A Study of Rituximab (MabThera®/Rituxan®) in Patients With Rheumatoid Arthritis and Inadequate Response to Methotrexate

NCT00578305 | Completed Phase 3 Results

• 1 other identifier: MA21056
• Study Type: interventional
• Target: 185
• Locations: 18 countries
• Sites: 58

Brief Summary

This 3 arm study assessed the efficacy of rituximab (MabThera®/Rituxan®) in the prevention of progression of structural joint damage in participants with active rheumatoid arthritis who had an inadequate clinical response to methotrexate. Participants were randomized to receive rituximab 500 mg intravenously (iv), rituximab 1000 mg iv, or placebo iv on days 1 and 15 every 24 weeks in the main study; all participants received concomitant methotrexate at a stable dose of 12.5-25 mg/week throughout the study. Further courses of rituximab were provided to eligible participants. Structural joint damage was assessed by magnetic resonance imaging (MRI) at baseline and at intervals during the study.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Week 24

  The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 10 with each integer unit increment representing a 10% loss of articular bone using the following scale. 0.0=normal, no erosion; 0.5=1-5% erosion; 1.0=6-10% erosion; 1.5=11-15% erosion; 2.0=16-20% erosion; etc, up to 10.0=96-100% erosion. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more erosion. A negative change score indicates improvement.

  Baseline to Week 24

Secondary Outcomes (16)

• Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Weeks 12 and 52

  Baseline to Week 52

• Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52

  Baseline to Week 52

• Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52

  Baseline to Week 52

• Percentage of Participants With no Newly Eroded Joints at Weeks 24 and 52

  Baseline to Week 52

• Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52

  Baseline to Week 52

Study Arms (3)

Rituximab 500 mg

EXPERIMENTAL

Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.

Biological: Rituximab; Drug: Methylprednisolone; Drug: Methotrexate; Drug: Folic acid or folate

Rituximab 1000 mg

EXPERIMENTAL

Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.

Biological: Rituximab; Drug: Methylprednisolone; Drug: Methotrexate; Drug: Folic acid or folate

Placebo

PLACEBO COMPARATOR

Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.

Drug: Placebo; Drug: Methylprednisolone; Drug: Methotrexate; Drug: Folic acid or folate

Interventions

Rituximab BIOLOGICAL

Rituximab was supplied as a sterile liquid for iv administration.

Also known as: MabThera®, Rituxan®

Rituximab 1000 mg; Rituximab 500 mg

Placebo DRUG

Placebo was supplied as a sterile liquid in single-use vials for iv administration.

Placebo

Methylprednisolone DRUG

Placebo; Rituximab 1000 mg; Rituximab 500 mg

Methotrexate DRUG

Placebo; Rituximab 1000 mg; Rituximab 500 mg

Folic acid or folate DRUG

Placebo; Rituximab 1000 mg; Rituximab 500 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients, 18-80 years of age.
• Active rheumatoid arthritis for ≥ 3 months and ≤ 10 years.
• Evidence of erosive disease and/or clinical synovitis in a signal joint.
• Inadequate response to 12.5-25 mg/week methotrexate for ≥ 12 weeks.

You may not qualify if:

• Rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis. - Any surgical procedure within 12 weeks prior to baseline.
• Previous treatment with a biologic agent or with a B cell modulating or cell depleting therapy.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (60)

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Buenos Aires, C1280AEB, Argentina

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Goiânia, Goiás, 74110010, Brazil

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Curtiba, Paraná, 80030-110, Brazil

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Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

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São Paulo, São Paulo, 04023-900, Brazil

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Winnipeg, Manitoba, R3E0W3, Canada

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St. John's, Newfoundland and Labrador, A1A 5E8, Canada

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Ottawa, Ontario, K1H 1A2, Canada

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Ottawa, Ontario, K2G 6E2, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Montreal, Quebec, H2L 1S6, Canada

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Montreal, Quebec, H3Z 2Z3, Canada

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Québec, Quebec, G1V 3M7, Canada

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Saskatoon, Saskatchewan, S7M 0Z9, Canada

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Brno, 625 00, Czechia

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České Budějovice, 370 01, Czechia

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Prague, 128 50, Czechia

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Copenhagen, 2100, Denmark

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Hillerød, 3400, Denmark

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Hvidovre, 2650, Denmark

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Tallinn, 11312, Estonia

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Tallinn, 13419, Estonia

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Montpellier, 34295, France

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Nice, 06202, France

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Orléans, 45032, France

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Toulouse, 31059, France

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Bad Aibling, 83043, Germany

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Berlin, 10117, Germany

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Dresden, 01307, Germany

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Erlangen, 91054, Germany

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Halle, 06120, Germany

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Hanover, 30625, Germany

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Athens, 115 27, Greece

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Pátrai, 265 04, Greece

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Thessaloniki, 54636, Greece

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Riga, 1002, Latvia

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Riga, 1038, Latvia

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Vilnius, LT-08661, Lithuania

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Amsterdam, 1105 AZ, Netherlands

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Oslo, 0370, Norway

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Bucharest, 020475, Romania

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Cluj-Napoca, 400006, Romania

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Kazan', 420097, Russia

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Moscow, 115522, Russia

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Saint Petersburg, 195067, Russia

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Voronezh, 394066, Russia

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Belgrade, 11000, Serbia

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Niška Banja, 18250, Serbia

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Barcelona, Barcelona, 08003, Spain

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Barcelona, Barcelona, 08907, Spain

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Madrid, Madrid, 28046, Spain

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Málaga, Malaga, 29010, Spain

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Seville, Sevilla, 41009, Spain

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Valencia, Valencia, 46017, Spain

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Bern, 3010, Switzerland

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Adana, 01330, Turkey (Türkiye)

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Ankara, 06018, Turkey (Türkiye)

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Istanbul, 34098, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Related Publications (1)

• Peterfy C, Emery P, Tak PP, Ostergaard M, DiCarlo J, Otsa K, Navarro Sarabia F, Pavelka K, Bagnard MA, Gylvin LH, Bernasconi C, Gabriele A. MRI assessment of suppression of structural damage in patients with rheumatoid arthritis receiving rituximab: results from the randomised, placebo-controlled, double-blind RA-SCORE study. Ann Rheum Dis. 2016 Jan;75(1):170-7. doi: 10.1136/annrheumdis-2014-206015. Epub 2014 Oct 29.

  PMID: 25355728 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab; Methylprednisolone; Methotrexate; Folic Acid

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; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: December 21, 2007
• Study Start: November 1, 2007
• Primary Completion: November 1, 2009
• Study Completion: May 1, 2013
• Last Updated: April 10, 2015
• Results First Posted: April 10, 2015

Record last verified: 2015-03

Locations

CA (10); NL (1); NO (1); RO (2); LI (1); CZ (3); ES (6); LA (2); SE (2); DE (6); CH (1); RU (4); BR (4); GR (3); AR (1); DK (3); FR (4); TU (4)