Palmoplantar Pustulosis (PPP)
Conditions
Brief summary
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.
Interventions
DRUGSpesolimab
Subcutaneous injections of Spesolimab starting at week 16, for a total treatment time until week 52.
DRUGPlacebo
Subcutaneous injections of placebo matching Spesolimab from week 0 to 16.
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 16 From Baseline | week 0 (baseline) and week 16 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 16 | week 0 (baseline) and 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. |
| Palmoplantar Pustulosis Severity Index (PPP SI) Change From Baseline at Week 16 | week 0 (baseline) and 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. |
| Number of Patients Achieving a 50% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI50) | 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). 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. |
| Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 4 | week 0 (baseline) and 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. |
| Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Clear/Almost Clear (0 or 1) at Week 16 | 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. 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. |
| Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Pustules Clear/Almost Clear (0 or 1) at Week 16 | 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. 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. |
| The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 52 From Baseline | week 0 (baseline) and week 52 | 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. |
| Number of Patients Achieving a 75% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI75) | 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). 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. |
Countries
Australia, Belgium, Canada, Czechia, France, Germany, Hungary, Japan, Netherlands, Poland, Russia, South Korea, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
This was a randomised, placebo-controlled, double-blind, parallel-design trial comparing 5 treatment arms over 52 weeks. Randomisation was stratified for Japan versus non-Japan. Patients who completed the treatment period without premature discontinuation and obtained an individual health benefit, per investigator judgement, could continue treatment with spesolimab in the open-label extension trial 1368-0024.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo & Spesolimab Subcutaneous injections of placebo matching Spesolimab, with subcutaneous injections of Spesolimab starting at week 16, for a total treatment time of 52 weeks. | 43 |
| Spesolimab 'Speso Low' Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks. | 22 |
| Spesolimab 'Speso Medium-low' Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks. | 21 |
| Spesolimab 'Speso Medium-high' Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks. | 22 |
| Spesolimab 'Speso High' Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks. | 44 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 1 | 1 | 3 | 3 |
| Overall Study | Could not keep appointments due to work | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Difficult for patient to come to the hospital | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 | 1 | 0 | 4 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
| Overall Study | not willing to travel due to Covid-19 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Patient did not come for consecutive visits | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Patient wants to discontinue treatment | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Personal reasons | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Prostate carcinoma | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 1 | 1 |
| Overall Study | Withdrew consent | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo & Spesolimab | Spesolimab 'Speso Low' | Spesolimab 'Speso Medium-low' | Spesolimab 'Speso Medium-high' | Spesolimab 'Speso High' | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 10.1 | 54.2 years STANDARD_DEVIATION 12.3 | 51.6 years STANDARD_DEVIATION 7.9 | 52.8 years STANDARD_DEVIATION 9.2 | 53.4 years STANDARD_DEVIATION 13 | 54.4 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 20 Participants | 19 Participants | 21 Participants | 41 Participants | 141 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 11 Participants |
| Palmoplantar Pustulosis Area and Severity Index (PPP ASI) | 27.07 Score on a scale STANDARD_DEVIATION 12.44 | 23.85 Score on a scale STANDARD_DEVIATION 9.42 | 23.62 Score on a scale STANDARD_DEVIATION 11.02 | 26.65 Score on a scale STANDARD_DEVIATION 11.2 | 24.00 Score on a scale STANDARD_DEVIATION 10.25 | 25.18 Score on a scale STANDARD_DEVIATION 11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 9 Participants | 9 Participants | 9 Participants | 15 Participants | 60 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 11 Participants |
| Race (NIH/OMB) White | 21 Participants | 11 Participants | 10 Participants | 12 Participants | 26 Participants | 80 Participants |
| Sex: Female, Male Female | 35 Participants | 15 Participants | 16 Participants | 17 Participants | 27 Participants | 110 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 5 Participants | 5 Participants | 17 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 38 | 0 / 22 | 0 / 21 | 0 / 22 | 0 / 44 |
| other Total, other adverse events | 24 / 43 | 22 / 38 | 17 / 22 | 17 / 21 | 17 / 22 | 31 / 44 |
| serious Total, serious adverse events | 2 / 43 | 3 / 38 | 3 / 22 | 5 / 21 | 3 / 22 | 3 / 44 |
Outcome results
Primary
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.
