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

NCT00845832 | Terminated Phase 2 Results

• 2 other identifiers: WX219562008-005525-11
• Study Type: interventional
• Target: 24
• Locations: 8 countries
• Sites: 24

Brief Summary

This 2 part study will investigate the safety, tolerability and efficacy of MabT hera 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, follo wed by RoActemra at one of the ascending doses between 2mg/kg and 8mg/kg at week s 4, 8 and 12 (MabThera arm) or 8mg/kg (placebo arm). In Part 2, additional pati ents will be randomized to one of 2 groups to receive MabThera 0.5g on days 1 an d 15 followed by the selected dose (from Part 1)of RoActemra at weeks 4, 8 and 1 2, 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 tar get sample size is \<100 individuals.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR)

  The Disease Activity Score based on 28 joint count (DAS28) and Erythrocyte Sedimentation Rate (ESR), is a measure of the participant's disease activity. It is based on the Tender Joint Count (TJC \[28 joints\]), Swollen Joint Count (SJC \[28 joints\]), participant's global assessment of disease activity (PtGA) Visual Analog Scale (VAS) in millimeters (mm), and ESR in millimeters per hour (mm/hour). DAS28-ESR scores range from 0 - 10. Definition of LDA was based on DAS28-ESR scores. To achieve LDA the DAS28-ESR had to be (less than or equal to) ≤ 3.2. DAS28-ESR equals (=) (0.56 times (\*) (square root)√ TJC plus (+) (0.28 \* √ SJC + (0.70 \* ln(ESR))+(0.014 \* (Global Health) GH) Where: TJC = based on 28 joints SJC = based on 28 joints ESR = erythrocyte sedimentation rate in mm/hour GH = participant's global assessment of disease activity ln = natural log

  Week 16

Secondary Outcomes (12)

• Percentage of Participants Achieving Remission at Week 16 Assessed Using DAS28-ESR

  Week 16

• Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16

  Week 16

• Change From Baseline in DAS28-ESR

  Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48

• Clinical Disease Activity Index Scores

  Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48

• Simplified Disease Activity Index (SDAI) Scores

  Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, and 48

Study Arms (2)

1

EXPERIMENTAL

Drug: rituximab [MabThera/Rituxan]; Drug: tocilizumab [RoActemra/Actemra]

2

ACTIVE COMPARATOR

Drug: Placebo; Drug: tocilizumab [RoActemra/Actemra]

Interventions

Placebo DRUG

iv on days 1 and 15 (Parts 1 and 2)

2

rituximab [MabThera/Rituxan] DRUG

0.5g iv on days 1 and 15 (Parts 1 and 2)

1

tocilizumab [RoActemra/Actemra] DRUG

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

1; 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (24)

Unknown Facility

Le Kremlin-Bicêtre, 94275, France

Location

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Montpellier, 34295, France

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Paris, 75679, France

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Strasbourg, 67098, France

Location

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Berlin, 10117, Germany

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Berlin, 14059, Germany

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Cologne, 50924, Germany

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Heidelberg, 69120, Germany

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Würzburg, 97080, Germany

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Athens, 15121, Greece

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Thessaloniki, 54636, Greece

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Amsterdam, 1105 AZ, Netherlands

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Leiden, 2333 ZA, Netherlands

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Bytom, 41-902, Poland

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Lublin, 20-607, Poland

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Poznan, 60-218, Poland

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Santander, Cantabria, 39008, Spain

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Santiago de Compostela, La Coruña, 15706, Spain

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Madrid, Madrid, 28007, Spain

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Seville, Sevilla, 41009, Spain

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Bern, 3010, Switzerland

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Lausanne, 1011, Switzerland

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Newcastle upon Tyne, NE1 4LP, United Kingdom

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Unknown Facility

Southampton, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab; tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann- LaRoche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2009
• First Posted: February 18, 2009
• Study Start: March 1, 2009
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: December 24, 2014
• Results First Posted: December 24, 2014

Record last verified: 2014-12

Locations

DE (5); GR (2); CH (2); FR (4); ES (4); PL (3); GB (2); NL (2)