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
Condition: Spondylitis, Ankylosing
MeSH terms: Spondylitis; Spondylarthritis; Spondylitis, Ankylosing
Intervention: Tocilizumab; Placebo
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 113.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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).

          -  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          -  Traditional disease-modifying anti-rheumatic drugs (DMARDs) must be withdrawn for at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.