Time frame: week 0 (baseline) and week 16
Population: Full Analysis Set (FAS): This patient set includes all patients who were randomised and received at least one dose of study drug. Only subjects with non missing endpoint data were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 16 From Baseline | -33.6 Percentage of change in PPP ASI |
| Spesolimab 'Speso Low' | The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 16 From Baseline | -44.2 Percentage of change in PPP ASI |
| Spesolimab 'Speso Medium-low' | The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 16 From Baseline | -48.3 Percentage of change in PPP ASI |
| Spesolimab 'Speso Medium-high' | The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 16 From Baseline | -46.2 Percentage of change in PPP ASI |
| Spesolimab 'Speso High' | The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 16 From Baseline | -38.9 Percentage of change in PPP ASI |
p-value: 0.217995% CI: [-27.4, 6.3]Mixed Models Analysis
p-value: 0.088395% CI: [-31.5, 2.2]Mixed Models Analysis
p-value: 0.141495% CI: [-29.4, 4.3]Mixed Models Analysis
p-value: 0.451495% CI: [-19.1, 8.6]Mixed Models Analysis
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.212MCP-Mod linear model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.1057MCP-Mod Emax model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.5241MCP-Mod Exponential model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.2773MCP-Mod Logistic model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.3867MCP-Mod Sigmoid Emax model fit
Secondary
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.
Time frame: week 0 (baseline) and week 16.
Population: Full Analysis Set (FAS): This patient set includes all patients who were randomised and received at least one dose of study drug. Only subjects with non missing endpoint data were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 16 | -14.7 Score on a scale |
| Spesolimab 'Speso Low' | Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 16 | -18.7 Score on a scale |
| Spesolimab 'Speso Medium-low' | Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 16 | -13.8 Score on a scale |
| Spesolimab 'Speso Medium-high' | Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 16 | -18.9 Score on a scale |
| Spesolimab 'Speso High' | Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 16 | -22.4 Score on a scale |
p-value: 0.559595% CI: [-17.7, 9.6]Mixed Models Analysis
p-value: 0.896895% CI: [-12.7, 14.5]Mixed Models Analysis
p-value: 0.545695% CI: [-17.9, 9.5]Mixed Models Analysis
p-value: 0.176295% CI: [-19, 3.5]Mixed Models Analysis
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.1726MCP-Mod linear model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.2353MCP-Mod Emax model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.1346MCP-Mod Exponential model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.195MCP-Mod Logistic model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.1681MCP-Mod Sigmoid Emax model fit
Secondary
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.
Time frame: week 0 (baseline) and week 4.
Population: Full Analysis Set (FAS): This patient set includes all patients who were randomised and received at least one dose of study drug. Only subjects with non missing endpoint data were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 4 | -9.3 Score on a scale |
| Spesolimab 'Speso Low' | Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 4 | -15.4 Score on a scale |
| Spesolimab 'Speso Medium-low' | Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 4 | -14.7 Score on a scale |
| Spesolimab 'Speso Medium-high' | Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 4 | -12.8 Score on a scale |
| Spesolimab 'Speso High' | Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 4 | -18.7 Score on a scale |
95% CI: [-19.3, 7.1]
95% CI: [-18.8, 8]
95% CI: [-16.6, 9.7]
95% CI: [-20.3, 1.4]
Secondary
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.
Time frame: week 0 (baseline) and week 16
Population: Full Analysis Set (FAS): This patient set includes all patients who were randomised and received at least one dose of study drug and who had a baseline for the primary efficacy endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Patients Achieving a 50% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI50) | 12 Participants |
| Spesolimab 'Speso Low' | Number of Patients Achieving a 50% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI50) | 7 Participants |
| Spesolimab 'Speso Medium-low' | Number of Patients Achieving a 50% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI50) | 10 Participants |
| Spesolimab 'Speso Medium-high' | Number of Patients Achieving a 50% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI50) | 12 Participants |
| Spesolimab 'Speso High' | Number of Patients Achieving a 50% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI50) | 18 Participants |
95% CI: [-0.17, 0.281]
95% CI: [-0.048, 0.432]
95% CI: [0.02, 0.496]
95% CI: [-0.067, 0.314]
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0613MCP-Mod linear model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0628MCP-Mod Emax model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.1449MCP-Mod Exponential model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.046MCP-Mod Logistic model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0677MCP-Mod Sigmoid Emax model fit
Secondary
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.
Time frame: week 0 (baseline) and week 16
Population: Full Analysis Set (FAS): This patient set includes all patients who were randomised and received at least one dose of study drug and who had a baseline for the primary efficacy endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Patients Achieving a 75% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI75) | 3 Participants |
| Spesolimab 'Speso Low' | Number of Patients Achieving a 75% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI75) | 3 Participants |
| Spesolimab 'Speso Medium-low' | Number of Patients Achieving a 75% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI75) | 6 Participants |
| Spesolimab 'Speso Medium-high' | Number of Patients Achieving a 75% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI75) | 4 Participants |
| Spesolimab 'Speso High' | Number of Patients Achieving a 75% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI75) | 9 Participants |
95% CI: [-0.069, 0.256]
95% CI: [0.018, 0.405]
95% CI: [-0.042, 0.303]
95% CI: [-0.018, 0.25]
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0536MCP-Mod linear model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0476MCP-Mod Emax model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.1076MCP-Mod Exponential model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0606MCP-Mod Logistic model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0824MCP-Mod Sigmoid Emax model fit
Secondary
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.
