A Study of Tocilizumab as Monotherapy and in Combination With Methotrexate Versus Methotrexate in Patients With Early Moderate to Severe Rheumatoid Arthritis

Roche

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: Tocilizumab; Drug: Placebo to methotrexate; Drug: Methotrexate; Drug: Placebo to tocilizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01007435

WA19926

2009-012759-12

Details and patient eligibility

About

This randomized, double-blind, parallel group study will assess the safety, disease remission, and prevention of structural joint damage in patients with early moderate to severe rheumatoid arthritis treated with tocilizumab as monotherapy or in combination with methotrexate, versus methotrexate alone. Patients will be randomized to receive either (A) tocilizumab (8 mg/kg iv every 4 weeks) plus placebo, (B) tocilizumab (8 mg/kg iv every 4 weeks) plus methotrexate (7.5-20 mg po weekly), (C) tocilizumab (4 mg/kg iv every 4 weeks) plus methotrexate (7.5-20 mg po weekly), or (D) placebo plus methotrexate (7.5-20 mg po weekly). Patients in groups C and D who have not achieved low disease activity at week 52 can receive tocilizumab 8 mg/kg iv every 4 weeks. Anticipated time on study treatment is 104 weeks.

Enrollment: 1,162 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients ≥ 18 years of age.
• Rheumatoid arthritis of ≤ 2 years duration.
• Disease Activity Score 28 (DAS28) > 3.2.
• Swollen joint count (SJC) ≥ 4 of 66 joints, tender joint count (TJC) ≥ 6 of 68 joints.
• Rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) positive (if RF and anti-CCP negative > 1 erosion required at screening).
• Erythrocyte sedimentation rate (ESR) ≥ 28 mm/h or C-reactive protein (CRP) ≥ 10 mg/L at screening.

Exclusion criteria

• Previous treatment with tocilizumab.
• Previous treatment with methotrexate or biologic agent.
• Rheumatic autoimmune disease other than rheumatoid arthritis (RA).
• History of or current inflammatory joint disease other than RA.
• Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in RA.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,162 participants in 4 patient groups

(A) Tocilizumab 8 mg/kg + placebo to methotrexate

Experimental group

Description:

Patients received tocilizumab 8 mg/kg iv every 4 weeks + placebo to methotrexate orally once a week for 104 weeks.

Treatment:

Drug: Placebo to methotrexate

Drug: Tocilizumab

(B) Tocilizumab 8 mg/kg + methotrexate

Experimental group

Description:

Patients received tocilizumab 8 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks.

Treatment:

Drug: Methotrexate

Drug: Tocilizumab

(C) Tocilizumab 4 mg/kg + methotrexate

Experimental group

Description:

Patients received tocilizumab 4 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks.

Treatment:

Drug: Methotrexate

Drug: Tocilizumab

(D) Placebo to tocilizumab + methotrexate

Active Comparator group

Description:

Patients received placebo tocilizumab intravenously (iv) every 4 weeks + methotrexate orally once a week for 104 weeks.

Treatment:

Drug: Placebo to tocilizumab

Drug: Methotrexate