Clinical trial NCT00721123
Conditions: Rheumatoid Arthritis
Sponsor: Hoffmann-La Roche
Start date: 2005-08-01; Completion date: 2012-05-01
Enrollment: 538 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This open-label, international multi-center extension study WA18695 was designed to assess the long term safety of tocilizumab in patients who had moderate to severe active rheumatoid arthritis (RA). Patients enrolled in the WA18695 study had previously received treatment in the 24-week, placebo-controlled, Phase III Study WA17822. Eligible patients were assigned to treatment with 8 mg/kg tocilizumab every 4 weeks for a maximum of 5 years.

Detailed description:
The primary objective of this extension study was to assess the long-term safety of 8 mg/kg tocilizumab with regard to adverse events (AEs) and laboratory result abnormalities.

The secondary objectives were as follows:

* To explore the possibility of reducing concomitant steroid treatment
* To determine the long-term efficacy of 8 mg/kg tocilizumab with regard to reduction in signs and symptoms
* To better understand and predict tocilizumab efficacy, response, safety, and progression of rheumatoid arthritis (RA) and associated diseases with regard to its effect on biomarkers

No viable biomarkers for TCZ treatment effects were identified from the controlled studies. There were, therefore, no biomarkers that warranted further investigation in long-term studies, so no biomarker data are reported.

The extension study WA18695 was an open-label, international multi-center study in patients with moderate to severe active rheumatoid arthritis (RA) who had completed treatment in the 24 weeks placebo-controlled Phase III study WA17822. Patients entering WA17822 had an inadequate response to methotrexate (MTX), and, during WA17822, patients had received treatment with intravenous infusions of tocilizumab 4 mg/kg, 8 mg/kg, or placebo every 4 weeks with background MTX therapy.

All patients who completed the planned course of treatment or escape therapy in the WA17822 study were eligible to enter the WA18695 long-term extension study, where they were assigned to treatment with 8 mg/kg RoActemra/Actemra plus MTX. The dose of RA medications such as MTX and nonsteroidal anti-inflammatory drugs (NSAIDs), but excluding corticosteroids, was to be kept stable for the first 48 weeks of the WA18695 study. During this time dose reductions in these treatments were only allowed as clinically required for safety reasons. After week 48, the administration of disease-modifying antirheumatic drugs (DMARDs) and NSAIDs could be changed, according to the investigator's practice and as tolerated by the patient.

Arms: arm 1: All participants received tocilizumab 8 mg/kg to a maximum of 800 mg, administered by intravenous (IV) infusion over one hour, every 4 weeks. Concomitant therapies were limited to dosage and administration constraints detailed in the protocol.
Interventions: intervention 1: Tocilizumab
Intervention descriptions: intervention 1: Tocilizumab (myeloma receptor antibody \[MRA\]) was supplied in sterile solution of 20 mg TCZ/mL for aseptic preparation of infusion bags for IV administration.

Protocol documents: