Extension Study to Assess the Efficacy and Safety of Repeat Treatment With Rituximab (MabThera) in Participants With Active Rheumatoid Arthritis (RA)

NCT02093026 | Completed Phase 2 Results

• 2 other identifiers: WA16855U2653g
• Study Type: interventional
• Target: 465
• Locations: 16 countries
• Sites: 92

Brief Summary

This study will assess the long-term safety and efficacy of repeat treatment courses of rituximab, in combination with methotrexate in a disease-modifying anti-rheumatic drug (DMARD) inadequate responder population of participants who were previously randomized into studies WA16291 (NCT02693210) or WA17043/U2644g (NCT00074438). The study permits multiple re-treatments until the protocol-defined end-of-treatment date (31 December 2011). Participants will then enter a safety follow-up (SFU) period of at least 48 weeks. This will provide at least 7 years follow-up data on all participants initially randomized into WA16291 or WA17043/U2644g. Approximately 600 participants will potentially be eligible to enter this open label extension study from their respective feeder studies.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (7)

• Percentage of Participants With an American College of Rheumatology 20 (ACR20) Response After First Course

  A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in tender joint count (TJC) and swollen joint count (SJC) (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[visual analog scale (VAS): 0=no disease activity to 100=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0=no disease activity to 100=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0=no pain to 100=unbearable pain\]; 4) Health Assessment Questionnaire \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do\] and 5) an acute-phase reactant (either C-reactive protein \[CRP\] or erythrocyte sedimentation rate \[ESR\]). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.

  24 weeks after first course of rituximab (up to approximately 26 weeks)

• Percentage of Participants With ACR20 Response After Second Course

  A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0=no disease activity to 100=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0=no disease activity to 100=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0=no pain to 100=unbearable pain\]; 4) Health Assessment Questionnaire \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do\] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.

  24 weeks after second course of rituximab (median duration of 90.9 weeks)

• Percentage of Participants With ACR20 Response After Third Course

  A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0=no disease activity to 100=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0=no disease activity to 100=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0=no pain to 100=unbearable pain\]; 4) Health Assessment Questionnaire \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do\] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.

  24 weeks after third course of rituximab (median duration of 162.9 weeks)

• Percentage of Participants With ACR20 Response After Fourth Course

  A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0=no disease activity to 100=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0=no disease activity to 100=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0=no pain to 100=unbearable pain\]; 4) Health Assessment Questionnaire \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do\] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.

  24 weeks after fourth course of rituximab (median duration of 232 weeks)

• Percentage of Participants With ACR20 Response After Fifth Course

  A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0=no disease activity to 100=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0=no disease activity to 100=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0=no pain to 100=unbearable pain\]; 4) Health Assessment Questionnaire \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do\] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.

  24 weeks after fifth course of rituximab (median duration of 297.3 weeks)

• Percentage of Participants With ACR20 Response After Sixth Course

  A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0=no disease activity to 100=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0=no disease activity to 100=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0=no pain to 100=unbearable pain\]; 4) Health Assessment Questionnaire \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do\] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.

  24 weeks after sixth course of rituximab (median duration of 354.4 weeks)

• Percentage of Participants With ACR20 Response After Seventh Course

  A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0=no disease activity to 100=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0=no disease activity to 100=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0=no pain to 100=unbearable pain\]; 4) Health Assessment Questionnaire \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do\] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.

  24 weeks after seventh course of rituximab (median duration of 406.7 weeks)

Secondary Outcomes (8)

• Percentage of Participants With ACR50 and ACR70 Response

  24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)

• American College of Rheumatology Index of Improvement (ACRn) Response

  24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)

• Percentage of Participants With Low Disease Activity and Clinical Remission Based on DAS28-ESR

  24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)

• Percentage of Participants With European League Against Rheumatism (EULAR) Response of 'Good' or 'Moderate'

  24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)

• Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at 24 Weeks Following Each Course

  24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)

Study Arms (1)

Rituximab

EXPERIMENTAL

Participants will receive rituximab 1 gram intravenously (IV) on Days 1 and 15 of each course of retreatment. In addition, participants will receive methotrexate 10-25 milligrams per week (mg/week) orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid greater than or equal to (\>=) 5 mg/week or equivalent. Participants will receive retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first \[Day 1\] infusion of the last course of rituximab). Repeat treatment will be based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints \>=2.6). Retreatment with rituximab will be continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever is sooner.

Drug: Rituximab; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Folic Acid

Interventions

Rituximab DRUG

Participants will receive rituximab 1 gram IV on Days 1 and 15 of each course of retreatment.

Also known as: MabThera, Rituxan

Rituximab

Methotrexate DRUG

Participants will receive methotrexate 10-25 mg/week orally or parenterally.

Rituximab

Methylprednisolone DRUG

Participants will receive methylprednisolone 100 mg IV 30 minutes prior to each rituximab infusion.

Rituximab

Folic Acid DRUG

Participants will receive folic acid \>= 5 mg/week or equivalent.

