Double Blind, Placebo Controlled Study to Assess Efficacy of AIN457 in Moderate to Severe Ankylosing Spondylitis
Condition: Ankylosing Spondylitis
MeSH terms: Spondylitis; Spondylarthritis; Spondylitis, Ankylosing
Intervention: AIN457; Placebo
Intervention description: AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.; Placebo to AIN457
Phase: Phase 2
Study type: Interventional
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: ankylosing spondylitis

Summary:

      Evaluate the safety, tolerability and pharmacokinetics of AIN457 when administered as
      treatment of moderate to severe ankylosing spondylitis (AS).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with moderate to severe AS fulfilling the modified New York criteria for a
             diagnosis of AS and whose disease was not controlled on NSAIDS (on at least one NSAID
             over a period of at least 3 months at maximum dose). Minimum disease activity for
             inclusion of patients was assessed based on the ASAS core set domains: back pain &
             nocturnal pain score ≥ 4 despite concurrent NSAID use, PLUS a BASDAI score ≥ 4.
             Elevated CRP or ESR was not mandatory for study inclusion

          -  No evidence of liver disease or liver injury as indicated by abnormal liver function
             tests such as serum glutamic oxaloacetic transaminase (SGOT/AST), serum glutamic
             pyruvic transaminase (SGPT/ALT), gamma glutamyl transpeptidase (GGT), alkaline
             phosphatase, or serum bilirubin. The investigator was guided by criteria as outlined
             under exclusion criteria

        Exclusion Criteria:

          -  For patients who were previously treated with TNF blockers, the following washout
             periods were required for these patients to be eligible to participate in the trial:

          -  month washout period prior to baseline for alefacept

          -  month washout period prior to baseline for adalimumab and certolizumab

          -  month washout prior to baseline for etanercept or infliximab

          -  For patients who were previously treated with immunosuppressive agents other than MTX,
             SSZ, and systemic corticosteroids, a 1-month washout period prior to baseline was
             required. Immunosuppressive agents included but were not limited to cyclosporine,
             mycophenolate, tacrolimus, and 5-aminosalicylic acid (5-ASA). Prednisone had to be
             kept at a stable dose 4 weeks before baseline and throughout the study and not to
             exceed 10 mg/day.

          -  MTX had to be kept at a stable dose 4 weeks before baseline and throughout the study
             and not to exceed 25 mg/week.

          -  SSZ had to be kept at a stable dose 4 weeks before baseline and throughout the study.

          -  In case of previous leflunomide treatment, a wash-out with oral cholestyramine could
             be considered as an alternative wash-out procedure to increase the elimination of
             leflunomide. Based on the notion that cholestyramine reduces plasma levels of the
             active leflunomide metabolite by approximately 40% in 24 hours and by 49% in 48 hours,
             cholestyramine was to be given orally at a dose of 8 g t.i.d. daily for 10 days. The
             patient could then be dosed with study drug not earlier than 2 weeks after the start
             of the cholestyramine wash-out procedure.

          -  Patients who were on NSAIDs had to be kept at a stable dose 4 weeks prior to baseline
             and throughout the study.

          -  Positive human immunodeficient virus (HIV: ELISA and Western blot) test result,
             Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. Any active systemic
             infection within the past 2 weeks including a positive chest X-ray.

          -  Current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic,
             hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral,
             psychiatric, chronic inflammatory diseases with the exception of psoriatic arthritis
             or other disease which in the clinical judgment of the investigator would make the
             patient unsuitable for the trial