A Study to Test How Effective and Safe Different Doses of... | NCT04015518 | Trialant
NCT04015518
Sponsor
Boehringer Ingelheim
Status
Completed
Last Update Posted
Oct 16, 2025Actual
Enrollment
152Actual
Phase
Phase 2
Conditions
Palmoplantar Pustulosis (PPP)
Interventions
Spesolimab
Placebo
Spesolimab
Spesolimab
Spesolimab
Spesolimab
Countries
United States
Australia
Belgium
Canada
Czechia
France
Germany
Hungary
Japan
Netherlands
Poland
Russia
South Korea
Taiwan
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT04015518
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
1368-0016
Secondary IDs
ID
Type
Description
Link
2018-003078-28
EudraCT Number
Brief Title
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
Official Title
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)
Acronym
Not provided
Organization
Boehringer IngelheimINDUSTRY
Status Module
Record Verification Date
Oct 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jul 31, 2019Actual
Primary Completion Date
Aug 6, 2020Actual
Completion Date
Jul 28, 2021Actual
First Submitted Date
Jul 9, 2019
First Submission Date that Met QC Criteria
Jul 9, 2019
First Posted Date
Jul 11, 2019Actual
Results Waived
Not provided
Results First Submitted Date
Jul 1, 2022
Results First Submitted that Met QC Criteria
Jul 1, 2022
Results First Posted Date
Jul 28, 2022Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Mar 17, 2021
Certification/Extension First Submitted that Passed QC Review
Mar 17, 2021
Certification/Extension First Posted Date
Mar 19, 2021Actual
Last Update Submitted Date
Oct 8, 2025
Last Update Posted Date
Oct 16, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Boehringer IngelheimINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Detailed Description
Not provided
Conditions Module
Conditions
Palmoplantar Pustulosis (PPP)
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
152Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Placebo & Spesolimab
Other
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
Drug: Placebo
Spesolimab 'Speso Low'
Experimental
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
Drug: Spesolimab
Spesolimab 'Speso Medium-low'
Experimental
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
Drug: Spesolimab
Spesolimab 'Speso Medium-high'
Experimental
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
Drug: Spesolimab
Spesolimab 'Speso High'
Experimental
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
Drug: Spesolimab
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Spesolimab
Drug
Subcutaneous injections of Spesolimab starting at week 16, for a total treatment time until week 52.
Placebo & Spesolimab
Outcomes Module
Primary Outcomes
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 Outcomes
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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.
Lebwohl MG, Thoma C, Haeufel T. Spesolimab use in generalised pustular psoriasis flares - Authors' reply. Lancet. 2024 Aug 31;404(10455):847-848. doi: 10.1016/S0140-6736(24)01557-5. No abstract available.
Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).
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.
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.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
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.
Subcutaneous injections of placebo matching Spesolimab from week 0 to 16.
Placebo & Spesolimab
Spesolimab
Drug
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
Spesolimab 'Speso Low'
Spesolimab
Drug
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
Spesolimab 'Speso Medium-low'
Spesolimab
Drug
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
Spesolimab 'Speso Medium-high'
Spesolimab
Drug
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
Spesolimab 'Speso High'
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
Beverly Hills
California
90211
United States
Therapeutics Clinical Research
San Diego
California
92123
United States
Advanced Medical Research PC
Sandy Springs
Georgia
30328
United States
Epiphany Dermatology of Kansas, LLC
Overland Park
Kansas
66215
United States
University of Missouri Health System
Columbia
Missouri
65212
United States
Washington University School of Medicine
St Louis
Missouri
63108
United States
Skin Specialists, P.C.
