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

NCT00809159 | Completed Phase 2 Results

• 2 other identifiers: CAIN457A22092008-002631-33
• Study Type: interventional
• Target: 60
• Locations: 4 countries
• Sites: 20

Brief Summary

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

Conditions

Ankylosing Spondylitis

Keywords

ankylosing spondylitis

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Achieved ASAS20 Response

  Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of 20% or more and absolute improvement of at least 1 units (on a scale of 0 \[least\] to 10 \[worst\]) from Baseline in at least 3 of the following 4 domains, with absence of deterioration (worsening of at least 20% an absolute Worsening of at least 1 unit) in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] scores

  6 Weeks

• Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score From Baseline to 6 Weeks After First Infusion in Part 2

  ASAS20 as described in Primary Outcome. ASAS40 responder had improvement of 40% or more and absolute improvement of at least 2 units (on a scale of 0 \[least\] to 10 \[worst\]) from Baseline in at least 3 of the following 4 domains, with no deterioration in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] scores). ASAS 5/6 responder had improvement of 20% or more) from Baseline in at least 5 of the following 6 domains: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (BASFI); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] scores); Spinal Mobility (BASFI); Acute phase reactant (CRP)

  6 Weeks

Secondary Outcomes (21)

• Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1

  Day8,15,29,week 6, 8, 10, 12, 16, 20, 24, 28

• Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined

  Day 8,15,29,week 6, 8, 10, 12, 16, 20, 24, 28

• Magnetic Resonance Imaging (MRI) Inflammatory Scores at Baseline, Week 6 in Part 1

  Baseline, week 6, week 28

• Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1

  Week 28

• Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1 and 2

  Week 28

Study Arms (5)

Part 1 - AIN457A 10 mg/kg

EXPERIMENTAL

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

Biological: AIN457

Part 1 - Placebo

PLACEBO COMPARATOR

Placebo to AIN457A was administered intravenously as a single dose

Drug: Placebo

Parts 1 and 2 - AIN457A 1.0 mg/kg

EXPERIMENTAL

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.

Biological: AIN457

Part 1 and 2 - AIN457 0.1 mg/kg

EXPERIMENTAL

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.

Biological: AIN457

Part 1 and 2 - AIN457 10 mg/kg

EXPERIMENTAL

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.

Biological: AIN457

Interventions

AIN457 BIOLOGICAL

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

Part 1 - AIN457A 10 mg/kg; Part 1 and 2 - AIN457 0.1 mg/kg; Part 1 and 2 - AIN457 10 mg/kg; Parts 1 and 2 - AIN457A 1.0 mg/kg

Placebo DRUG

Placebo to AIN457

Part 1 - Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (20)

Novartis Investigative Site

Paradise Valley, Arizona, 85253, United States

Location

Novartis Investigative Site

Springfield, Illinois, 62703, United States

Location

Novartis Investigative Site

Springfield, Illinois, 62704, United States

Location

Novartis Investigative Site

Oklahoma City, Oklahoma, 73112, United States

Location

Novartis Investigative Site

Duncansville, Pennsylvania, 16635, United States

Location

Novartis Investigative Site

North Charleston, South Carolina, 29406, United States

Location

Novartis Investigative Site

Jackson, Tennessee, 38305, United States

Location

Novartis Investigative Site

Knoxville, Tennessee, 37909, United States

Location

Novartis Investigative Site

Benbrook, Texas, 76126, United States

Location

Novartis Investigative Site

Spokane, Washington, 99204, United States

Location

Novartis Investigative Site

Berlin, State of Berlin, 12200, Germany

Location

Novartis Investigative Site

Hamburg, 22081, Germany

Location

Novartis Investigative Site

Herne, 44649, Germany

Location

Novartis Investigative Site

München, D-80639, Germany

Location

Novartis Investigative Site

Meerssen, KR, 6231, Netherlands

Location

Novartis Investigative Site

Amsterdam, 22700, Netherlands

Location

Novartis Investigative Site

Maastricht, 5800, Netherlands

Location

Novartis Investigative Site

Leeds, LS7 4SA, United Kingdom

Location

Novartis Investigative Site

Newcastle upon Tyne, NE2 4HH, United Kingdom

Location

Novartis Investigative Site

Oxford, OX3 7LD, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 26248638 DERIVED

• 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.

  PMID: 24035250 DERIVED

MeSH Terms

Conditions

Spondylitis, Ankylosing

Interventions

secukinumab

Condition Hierarchy (Ancestors)

Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Results Point of Contact

• Title: Study Director
• Organization: Novartis

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2008
• First Posted: December 17, 2008
• Study Start: March 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: December 9, 2015
• Results First Posted: September 18, 2015

Record last verified: 2015-08

Locations

US (10); DE (4); GB (3); NL (3)