Extension Study to Assess Effects of Non-interrupted Versus Interrupted and Long Term Treatment of Two Dose Regimes of Secukinumab in Subjects With Hidradenitis Suppurativa

Study Overview
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Brief Summary
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The purpose of this extension study is to evaluate maintenance of HiSCR response at Week 104 in either continuous or interrupted therapy (using a randomized withdrawal period) of two dose regimens and to assess long-term efficacy, safety and tolerability of secukinumab in subjects with moderate to severe hidradenitis suppurativa completing either of the 2 Phase III studies. This is an expanded access trial for the core trials AIN457M2301 (NCT03713619) and AIN457M2302 (NCT03713619).

Detailed Description
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This is a multicenter extension study to both core Phase III studies CAIN457M2301 and CAIN457M2302 (Core studies). This study contains a randomized withdrawal design, double blinded and placebo controlled up to Week 104 or loss of response. The subjects with HiSCR response after 52 weeks of treatment in the Core studies will be randomized at 2:1 ratio to either continue on one of the two secukinumab dosing regimens assigned in Core studies for another 52 weeks or will be placed on placebo. The primary endpoint is loss of response (LOR) assessed during the 52-week treatment duration (up to Week 104). Subjects who attained LOR will be transferred to open-label treatment to continue until the end of the study. Subjects on placebo who did not reach LOR up to Week 104 will be offered to continue in the open-label treatment or discontinue the study. Thus for subjects who were HiSCR responders at Week 52 of Core studies, the open label treatment duration will vary and start either from the time of LOR or from Week 104 dose and last until Week 260 followed by 8 weeks of a post treatment follow-up period to week 268. Subjects who were HiSCR non-responders at the end of Core studies will be offered to continue in open-label treatment until Week 260. Subjects who prematurely discontinue the study, or who complete the study will enter a post-treatment follow up period (8 weeks) The primary objective is to evaluate maintenance of HiSCR reponse at Week 104 in either continuous or interrupted therapy compared to placebo. Secondary objectives are to assess the long-term safety and tolerability evaluated by adverse events, abnormal laboratory values and vital signs.

Official Title
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A Multicenter, Double-blind, Randomized Withdrawal Extension Study of Subcutaneous Secukinumab to Demonstrate Long-term Efficacy, Safety and Tolerability in Subjects With Moderate to Severe Hidradenitis Suppurativa

Conditions
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Hidradenitis Suppurativa

Intervention / Treatment
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* Drug: secukinumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written informed consent must be obtained before any assessment is performed subject must have completed the study treatment period (52 weeks) in the core studies (AIN457M2301 or AIN457M2302)and have been receiving secukinumab treatment during Treatment Period 2 Exclusion Criteria: protocol deviation in the core study which will prevent the meaningful analysis of the extension study ongoing or planned use of prohibited HS or non-HS treatment participation in the extension could expose the subject to an undue safety risk current sever progressive or uncontrolled disease which renders the subject unsuitable for the study.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, double-blind, randomized withdrawal extension, parallel group study followed by an open-label, active-treatment period with two secukinumab dose regimens in approximately 856 patients with moderate to severe HS
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: secukinumab 1 HiSCR Responder<br>HiSCR responder in core trial, secukinumab 300mg every 2 weeks | Drug: secukinumab<br>* secukinumab 300mg every 2 or every 4 weeks<br>* Other names: AIN457;|
| Active Comparator: secukinumab 2 HiSCR Responder<br>HiSCR responder in core trial, secukinumab 300mg every 4 weeks | Drug: secukinumab<br>* secukinumab 300mg every 2 or every 4 weeks<br>* Other names: AIN457;|
| Placebo Comparator: placebo 1 HiSCR Responder<br>HiSCR responder in core trial, placebo to secukinumab 300mg every 2 weeks | Drug: secukinumab<br>* secukinumab 300mg every 2 or every 4 weeks<br>* Other names: AIN457;|
| Placebo Comparator: placebo 2 HiSCR Responder<br>HiSCR responder in core trial, placebo to secukinumab 300 mg every 4 weeks | Drug: secukinumab<br>* secukinumab 300mg every 2 or every 4 weeks<br>* Other names: AIN457;|
| Active Comparator: HiSCR non-responders<br>non-responder to core trial treatment; secukinumab 300mg every 2 weeks | Drug: secukinumab<br>* secukinumab 300mg every 2 or every 4 weeks<br>* Other names: AIN457;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to loss of response (LOR) in HiSCR reponders | Loss of response is defined as: at least a 50% increase in abscess and/or nodules count (AN) compared to the average AN count from the 3 previous visits and the increase was at least of 3 AN from the average AN count of the 3 previous visits. at least a 30% increase in AN compared to the average AN count from the 3 previous visits with an increase of at least 2 AN from the average count of the 3 previous visits or a further increase in the AN count of at least 2 AN . | Weeks 52 - 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative rate of subjects who experience a flare in core HiScr responders | Subjects who experience at least one flare by Week 104. flare is defined as at least a 25% increase in AN count with a minimum increase of 2 AN relative to baseline. | Week 104 | 
| subjects achieving NRS30 | HS-related skin pain; subjects achieving NRS30 at week 104, defined as at least a 30% reduction and at least one unit reduction from baseline in the subject's Global Assessment of Skin Pain | Week 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acne inversa, Hidradenitis suppurativa, maladie de Vemeuil, inflammatory disease, AIN457, AIN457M, secukinumab, Loss of response, HiSCR, IL-17A