Lunsayil 1: A Study to Test Whether Spesolimab Helps People With a Skin Disease Called Hidradenitis Suppurativa

Study Overview
=================
Brief Summary
-----------------
This study is open to adults with moderate to severe hidradenitis suppurativa (HS). The purpose of this study is to find out whether a medicine called spesolimab helps people with HS. People who have previously taken specific medicines such as immunosuppressive biologics other than Tumor necrosis factor (TNF) inhibitors cannot take part. This study has 2 parts. In Part 1, participants are divided into 4 groups of almost equal size. 3 groups get different doses of spesolimab, 1 group gets placebo. All participants get injections into a vein or under the skin. Placebo injections look like spesolimab injections, but do not contain any medicine. Every participant has an equal chance of being in each group. In the beginning, participants get the study medicine every week and later every 2 weeks. After 4 months, participants in the placebo group switch to spesolimab treatment. In Part 2, participants are divided into 2 groups. One group gets a suitable dose of spesolimab that was found in Part 1 of the study. The other group gets placebo. After 4 months, participants in the placebo group switch to spesolimab treatment. Participants join only one of the two parts. They are in the study for about 1 year. During this time, they visit the study site in the beginning every week and later every 2 weeks. Some of the visits can be done at the participant's home instead of the study site. The doctors regularly check participants' HS 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.

Detailed Description
-----------------
Main endpoints for Part 2 will be supported by Part 1 results available at time of primary analysis.

Official Title
-----------------
Randomised, Double-blind, Placebo-controlled, Phase IIb/Phase III Study to Evaluate the Efficacy and Safety of Spesolimab in Patients With Moderate to Severe Hidradenitis Suppurativa. Lunsayil 1.

Conditions
-----------------
Hidradenitis Suppurativa

Intervention / Treatment
-----------------
* Drug: Spesolimab Formulation 1
* Drug: Spesolimab Formulation 2
* Drug: Placebo matching Spesolimab Formulation 1
* Drug: Placebo matching Spesolimab Formulation 2


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Of full age of consent at screening. Signed and dated written informed consent in accordance with International Council on Harmonisation-Good clinical practice (ICH-GCP) and local legislation prior to admission to the trial. Moderate to severe HS. HS lesions in at least 2 distinct anatomic areas. Biologic naive or Tumor Necrosis Factor inhibitor (TNFi)-exposed for HS. For biologic naïve, inadequate response to an adequate course of appropriate oral antibiotics for treatment of HS in the last 1 year prior to the Baseline visit, as per investigator discretion. All participants must have previous exposure to antibiotics for HS. Total AN count of greater than or equal to 5. Total dT count of at least 1 at Baseline visit. Further inclusion criteria apply. Exclusion Criteria: Participants who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial. Prior exposure to any immunosuppressive/immunomodulatory biologic other than TNFi for HS. Prior exposure to Interleukin 36 receptor (IL-36R) inhibitors including spesolimab. Treated with any investigational device or investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives of the drug, whichever is longer. Women who are pregnant, nursing, or who plan to become pregnant while in the trial. Participants with history of allergy/hypersensitivity to the systemically administered trial medication agent or its excipients. Participants with a transplanted organ (with exception of a corneal transplant >12 weeks prior to screening) or who has ever received stem cell therapy (e.g., Remestemcel-L). Participants with any documented active or suspected malignancy or history of malignancy within 5 years prior to the screening visit, except appropriately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ carcinoma of uterine cervix. Further exclusion criteria apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part I: Low dose group<br> | Drug: Spesolimab Formulation 1<br>* Spesolimab Formulation 1<br>* Other names: Spevigo®;Drug: Spesolimab Formulation 2<br>* Spesolimab Formulation 2<br>* Other names: Spevigo®;|
| Experimental: Part I: Medium dose group<br> | Drug: Spesolimab Formulation 1<br>* Spesolimab Formulation 1<br>* Other names: Spevigo®;Drug: Spesolimab Formulation 2<br>* Spesolimab Formulation 2<br>* Other names: Spevigo®;|
| Experimental: Part I: High dose group<br> | Drug: Spesolimab Formulation 1<br>* Spesolimab Formulation 1<br>* Other names: Spevigo®;Drug: Spesolimab Formulation 2<br>* Spesolimab Formulation 2<br>* Other names: Spevigo®;|
| Placebo Comparator: Part I: Placebo group<br> | Drug: Placebo matching Spesolimab Formulation 1<br>* Placebo matching Spesolimab Formulation 1<br>Drug: Placebo matching Spesolimab Formulation 2<br>* Placebo matching Spesolimab Formulation 2<br>|
| Experimental: Part II: Active (treatment) group<br> | Drug: Spesolimab Formulation 2<br>* Spesolimab Formulation 2<br>* Other names: Spevigo®;|
| Placebo Comparator: Part II: Placebo group<br> | Drug: Placebo matching Spesolimab Formulation 2<br>* Placebo matching Spesolimab Formulation 2<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Percent change from baseline in Draining fistula/tunnel (dT) count at Week 8 |  | At baseline and at week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Percent change from baseline in dT count at Week 16 (part 1) |  | At baseline and at week 16 | 
| Part 1: Absolute change from baseline in International hidradenitis suppurativa severity score system (IHS4) value at Week 8 | The IHS4 score is arrived at by the number of nodules (multiplied by 1) plus the number of abscesses (multiplied by 2) plus the number of draining tunnels (multiplied by 4). A total score of 3 or less signifies mild, 4-10 signifies moderate and 11 or higher signifies severe disease. | At baseline and at week 8 | 
| Part 1: Absolute change from baseline in IHS4 value at Week 16 |  | At baseline and at week 16 | 
| Part 1: Occurrence of treatment emergent adverse events (TEAEs) |  | up to 64 weeks |