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

Novartis

Status and phase: Completed; Phase 2

Conditions: Ankylosing Spondylitis

Treatments: Biological: AIN457; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00809159

2008-002631-33

CAIN457A2209

Details and patient eligibility

About

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

Enrollment: 60 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

60 participants in 5 patient groups, including a placebo group

Part 1 - AIN457A 10 mg/kg

Experimental group

Description:

AIN457A 10.0 mg/kg was administered intravenously as a single dose.

Treatment:

Biological: AIN457

Part 1 - Placebo

Placebo Comparator group

Description:

Placebo to AIN457A was administered intravenously as a single dose

Treatment:

Drug: Placebo

Parts 1 and 2 - AIN457A 1.0 mg/kg

Experimental group

Description:

AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.

Treatment:

Biological: AIN457

Part 1 and 2 - AIN457 0.1 mg/kg

Experimental group

Description:

AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.

Treatment:

Biological: AIN457

Part 1 and 2 - AIN457 10 mg/kg

Experimental group

Description:

AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.

Treatment:

Biological: AIN457