A Study to Assess the Effect of Tocilizumab + Methotrexate on Prevention of Structural Joint Damage in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA)

Roche

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: Methotrexate; Drug: tocilizumab [RoActemra/Actemra]; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00106535

WA17823

Details and patient eligibility

About

This 3 arm study will compare the safety and efficacy, with respect to a reduction in signs and symptoms and prevention of joint damage, of tocilizumab versus placebo, both in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis. Patients will be randomized to receive tocilizumab 4 mg/kg IV, tocilizumab 8 mg/kg IV or placebo IV, every 4 weeks. All patients will also receive methotrexate, 10-25 mg/week. The anticipated time on study treatment is 1-2 years and the target sample size is 500+ individuals. After completion of the 2 year study participants could participate in the optional 3 year open label extension phase (year 3 to 5).

Enrollment: 1,196 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• adult patients at least 18 years of age with moderate to severe active RA for at least 6 months;
• inadequate response to a stable dose of MTX;
• patients of reproductive potential must be using reliable methods of contraception.

Exclusion criteria

• major surgery (including joint surgery) within 8 weeks before entering study, or planned surgery within 6 months after entering study;
• prior treatment failure with an anti-tumor necrosis factor agent;
• women who are pregnant or breast-feeding.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,196 participants in 3 patient groups, including a placebo group

Tocilizumab 4 mg/kg + Methotrexate

Experimental group

Description:

Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with \< 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a \>70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.

Treatment:

Drug: tocilizumab [RoActemra/Actemra]

Drug: Methotrexate

Tocilizumab 8 mg/kg + Methotrexate

Experimental group

Description:

Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with \< 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a \>70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.

Treatment:

Drug: tocilizumab [RoActemra/Actemra]

Drug: Methotrexate

Placebo + Methotrexate

Placebo Comparator group

Description:

Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with \< 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a \>70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.

Treatment:

Drug: Methotrexate

Drug: Placebo