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 (TOSCA)

Roche

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: csDMARDs; Drug: Tocilizumab; Drug: Methotrexate

Study type: Interventional

Funder types: Industry

Identifiers

NCT02001987

2013-001718-14 (EudraCT Number)

ML28693

Details and patient eligibility

About

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.

Enrollment: 139 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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
• Any infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening
• Active tuberculosis requiring treatment within the previous 3 years
• Positive for hepatitis B or C
• Primary or secondary immunodeficiency disorder
• Active cancer, or cancer diagnosed within the previous 10 years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised or cured), 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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139 participants in 1 patient group

Tocilizumab

Experimental group

Description:

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.

Treatment:

Drug: Tocilizumab

Drug: csDMARDs

Drug: Methotrexate