Double Blind, Placebo Controlled Study to Assess Efficacy of AIN457 in Moderate to Severe Ankylosing Spondylitis

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