A Study to Test Whether Spesolimab Helps People With a Skin Disease Called Netherton Syndrome

Study Overview
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Brief Summary
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This study is open to people with a skin disease called Netherton syndrome (NS). People can join the study if they are 12 years and older. The purpose of this study is to find out whether a medicine called spesolimab helps people with NS. Participants are divided into a spesolimab and a placebo group. Placebo injections look like spesolimab injections but do not contain any medicine. Every participant has a 2 in 3 chance of being in the spesolimab group. In the beginning, participants get the study medicine as an injection into a vein. Afterwards, they get it as an injection under the skin every month. After 4 months, participants in the placebo group switch to spesolimab treatment. Participants are in the study for about 1 year. During this time, they visit the study site 16 times. Where possible, 4 of 16 visits can be done at the participant's home instead of the study site. The doctors regularly check participants' NS symptoms. The results are compared between the groups to see whether spesolimab works. The doctors also regularly check participants' general health and take note of any unwanted effects.

Official Title
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EvasayilTM : A Placebo-controlled Trial to Evaluate the Efficacy and Safety of Spesolimab in the Treatment of Patients With Netherton Syndrome

Conditions
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Netherton Syndrome

Intervention / Treatment
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* Drug: Spesolimab - solution for infusion
* Drug: Placebo matching to spesolimab - solution for infusion
* Drug: Spesolimab - solution for injection
* Drug: Placebo matching to spesolimab - solution for injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients, aged 12 years and older (weight minimum is 35kg). Confirmed diagnosis of Netherton syndrome (NS) (causative SPINK5 mutations) at baseline (Visit 2). At least moderate severity of erythema at baseline (visit 2) (Ichthyosis Area Severity Index (IASI) score ≥ 16 and IASI-Erythema (E) score ≥8) and ≥ 3 on Investigator Global Assessment (IGA) score. Signed and dated written informed consent and assent in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission in the trial Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the clinical trial protocol (CTP) as well as in the patient, parent(s) (or patient's legal guardian) information. Exclusion Criteria: Patients who have used topical corticosteroids (medium to high, US class I-V), topical retinoids, topical calcineurin inhibitors or keratolytics within 1 week prior to randomisation Patients who have used emollient on the area to be biopsied in the previous 24 hours Patients who have used systemic retinoids, other systemic immunosuppressants, systemic corticosteroids or phototherapy within 4 weeks prior to randomisation Patients who have used systemic antibiotics within 2 weeks prior to randomisation Patients who have received live vaccines within 4 weeks prior to randomisation Patients who have received investigational products, biologics or immunoglobulins within 4 weeks or 5 half-lives (whichever is longer) prior to randomisation Severe, progressive, or uncontrolled hepatic disease, defined as >3-fold Upper Limit of Normal (ULN) elevation in Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) or alkaline phosphatase, or >2-fold ULN elevation in total bilirubin Patients who have any prior exposure to BI 655130 or another interleukin 36 receptor (IL-36R) inhibitor biologics Further exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 12 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Spesolimab - solution for infusion<br>* Solution for infusion<br>* Other names: BI 655130;Drug: Placebo matching to spesolimab - solution for infusion<br>* Solution for infusion<br>Drug: Spesolimab - solution for injection<br>* Solution for injection<br>* Other names: BI 655130;Drug: Placebo matching to spesolimab - solution for injection<br>* Solution for injection<br>|
| Experimental: Spesolimab<br> | Drug: Spesolimab - solution for infusion<br>* Solution for infusion<br>* Other names: BI 655130;Drug: Placebo matching to spesolimab - solution for infusion<br>* Solution for infusion<br>Drug: Spesolimab - solution for injection<br>* Solution for injection<br>* Other names: BI 655130;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IASI response | Ichthyosis Area Severity Index (IASI) response is defined as a decrease of at least 50 % absolute change in IASI score from baseline at Week 16. | At baseline and at Week 16. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Key secondary endpoint: IGA response | Investigator Global Assessment (IGA) | at Week 16. | 
| IGA response | Investigator Global Assessment (IGA) | up to Week 12. | 
| Occurrence of bacterial or fungal mucocutaneous infection |  | up to Week 16. | 
| IASI response | Ichthyosis Area Severity Index (IASI) | At baseline and up to Week 12. | 
| IASI subscore response | Ichthyosis Area Severity Index (IASI) | At baseline and up to Week 12. | 
| Percent change from baseline in IASI score | Ichthyosis Area Severity Index (IASI) | At baseline and up to Week 16. | 
| Percent change from baseline in NASA score | Netherton Area Severity Assessment Score (NASA) | At baseline and up to Week 16. | 
| Absolute change from baseline in NRS pain | The Numeric Pain Rating Scale (NRS) | At baseline and up to Week 16. | 
| Absolute change from baseline in NRS itch | The Numeric Rating Scale (NRS) | At baseline and up to Week 16. | 
| Absolute change from baseline in DLQI/CDLQI score | Dermatology Life Quality Index (DLQI)/Children Dermatology Life Quality Index (CDLQI) | At baseline and up to Week 16. | 
| The occurrence of treatment emergent adverse events |  | up to Week 68. |