A Non-Comparative Study to Assess the Safety of MabThera (Rituximab) in Patients With Rheumatoid Arthritis.

NCT00502996 | Completed Phase 3 Results

• 1 other identifier: ML19385
• Study Type: interventional
• Target: 246
• Locations: 10 countries
• Sites: 49

Brief Summary

This single arm study will assess the safety of MabThera plus methotrexate in patients with rheumatoid arthritis who have had a lack of response to 1-5 DMARDs or biological agents. Patients will receive MabThera (1g i.v.) on days 1 and 15, concomitantly with methotrexate \>=15mg p.o./week. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Any Adverse Event, Any Serious Adverse Event, and Death

  An Adverse event (AE) was considered any unfavorable medical event in a participant of clinical research who received the study drug and that not necessarily had a causal relationship with this treatment. An AE could, therefore, being any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. A serious adverse event (SAE) is any experience that suggested a significant risk, contraindication, caution, and at any dose fulfills at least one of the following criteria: adverse event considered as fatal (resulting in death), life threatening, defect of birth/congenital abnormality, required hospitalization or extension of hospital length of stay, significant medical intervention, resulted in significant disability/impairment.

  Up to Week 48

• Number of Participants With AEs According to Degree of Intensity

  An AE is any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. The Intensity of AEs was classified as Grade 1, Grade 2, Grade 3 and Grade 4. Grade 1: Discomfort was noticed, but the normal daily activity was not interrupted. Grade 2: Discomfort was enough to reduce the normal daily activity. Grade 3: There was disability for work or develop normal daily activities. Grade 4: It represented an immediate threat to life (these events were reported as SAEs).

  Up to Week 48

• Number of Participants With AEs Leading to Discontinuation and Any Drug Related AEs and SAEs

  An AE is any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. A SAE is any experience that suggested a significant risk, contraindication, caution, and at any dose, fulfills, at least, one of the following criteria: adverse event considered as fatal (resulting in death), life threatening, defect of birth/congenital abnormality, required hospitalization or extension of hospital length of stay, significant medical intervention, resulted in significant disability/impairment. Relationship between AEs and medication under investigation was evaluated through the classification "Yes" and "No". A relationship classified as "Yes" implied a significant causal relationship with the medication under investigation which was evaluated based on enough evidences, facts or arguments.

  Up to Week 48

• Number of Participants With AEs of Special Interest During the Study

  Adverse event of special interest during the study treatment and follow up period included infections. The participants with AEs of special interest were reported at Screening, End of treatment (EOT), and End of Follow-up (EOFU) visit.

  Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48)

Secondary Outcomes (17)

• Mean Values of Hematology Parameters at Screening and EOT Visit (Hemoglobin and Mean Corpuscular Hemoglobin Concentration)

  Screening (Days -28 to 0) and EOT (Week 24)

• Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils)

  Screening (Days -28 to 0) and EOT (Week 24)

• Mean Values of Hematology Parameter at Screening and EOT Visit (Mean Corpuscular Volume)

  Screening (Days -28 to 0) and EOT (Week 24)

• Mean Values of Hematology Parameter at Screening and EOT Visit (Erythrocytes)

  Screening (Days -28 to 0) and EOT (Week 24)

• Mean Values of Hematology Parameters at Screening and EOT Visit (Leucocytes and Platelets)

  Screening (Days -28 to 0) and EOT (Week 24)

Study Arms (1)

Rituximab

EXPERIMENTAL

Eligible participants receiving Rituximab (MabThera/Rituxan) 1 gram/dose (g/dose) intravenously (IV) on Day 1 and Day 15 followed by previous pre-medication (methylprednisolone 100 mg IV, antihistamine and antipyretic) and concomitant treatment of Methotrexate at least 15 mg per oris (PO) weekly were observed during the study period of 24 weeks. After treatment completion, participants were followed-up for safety up to 24 weeks.

Drug: Methotrexate; Drug: rituximab [MabThera/Rituxan]

Interventions

Methotrexate DRUG

\>=15 mg po/week

Rituximab

rituximab [MabThera/Rituxan] DRUG

1g iv on days 1 and 15

Rituximab

Eligibility Criteria

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

You may qualify if:

• adult patients, \>=18 years of age;
• rheumatoid arthritis \>=6 months;
• lack of response to 1-5 DMARDs or biological agents;
• rheumatoid factor positive.

You may not qualify if:

• other chronic inflammatory articular disease or systemic rheumatic disease;
• joint or bone surgery during 8 weeks prior to randomization;
• previous treatment with any cell-depleting therapy.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (49)

Unknown Facility

Buenos Aires, 1425, Argentina

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Buenos Aires, C1280AEB, Argentina

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Buenos Aires, C1426AAL, Argentina

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Córdoba, 5000, Argentina

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San Miguel de Tucumán, 4000, Argentina

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Belém, 66063-240, Brazil

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Brasília, 70322000, Brazil

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Brasília, 70390-904, Brazil

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Campinas, 13015-001, Brazil

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Campinas, 13025-141, Brazil

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Curitiba, 80730-000, Brazil

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Florianópolis, 88040-970, Brazil

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Fortaleza, 60155-290, Brazil

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Fortaleza, 60430-370, Brazil

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Goiânia, 74110010, Brazil

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Nova Lima, 34000-000, Brazil

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Porto Alegre, 90610-000, Brazil

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Recife, 50000-000, Brazil

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Ribeirão Preto, 14048-900, Brazil

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Rio de Janeiro, 20551-030, Brazil

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Rio de Janeiro, 21941-590, Brazil

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Rio de Janeiro, 22050-000, Brazil

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Rio de Janeiro, 22640102, Brazil

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Salvador, 40050-410, Brazil

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São Paulo, 03128-050, Brazil

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São Paulo, 04026-000, Brazil

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São Paulo, 04038-002, Brazil

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São Paulo, 04038-040, Brazil

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São Paulo, 04039-004, Brazil

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São Paulo, 05403-000, Brazil

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Vitória, 29043-910, Brazil

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Santiago, Chile

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Barranquilla, Colombia

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Bogotá, Colombia

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Cuenca, 1394, Ecuador

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Guayaquil, Ecuador

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Quito, 1394, Ecuador

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San Salvador, El Salvador

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Mexico City, 02990, Mexico

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Mexico City, 06920, Mexico

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Mexico City, 14080, Mexico

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San Luis Potosí City, 78240, Mexico

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Jesus Maria, Peru

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Lima, 13, Peru

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San Isidro, LIMA 27, Peru

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Montevideo, 11600, Uruguay

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Barquisimeto, 3005, Venezuela

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Caracas, 1010, Venezuela

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Caracas, 1040, Venezuela

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MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate; Rituximab

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)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 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: Roche Trial Information Hotline
• Organization: F. Hoffmann-La Roche AG

global.trial_information@roche.com

+41 61 6878333

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2007
• First Posted: July 18, 2007
• Study Start: February 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: October 14, 2016
• Results First Posted: October 14, 2016

Record last verified: 2016-08

Locations

CO (2); ME (4); UR (1); VE (3); CL (1); EC (3); BR (26); AR (5); EL (1); PE (3)