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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Biological: AIN457A


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AIN457<br> | Biological: AIN457A<br> <br> |

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ankylosing spondylitis, IgG1K monoclonal antibody, Interleukin -17A neutralizing