A Study of RoActemra/Actemra (Tocilizumab) Versus Adalimumab in Combination With Methotrexate (MTX) in Patients With Moderate to Severe Active Rheumatoid Arthritis And an Inadequate Response to Treatment With Only One Tumor Necrosis Factor (TNF)-Inhibitor

Roche

Status and phase: Terminated; Phase 4

Conditions: Rheumatoid Arthritis

Treatments: Drug: folate; Drug: methotrexate; Drug: tocilizumab [RoActemra/Actemra]; Drug: placebo to adalimumab; Drug: placebo to tocilizumab; Drug: adalimumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01283971

MA25522

2010-023587-40 (EudraCT Number)

Details and patient eligibility

About

This randomized, parallel-group study will assess the efficacy and safety of RoActemra/Actemra (tocilizumab) versus adalimumab, both in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis. Patients, already treated with MTX at stable doses, will be randomized to receive either RoActemra/Actemra 8 mg/kg intravenously (IV) every 4 weeks or adalimumab 40 mg subcutaneous (SC) every 2 weeks. All patients will receive methotrexate (10-25 mg weekly) and folate (at least 5 mg weekly). The anticipated time on study treatment is 24 weeks.

Enrollment: 96 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients, >/= 18 years of age
• Rheumatoid arthritis of >/= 6 months duration (according to American College of Rheumatology (ACR) criteria)(according to ACR criteria)
• Inadequate response due to inefficacy of treatment (for at least 3 months) with only one approved Tumor Necrosis Factor (TNF)-agent other than adalimumab Depending on the TNF-inhibitor, last dose of TNF-inhibitor should have been 1 to 8 weeks before randomization to the study
• On methotrexate treatment for >/=12 weeks immediately prior to baseline, with stable dose (10-25 mg/week) for the last 8 weeks
• Disease Activity Score (DAS28) >3.2 at baseline
• Oral corticosteroids (</=10 mg/day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs) are permitted if the dose has been stable for >/=6 weeks prior to baseline.

Exclusion criteria

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 6 months following randomization
• Rheumatic autoimmune disease other than rheumatoid arthritis
• Prior history of or current inflammatory joint disease other than rheumatoid arthritis
• Functional class IV (ACR criteria)
• History of severe allergic reaction to human, humanized or murine monoclonal antibodies
• Known active current or history of recurrent infection (including tuberculosis)
• Primary or secondary immunodeficiency (history of or currently active)
• Body weight >150 kg
• Previous treatment with any cell-depleting therapies
• Previous treatment with tocilizumab
• Intra-articular or parenteral corticosteroids within 6 weeks prior to baseline.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

96 participants in 2 patient groups

Tocilizumab + Methotrexate

Experimental group

Description:

Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.

Treatment:

Drug: folate

Drug: tocilizumab [RoActemra/Actemra]

Drug: placebo to adalimumab

Drug: methotrexate

Adalimumab + Methotrexate

Active Comparator group

Description:

Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.

Treatment:

Drug: adalimumab

Drug: placebo to tocilizumab

Drug: folate

Drug: methotrexate