A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARDs) (ALABASTER)

Study Overview
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Brief Summary
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This open-label, single arm study will assess the safety and efficacy of RoActem ra/Actemra (tocilizumab) in combination with methotrexate in patients with activ e moderate to severe rheumatoid arthritis who have an inadequate response to dis ease-modifying antirheumatic drugs (DMARDs). Patients will receive RoActemra/Act emra at a dose of 8 mg/kg (maximum 800 mg) intravenously every 4 weeks for a tot al of 6 infusions. Methotrexate will be continued at a stable dose. Anticipated time on study treatment is 24 weeks.

Official Title
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Actemra - Local Bosnian Open, Multicentric, Trial to Evaluate Safety, Tolerability and Efficacy of Tocilizumab in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis After Inadequate Response to DMARDs

Conditions
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Rheumatoid Arthritis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >/= 18 years of age Active moderate to severe rheumatoid arthritis (RA) On methotrexate treatment (oral or parenteral) for at least 12 weeks, at stable dose of at least 15 mg/week for at least 6 weeks Oral corticosteroids must have been at stable dose of </= 10 mg/day prednisone (or equivalent) for at least 25 out of 28 days prior to first dose of study drug Body weight </= 150 kg Exclusion Criteria: Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months of study entry Rheumatic autoimmune disease other than RA Functional class IV according to American College of Rheumatology (ACR) classification Prior history of or current inflammatory joint disease other then RA Treatment with traditional DMARDs other than methotrexate within 1 month (for leflunomide 3 months) prior to baseline Treatment with any biologic drug that is used in the treatment or RA Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline Known active current or history of recurrent infection History of or currently active primary or secondary immunodeficiency Positive for HIV

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br> | Drug: methotrexate<br>* stable dose as prescribed<br>Drug: tocilizumab [RoActemra/Actemra]<br>* 8 m/kg (maximum 800 mg) intravenously every 4 weeks for a total of 6 infusions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs) | AEs, SAEs and AESI were recorded from the Screening Visit until the final visit at Week 24. | Screening Visit, Baseline, Weeks 4, 8, 12, 16, 20 and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Disease Activity Score Based on 28 Joint Count (DAS28) by Visit | DAS28 was calculated using the 28 joints count, the C-reactive protein levels (CRP) and participant's global assessment (PtGA) of disease activity. The following formula was used to determine DAS28. DAS28 (equals) = 0.56 × (square root of) √(TJC28) + 0.28 × √(SJC28) + 0.36 × ln(CRP+1) + 0.014 × GH + 0.96 where, TJC28 = tender joint count on 28 joints, SJC28 = swollen joint count on 28 joints, ln = natural log, CRP = C-reactive protein (mg/L), and GH = general health, determined by participant's global assessment of disease activity (100- millimeter [mm] visual analog scale [ VAS]). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. | Baseline, Weeks 8, 16 and 24 | 
| Percentage of Participants Achieving Low Disease Activity (LDA) and Clinical Remission (CR) as Assessed Using DAS28 | DAS28 was calculated using the 28 joints count, the CRP and PtGA of disease activity. The following formula was used to determine DAS28. DAS28 = 0.56 × √(TJC28) + 0.28 × √(SJC28) + 0.36 × ln(CRP+1) + 0.014 × GH + 0.96 where, TJC28 = tender joint count on 28 joints, SJC28 = swollen joint count on 28 joints, ln = natural log, CRP = C-reactive protein (mg/L), and GH = general health, determined by participant's global assessment of disease activity (100-mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Participants were considered to have low disease activity when DAS28 was less than or equal to (≤) 3.2 and in clinical remission when DAS28 scores were less than (<) 2.6 | Weeks 8, 16 and 24 | 
| Swollen and Tender Joint Counts | 66 and 68 joints were assessed by the physician for tenderness or swelling respectively. The joints were counted as tender/not tender (tender=1; not tender=0) and swollen/not swollen (swollen=1; not swollen=0) and scored. The scores ranged from 0 to 66 for TJC and 0 to 68 for SJC. A negative change from baseline represents an improvement. | Baseline, Weeks 8, 16 and 24 | 
| Physician's Global Assessment of Disease Activity | Physician's global assessment of disease activity was performed using a 100 mm VAS ranging from no arthritis activity (0) to maximal arthritis activity (100). The distance in mm from the left edge of the scale was measured. Higher scores indicated higher disease activity. A negative change from baseline represents an improvement. | Baseline, Weeks 8, 16 and 24 | 
| Participant's Global Assessment of Disease Activity | Participant's global assessment of disease activity was performed using a 100 mm VAS ranging from no arthritis activity (0) to maximal arthritis activity (100). The distance in mm from the left edge of the scale was measured. Higher scores indicated higher disease activity. A negative change from baseline represents an improvement. | Baseline, Weeks 8, 16 and 24 | 
| Participant's Global Assessment of Pain | Participant's global assessment of pain was performed using a 100 mm VAS ranging from no pain (0) at the left edge to unbearable pain (100) at the right edge. The distance in mm from the left edge of the scale was measured. A negative change from baseline represents an improvement. | Baseline, Weeks 8, 16 and 24 | 
| CRP Levels | CRP is a marker of acute phase inflammation and is measured in mg/L. A negative change from baseline represents an improvement. | Baseline, Weeks 8, 16 and 24 | 
| Erythrocyte Sedimentation Rate (ESR) | ESR is a marker of inflammation and is measured in millimeters per hour (mm/hour). A negative change from baseline represents an improvement. | Baseline, Weeks 8, 16 and 24 |