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)

Genentech

Status and phase: Terminated; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: Ocrelizumab; Drug: Leflunomide; Drug: Methotrexate; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00476996

2006-005330-20 (EudraCT Number)

ACT3986g

WA20495 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 836 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• Rheumatic autoimmune disease or inflammatory joint disease, other than RA
• Any surgical procedure in past 12 weeks,or planned within 48 weeks of baseline

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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836 participants in 3 patient groups, including a placebo group

Ocrelizumab 200 mg x 2 IV + Non-Biologic DMARD Therapy

Experimental group

Description:

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

Treatment:

Drug: Ocrelizumab

Drug: Leflunomide

Drug: Methotrexate

Drug: Ocrelizumab

Ocrelizumab 500 mg x 2 IV + Non-Biologic DMARD Therapy

Experimental group

Description:

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

Treatment:

Drug: Ocrelizumab

Drug: Leflunomide

Drug: Methotrexate

Drug: Ocrelizumab

Placebo x 2 IV + Non-Biologic DMARD Therapy

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Leflunomide

Drug: Methotrexate