a study of roactemra/actemra (tocilizumab) in patients with ankylosing spondylitis who have failed treatment with nsaids

Conditions: Spondylitis, Ankylosing

Summary: this randomized, double-blind, placebo-controlled study will evaluate the safety and efficacy of roactemra/actemra (tocilizumab) in patients with ankylosing spondylitis (as) who have failed treatment with non-steroidal anti-inflammatory drugs and are naïve to tumor necrsos factor (tnf) antagonist therapy. in part 1 of the study, patients will be randomized to receive either roactemra/actemra 8 mg/kg intravenously (iv) or placebo every 4 weeks for 12 weeks. in part 2, patients will be randomized to receive roactemra at either 8 mg/kg or 4 mg/kg iv or placebo every 4 weeks for 24 weeks. the double-blind treatment period will be followed by open-label treatment with roactemra/actemra 8 mg/kg iv every 4 weeks until week 208 for all patients. anticipated time on study treatment is 208 weeks.

this study was planned as a phase ii/iii seamless, multicenter, randomized, double-blind, placebo-controlled study in patients with as who were naïve to tnf antagonist therapy. the study consisted of 2 parts, each preceded by a screening visit and followed by a common open-label extension phase. recruitment into part 2 commenced after completion of enrollment for part 1. part 1 was designed as a phase ii study exploring the efficacy and safety of tocilizumab therapy versus placebo. part 1 was intended to determine whether part 2 of the study would continue, based on a week 12 analysis. part 2 was designed to provide pivotal phase iii efficacy and safety data for tocilizumab in patients with as. approximately 400 patients were to be enrolled. once randomization into part 1 was complete, randomization into part 2 of the study was to be initiated. based on the results of the week 12 part 1 analyses of the primary endpoint (asas20) and secondary endpoints, and in consideration of all available safety data, a benefit/risk assessment was made and it was decided to halt the study because of lack of overall efficacy. most patients did not complete the 24-week double-blind treatment period in part 2.

Eligibility criteria:
inclusion criteria * adult patients, ≥ 18 years of age * ankylosing spondylitis as defined by the modified new york criteria for ≥ 3 months prior to baseline * active disease at screening and baseline (bath ankylosing spondylitis disease activity index \[basdai\] ≥4.0, spinal pain visual analog scale \[vas\] ≥40) * inadequate response or intolerant to 1 or more previous non-steroidal anti-inflammatory drugs (nsaids) * traditional disease-modifying anti-rheumatic drugs (dmards) must be withdrawn for at least 4 weeks prior to baseline (methotrexate, sulfasalazine and hydroxychloroquine or chloroquine may be allowed if at stable dose for at least 4 weeks prior to baseline) * oral corticosteroids (≥ 10 mg/day prednisone or equivalent) and nsaids/cox-2 inhibitors must be at stable dose for at least 4 weeks prior to baseline exclusion criteria: * major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after randomization * total ankylosis of spine (as determined by investigator) * inflammatory rheumatic disease other than ankylosing spondylitis * active, acute uveitis at baseline * treatment with tumor necrosis factor (tnf) antagonist therapy at any time prior to baseline * intra-articular or tendon injections or parenteral corticosteroids within 4 weeks prior to screening * history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies * active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infection * history of or currently active primary or secondary immunodeficiency * body weight \> 150 kg