A Study of Subcutaneously Administered Tocilizumab in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This open-label randomized 2arm study will investigate the pharmacokinetics, pharmacodynamics, efficacy and safety of subcutaneously administered tocilizumab in patients with rheumatoid arthritis who have shown an inadequate response to methotrexate. Patients will be randomized to receive tocilizumab 162 mg sc either weekly or every other week, in combination with methotrexate, for 12 weeks. Assessments will be made at regular intervals during treatment and on the 3 weeks of follow-up.Target sample size is < 50 individuals.

Official Title
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Open-label, Multicenter, Randomized, Parallel Study to Investigate pk, pd, Efficacy and Safety of Tocilizumab (TCZ, RO4877533) Following Subcutaneous Administration of TCZ 162 mg Weekly or Every Other Week in Combination With Methotrexate in Patients With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: folic acid
* Drug: methotrexate
* Drug: tocilizumab [RoActemra/Actemra]
* Drug: tocilizumab [RoActemra/Actemra]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adults 18 - 75 years of age active rheumatoid arthritis of >/= 6 months duration inadequate response to at least 12 weeks of methotrexate, the last 8 prior to baseline on stable dose swollen joint count (SJC)>/=4, tender joint count (TJC)>/=6 at screening and baseline DMARDs and anti-TNFs, other than methotrexate, withdrawn prior to baseline oral corticosteroids (</= 10mg/day prednisone or equivalent) and NSAIDS on stable dose </= 4 weeks prior to baseline Exclusion Criteria: rheumatic autoimmune disease other than rheumatoid arthritis prior history or current inflammatory joint disease other than rheumatoid arthritis major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following enrollment functional class IV by ACR classification

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: folic acid<br>* >/= 5 mg po weekly<br>Drug: methotrexate<br>* 7.5 - 25 mg weekly (oral or parenteral)<br>Drug: tocilizumab [RoActemra/Actemra]<br>* 162 mg sc weekly (QW)for 12 weeks<br>|
| Active Comparator: 2<br> | Drug: folic acid<br>* >/= 5 mg po weekly<br>Drug: methotrexate<br>* 7.5 - 25 mg weekly (oral or parenteral)<br>Drug: tocilizumab [RoActemra/Actemra]<br>* 162 mg sc every other week (Q2W) for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of TCZ after QW or Q2W sc administration |  | multiple sampling after 1st and last dose, weeks 1 and 12, at bi-weekly intervals during treatment and twice on follow-up | 
| Pharmacodynamic responses of CRP |  | sampling in weeks 1 and 2 and at weekly or bi-weekly intervals throughout treatment | 
| Safety and tolerability, including injection site reaction |  | laboratory assessments every 2nd week on treatment and after 3 weeks follow-up, injection site evaluation after 1st, 2nd and last injection. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy according to ACR and DAS-EULAR parameters |  | assessments on day 1 of weeks 1, 4, 8 and 12 | 
| PD responses of IL-6, sIL-6R and anti TCZ antibody |  | multiple sampling after 1st and last dose, weeks 1 and 12, at bi-weekly intervals during treatment and twice on follow-up |