A Study Comparing Infusion Rates of Tocilizumab in Patients With Moderate to Severe Rheumatoid Arthritis

Study Overview
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Brief Summary
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This 2 arm study will compare the incidence of tocilizumab-related infusion reactions, using 2 different infusion times, in patients with moderate to severe rheumatoid arthritis who have shown an inadequate response to DMARDs (Disease Modifying Anti Rheumatic Drugs) or anti-TNFs.Patients will be randomized to one of 2 groups, to receive tocilizumab 8mg/kg iv every 4 weeks either a)over a 1h infusion time for all administrations or b) a 1h infusion time for the first administration, followed by a 31 minute infusion time for subsequent administrations (unless drug-related infusion reactions occur).The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Official Title
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Phase II Multi-centre, Randomized, Parallel Group, Pilot Trial to Compare the Incidence of Tocilizumab Related Infusion Reactions in Moderate to Severe RA Patients When Infusion is Made Over 1 Hour Against 31 Minutes

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: tocilizumab [RoActemra/Actemra]
* 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 or severe rheumatoid arthritis; active disease for >6 months; inadequate response to a stable dose of non-biologic DMARDs or antiTNFs. Exclusion Criteria: rheumatic autoimmune disease other than rheumatoid arthritis; prior history of, 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.

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: tocilizumab [RoActemra/Actemra]<br>* 8mg/kg iv every 4 weeks for 6 infusions; first infusion 1h duration, subsequent infusions 31 minutes duration<br>|
| Active Comparator: 2<br> | Drug: tocilizumab [RoActemra/Actemra]<br>* 8mg/kg iv every 4 weeks for 6 infusions; each infusion 1h duration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Infusion Reaction Within 24 Hours After Infusion | An infusion reaction was defined as any adverse event (AE) that occurred during the infusion or during the 24 hours following the infusion. | Screening, Baseline, and Weeks 4, 8, 12, 16, 20, and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Discontinuing Tocilizumab in Response to an AE or Serious AE (SAE) |  | Weeks 4, 8, 12, 16, 20 and Final Visit | 
| Percentage of Participants Discontinuing Tocilizumab for Any Reason |  | Weeks 4, 8, 12, 16, 20 and Final Visit | 
| Percentage of Participants With a Reduction of at Least 1.2 Units on the Disease Activity Scale Based on 28-Joint Count (DAS28) by Visit | DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and Patient's Global Assessment of Disease (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 less than or equal to (≤)3.2 equals (=) low disease activity, DAS28 greater than (>)3.2 to 5.1 = moderate to high disease activity; DAS28 less than (<) 2.6 = remission. A reduction of at least 1.2 units was considered a clinically significant difference. | Weeks 4, 8, 12, 16, 20 and Final Visit | 
| Percentage of Participants Achieving a DAS28 Score <3.2 by Visit | DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr), and Patient's Global Assessment of Disease (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 ≤3.2=low disease activity, DAS28 >3.2 to 5.1=moderate to high disease activity; DAS28 <2.6=remission. | Weeks 4, 8, 12, 16, 20 and Final Visit | 
| Percentage of Participants Achieving a DAS28 Score <2.6 (Remission) | DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr) and Patient's Global Assessment of Disease (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 ≤3.2=low disease activity, DAS28 >3.2 to 5.1=moderate to high disease activity; DAS28 <2.6=remission. | Weeks 4, 8, 12, 16, 20 and Final Visit | 
| DAS28 Score by Visit | DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr) and Patient's Global Assessment of Disease (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 ≤3.2=low disease activity, DAS28 >3.2 to 5.1=moderate to high disease activity; DAS28 <2.6=remission. Last observation carried forward (LOCF) visit took the last non-missing post-baseline available value. | Weeks 4, 8, 12, 16, 20, and Final Visit | 
| Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response) | ACR20 response defined as an improvement of ≥20% in swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) as well as ≥20% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; Health Assessment Questionnaire - Disability Index (HAQ-DI); and acute phase reactive factors (ESR or C-Reactive Protein [CRP]) | Weeks 4, 8, 12, 16, 20 and Final Visit | 
| Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) | ACR50 response defined as an improvement of ≥50% in SJC (66 joints) and TJC (68 joints) as well as ≥50% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP). | Weeks 4, 8, 12, 16, 20 and Final Visit | 
| Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) | ACR70 response defined as an improvement of ≥70% in SJC (66 joints) and TJC (68 joints) as well as ≥70% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP). | Weeks 4, 8, 12, 16, 20 and Final Visit | 
| Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response) | ACR90 response defined as an improvement of ≥90% in SJC (66 joints) and TJC (68 joints) as well as ≥90% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP). | Weeks 4, 8, 12, 16, 20 and Final Visit | 
| C-Reactive Protein (CRP) Levels | CRP is an inflammation marker. High levels of this protein indicate inflammation in diseases such as Rheumatoid Arthritis. CRP is measured in milligrams per liter (mg/L). | Screening, Baseline, Weeks 4, 8, 12, 16, 20, and Final Visit | 
| Erythrocyte Sedimentation Rate | ESR is an acute phase reactant measured in mm/hr. Reduction in ESR indicates improvement. | Baseline, Weeks 2, 4, 8, 12,16, 20, and 24 | 
| HAQ-DI Score by Visit | HAQ-DI is a self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessment based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ-DI scores range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ-DI total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. | Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24 | 
| Percentage of Participants With Improvement of at Least 0.22 in HAQ-DI | HAQ-DI is a self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessment based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ-DI scores range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ-DI total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. An improvement of 0.22 units in HAQ-DI was considered to be a clinically significant improvement. | Weeks 4, 8, 12, 16, 20 and Final Visit |