A Study on Safety and Efficacy of Tocilizumab (RoActemra/Actemra) Alone or in Combination With Non-Biologic Antirheumatics in Participants With Rheumatoid Arthritis

NCT ID: NCT01987479

Last Updated: 2017-06-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-30
• Study Completion Date: 2016-05-26

Brief Summary

This multi-center, open-label single arm Phase IIIb study will evaluate the safety and efficacy of subcutaneous (SC) tocilizumab administered as monotherapy and/or in combination with methotrexate or other non-biologic disease modifying antirheumatic drugs (DMARDs) in participants with rheumatoid arthritis (RA) with an inadequate response to non-biologic DMARDs.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tocilizumab Alone or in Combination with Methotrexate or DMARD

Participants will receive a weekly SC injection of tocilizumab 162 milligrams (mg) as monotherapy or in combination with methotrexate or other non-biologic DMARDs for 24 weeks.

Group Type: EXPERIMENTAL

Non-Biologic DMARDs

Intervention Type: DRUG

Treatment with non-biologic DMARDs, at a stable dose that was initiated at least 4 weeks prior to baseline, is permitted during the study and is at the investigator's discretion.

Tocilizumab

Intervention Type: DRUG

Tocilizumab 162 mg will be administered once a week by SC injection and as a single fixed dose, irrespective of body weight, for the treatment duration of 24 weeks.

Methotrexate

Intervention Type: DRUG

Methotrexate will be administered per investigator's discretion.

Interventions

Non-Biologic DMARDs

Treatment with non-biologic DMARDs, at a stable dose that was initiated at least 4 weeks prior to baseline, is permitted during the study and is at the investigator's discretion.

Intervention Type: DRUG

Tocilizumab

Tocilizumab 162 mg will be administered once a week by SC injection and as a single fixed dose, irrespective of body weight, for the treatment duration of 24 weeks.

Intervention Type: DRUG

Methotrexate

Methotrexate will be administered per investigator's discretion.

Intervention Type: DRUG

Other Intervention Names

RoActemra, Actemra

Eligibility Criteria

Inclusion Criteria

• Participants with a diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria.
• Oral corticosteroids (≤10 mg/day prednisone or equivalent), nonsteroidal anti-inflammatory drugs (NSAIDs) and non-biologic DMARDs are permitted if on a stable dose regimen for greater than or equal to (≥]) 4 weeks prior to Baseline.
• Use of effective contraception throughout the study as defined by protocol; female participants of childbearing potential cannot be pregnant.

Exclusion Criteria

• Presence of clinically significant medical conditions.
• History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal disease that might predispose to perforation.
• Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections.
• Any infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening.
• Clinically significant findings on laboratory tests.
• Positive hepatitis B surface antigen or hepatitis C antibody.
• Active tuberculosis requiring treatment within the previous 3 years.
• Evidence of active malignant disease, malignancies diagnosed within the previous 10 years, or breast cancer diagnosed within the previous 20 years.
• History of alcohol, drug, or chemical abuse within 1 year prior to Screening.
• Neuropathies or other conditions that might interfere with pain evaluation.
• 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 RA, including systemic lupus erythematosis, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). Secondary Sjögren's syndrome with RA is permitted.
• Functional Class IV as defined by the ACR Classification of Functional Status in RA.
• Diagnosis of juvenile idiopathic arthritis or juvenile RA, and/or RA before the age of 16 years.
• Prior history of or current inflammatory joint disease other than RA.
• Exposure to tocilizumab (either intravenous or SC) at any time prior to Baseline.
• Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of Screening.
• Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
• Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline.
• Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline.

• Minimum Eligible Age: 18 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

ZGT Almelo; Reumatologie

Almelo, , Netherlands

Jan Van Breemen Instituut

Amsterdam, , Netherlands

Gelre Ziekenhuizen; Reumatologie

Apeldoorn, , Netherlands

Amphia ziekenhuis, locatie langendijk

Breda, , Netherlands

Albert Schweitzer Ziekenhuis ; Dordwijk

Dordrecht, , Netherlands

Universitair Medisch Centrum Groningen; Department of Rheumatology

Groningen, , Netherlands

Martini Ziekenhuis

Groningen, , Netherlands

Kennemer Gasthuis

Haarlem, , Netherlands

Atrium Medisch Centrum

Heerlen, , Netherlands

Spaarne Ziekenhuis; Inwendige Geneeskunde

Hoofddorp, , Netherlands

Medisch Centrum Leeuwarden; Reumatology

Leeuwarden, , Netherlands

Academisch Ziekenhuis Leiden; Dept of Rheumatology

Leiden, , Netherlands

Maastricht University Medical Centre; Rheumatology

Maastricht, , Netherlands

Erasmus Medisch Centrum; Reumatologie

Rotterdam, , Netherlands

Maasstadziekenhuis; Reumatologie

Rotterdam, , Netherlands

Vlietland Hospital

Schiedam, , Netherlands

Antonius Ziekenhuis Sneek; Department of Rheumatology

Sneek, , Netherlands

Leyenburg Ziekenhuis; Internal Medecine

The Hague, , Netherlands

St. Bronovo-Nebo

The Hague, , Netherlands

University Medical Centre Utrecht; Reumatologie en Klinische Immunologie

Utrecht, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 30649524 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29244149 (View on PubMed)

Other Identifiers

2013-000342-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ML28702

Identifier Type: -

Identifier Source: org_study_id