Time frame: week 0 (baseline) and week 16
Population: Full Analysis Set (FAS): This patient set includes all patients who were randomised and received at least one dose of study drug and who had a baseline for the primary efficacy endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Clear/Almost Clear (0 or 1) at Week 16 | 2 Participants |
| Spesolimab 'Speso Low' | Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Clear/Almost Clear (0 or 1) at Week 16 | 6 Participants |
| Spesolimab 'Speso Medium-low' | Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Clear/Almost Clear (0 or 1) at Week 16 | 4 Participants |
| Spesolimab 'Speso Medium-high' | Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Clear/Almost Clear (0 or 1) at Week 16 | 4 Participants |
| Spesolimab 'Speso High' | Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Clear/Almost Clear (0 or 1) at Week 16 | 9 Participants |
95% CI: [0.04, 0.422]
95% CI: [-0.018, 0.339]
95% CI: [-0.022, 0.328]
95% CI: [0.009, 0.282]
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0333MCP-Mod linear model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0221MCP-Mod Emax model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0707MCP-Mod Exponential model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0578MCP-Mod Logistic model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0771MCP-Mod Sigmoid Emax model fit
Secondary
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.
Time frame: week 0 (baseline) and week 16
Population: Full Analysis Set (FAS): This patient set includes all patients who were randomised and received at least one dose of study drug and who had a baseline for the primary efficacy endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Pustules Clear/Almost Clear (0 or 1) at Week 16 | 5 Participants |
| Spesolimab 'Speso Low' | Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Pustules Clear/Almost Clear (0 or 1) at Week 16 | 7 Participants |
| Spesolimab 'Speso Medium-low' | Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Pustules Clear/Almost Clear (0 or 1) at Week 16 | 6 Participants |
| Spesolimab 'Speso Medium-high' | Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Pustules Clear/Almost Clear (0 or 1) at Week 16 | 8 Participants |
| Spesolimab 'Speso High' | Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Pustules Clear/Almost Clear (0 or 1) at Week 16 | 14 Participants |
95% CI: [-0.005, 0.427]
95% CI: [-0.032, 0.401]
95% CI: [0.032, 0.471]
95% CI: [0.024, 0.367]
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0158MCP-Mod linear model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.012MCP-Mod Emax model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0429MCP-Mod Exponential model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0229MCP-Mod Logistic model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.03MCP-Mod Sigmoid Emax model fit
Secondary
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.
Time frame: week 0 (baseline) and week 16.
Population: Full Analysis Set (FAS): This patient set includes all patients who were randomised and received at least one dose of study drug. Only subjects with non missing endpoint data were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Palmoplantar Pustulosis Severity Index (PPP SI) Change From Baseline at Week 16 | -2.7 Score on a scale |
| Spesolimab 'Speso Low' | Palmoplantar Pustulosis Severity Index (PPP SI) Change From Baseline at Week 16 | -3.3 Score on a scale |
| Spesolimab 'Speso Medium-low' | Palmoplantar Pustulosis Severity Index (PPP SI) Change From Baseline at Week 16 | -3.2 Score on a scale |
| Spesolimab 'Speso Medium-high' | Palmoplantar Pustulosis Severity Index (PPP SI) Change From Baseline at Week 16 | -3.5 Score on a scale |
| Spesolimab 'Speso High' | Palmoplantar Pustulosis Severity Index (PPP SI) Change From Baseline at Week 16 | -2.8 Score on a scale |
p-value: 0.281295% CI: [-1.8, 0.5]Mixed Models Analysis
p-value: 0.335795% CI: [-1.7, 0.6]Mixed Models Analysis
p-value: 0.180995% CI: [-2, 0.4]Mixed Models Analysis
p-value: 0.832295% CI: [-1.1, 0.9]Mixed Models Analysis
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.4035MCP-Mod linear model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.2563MCP-Mod Emax model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.681MCP-Mod Exponential model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.4665MCP-Mod Logistic model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of Spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, Emax, exponential, logistic, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.5565MCP-Mod Sigmoid Emax model fit
Secondary
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.
Time frame: week 0 (baseline) and week 52
Population: Full Analysis Set (FAS): This patient set includes all patients who were randomised and received at least one dose of study drug. Only subjects with non missing endpoint data were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 52 From Baseline | -54.6 Percentage of change in PPP ASI |
| Spesolimab 'Speso Low' | The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 52 From Baseline | -73.3 Percentage of change in PPP ASI |
| Spesolimab 'Speso Medium-low' | The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 52 From Baseline | -73.8 Percentage of change in PPP ASI |
| Spesolimab 'Speso Medium-high' | The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 52 From Baseline | -81.2 Percentage of change in PPP ASI |
| Spesolimab 'Speso High' | The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 52 From Baseline | -60.0 Percentage of change in PPP ASI |
95% CI: [-37.2, -0.2]
95% CI: [-38.3, -0.2]
95% CI: [-45.5, -7.8]
95% CI: [-21.1, 10.2]