A Study of RoActemra/Actemra (Tocilizumab) in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to DMARDs or Anti-TNF

Study Overview
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Brief Summary
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This open-label, single arm study will evaluate the safety and efficacy of RoActemra/Actemra (tocilizumab) in patients with active, moderate to severe rheumatoid arthritis who have an inadequate response to disease-modifying antirheumatic drugs (DMARDs) or anti-TNF. Patients will receive RoActemra/Actemra at a dose of 8 mg/kg (max 800 mg) intravenously every 4 weeks for a total of 6 infusions. Non-biologic DMARD therapy may be continued throughout the study. Anticipated time on study treatment is 24 weeks.

Official Title
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Tocilizumab Efficacy and Safety in RA Patients After Inadequate Response to DMARDs or Anti-TNF

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 patients, >/= 18 years of age Active moderate to severe rheumatoid arthritis of >/= 6 months duration >/=1 non-biologic DMARD and/or anti-TNF therapy at stable dose for >/=8 weeks at any time prior to study treatment Inadequate clinical response to non-biologic DMARD or anti-TNF therapy Oral corticosteroids must be at stable dose for at least 25 out of 28 days prior to first dose of study drug Exclusion Criteria: Pregnant or lactating women Major surgery (including joint surgery) within 8 weeks prior to screening or major surgery planned within 6 months of enrolment Rheumatic autoimmune disease other than RA Functional class IV (ACR classification) Prior history of or current joint disease other than RA Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline Previous treatment with RoActemra/Actemra Known active current or history of recurrent infection History of or currently active primary or secondary immunodeficiency Active tuberculosis requiring treatment within the previous 3 years 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br> | Drug: tocilizumab [RoActemra/Actemra]<br>* 8 mg/kg (max. 800 mg) iv every 4 weeks, 6 infusions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Activity as Measured by Disease Activity Score 28 (DAS28) | The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (erythrocyte sedimentation rate [ESR] in millimeters per hour [mm/hr]), and general health status (participant global assessment of disease activity using visual analog scale [VAS], range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. | Up to 1 year | 
| Number of Participants Who Achieved Remission (DAS28 < 2.6) | The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. | Up to 1 year | 
| Time to Das28 Remission | Time to DAS28 Remission was the Time in days from the first infusion of study drug to the achievement of a DAS28 score < 2.6 units. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. | Up to 1 year | 
| Number of Participants Who Achieved a Clinically Meaningful Improvement in DAS28 (Reduction of At Least 1.2 Units) | DAS28 Clinically Significant Improvement was defined as a DAS28 score reduction of at least 1.2 units from Baseline. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. | Up to 1 year | 
| Number of Participants Who Achieved Low Disease Activity (DAS28 < 3.2) | DAS28 low disease activity was defined as a DAS28 score reduction of at least 3.2 units from Baseline. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. | Up to 1 year | 
| Number of Participants Who Achieved Clinically Meaningful Health Assessment Questionnaire Response | Health Assessment Questionnaire (HAQ) is a self-completed participant questionnaire specific for Rheumatoid Arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. To calculate HAQ, the participant must have a domain score for at least 6 out of 8 domains. The HAQ is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement. Clinically meaningful HAQ response was defined as an improvement of at least 0.22 units from baseline in the HAQ Disability Index. | Up to 1 year | 
| Changes in Participant's Fatigue Assessed Using the Mean FACIT-Fatigue Score | The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participants fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). | Up to 1 year | 
| Change in Fatigue as Measured Using the Fatigue Visual Analog Scale | The VAS for Fatigue (VAS-F) consists of a 100 mm line, with 0 (No Fatigue) on one end, and 100 (Extreme Fatigue) on the other end, which a participant marks to indicate how much fatigue he or she feels. The marked point in mm is converted into a numeric value from 0 to 100, where 0=no fatigue and 100=maximum fatigue. Increasing numbers=increasing fatigue. | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any Adverse Event and Serious Adverse Event | An adverse event (AE) is defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event. | Up to 1 year | 
| Number of Participants With AE or SAE Related Discontinuation of Tocilizumab | It included participants who discontinued from the study due to occurrence of AE or SAE. | Up to 1 year | 
| Number of Participants Who Achieved ACR20, ACR50, ACR70 and ACR90 Response | ACR20, ACR50, ACR70, and ACR90 are defined as greater than or equal to (≥)20 percent (%), ≥50%, ≥70%, or ≥90% improvement, respectively, in swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints). It also comprises ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in 3 of the following 5 assessments: Patient's Global Assessment of Pain (VAS); Patient's Global Assessment of Disease Activity (VAS); Investigator/Physician's Global Assessment of Disease Activity (VAS); participant's assessment of disability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI); or acute phase reactant (ESR or C-reactive protein [CRP]). | Up to 1 year | 
| Number of Participants With C-Reactive Protein Abnormality | CRP is a biological marker of inflammation. A reduction in CRP indicates improvement. It is measured in milligram per liter (mg/L). | Up to 1 year | 
| Number of Participants With Erythrocyte Sedimentation Rate Abnormality | ESR is an acute phase reactant and is a measure of inflammation. It is measured in millimeter per hour (mm/hr). | Up to 1 year |