An Extension Study of WA19926 of the Long-Term Safety of Tocilizumab (RoActemra/Actemra) in Patients With Early Moderate to Severe Rheumatoid Arthritis

Study Overview
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Brief Summary
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This open-label, single arm, multicenter long-term extension study of WA19926 evaluated the safety and efficacy of tocilizumab (RoActemra/Actemra) in participants with moderate to severe rheumatoid arthritis who completed the 104-week WA19926 core study. Eligible patients received tocilizumab 8 mg/kg intravenously every 4 weeks for up to 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult participants, >/= 18 years of age Participants who complete their last WA19926 core study visit (Week 104) and who may benefit from study drug treatment according to the Investigator's assessment No current or recent adverse event or laboratory finding preventing the use of the study drug dose of RoActemra/Actemra 8 mg/kg at baseline visit Women of childbearing potential must agree to use adequate contraception as defined by protocol during the treatment period Exclusion Criteria: Pregnant females Participants who have withdrawn prematurely from the WA19926 core study for any reason Treatment with any investigational agent or cell-depleting therapies since the last administration of study drug in WA19926 Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL) 1 agent, or a T-cell costimulation modulator since the last administration of study drug in WA19926 Immunization with a live/attenuated vaccine since the last administration of study drug in WA19926 Diagnosis since last WA19926 visit (Week 104) of rheumatic autoimmune disease other than rheumatoid arthritis Diagnosis since last WA19926 visit (Week 104) of inflammatory joint disease other than rheumatoid arthritis History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, including tocilizumab and its excipients Evidence of severe uncontrolled concomitant disease or disorder Known active or history of recurrent infections Active tuberculosis requiring treatment in the previous 3 years History of alcohol, drug or chemical abuse since inclusion in the WA19926 study

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: Tocilizumab<br> | Drug: Tocilizumab<br>* 8 mg/kg administered intravenously (IV) every 4 weeks for 104 weeks<br>* Other names: Actemra;|

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 is any untoward medical occurrence in a study participant given administered a pharmaceutical product, regardless of the cause of the AE. 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. AESIs included serious infections (including opportunistic infections) and abnormal liver function tests. | Up to 112 weeks | 
| Percentage of Adverse Events (AEs) Leading to Dose Modification and AEs Leading to Study Withdrawal | An AE is any untoward medical occurrence in a study participant given administered a pharmaceutical product, regardless of the cause of the AE. | Up to 112 weeks | 
| Percentage of Adverse Events With Severity as Mild, Moderate, and Severe |  | Up to 112 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in the Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Over Time | The DAS28-ESR Scale is a measure of a participant's disease activity. It is based on tender joint count (28 joints), swollen joint count (28 joints), a participant's assessment of disease activity, and erythrocyte sedimentation rate. DAS28-ESR is expressed as a score on a scale with a minimum score of 0 (low disease activity ) to a maximum score of 10 (high disease activity). A negative mean percent change from baseline indicates a decrease in disease activity, and a positive mean percent change from baseline indicates an increase in disease activity. | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104 | 
| Percent Change From Baseline in the Simplified Disease Activity Index (SDAI) Over Time | The Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: tender joint count (TJC) and swollen joint count (SJC), based on a 28-joint assessment, patient and physician global assessment assessed on 0-10 centimeter (cm) visual analogue scale (VAS), where 0 = no disease activity and 10 = worst disease activity, and level of C-reactive protein (CRP, mg/dL). SDAI total score = 0-86. 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. A negative mean percent change from baseline indicates a decrease in disease activity, and a positive mean percent change from baseline indicates an increase in disease activity. | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104 | 
| Change From Baseline in Tender Joint Count 66 (TJC 66) Over Time | Number of tender joints was determined by examination of 66 joints, as assessed through pressure and passive joint motion during physical examination. | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104 | 
| Change From Baseline in Swollen Joint Count 66 (SJC 66) Over Time | Number of swollen joints was determined by examination of 66 joints, as assessed through pressure and passive joint motion during physical examination. | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104 | 
| Percentage of Participants With Treatment-Free Remission According to DAS28-ESR/SDAI Remission Criteria | Treatment-free remission is remission at two consecutive assessment visits (every 12 weeks) after discontinuing study drug on the second assessment visit. Clinical remission is DAS28-ESR score <2.6 and/or SDAI score ≤3.3. The DAS28-ESR scale is a measure of a participant's disease activity based on tender joint count (28 joints), swollen joint count (28 joints), a participant's assessment of disease activity, and ESR. DAS28-ESR scored on a scale with a minimum score of 0 (low disease activity) to a maximum score of 10 (high disease activity). The SDAI is sum of TJC and SJC, based on a 28-joint assessment, patient and physician global assessment assessed on 0-10 centimeter visual analogue scale (VAS), where 0 = no disease activity and 10 = worst disease activity, and level of C-reactive protein (CRP, mg/dL). SDAI total score = 0-86. 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. | Up to 104 weeks | 
| Time to Rheumatoid Arthritis Recurrence in Participants Who Achieved Treatment-Free Remission | Time to rheumatoid arthritis (RA) recurrence = period from treatment-free remission to RA recurrence. RA recurrence was worsening of disease activity with treatment beyond supportive therapy. | Up to 104 weeks | 
| Percent Change in Participant's General Assessment of Disease Activity (Severity of Disease) VAS Over Time | The participant's overall assessment of their current disease activity was displayed on a 100-millimeter (mm) horizontal VAS. The left-hand extreme (0 mm) of the line was described as no disease activity (symptom free and no arthritis symptoms) and the right-hand extreme (100 mm) was described as maximum disease activity (maximum arthritis disease activity). The change in Patient Global Assessment of Disease Activity was determined as the difference in values from baseline at each visit. | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104 | 
| Percent Change in Participant's Assessment of Pain (VAS) Over Time | Participants' pain was assessed using a 10-mm horizontal VAS (0 to 10 mm) where 0=pain absent and 10=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain; the distance from the left edge to the mark was recorded. | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104 | 
| Change From Baseline in Health Assessment Questionnaire (HAQ-DI) Score Over Time | The HAQ-DI was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from 4 response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability. | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104 |