A Study of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Who Don't Have a Response to Anti-TNF-α Therapy (SCRIPT)
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT00476996
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This study will evaluate the efficacy and safety of ocrelizumab, compared with placebo, in patients with active rheumatoid arthritis who have an inadequate response to at least one anti-TNF-alpha therapy. Patients will be randomized to receive placebo, 200mg of intravenous ocrelizumab, or 500mg of i.v. ocrelizumab on days 1 and 15. A repeat course of i.v. treatment will be administered at weeks 24 and 26. All patients will receive stable doses of either concomitant methotrexate (7.5-25mg/week) or leflunomide (10-20mg po daily) and may receive additional DMARDs. The treatment period is planned for 48 weeks (until primary analysis) and then participants will enter the open label phase until the drug is commercialized. Target sample size is 1000.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 836
- Adult patients, ≥ 18 years of age
- Rheumatoid arthritis for at least 3 months
- Inadequate response to previous or current treatment with at least one anti-TNF-alpha agent
- Receiving either leflunomide or methotrexate for ≥ 12 weeks, with a stable dose for the last 4 weeks
- Swollen joint count (SJC) ≥ 4 (66 joint count) and tender joint count (TJC) ≥ 4 (68 joint count) at screening and baseline.
- CRP ≥ 0.6 mg/dL using a high-sensitivity assay.
- Positive rheumatoid factor or positive anti-CCP antibody or both.
- Rheumatic autoimmune disease or inflammatory joint disease, other than RA
- Any surgical procedure in past 12 weeks,or planned within 48 weeks of baseline
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ocrelizumab 500 mg x 2 IV + Non-Biologic DMARD Therapy Leflunomide Participants will receive 2 IV infusions of 500 mg of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD Ocrelizumab 500 mg x 2 IV + Non-Biologic DMARD Therapy Ocrelizumab Participants will receive 2 IV infusions of 500 mg of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD Ocrelizumab 500 mg x 2 IV + Non-Biologic DMARD Therapy Methotrexate Participants will receive 2 IV infusions of 500 mg of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD Placebo x 2 IV + Non-Biologic DMARD Therapy Placebo Participants will receive ocrelizumab matching placebo IV in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD Ocrelizumab 200 mg x 2 IV + Non-Biologic DMARD Therapy Ocrelizumab Participants will receive 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD Placebo x 2 IV + Non-Biologic DMARD Therapy Leflunomide Participants will receive ocrelizumab matching placebo IV in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD Ocrelizumab 200 mg x 2 IV + Non-Biologic DMARD Therapy Leflunomide Participants will receive 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD Ocrelizumab 200 mg x 2 IV + Non-Biologic DMARD Therapy Methotrexate Participants will receive 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD Placebo x 2 IV + Non-Biologic DMARD Therapy Methotrexate Participants will receive ocrelizumab matching placebo IV in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
- Primary Outcome Measures
Name Time Method Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses Weeks 24 and 48 ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale \[VAS\]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving an ACR70 Response Weeks 24 and 48 ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: physician's global assessment of disease activity (MDG), patient's global assessment of disease activity (PGA), patient's assessment of pain, HAQ-DI and CRP.
Percentage of Participants With a Major Clinical Response Week 48 Major clinical response was defined as achieving an ACR70 response and maintaining this response for a consecutive period of at least 6 months.
Percentage of Participants With a Reduction in the HAQ-DI Score Weeks 24 and 48 Health Assessment Questionnaire - Disability Index (HAQ-DI): The Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA. It consists of 20 questions referring to eight component. Reduction in the HAQ-DI score of 0.25 units from baseline to weeks 24 and 48 represented a minimal clinically relevant improvement.
Percentage of Participants Achieving Disease Activity Score (DAS28) Remission Weeks 24 and 48 The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Change in DAS28 From Baseline Weeks 24 and 48 The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10.
Percentage of Participants Achieving an ACR50 Response Weeks 24 and 48 ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: physician's global assessment of disease activity (MDG), patient's global assessment of disease activity (PGA), patient's assessment of pain, Health Assessment Questionnaire with Disability Index (HAQ-DI), and C-Reactive Protein (CRP).
Percentage of Participants With EULAR Response Rates of Good/ Moderate Weeks 24 and 48 The EULAR response rate was based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none.
Trial Locations
- Locations (264)
Pinnacle Research Group; Llc, Central
🇺🇸Anniston, Alabama, United States
Rheumatology Associates
🇺🇸Birmingham, Alabama, United States
Rheumatology Associates of North Alabama
🇺🇸Huntsville, Alabama, United States
Arizona Arthritis & Rheumatology Research, Pllc
🇺🇸Mesa, Arizona, United States
Arthrocare, Arthritis Care and Research, P.C.
🇺🇸Mesa, Arizona, United States
Catalina Pointe Clinical Research, Inc.
🇺🇸Tucson, Arizona, United States
Uni of Arizona Health Science Center; Dept of Rheumatology/Immunology
🇺🇸Tucson, Arizona, United States
CHI St. Vincent Medical Group Hot Springs
🇺🇸Hot Springs, Arkansas, United States
Little Rock Diagnostic Clinic
🇺🇸Little Rock, Arkansas, United States
Allergy & Rheumatology Centre
🇺🇸La Jolla, California, United States
Scroll for more (254 remaining)Pinnacle Research Group; Llc, Central🇺🇸Anniston, Alabama, United States