Omaha
Nebraska
68144
United States
The Psoriasis Treatment Center of Central New Jersey
University Hospital Kyoto Prefectural University of Medicine
Kyoto, Kyoto
602-8566
Japan
Tohoku University Hospital
Miyagi, Sendai
980-8574
Japan
Shinshu University Hospital
Nagano, Matsumoto
390-8621
Japan
Okayama University Hospital
Okayama, Okayama
700-8558
Japan
University of the Ryukyus Hospital
Okinawa, Nakagami-gun
903-0215
Japan
Kindai University Hospital
Osaka, Osaka-sayama
589-8511
Japan
Nakatsu Dermatology Clinic
Osaka, Osaka
531-0072
Japan
Osaka City University Hospital
Osaka, Osaka
545-8586
Japan
Osaka University Hospital
Osaka, Suita
565-0871
Japan
Shiga University of Medical Science Hospital
Shiga, Otsu
520-2192
Japan
Jichi Medical University Hospital
Tochigi, Shimotsuke
329-0498
Japan
Teikyo University Hospital
Tokyo, Itabashi-ku
173-8606
Japan
Nihon University Itabashi Hospital
Tokyo, Itabashi-ku
173-8610
Japan
Tokyo Medical University Hospital
Tokyo, Shinjuku-ku
160-0023
Japan
Seibo Hospital
Tokyo, Shinjuku
161-8521
Japan
Shirasaki Dermatology and Neurology Clinic
Toyama, Takaoka
933-0871
Japan
Wakayama Medical University Hospital
Wakayama, Wakayama
641-8509
Japan
Amphia Ziekenhuis
Breda
4818 CK
Netherlands
Barbara Rewerska Diamond Clinic, Krakow
Krakow
31-559
Poland
Dermoklinika medical center, Lodz
Lodz
90-436
Poland
Independent Public Clin.Hosp.no1 Lublin
Lublin
20-081
Poland
Municipal Hospital Complex in Olsztyn
Olsztyn
10-229
Poland
Dermmedica Sp. z o.o., Wroclaw
Wroclaw
51-318
Poland
SBHI Chelyabinsk Reg.Clin.Derma.Dispen.
Chelyabinsk
454048
Russia
LLC "Medical Center Azbuka Zdorovia"
Kazan'
420111
Russia
Dermatovenereological Dispensary #10, St. Petersburg
Saint Petersburg
194021
Russia
Gachon University Gil Medical Center
Incheon
21565
South Korea
Seoul National University Bundang Hospital
Seongnam
13620
South Korea
Seoul National University Hospital
Seoul
03080
South Korea
National Taiwan University Hospital
Taipei
10002
Taiwan
Royal Devon and Exeter Hospital
Exeter
EX2 5DW
United Kingdom
Guy's Hospital
London
SE1 9RT
United Kingdom
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
FG002
Spesolimab 'Speso Medium-low'
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
FG003
Spesolimab 'Speso Medium-high'
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
FG004
Spesolimab 'Speso High'
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
FG00043 subjects
FG00122 subjects
FG00221 subjects
FG00322 subjects
FG00444 subjects
Full Analysis Set (FAS)
FG00043 subjects
FG00122 subjects
FG00221 subjects
FG00322 subjects
FG00444 subjects
COMPLETED
FG00032 subjects
FG00119 subjects
FG00218 subjects
FG00317 subjects
FG00432 subjects
NOT COMPLETED
FG00011 subjects
FG0013 subjects
FG0023 subjects
FG0035 subjects
FG00412 subjects
Type
Comment
Reasons
Adverse Event
FG0006 subjects
FG0011 subjects
FG0021 subjects
FG0033 subjects
FG0043 subjects
Lack of Efficacy
FG0001 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0031 subjects
FG004
Patient did not come for consecutive visits
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
not willing to travel due to Covid-19
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Patient wants to discontinue treatment
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Difficult for patient to come to the hospital
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Pregnancy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Personal reasons
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrew consent
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Prostate carcinoma
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Could not keep appointments due to work
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Safety analysis set (SAF): This patient set includes all patients who were randomised and received at least one dose of study drug.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
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.
