A Study of Tocilizumab as Monotherapy or in Combination With DMARDs in Patients With Moderate to Severe Active Rheumatoid Arthritis
- Registration Number
- NCT01089023
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This open-label single-arm study will evaluate the safety, tolerability and efficacy of tocilizumab \[RoActemra/Actemra\] in patients with moderate to severe rheumatoid arthritis who experience an inadequate clinical response to a stable dose of non-biologic disease modifying anti-rheumatic drugs (DMARD) or anti-tumor necrosis factors (TNFs). RoActemra/Actemra will be administered as a monotherapy or in combination with DMARDs. RoActemra/Actemra will be administered as intravenous infusion at a dose of 8 mg/kg every 4 weeks for a total of 6 infusions. The anticipated time on study treatment is 24 weeks. The target sample size is 50-150 patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 95
- adult patients, >/=18 years of age
- moderate to severe rheumatoid arthritis (DAS28 >3.2) of 6 months duration
- inadequate clinical response to non-biologic DMARDs or anti-TNF
- bodyweight </=150 kg
- rheumatic autoimmune disease or inflammatory joint disease other than RA
- major surgery within 8 weeks prior to screening or planned major surgery within 6 months following screening
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 tocilizumab [RoActemra/Actemra] -
- Primary Outcome Measures
Name Time Method Percentage of Participants Reporting Any Adverse Event - Overall Summary of Events Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24 Percentage of participants with a serious adverse event (SAE), who died, with an adverse event (AE), or study drug related AE during the study.
- Secondary Outcome Measures
Name Time Method Percentage of Participants by Disease Activity Score Based on 28-Joint Count (DAS28) Category Baseline and Weeks 4, 8, 12, 16, 20, and 24 DAS28 was 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 global health assessment (participant rated global assessment of disease activity using 10-mm Visual analog scale - VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. A DAS28 score of greater than (\>)5.1 indicated high disease activity, a score of \>3.2 but less than or equal to (≤)5.1 indicated moderate disease activity, a score of greater than or equal to (≥)2.6 but ≤3.2 indicated low disease activity, and a score of less than \<2.6 indicated disease remission. Week 24 is the Follow-Up visit.
Time to DAS28 Response by DAS28 Category Weeks 4, 8, 12, 16, 20, and 24 Time to response is the number of days from date of first infusion to date of event. DAS28 response was defined as achievement of Low Disease Activity (DAS28 ≥2.6 to ≤3.2), Remission (DAS28 \<2.6), or Clinically Meaningful Improvement (change of \>1.2 from baseline).
Erythrocyte Sedimentation Rate Baseline and Weeks 4, 8, 12, 16, 20, and 24 ESR (measured in mm/hr) is an inflammation marker used to determine acute phase response.
Percentage of Participants Achieving a Clinically Meaningful Improvement as Measured by DAS28 Weeks 4, 8, 12, 16, 20, and 24 DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr) and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Participants achieved a clinically meaningful improvement in DAS28 if there was a reduction of at least 1.2 units from baseline.
Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) of at Least 0.22 Units Weeks 4, 8, 12, 16, 20, and 24 HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.
C-Reactive Protein (CRP) Values by Study Visit Baseline and Weeks 4, 8, 12, 16, 20, and 24 CRP is an acute phase inflammatory marker. The serum concentration of CRP is measured in milligrams per liter (mg/L). A reduction in the level is considered an improvement.
Percentage of Participants With Improvement in Physical Function by HAQ-DI Category Baseline, Weeks 4, 8, 12, 16, 20, and 24 Physical function scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. The HAQ-DI score at every visit was categorized into none to mild disability (HAQ-DI \<1), moderate disability (1≤ HAQ-DI \<2) and severe disability (HAQ-DI ≥2). The percentages of the participants falling in each of these categories with respect to the visits were determined.
HAQ-DI Score by Visit Baseline and Weeks 4, 8, 12, 16, 20, and 24 HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3..