A Study of Ocrelizumab in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Are Naive to Methotrexate (FILM)

Rheumatoid Arthritis Clinical Trial

— FILM  

Official title:

A Randomized, Double-Blind, Parallel Group, International Study to Evaluate the Safety and Efficacy of Ocrelizumab in Combination With Methotrexate (MTX) Compared to MTX Alone in Methotrexate- Naive Patients With Active Rheumatoid Arthritis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00485589
• Other study ID #: ACT3984g
• Secondary ID: WA20497
• Status: Terminated
• Phase: Phase 3
• Start date: June 11, 2007
• Est. completion date: August 29, 2013

Study information

• Verified date: October 2020
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy and safety of ocrelizumab, compared with placebo, in combination with methotrexate in patients with active rheumatoid arthritis who are naive to methotrexate. Patients will be randomized to receive placebo, ocrelizumab 200mg i.v. or ocrelizumab 500mg i.v. on Days 1 and 15. Repeat courses of i.v. treatment will be administered at weeks 24, 52 and 76. All patients will receive concomitant methotrexate (7.5 mg escalating to 20mg p.o. weekly). The anticipated time on study treatment is 2+ years, and the target sample size is 500+ individuals.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 613
• Est. completion date: August 29, 2013
• Est. primary completion date: January 29, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Age = 18

• Rheumatoid arthritis for 3 months-5 years

• Naive to methotrexate

• If receiving steroids or NSAIDs, must be on a stable dose for 4 weeks prior to baseline

Exclusion criteria:

• Rheumatic autoimmune disease or inflammatory joint disease other than RA

• Prior receipt of any biologic therapy for RA

• Concurrent treatment with any DMARD

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Methotrexate
Oral repeating dose
• Ocrelizumab
Intravenous repeating dose
• Placebo
Intravenous repeating dose

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Genentech, Inc.	Roche Pharma AG

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Modified Total Sharp Score (mTSS) at Week 52	The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement.	Baseline to Week 52
Secondary	Percentage of Participants Without Radiographic Progression (RP) at Week 52	RP was defined as a change from Baseline in the modified Total Sharp Score (mTSS) = 0. The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement.	Week 52
Secondary	Percentage of Participants With an Improvement = 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Week 52	Improvement must be seen in tender (68) and swollen (66) joint counts. Joints were assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation. Improvement must also be seen in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line "none" [symptom-free and no arthritis symptoms] and the extreme right end "maximum" [maximum arthritis disease activity]; patient assessment of pain in the previous 24 hours on a VAS (extreme left end of the line "none" and the extreme right end "unbearable"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C-reactive protein (CRP), or erythrocyte sedimentation rate if CRP was missing.	Baseline to Week 52
Secondary	Percentage of Participants in Disease Activity Score 28 (DAS28) Remission at Weeks 24 and 52	A participant was in DAS28 remission if their DAS28 score < 2.6). The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × v(TJC28)) + (0.28 × v(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where a higher score indicates more disease activity.	Week 24 and Week 52