February 17, 2009
Last Updated: March 3, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses processed this record on November 24, 2014