Safety and Tolerability of AIN457 in Adults (18-65 Years) With Moderate to Severe Ankylosing Spondylitis

An Open Label Non-randomized Extension Study to Evaluate the Safety and Tolerability of AIN457 (Anti Interleukin-17 Monoclonal Antibody) in Patients With Moderate to Severe Ankylosing Spondylitis

This study is designed as an extension study to the proof-of-concept trial CAIN457A2209 in patients with moderate to severe ankylosing spondylitis and aims to provide continuous treatment with AIN457 for patients in the core trial, to obtain safety and tolerability information. The study will address the evaluation of efficacy following doses of Intravenous infusion (IV) of 3 mg/kg AIN457 given every 4 weeks over a period initially up to 6 months (Part 1) and based on the risk/benefit balance of AIN457 in ankylosing spondylitis a decision was taken to continue dosing for another 6 month period (Part 2).

Study Overview

• Status: Completed
• Conditions: Ankylosing Spondylitis
• Intervention / Treatment: Biological: AIN457A

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12203
    • Novartis Investigative Site
  • Hamburg, Germany, 22081
    • Novartis Investigative Site
  • Herne, Germany, 44625
    • Novartis Investigative Site
  • Munchen, Germany, D-80639
    • Novartis Investigative Site
• Netherlands
  • DE
    • Amsterdamn, DE, Netherlands, 1100
      • Novartis Investigative Site
• United Kingdom
  • Newcastle upon Tyne, United Kingdom, NE2 4HH
    • Novartis Investigative Site
• United States
  • Arizona
    • Paradise Valley, Arizona, United States, 85253
      • Novartis Investigative Site
  • Illinois
    • Springfield, Illinois, United States, 62704
      • Novartis Investigative Site
    • Springfield, Illinois, United States, 62703
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Novartis Investigative Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Novartis Investigative Site
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Novartis Investigative Site
    • Knoxville, Tennessee, United States, 37909
      • Novartis Investigative Site
  • Texas
    • Benbrook, Texas, United States, 76126
      • Novartis Investigative Site
  • Washington
    • Spokane, Washington, United States, 99204
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who took part and completed in the core CAIN457A2209 study
• Patients who discontinued the core study due to unsatisfactory therapeutic effect at their Visit 14 (Week 16) or later could enter the extension study within 3 weeks of completing the study discontinuation visit of the core study, provided that at their discontinuation visit they fulfilled either one of the criteria below. Patients who did not enter the extension study within 3 weeks of completing the study discontinuation visit of the core study, were required to come for an additional baseline visit (Visit 17) and were required to fulfill either one of the criteria below:
• No improvement (compared with the core study baseline) in two out of the following four domains: patient global assessment, pain, BASFI and the mean of the two morning stiffness questions from the BASDAI. OR
• Deterioration (compared with the core study baseline) in one of the four domains (deterioration defined as >=20% worsening and an absolute worsening of >=1 unit)

Exclusion Criteria:

• Patients for whom continued treatment with AIN457 is not considered appropriate by the treating physician.
• Patients who were non-compliant or who demonstrated a major protocol deviation in the core CAIN457A2209 study.
• Patients who discontinued from the core CAIN457A2209 study before Visit 14 (Week 16), and patients who completed the core study
• Pregnant or lactating women
• Presence of active infection
• Positive PPD or HIV test in patients where repeated testing was deemed appropriate due to their risk profile

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AIN457	Biological: AIN457A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reported Adverse Events (AE's)	AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen.	From start of the study up to 64 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reported Positive Antibodies for Secukinumab	Immunogenicity (anti-drug antibodies) was assessed using an MSD bridging assay and a 3-tiered approach (screening, confirmation, titration).	Pre-dose, Week 0, 8, 24, 40 and Week 64
Total Interleukin (IL)- 17A Concentration in Blood at Steady-State	Total serum IL17A was not measured due to assay limitations.	Pre-dose and at the end of infusion (up to 64 weeks)
Maximum (Peak) Observed in Serum at Steady-State (Cmax,ss)	Concentration of Secukinumab at the end of infusion (Cmax,ss) was reported.	At end of infusion (Week 64)
Minimum (Trough) Observed in Serum at Steady State (Cmin,ss)	The concentration of secukinumab at pre-dose (Cmin,ss) in serum was reported.	Pre-dose (Week 0)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: April 22, 2010
• First Submitted That Met QC Criteria: April 22, 2010
• First Posted (Estimate): April 23, 2010

Study Record Updates

• Last Update Posted (Actual): June 24, 2021
• Last Update Submitted That Met QC Criteria: June 2, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Ankylosing spondylitis; IgG1K monoclonal antibody; Interleukin -17A neutralizing
• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing
• Other Study ID Numbers: CAIN457A2209E1; 2009-011591-30