BG001
Spesolimab 'Speso Low'
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
BG002
Spesolimab 'Speso Medium-low'
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
BG003
Spesolimab 'Speso Medium-high'
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
BG004
Spesolimab 'Speso High'
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00043
BG00122
BG00221
BG00322
BG00444
BG005152
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00057.7± 10.1
BG00154.2± 12.3
BG00251.6± 7.9
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00035
BG00115
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Palmoplantar Pustulosis Area and Severity Index (PPP ASI)
The PPP ASI is an investigator assessment of the extent and severity of pustular and plaque lesions on the palms and soles presenting 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).
Mean
Standard Deviation
Score on a scale
Title
Denominators
Categories
Title
Measurements
BG00027.07± 12.44
BG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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.
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.
Posted
Least Squares Mean
95% Confidence Interval
Percentage of change in PPP ASI
week 0 (baseline) and week 16
ID
Title
Description
OG000
Placebo
Subcutaneous injections of placebo matching Spesolimab from week 0 to 16.
OG001
Spesolimab 'Speso Low'
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
OG002
Spesolimab 'Speso Medium-low'
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
OG003
Spesolimab 'Speso Medium-high'
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
OG004
Spesolimab 'Speso High'
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
Units
Counts
Participants
OG00038
OG00120
OG00221
OG003
Title
Denominators
Categories
Title
Measurements
OG000-33.6(-43.5 to -23.7)
OG001-44.2(-57.8 to -30.6)
OG002-48.3(-61.8 to -34.7)
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Models Analysis
Kenward-Roger was used to estimate denominator degrees of freedom.
0.2179
Difference of adjusted means
-10.5
Standard Error of the Mean
8.5
2-Sided
95
-27.4
6.3
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
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.
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.
Posted
Least Squares Mean
95% Confidence Interval
Score on a scale
week 0 (baseline) and week 4.
ID
Title
Description
OG000
Placebo
Subcutaneous injection of placebo matching Spesolimab 150 milligram (mg)/syringe, Loading period with 4 injections per visit (weekly up to Week 4).
OG001
Spesolimab 'Speso Low'
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.
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.
Posted
Least Squares Mean
95% Confidence Interval
Score on a scale
week 0 (baseline) and week 16.
ID
Title
Description
OG000
Placebo
Subcutaneous injections of placebo matching Spesolimab from week 0 to 16.
OG001
Spesolimab 'Speso Low'
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.
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.
Posted
Least Squares Mean
95% Confidence Interval
Score on a scale
week 0 (baseline) and week 16.
ID
Title
Description
OG000
Placebo
Subcutaneous injections of placebo matching Spesolimab from week 0 to 16.
OG001
Spesolimab 'Speso Low'
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.
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.
Posted
Count of Participants
Participants
week 0 (baseline) and week 16
ID
Title
Description
OG000
Placebo
Subcutaneous injections of placebo matching Spesolimab from week 0 to 16.
OG001
Spesolimab 'Speso Low'
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
OG002
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.
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.
Posted
Count of Participants
Participants
week 0 (baseline) and week 16
ID
Title
Description
OG000
Placebo
Subcutaneous injections of placebo matching Spesolimab from week 0 to 16.
OG001
Spesolimab 'Speso Low'
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
OG002
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.
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.
Posted
Count of Participants
Participants
week 0 (baseline) and week 16
ID
Title
Description
OG000
Placebo
Subcutaneous injections of placebo matching Spesolimab from week 0 to 16.
OG001
Spesolimab 'Speso Low'
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
OG002
Spesolimab 'Speso Medium-low'
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
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.
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.
Posted
Count of Participants
Participants
week 0 (baseline) and week 16
ID
Title
Description
OG000
Placebo
Subcutaneous injections of placebo matching Spesolimab from week 0 to 16.
OG001
Spesolimab 'Speso Low'
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
OG002
Spesolimab 'Speso Medium-low'
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
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.
