A Study Comparing Infusion Rates of Tocilizumab in Patients With Moderate to Severe Rheumatoid Arthritis
- Registration Number
- NCT00887341
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 76
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 tocilizumab [RoActemra/Actemra] - 2 tocilizumab [RoActemra/Actemra] -
- Primary Outcome Measures
Name Time Method Percentage of Participants With an Infusion Reaction Within 24 Hours After Infusion Screening, Baseline, and Weeks 4, 8, 12, 16, 20, and 24 An infusion reaction was defined as any adverse event (AE) that occurred during the infusion or during the 24 hours following the infusion.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving a DAS28 Score <3.2 by Visit Weeks 4, 8, 12, 16, 20 and Final 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.
Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response) Weeks 4, 8, 12, 16, 20 and Final Visit 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 \[CRP\])
Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) Weeks 4, 8, 12, 16, 20 and Final Visit 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).
Percentage of Participants Discontinuing Tocilizumab for Any Reason Weeks 4, 8, 12, 16, 20 and Final Visit Percentage of Participants Achieving a DAS28 Score <2.6 (Remission) Weeks 4, 8, 12, 16, 20 and Final 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.
Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) Weeks 4, 8, 12, 16, 20 and Final Visit 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).
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 With a Reduction of at Least 1.2 Units on the Disease Activity Scale Based on 28-Joint Count (DAS28) by Visit Weeks 4, 8, 12, 16, 20 and Final 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.
DAS28 Score by Visit Weeks 4, 8, 12, 16, 20, and Final 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.
Erythrocyte Sedimentation Rate Baseline, Weeks 2, 4, 8, 12,16, 20, and 24 ESR is an acute phase reactant measured in mm/hr. Reduction in ESR indicates improvement.
C-Reactive Protein (CRP) Levels Screening, Baseline, Weeks 4, 8, 12, 16, 20, and Final Visit 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).
HAQ-DI Score by Visit Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24 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.
Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response) Weeks 4, 8, 12, 16, 20 and Final Visit 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).
Percentage of Participants With Improvement of at Least 0.22 in HAQ-DI Weeks 4, 8, 12, 16, 20 and Final 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. An improvement of 0.22 units in HAQ-DI was considered to be a clinically significant improvement.