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

NCT ID: NCT00578305

Last Updated: 2015-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 185 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2013-05-31

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.

Detailed Description

There were 3 phases in the study: A 52 week long main study, a study extension phase, and a 48 week long safety follow-up phase.

The first course of treatment with placebo or rituximab was initiated on Day 1 of the 52 week long main study. A second course of treatment was initiated after Week 24, if the participant met eligibility criteria. After Week 52, eligible participants received further treatment courses at intervals ≥ 6 months in the study extension phase. No treatments were administered in the safety follow-up phase.

Participants had to meet the following eligibility criteria to receive rituximab in the study extension phase.

• Minimum of 24 weeks had passed since the first infusion of the last course of study medication.
• C-reactive protein-based Disease Activity Score 28 (DAS28-CRP) ≥ 2.6.
• Absolute neutrophil count not below 1.5 x 103/μL.
• Patient had not developed contraindications for receiving rituximab, such as:

1. Any new or uncontrolled concomitant disease such as, but not limited to, cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders.

2. Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection.

3. Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization, or treatment with iv anti-infectives within 4 weeks prior to infusion or completion of oral anti-infectives within 2 weeks prior to infusion.

• Patient was not pregnant or breast feeding.
• Patients who entered the study and were found to be hepatitis B surface antigen (HBsAg) negative, hepatitis B core antibody (HBcAb) positive, were to be negative for hepatitis B viral DNA (< 29 IU/mL) and were to have aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) results within the last 12 weeks.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Rituximab 500 mg

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.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: BIOLOGICAL

Rituximab was supplied as a sterile liquid for iv administration.

Methylprednisolone

Intervention Type: DRUG

Methotrexate

Intervention Type: DRUG

Folic acid or folate

Intervention Type: DRUG

Rituximab 1000 mg

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.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: BIOLOGICAL

Rituximab was supplied as a sterile liquid for iv administration.

Methylprednisolone

Intervention Type: DRUG

Methotrexate

Intervention Type: DRUG

Folic acid or folate

Intervention Type: DRUG

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Methylprednisolone

Intervention Type: DRUG

Methotrexate

Intervention Type: DRUG

Folic acid or folate

Intervention Type: DRUG

Interventions

Rituximab

Rituximab was supplied as a sterile liquid for iv administration.

Intervention Type: BIOLOGICAL

Placebo

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

Intervention Type: DRUG

Methylprednisolone

Intervention Type: DRUG

Methotrexate

Intervention Type: DRUG

Folic acid or folate

Intervention Type: DRUG

Other Intervention Names

MabThera®; Rituxan®

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Buenos Aires, , Argentina

Goiânia, Goiás, Brazil

Curtiba, Paraná, Brazil

Porto Alegre, Rio Grande do Sul, Brazil

São Paulo, São Paulo, Brazil

Winnipeg, Manitoba, Canada

St. John's, Newfoundland and Labrador, Canada

Ottawa, Ontario, Canada

Ottawa, Ontario, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Montreal, Quebec, Canada

Montreal, Quebec, Canada

Québec, Quebec, Canada

Saskatoon, Saskatchewan, Canada

Brno, , Czechia

České Budějovice, , Czechia

Prague, , Czechia

Copenhagen, , Denmark

Hillerød, , Denmark

Hvidovre, , Denmark

Tallinn, , Estonia

Tallinn, , Estonia

Montpellier, , France

Nice, , France

Orléans, , France

Toulouse, , France

Bad Aibling, , Germany

Berlin, , Germany

Dresden, , Germany

Erlangen, , Germany

Halle, , Germany

Hanover, , Germany

Athens, , Greece

Pátrai, , Greece

Thessaloniki, , Greece

Riga, , Latvia

Riga, , Latvia

Vilnius, , Lithuania

Amsterdam, , Netherlands

Oslo, , Norway

Bucharest, , Romania

Cluj-Napoca, , Romania

Kazan', , Russia

Moscow, , Russia

Saint Petersburg, , Russia

Voronezh, , Russia

Belgrade, , Serbia

Niška Banja, , Serbia

Barcelona, Barcelona, Spain

Barcelona, Barcelona, Spain

Madrid, Madrid, Spain

Málaga, Malaga, Spain

Seville, Sevilla, Spain

Valencia, Valencia, Spain

Bern, , Switzerland

Adana, , Turkey (Türkiye)

Ankara, , Turkey (Türkiye)

Istanbul, , Turkey (Türkiye)

Izmir, , Turkey (Türkiye)

Countries

Argentina; Brazil; Canada; Czechia; Denmark; Estonia; France; Germany; Greece; Latvia; Lithuania; Netherlands; Norway; Romania; Russia; Serbia; Spain; Switzerland; Turkey (Türkiye)

References

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.

Reference Type: DERIVED

PMID: 25355728 (View on PubMed)

Other Identifiers

MA21056

Identifier Type: -

Identifier Source: org_study_id