Clinical trial NCT01034137
Conditions: Rheumatoid Arthritis
Keywords: Treat-to-target, tight control, strategy study, TCZ, MTX
Sponsor: Hoffmann-La Roche
Start date: 2010-01-01; Completion date: 2014-09-01
Enrollment: 317 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This randomized, double-blind, placebo-controlled study will compare the efficacy with regard to sustained remission and safety of tocilizumab and methotrexate, in combination or as monotherapy, in treatment-naïve patients with early rheumatoid arthritis. Patients will be randomized to receive either tocilizumab (8mg/kg iv every 4 weeks) plus weekly methotrexate (po in ascending doses), or tocilizumab (8mg/kg iv every 4 weeks) plus placebo, or methotrexate plus placebo. Anticipated time on study treatment is 2 years, and target sample size is 300.

Detailed description:
Multi-center, randomized, double-blind, placebo-controlled (double placebo) three-arm parallel group, comparative study. Patients were randomized in a 1:1:1 ratio to one of the following treatments:

* TCZ 8 milligram (mg)/kilogram (kg) + MTX (Group I: TCZ+MTX)
* TCZ 8 mg/kg + placeboMTX (Group II: TCZ+placebo)
* MTX + placeboTCZ (Group III: MTX+placebo)

Randomization was stratified by participating center and baseline Disease Activity Score, scoring 28 joints (DAS28) level (\<5.1 vs. ≥5.1). Patients were evaluated every 4 weeks and at each visit a decision on dosage changes was made based on efficacy parameters (DAS28) and occurrence of adverse events (AEs). Patients received MTX/placeboMTX in climbing dosages. Hydroxychloroquine (HCQ) was added when remission was not reached with the maximum tolerable dosage (MTD) of MTX/placeboMTX. If after 12 additional weeks remission was not reached, HCQ was stopped and replaced by standard of care therapy (in Group I) or placebo therapy was replaced by the corresponding verum resulting in TCZ+MTX combination therapy (in Groups II and III). In case remission was reached, MTX/placeboMTX and TCZ/placeboTCZ had to be decreased. Patients were followed for a maximum of 24 months

Arms: arm 1: Participants will receive intravenous (IV) TCZ 8 mg/kg every four weeks for a maximum of 26 infusions + oral capsules of MTX 10-30 mg/week in climbing dosages of 5 mg starting at 10 mg up till a maximum dosage of 30 mg/week. The weekly dose of MTX will be taken on one particular day of the week. arm 2: Participants will receive IV TCZ 8 mg/kg every four weeks for a maximum of 26 infusions + weekly oral matching placebo MTX capsules in climbing dosages. The weekly dose of placebo MTX will be taken on one particular day of the week. arm 3: Participants will receive weekly oral MTX in climbing dosages of 5 mg starting at 10 mg up till a maximum dosage of 30 mg/week + matching placebo TCZ IV 8 mg/kg every four week for a maximum of 26 infusions. The weekly dose of MTX will be taken on one particular day of the week.
Interventions: intervention 1: methotrexate intervention 2: placebo MTX intervention 3: placebo TCZ intervention 4: tocilizumab [RoActemra/Actemra]
Intervention descriptions: intervention 1: orally weekly in ascending dosages, starting at 10mg/week intervention 2: orally weekly intervention 3: iv every 4 weeks intervention 4: 8mg/kg iv every 4 weeks

Protocol documents: