A Study to Compare Subcutaneous Versus Intravenous Administration of RoActemra/Actemra (Tocilizumab) in Participants With Moderate to Severe Active Rheumatoid Arthritis

Roche

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: tocilizumab IV; Drug: placebo to tocilizumab IV; Drug: Disease-modifying antirheumatic drugs (DMARDs); Drug: placebo to tocilizumab SC; Drug: tocilizumab SC

Study type: Interventional

Funder types: Industry

Identifiers

NCT01194414

WA22762

2010-018375-22

Details and patient eligibility

About

This randomized, double-blind, parallel group study compares the efficacy and safety of subcutaneous (sc) versus intravenous (iv) administration of tocilizumab in participants with moderate to severe active rheumatoid arthritis. Participants were randomized to receive either tocilizumab 162 mg sc weekly plus iv placebo every 4 weeks, or tocilizumab 8 mg/kg iv every 4 weeks plus sc placebo weekly during the double-blind period from baseline to Week 24. The double-blind period was followed by a 72-week open-label treatment with some switching of sc and iv administration. No placebo was administered in the open-label phase. Participants continued on their stable dose of disease-modifying antirheumatic drugs (DMARDs) throughout the study. Anticipated time on study treatment was 2 years.

Enrollment: 1,262 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult participants, ≥ 18 years of age
• Rheumatoid arthritis of ≥ 6 months duration, according to American College of Rheumatology (ACR) criteria
• Swollen joint count (SJC) ≥ 4 (66 joint count), tender joint count (TJC) ≥ 4 (68 joint count) at screening and baseline
• Inadequate response to current DMARD therapy
• Permitted DMARDs must be at stable dose for ≥ 8 weeks prior to baseline
• Oral corticosteroids (≤ 10 mg/day prednisone or equivalent) and NSAIDs (up to maximum recommended dose) must be at stable dose for ≥ 4 weeks prior to baseline

Exclusion criteria

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization
• Rheumatic autoimmune disease other than RA
• Functional class IV (ACR classification)
• Diagnosis of juvenile idiopathic arthritis (JIA) or juvenile rheumatoid arthritis (JRA) and/or RA before the age of 16
• Prior history of or current inflammatory joint disease other than RA
• Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
• Previous treatment with tocilizumab
• Active current or history of recurrent infection

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,262 participants in 4 patient groups

Tocilizumab SC

Experimental group

Description:

Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.

Treatment:

Drug: Disease-modifying antirheumatic drugs (DMARDs)

Drug: tocilizumab SC

Drug: placebo to tocilizumab IV

Tocilizumab IV

Experimental group

Description:

Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.

Treatment:

Drug: Disease-modifying antirheumatic drugs (DMARDs)

Drug: tocilizumab IV

Drug: placebo to tocilizumab SC

Tocilizumab SC Then Tocilizumab IV

Experimental group

Description:

Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.

Treatment:

Drug: Disease-modifying antirheumatic drugs (DMARDs)

Drug: tocilizumab SC

Drug: placebo to tocilizumab IV

Drug: tocilizumab IV

Tocilizumab IV Then Tocilizumab SC

Experimental group

Description:

Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.

Treatment:

Drug: Disease-modifying antirheumatic drugs (DMARDs)

Drug: tocilizumab SC

Drug: tocilizumab IV

Drug: placebo to tocilizumab SC