A Long-Term Safety Extension Study of WA19926 in Participants With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This extension study of WA19926 will assess the long-term safety and the efficacy of RoActemra/Actemra (tocilizumab) treatment in participants with rheumatoid arthritis. Participants who have completed the core study WA19926 are eligible to participate. Participants will receive RoActemra/Actemra 8 mg/kg intravenously every 4 weeks. The anticipated time on study drug is 104 weeks.

Official Title
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A MULTICENTER, OPEN-LABEL, SINGLE ARM, LONG-TERM EXTENSION STUDY OF WA19926 TO DESCRIBE SAFETY DURING TREATMENT WITH TOCILIZUMAB IN PATIENTS WITH EARLY, MODERATE TO SEVERE RHEUMATOID ARTHRITIS

Conditions
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Rheumatoid Arthritis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult participants, >/=18 years of age who have completed the core study WA19926 and according to the investigator may benefit from RoActemra/Actemra treatment No current or recent adverse event or laboratory finding preventing the use of the study drug dose at baseline Receiving treatment on an outpatient basis Exclusion Criteria: Females who are pregnant Participants who have prematurely withdrawn from the core study WA19926 for any reason Treatment with any investigational drug since the last administration of the study drug in the core study WA19926 Treatment with an anti-tumor necrosis (TNF), anti-interleukin 1 agent or T-cell costimulation modulator since the last administration of the study drug in the core study WA19926 Immunization with live/attenuated vaccine since the last administration of the study drug in the core study WA19926 Diagnosis since the last WA19926 visit of rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis Abnormal laboratory values

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RoActemra/Actemra single arm<br> | Drug: tocilizumab [RoActemra/Actemra]<br>* 8 mg/kg intravenously every 4 weeks for 104 weeks<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) | An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. Adverse Events of Special Interest for this study were: Serious and/or medically significant infections; myocardial infarction/Acute coronary syndrome; Gastrointestinal perforation; Malignancies; Anaphylaxis/hypersensitivity reactions; Demyelinating disorders; Stroke and Serious and/or medically significant bleeding and hepatic events. | End of Study (Week 104 or early withdrawal) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) | The DAS28 (ESR) score is a measure of the participant's disease activity. It is calculated using the tender joint count (28 joints), swollen joint count (28 joints), erythrocyte sedimentation rate (ESR) and general health status. The DAS28-ESR scale ranges from 0 to 10, where higher scores represent higher disease activity. DAS28 <=3.2 implied low disease activity, DAS >3.2 to 5.1 implied moderate disease activity, DAS >5.1 implied high disease activity, and DAS28 <2.6 = clinical remission. | Screening and End of Study (Week 104 or early withdrawal) | 
| Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) | The SDAI was defined as the numerical sum of 5 outcome parameters: tender and swollen joint count (based on a 28-joint assessment), participant and physician global assessment of disease activity on a 100 millimeter (mm) Visual analogue scale (VAS) (VAS; 0 = no disease activity and 100 = worst disease activity) and level of C-reactive protein (CRP) (milligram per deciliter [mg/dl], normal < 1 mg/dl). SDAI total score = 0-86 where a higher score reflects worsening disease. SDAI <=3.3 indicates clinical remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity. | Screening and End of Study (Week 104 or early withdrawal) | 
| Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) | Tender joint count was performed by a skilled assessor, evaluating 68 joints for tenderness. | Week 12 and Week 104 | 
| Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) | Swollen joint count was performed by a skilled assessor, evaluating 66 joints for swelling. | Week 12 and Week 104 | 
| Time to Rheumatoid Arthritis (RA) Flare | RA flare was defined as any worsening of the participant's disease activity that in the opinion of the Investigator required treatment intensification beyond supportive therapy which included restarting of the study drug treatment. Time to RA flare was defined as the period of drug-free remission until documentation of RA flare. Drug-free remission was defined as clinical remission (based on DAS28-ESR < 2.6 and /or SDAI ≤ 3.3) for two consecutive assessment visits, followed by discontinuation of tocilizumab, at the Investigator's discretion, at the second assessment visit. | End of Study (Week 104 or early withdrawal) | 
| Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity | The participant global assessment of disease activity was measured using a 100 mm VAS ranging from 0=very good to 100=very bad. | Week 12 and Week 104 | 
| Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain | A participant's overall assessment of pain on a VAS was assessed with a question concerning the amount of pain due to arthritis. Pain was assessed on a 100 mm VAS scale with a left-hand marker no pain (0 mm) or right-hand marker extreme pain (100 mm). | Week 12 and Week 104 | 
| Health Assessment Questionnaire Disability Index (HAQ-DI) | The Health Assessment Questionnaire Disability Index (HAQ-DI) is a participant-completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each item was scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores divided by the number of domains answered. Total possible scores range from 0 to 3, where 0=least difficulty, and 3=extreme difficulty. | End of Study (Week 104 or early withdrawal) |