Rituximab

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• participants with active RA
• completed 24 weeks of treatment in WA16291 or WA17043
• eligible for re-treatment, based on clinical symptoms (Disease Activity Score in 28 joints \>=2.6)
• females of childbearing potential using reliable contraception

You may not qualify if:

• participants who participated in rituximab studies WA16291 or WA17043 but withdrew into the safety follow-up phases of these trials
• previous rituximab non-responders
• current treatment with any other disease-modifying drug (apart from methotrexate), or any anti-tumor necrosis factor alfa, anti-interleukin-1, or other biologic therapies
• participants with known active infection of any kind
• evidence of any new or uncontrolled concomitant disease or development of any new contraindications which would preclude repeat treatment with rituximab
• history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• female participants who are pregnant or breastfeeding

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Genentech, Inc.: collaborator

Study Sites (92)

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Birmingham, Alabama, 35294, United States

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Peoria, Arizona, 85381, United States

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Little Rock, Arkansas, 72205, United States

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La Jolla, California, 92037, United States

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Long Beach, California, 92813, United States

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Rancho Mirage, California, 92270, United States

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San Diego, California, 92108, United States

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Colorado Springs, Colorado, 80920, United States

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Aventura, Florida, 33180, United States

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Boca Raton, Florida, 33486, United States

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Fort Lauderdale, Florida, 33334, United States

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Largo, Florida, 33773, United States

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South Miami, Florida, 33143, United States

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Boise, Idaho, 83702, United States

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Chicago, Illinois, 60611, United States

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Chicago, Illinois, 60637, United States

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Indianapolis, Indiana, 46202-5149, United States

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Indianapolis, Indiana, 46260, United States

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Boston, Massachusetts, 02215, United States

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Minneapolis, Minnesota, 55416, United States

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St Louis, Missouri, 63141, United States

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Lebanon, New Hampshire, 03756, United States

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Voorhees Township, New Jersey, 08043, United States

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Great Neck, New York, 11021, United States

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Plainview, New York, 11803, United States

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Rochester, New York, 14618, United States

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Smithtown, New York, 11787, United States

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Greenville, North Carolina, 27834, United States

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Winston-Salem, North Carolina, 27157, United States

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Beachwood, Ohio, 44122, United States

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Dayton, Ohio, 45402, United States

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Mayfield, Ohio, 44143, United States

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Tulsa, Oklahoma, 74104, United States

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Tulsa, Oklahoma, 74135, United States

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Portland, Oregon, 97239, United States

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Duncansville, Pennsylvania, 16635, United States

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Dallas, Texas, 75231, United States

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Houston, Texas, 77074, United States

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Salt Lake City, Utah, 84132, United States

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Seattle, Washington, 98104, United States

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Glendale, Wisconsin, 53217, United States

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Wausau, Wisconsin, 54401, United States

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Maroochydore, Queensland, 4558, Australia

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Melbourne, Victoria, 3168, Australia

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Perth, Western Australia, 6979, Australia

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Ghent, 9000, Belgium

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Curtiba, Paraná, 80030-110, Brazil

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Campinas, São Paulo, 13083-888, Brazil

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São Paulo, São Paulo, 04026-000, Brazil

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Calgary, Alberta, T2N 4Z6, Canada

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Vancouver, British Columbia, V5Z 1L7, Canada

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

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London, Ontario, N6A 4V2, Canada

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Prague, 128 50, Czechia

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Heinola, 18120, Finland

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Helsinki, 00290, Finland

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Cologne, 50924, Germany

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Leipzig, 04103, Germany

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Ratingen, 40882, Germany

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Regensburg, 93053, Germany

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Würzburg, 97080, Germany

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Haifa, 3109601, Israel

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Haifa, 3339419, Israel

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Modena, Emilia-Romagna, 41100, Italy

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Udine, Friuli Venezia Giulia, 33100, Italy

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Genoa, Liguria, 16132, Italy

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Milan, Lombardy, 20157, Italy

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Mexico City, 06726, Mexico

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Mexico City, 10700, Mexico

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México, 44620, Mexico

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Monterrey, 64460, Mexico

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Auckland, 0620, New Zealand

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Auckland, 2025, New Zealand

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Bialystok, 15-351, Poland

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Lublin, 20-022, Poland

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Poznan, 61-545, Poland

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Warsaw, 02-637, Poland

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Wroclaw, 50-556, Poland

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Mérida, Badajoz, 06800, Spain

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Santiago de Compostela, La Coruña, 15706, Spain

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Madrid, Madrid, 28006, Spain

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Madrid, Madrid, 28007, Spain

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Madrid, Madrid, 28046, Spain

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Seville, Sevilla, 41014, Spain

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San Cristóbal de La Laguna, Tenerife, 38320, Spain

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Gothenburg, 413 45, Sweden

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Stockholm, 171 76, Sweden

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Birmingham, B29 6JD, United Kingdom

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Cambridge, CB2 2QQ, United Kingdom

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Cannock, WS11 5XY, United Kingdom

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Leeds, LS7 4SA, United Kingdom

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Stoke-on-Trent, ST6 7AG, United Kingdom

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MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

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

Limitations and Caveats

The interpretation of the efficacy data over time should take into consideration that only the response of participants who continued in the study and received further courses of rituximab was captured.

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 CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2014
• First Posted: March 20, 2014
• Study Start: August 1, 2002
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: March 13, 2017
• Results First Posted: March 13, 2017

Record last verified: 2017-01

Locations

CA (4); NZ (2); CZ (1); IL (2); GB (5); ME (4); IT (4); SE (2); AU (3); BE (1); US (42); BR (3); ES (7); FI (2); DE (5); PL (5)