A Study of Tocilizumab (RoActemra) in Tocilizumab-Naive Participants With Rheumatoid Arthritis and Inadequate Response to Non-Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) and/or Biologic Therapy

NCT02001987 | Completed Phase 3 Results

• 2 other identifiers: ML286932013-001718-14
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 32

Brief Summary

This two part, multi-center, open-label, single-arm study will evaluate the efficacy and safety of tocilizumab as a monotherapy or in combination with methotrexate or other conventional synthetic disease modifying antirheumatic drugs (csDMARDs) in participants with moderate to severe active rheumatoid arthritis who have an inadequate response or are intolerant to non-biologic csDMARDs and/or biologic therapy.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Disease Activity Score Based on 28-joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24

  The DAS28-ESR was derived from assessments of erythrocyte sedimentation rate (ESR), tender joint count (TJC), swollen joint count (SJC), and Patient Global Assessment of disease activity (PGA) according to 100-millimeter (mm) Visual Analog Scale (VAS). DAS28-ESR scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. TJC was defined as the number of painful joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in millimeters per hour (mm/h). DAS28-ESR scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 24 was averaged among all participants, where negative changes indicated an improvement in disease activity.

  Baseline, Week 24

Secondary Outcomes (52)

• Change From Baseline in DAS28-ESR at Weeks 2, 4, 8, 12, 16, 20, and 24

  Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24

• Percentage of Participants With DAS28-ESR Low Disease Activity (LDA) and Remission at Week 24

  Week 24

• Change From Baseline in DAS28-ESR at Week 24 and at Last Assessment

  Baseline, Week 24, last assessment (up to Week 76)

• Percentage of Participants With DAS28-ESR LDA and Remission at Week 24 and at Last Assessment

  Week 24, last assessment (up to Week 76)

• Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response at Week 24

  Baseline, Week 24

Study Arms (1)

Tocilizumab

EXPERIMENTAL

Participants will receive tocilizumab at a dose of 162 milligrams (mg) as subcutaneous (SC) injection once a week administered as monotherapy or in combination with methotrexate or other csDMARDs (at investigator's discretion) for 24 weeks. Participants who complete the core study period will be allowed to enter a long-term-extension (LTE) period to continue study treatment for up to a maximum of another 52 weeks or until the commercial availability of SC tocilizumab, whichever occurs first.

Drug: Tocilizumab; Drug: Methotrexate; Drug: csDMARDs

Interventions

Tocilizumab DRUG

Tocilizumab will be administered at a dose of 162 mg as SC injection once a week.

Also known as: RoActemra, RO4877533

Tocilizumab

Methotrexate DRUG

Methotrexate will be administered at a stable dose that was initiated at least 4 weeks prior to Baseline, at investigator's discretion.

Tocilizumab

csDMARDs DRUG

csDMARDs (at investigator's discretion) will be administered at a stable dose that was initiated at least 4 weeks prior to Baseline, at investigator's discretion.

Tocilizumab

Eligibility Criteria

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

You may qualify if:

• Participants with a diagnosis of active rheumatoid arthritis according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria and receiving outpatient treatment
• Oral corticosteroids (\</= 10 mg/day prednisone or equivalent), nonsteroidal anti-inflammatory drugs (NSAIDs), and permitted csDMARDs are allowed at a stable dose for at least 4 weeks prior to Baseline
• At Screening either CRP \>/=10 mg/L or ESR \>/=20 mm/h and SJC \>/=3 (based on 44 joints)
• Inadequate response (IR) to tumor necrosis factor, abatacept and/or non-biological DMARDs

You may not qualify if:

• Major surgery (including joint surgery) within 8 weeks prior to Screening or planned major surgery within 6 months following Baseline
• Rheumatic autoimmune disease other than rheumatoid arthritis; Secondary Sjögren's syndrome with rheumatoid arthritis is permitted
• Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
• Diagnosis of juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or rheumatoid arthritis before the age of 16
• Prior history of or current inflammatory joint disease other than rheumatoid arthritis
• Exposure to tocilizumab at any time prior to Baseline
• Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever was longer) of Screening
• Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies or any alkylating agents such as chlorambucil, or with total lymphoid irradiation
• Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline
• Intraarticular or parenteral corticosteroids within 4 weeks prior to Baseline
• Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
• Serious uncontrolled concomitant disease or other significant condition
• History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal disease
• Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (32)

Unknown Facility

Amiens, 80054, France

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Unknown Facility

Bordeaux, 33076, France

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Unknown Facility

Brest, 29609, France

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Unknown Facility

Caen, 14033, France

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Unknown Facility

Cahors, 46005, France

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Unknown Facility

Clermont-Ferrand, 63003, France

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Unknown Facility

Échirolles, 38434, France

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Unknown Facility

La Source, 45100, France

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Unknown Facility

Le Mans, 72037, France

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Unknown Facility

Lille, 59037, France

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Unknown Facility

Limoges, 87042, France

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Unknown Facility

Lomme, 59462, France

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Lyon, 69437, France

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Marseille, 13274, France

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Marseille, 13285, France

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Metz-Tessy, 74370, France

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Unknown Facility

Monaco, 98012, France

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Unknown Facility

Montpellier, 34295, France

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Unknown Facility

Mulhouse, 68070, France

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Unknown Facility

Paris, 75475, France

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Unknown Facility

Paris, 75571, France

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Unknown Facility

Paris, 75651, France

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Unknown Facility

Paris, 75679, France

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Paris, 75877, France

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Rennes, 35033, France

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Rouen, 76031, France

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Unknown Facility

Saint-Mandé, 94163, France

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Unknown Facility

Saint-Priest-en-Jarez, 42277, France

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Unknown Facility

Strasbourg, 67098, France

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Unknown Facility

Thonon-les-Bains, 74203, France

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Unknown Facility

Toulouse, 31059, France

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Unknown Facility

Vandœuvre-lès-Nancy, 54511, France

Location

Related Publications (2)

• Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Devenport J, Petho-Schramm A. Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis. Rheumatology (Oxford). 2019 Jun 1;58(6):1056-1064. doi: 10.1093/rheumatology/key393.

  PMID: 30649524 DERIVED

• Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Bernasconi C, Petho-Schramm A. Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries. Rheumatology (Oxford). 2018 Mar 1;57(3):499-507. doi: 10.1093/rheumatology/kex443.

  PMID: 29244149 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab; Methotrexate

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

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

Study Record Dates

• First Submitted: November 29, 2013
• First Posted: December 5, 2013
• Study Start: January 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: November 2, 2018
• Results First Posted: November 2, 2018

Record last verified: 2018-03

Locations

FR (32)