A Study to Test How Effective and Safe Different Doses of BI 655130 Are in Patients With a Moderate to Severe Form of the Skin Disease Palmoplantar Pustulosis

Study Overview
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Brief Summary
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The primary objective is to provide dose-ranging data for 4 dose regimens of BI 655130 compared to placebo on the primary endpoint of percentage change from baseline in PPP ASI at Week 16. The target dose(s) will be estimated from the model by incorporating information on the minimum clinically relevant effect and accounting for safety. Supportive dose-ranging assessments will also be done on pre-specified secondary endpoints.

Official Title
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Multi-center, Double-blind, Randomised, Placebo-controlled, Phase IIb Dose-finding Study to Evaluate Safety and Efficacy of Different Subcutaneous Doses of BI 655130 in Patients With Moderate to Severe Palmoplantar Pustulosis (PPP)

Conditions
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Palmoplantar Pustulosis (PPP)

Intervention / Treatment
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* Drug: Spesolimab
* Drug: Placebo
* Drug: Spesolimab
* Drug: Spesolimab
* Drug: Spesolimab
* Drug: Spesolimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 75 years of legal age (according to local legislation) at screening. Diagnosis of Palmoplantar Pustulosis defined as presence of primary, persistent (>3 months duration), sterile, macroscopically visible pustules on the palms and/or soles, without or with plaque psoriasis elsewhere on the body. PPP PGA of at least moderate severity (≥3) at screening and baseline. A minimum PPP ASI score of 12 at screening and baseline. Male or female patients. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2). Signed and dated written informed consent in accordance with ICH GCP and local legislation prior to admission to the trial. Further criteria apply. Exclusion Criteria: Women who are pregnant, nursing, or who plan to become pregnant while in the trial. Severe, progressive, or uncontrolled condition such as renal, hepatic, haematological, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease, or signs and symptoms thereof. Presence or known history of anti-TNF-induced PPP-like disease. Patient with a transplanted organ (with exception of a corneal transplant >12 weeks Prior to screening) or who have ever received stem cell therapy (e.g., Prochymal). Known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly. Further criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Other: Placebo & Spesolimab<br>Subcutaneous injections of placebo matching Spesolimab, with subcutaneous injections of Spesolimab starting at week 16, for a total treatment time of 52 weeks. | Drug: Spesolimab<br>* Subcutaneous injections of Spesolimab starting at week 16, for a total treatment time until week 52.<br>Drug: Placebo<br>* Subcutaneous injections of placebo matching Spesolimab from week 0 to 16.<br>|
| Experimental: Spesolimab 'Speso Low'<br>Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks. | Drug: Spesolimab<br>* Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.<br>|
| Experimental: Spesolimab 'Speso Medium-low'<br>Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks. | Drug: Spesolimab<br>* Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.<br>|
| Experimental: Spesolimab 'Speso Medium-high'<br>Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks. | Drug: Spesolimab<br>* Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.<br>|
| Experimental: Spesolimab 'Speso High'<br>Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks. | Drug: Spesolimab<br>* Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 16 From Baseline | The percentage change in PPP ASI at Week 16 from baseline. The PPP ASI is a tool that provides a numeric scoring for patients overall PPP disease state, ranging from 0 (best) to 72 (worst). It is a linear combination of the percent of surface area of skin that is affected on the palms and soles of the body and the severity of erythema, pustules, and scaling (desquamation): The percent change from baseline is calculated as (PPP ASI current - PPP ASI baseline) / PPP ASI baseline * 100%. Least square (LS) means, differences and confidence intervals were estimated by (Restricted maximum likelihood)-based Mixed effect model for repeated measurements (MMRM) including the fixed, categorical effects of treatment at each visit, region and the continuous effect of baseline at each visit as well as random effects of subject. Values post rescue medication or 6 weeks following last study treatment before discontinuation were censored. Unstructured covariance matrix was used. | week 0 (baseline) and week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 4 | Change from baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) score at Week 4. The PPP Pain VAS is a unidimensional measure of pain intensity due to palmoplantar pustulosis on palms and/or soles. It is a continuous scale comprised of a horizontal or vertical line, 10 centimeters (cm) in length, anchored by word descriptors at each end (score ranges from no pain at 0 cm to very severe pain at 10 cm). The patient was asked to place a vertical ( | ) mark on the horizontal line to indicate the severity of the pain. Least square (LS) means, differences and confidence intervals were estimated by (Restricted maximum likelihood)-based MMRM including the fixed, categorical effects of treatment at each visit, region and the continuous effect of baseline at each visit as well as random effects of subject. Values post rescue medication or 6 weeks following last study treatment before discontinuation were censored. Unstructured covariance matrix was used. | week 0 (baseline) and week 4. | 
| Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 16 | Change from baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) score at Week 16. The PPP Pain VAS is a unidimensional measure of pain intensity due to palmoplantar pustulosis on palms and/or soles. It is a continuous scale comprised of a horizontal or vertical line, 10 centimeters (cm) in length, anchored by word descriptors at each end (score ranges from no pain at 0 cm to very severe pain at 10 cm). The patient was asked to place a vertical ( | ) mark on the horizontal line to indicate the severity of the pain. Least square (LS) means, differences and confidence intervals were estimated by (Restricted maximum likelihood)-based MMRM including the fixed, categorical effects of treatment at each visit, region and the continuous effect of baseline at each visit as well as random effects of subject. Values post rescue medication or 6 weeks following last study treatment before discontinuation were censored. Unstructured covariance matrix was used. | week 0 (baseline) and week 16. | 
| Palmoplantar Pustulosis Severity Index (PPP SI) Change From Baseline at Week 16 | PPP SI change from baseline at Week 16. The PPP SI is based on the severity score of individual components (erythema, pustules, and scaling/desquamation) of PPP ASI assessments. The most severely affected area based on pustules was identified by the investigator at baseline and assessed at all subsequent visits. The PPP SI was calculated by summing up the individual components of PPP ASI assessment (range 0 (best) to 12 (worst)) at each visit for the identified location. Least square (LS) means, differences and confidence intervals were estimated by (Restricted maximum likelihood)-based Mixed effect model for repeated measurements (MMRM) including the fixed, categorical effects of treatment at each visit, region and the continuous effect of baseline at each visit as well as random effects of subject. Values post rescue medication or 6 weeks following last study treatment before discontinuation were censored. Unstructured covariance matrix was used. | week 0 (baseline) and week 16. | 
| Number of Patients Achieving a 50% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI50) | Number of patients achieving a 50% decrease from baseline in Palmoplantar Pustulosis Area and Severity Index score at week 16 (PPP ASI50). The PPP ASI is an investigator assessment of the extent and severity of palmoplantar pustulosis lesions on the palms and soles in PPP patients. This tool provides a numeric scoring for patients overall PPP disease state, ranging from 0 (best) to 72 (worst). It is a linear combination of the percent of surface area of skin that is affected on the palms and soles of the body and the severity of erythema, pustules, and scaling (desquamation). When (PPP ASI baseline - PPP ASI current)/ PPP ASI baseline * 100% >= 50%, PPP ASI50 = 1. | week 0 (baseline) and week 16 | 
| Number of Patients Achieving a 75% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI75) | Number of patients achieving a 75% decrease from baseline in Palmoplantar Pustulosis Area and Severity Index score at week 16 (PPP ASI75). The PPP ASI is an investigator assessment of the extent and severity of palmoplantar pustulosis lesions on the palms and soles in PPP patients. This tool provides a numeric scoring for patients overall PPP disease state, ranging from 0 (best) to 72 (worst). It is a linear combination of the percent of surface area of skin that is affected on the palms and soles of the body and the severity of erythema, pustules, and scaling (desquamation). When (PPP ASI baseline - PPP ASI current)/ PPP ASI baseline * 100% >= 75%, PPP ASI75 = 1. | week 0 (baseline) and week 16 | 
| Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Clear/Almost Clear (0 or 1) at Week 16 | Number of patients with Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) clear/almost clear (0 or 1) at Week 16. The PPP PGA relies on investigator assessment of the patient's skin presentation on the palms and soles. The investigator scored the individual components (erythema, pustules, and scaling/crusting) from 0 (best) to 4 (worst) as clear, almost clear, mild, moderate or severe. PPP PGA categorization is based on the mean of the four individual components. | week 0 (baseline) and week 16 | 
| Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Pustules Clear/Almost Clear (0 or 1) at Week 16 | Number of patients with Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) pustules clear/almost clear (0 or 1) at Week 16. The PPP PGA relies on investigator assessment of the patient's skin presentation on the palms and soles. The investigator scored the pustules from 0 (best) to 4 (worst) as clear, almost clear, mild, moderate or severe. | week 0 (baseline) and week 16 | 
| The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 52 From Baseline | The percentage change in PPP ASI at Week 52 from baseline. The PPP ASI is an investigator assessment of the extent and severity of palmoplantar pustulosis lesions on the palms and soles in PPP patients. This tool provides a numeric scoring for patients overall PPP disease state, ranging from 0 (best) to 72 (worst). It is a linear combination of the percent of surface area of skin that is affected on the palms and soles of the body and the severity of erythema, pustules, and scaling (desquamation). LS means, differences and confidence intervals were estimated by (Restricted maximum likelihood)-based MMRM including the fixed, categorical effects of treatment at each visit, region and the continuous effect of baseline at each visit as well as random effects of subject. Values post rescue medication or 6 weeks following last study treatment before discontinuation were censored. Unstructured covariance matrix was used. | week 0 (baseline) and week 52 |