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

This randomised, double-blind, parallel group study will compare the efficacy and safety of subcutaneous (sc) versus intravenous (iv) administration of RoActemra/Actemra (tocilizumab) in patients with moderate to severe active rheumatoid arthritis. Patients will be randomised to receive either RoActemra/Actemra 162 mg sc weekly plus iv placebo every 4 weeks, or RoActemra/Actemra 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 will be followed by a 72-week open-label treatment with some switching of sc and iv administration. No placebo will be administered in the open-label phase. Patients will continue on their stable dose of disease-modifying anti-rheumatic drugs (DMARDs) throughout the study. Anticipated time on study treatment is 2 years.

Official Title

Randomised, Double-blind, Parallel Group Study Study of the Safety and Effect on Clinical Outcome of Tocilizumab SC Versus Tocilizumab IV, in Combination with Traditional Disease Modifying Anti-rheumatic Drugs (DMARDs), in Patients With Moderate to Severe Active Rheumatoid Arthritis

Conditions

Rheumatoid Arthritis

Study Type

Interventional

Study Design

Allocation: Randomised
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment

Further Details

Primary Outcome Measures:

Proportion of patients achieving clinical improvement of 20% according to American College of Rheumatology criteria (ACR20) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Safety comparison of sc versus iv administration: Adverse events and laboratory assessments [ Time Frame: through to study end (up to 4 years) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Long-term efficacy according to American College of Rheumatology criteria (ACR20, ACR50, ACR70) [ Time Frame: 97 weeks ] [ Designated as safety issue: No ]
Long-term efficacy according to Disease Activity Score (DAS28) [ Time Frame: 97 weeks ] [ Designated as safety issue: No ]
Long-term efficacy according to the Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: 97 weeks ] [ Designated as safety issue: No ]
Pharmacokinetics (AUC, Cmax, Tmax) and Pharmacodynamics (interleukin-6, soluble interleukin-6 receptor) of tocilizumab after sc administration [ Time Frame: 97 weeks ] [ Designated as safety issue: No ]
Immunogenicity of tocilizumab (TCZ) following sc administration: anti-TCZ antibodies [ Time Frame: 97 weeks ] [ Designated as safety issue: No ]
Effect of switch from iv to sc administration (efficacy, safety, PK, PD) [ Time Frame: from week 25 to week 97 ] [ Designated as safety issue: No ]

Arm Intervention

SC: Experimental Drug: tocilizumab

Interventions: [RoActemra/Actemra]

162 mg subcutaneously weekly

Drug: tocilizumab Drug: placebo
[RoActemra/Actemra] intravenously weekly, 24 weeks
Drug: placebo Drug: Disease-modifying
Drug: Disease-modifying anti-rheumatic drugs (DMARDs)
anti-rheumatic drugs (DMARDs) stable dose as prescribed

IV: Active Comparator Drug: tocilizumab

Interventions: [RoActemra/Actemra]

Drug: tocilizumab 8 mg/kg intravenously every 4
[RoActemra/Actemra] weeks
Drug: placebo Drug: placebo
Drug: Disease-modifying subcutaneously every 4 weeks for
anti-rheumatic drugs (DMARDs) 24 weeks

Drug: Disease-modifying

anti-rheumatic drugs (DMARDs)

stable dose as prescribed

Study Start

September 2010 – February 2014

Eligibility & Criteria

Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Adult patients, >/=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 RoActemra/Actemra
Active current or history of recurrent infection