A Study of Tocilizumab (RoActemra/Actemra) in Patients With Ankylosing Spondylitis Who Have Had an Inadequate Response to Previous Tumor Necrosis Factor (TNF) Antagonist Therapy

• Status: Terminated
• Trial end date: 2011-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of tocilizumab (RoActemra/Actemra) in patients with ankylosing spondylitis (AS) who had an inadequate response to previous tumor necrosis factor (TNF) antagonist therapy. Patients were randomized to receive tocilizumab at a dose of either 8 mg/kg or 4 mg/kg intravenously (iv) or placebo every 4 weeks for 24 weeks. The double-blind treatment period was followed by open-label treatment with tocilizumab 8 mg/kg iv every 4 weeks until Week 104 for all patients.

This study and all further clinical development of tocilizumab AS was halted after a review of 12-week data from Study NA22823, a randomized double-blind, placebo-controlled study in TNF antagonist naïve AS patients, failed to demonstrate efficacy.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche

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).

• Inadequate response to treatment with etanercept, infliximab, adalimumab, or golimumab because of inadequate efficacy.

• Tumor necrosis factor (TNF) antagonist therapy must have been discontinued at least 8 weeks prior to baseline (etanercept 4 weeks).

• Traditional disease-modifying anti-rheumatic drugs (DMARDs) must be withdrawn for at least 4 weeks prior to baseline (methotrexate, sulfasalazine, and hydroxychloroquine or chloroquine may be allowed if at stable dose for at least 4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/cyclooxygenase-2 [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.

• Previous treatment with tocilizumab.

• 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.