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

NCT ID: NCT00809159

Last Updated: 2015-12-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2011-05-31

Brief Summary

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

Conditions

Ankylosing Spondylitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: DOUBLE

Study Groups

Part 1 - AIN457A 10 mg/kg

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

Group Type: EXPERIMENTAL

AIN457

Intervention Type: BIOLOGICAL

AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.

Part 1 - Placebo

Placebo to AIN457A was administered intravenously as a single dose

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo to AIN457

Parts 1 and 2 - AIN457A 1.0 mg/kg

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.

Group Type: EXPERIMENTAL

AIN457

Intervention Type: BIOLOGICAL

AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.

Part 1 and 2 - AIN457 0.1 mg/kg

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.

Group Type: EXPERIMENTAL

AIN457

Intervention Type: BIOLOGICAL

AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.

Part 1 and 2 - AIN457 10 mg/kg

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.

Group Type: EXPERIMENTAL

AIN457

Intervention Type: BIOLOGICAL

AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.

Interventions

AIN457

AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.

Intervention Type: BIOLOGICAL

Placebo

Placebo to AIN457

Intervention Type: DRUG

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Paradise Valley, Arizona, United States

Novartis Investigative Site

Springfield, Illinois, United States

Novartis Investigative Site

Springfield, Illinois, United States

Novartis Investigative Site

Oklahoma City, Oklahoma, United States

Novartis Investigative Site

Duncansville, Pennsylvania, United States

Novartis Investigative Site

North Charleston, South Carolina, United States

Novartis Investigative Site

Jackson, Tennessee, United States

Novartis Investigative Site

Knoxville, Tennessee, United States

Novartis Investigative Site

Benbrook, Texas, United States

Novartis Investigative Site

Spokane, Washington, United States

Novartis Investigative Site

Berlin, State of Berlin, Germany

Novartis Investigative Site

Hamburg, , Germany

Novartis Investigative Site

Herne, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

Meerssen, KR, Netherlands

Novartis Investigative Site

Amsterdam, , Netherlands

Novartis Investigative Site

Maastricht, , Netherlands

Novartis Investigative Site

Leeds, , United Kingdom

Novartis Investigative Site

Newcastle upon Tyne, , United Kingdom

Novartis Investigative Site

Oxford, , United Kingdom

Countries

United States; Germany; Netherlands; United Kingdom

References

Baraliakos X, Borah B, Braun J, Baeten D, Laurent D, Sieper J, Emery P, McInnes IB, van Laar JM, Wordsworth P, Wollenhaupt J, Kellner H, Colin L, Vandenhende F, Radford K, Hueber W. Long-term effects of secukinumab on MRI findings in relation to clinical efficacy in subjects with active ankylosing spondylitis: an observational study. Ann Rheum Dis. 2016 Feb;75(2):408-12. doi: 10.1136/annrheumdis-2015-207544. Epub 2015 Aug 6.

Reference Type: DERIVED

PMID: 26248638 (View on PubMed)

Baeten D, Baraliakos X, Braun J, Sieper J, Emery P, van der Heijde D, McInnes I, van Laar JM, Landewe R, Wordsworth P, Wollenhaupt J, Kellner H, Paramarta J, Wei J, Brachat A, Bek S, Laurent D, Li Y, Wang YA, Bertolino AP, Gsteiger S, Wright AM, Hueber W. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2013 Nov 23;382(9906):1705-13. doi: 10.1016/S0140-6736(13)61134-4. Epub 2013 Sep 13.

Reference Type: DERIVED

PMID: 24035250 (View on PubMed)

Other Identifiers

2008-002631-33

Identifier Type: -

Identifier Source: secondary_id

CAIN457A2209

Identifier Type: -

Identifier Source: org_study_id