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)

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.

Timeline

Start

2007-05-15

Primary completion

2010-01-21

Completion

2018-05-14

Outcome

Met primary endpoint

Stopped (Enrollment): “Recruitment was fully completed for this study; however, the study was terminated during conduct after the primary endpoint analysis was completed.”

paper Patients in both of the ocrelizumab groups met the clinical primary efficacy end points. PMID 22389919 ↗

registry analysis (superiority test); Placebo x 2 IV + Non-Biologic DMARD vs Ocrelizumab 200 mg x 2 + Non-Biologic DMARD; p < 0.0001; Weighted Difference 20.4 (95% CI 12.8 to 27.9) NCT00476996 ↗

registry analysis (superiority test); Placebo x 2 IV + Non-Biologic DMARD vs Ocrelizumab 500 mg x 2 + Non-Biologic DMARD; p < 0.0001; Weighted Difference 25.2 (95% CI 17.7 to 32.7) NCT00476996 ↗

Publications

• Emery P, Rigby W, Tak PP, Dorner T, Olech E, Martin C, Millar L, Travers H, Fisheleva E. Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program. PLoS One. 2014 Feb 3;9(2):e87379. doi: 10.1371/journal.pone.0087379. eCollection 2014.
• Tak PP, Mease PJ, Genovese MC, Kremer J, Haraoui B, Tanaka Y, Bingham CO 3rd, Ashrafzadeh A, Travers H, Safa-Leathers S, Kumar S, Dummer W. Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an inadequate response to at least one tumor necrosis factor inhibitor: results of a forty-eight-week randomized, double-blind, placebo-controlled, parallel-group phase III trial. Arthritis Rheum. 2012 Feb;64(2):360-70. doi: 10.1002/art.33353.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Ocrelizumab	Monoclonal antibody	200 mg	Intravenous
Subject	Ocrelizumab	Monoclonal antibody	500 mg	Intravenous
Background	Leflunomide	Small molecule	10 mg	Oral
Background	Leflunomide	Small molecule	20 mg	Oral
Background	Methotrexate	Small molecule	7.5 mg	Oral
Background	Methotrexate	Small molecule	25 mg	Oral

Indications