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.
Posted
Least Squares Mean
95% Confidence Interval
Percentage of change in PPP ASI
week 0 (baseline) and week 52
ID
Title
Description
OG000
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.
OG001
Spesolimab 'Speso Low'
Time Frame
Adverse events: first until the last day of study drug administration + 112 days, up to 68 weeks.
Description
Safety analysis set (SAF): This patient set includes all patients who were randomised and received at least one dose of study drug.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo
Subcutaneous injections of placebo matching Spesolimab from week 0 to 16.
0
43
2
43
24
43
EG001
Spesolimab Post Placebo
Subcutaneous injections of Spesolimab starting at week 16, for a total treatment time until week 52.
0
38
3
38
22
38
EG002
Spesolimab 'Speso Low'
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
0
22
3
22
17
22
EG003
Spesolimab 'Speso Medium-low'
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
0
21
5
21
17
21
EG004
Spesolimab 'Speso Medium-high'
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
0
22
3
22
17
22
EG005
Spesolimab 'Speso High'
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
0
44
3
44
31
44
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Acute myocardial infarction
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0011 affected38 at risk
EG0020 affected22 at risk
EG0030 affected21 at risk
EG0040 affected22 at risk
EG0050 affected44 at risk
Angina unstable
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0011 affected38 at risk
EG0020 affected22 at risk
EG003
Atrial septal defect
Congenital, familial and genetic disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0011 affected38 at risk
EG0020 affected22 at risk
EG003
Retinal artery embolism
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0021 affected22 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA 24.0
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA 24.0
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Pneumothorax traumatic
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0021 affected22 at risk
EG003
Rib fracture
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Road traffic accident
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0021 affected22 at risk
EG003
Spinal compression fracture
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0021 affected22 at risk
EG003
Foot deformity
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Psoriatic arthropathy
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0011 affected38 at risk
EG0020 affected22 at risk
EG003
Rhabdomyolysis
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Basal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Breast cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Colon cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Prostate cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Cerebral infarction
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Bipolar disorder
Psychiatric disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Depression
Psychiatric disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Dyshidrotic eczema
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Henoch-Schonlein purpura
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Palmoplantar pustulosis
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Pustular psoriasis
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Circulatory collapse
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Palpitations
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG0030 affected21 at risk
EG0042 affected22 at risk
EG0050 affected44 at risk
Abdominal pain upper
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0011 affected38 at risk
EG0020 affected22 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 affected43 at risk
EG0012 affected38 at risk
EG0020 affected22 at risk
EG003
Dental caries
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0012 affected38 at risk
EG0020 affected22 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 affected43 at risk
EG0011 affected38 at risk
EG0023 affected22 at risk
EG003
Injection site erythema
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0012 affected38 at risk
EG0023 affected22 at risk
EG003
Injection site pain
General disorders
MedDRA 24.0
Systematic Assessment
EG0003 affected43 at risk
EG0012 affected38 at risk
EG0020 affected22 at risk
EG003
Injection site reaction
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0014 affected38 at risk
EG0023 affected22 at risk
EG003
Pyrexia
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0021 affected22 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0005 affected43 at risk
EG0013 affected38 at risk
EG0023 affected22 at risk
EG003
Rhinitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0003 affected43 at risk
EG0010 affected38 at risk
EG0021 affected22 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0020 affected22 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0021 affected22 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0023 affected22 at risk
EG003
Arthropod bite
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0011 affected38 at risk
EG0020 affected22 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0011 affected38 at risk
EG0020 affected22 at risk
EG003
Skin abrasion
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0022 affected22 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0006 affected43 at risk
EG0014 affected38 at risk
EG0023 affected22 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0024 affected22 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0022 affected22 at risk
EG003
Musculoskeletal stiffness
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 affected43 at risk
EG0011 affected38 at risk
EG0020 affected22 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0012 affected38 at risk
EG0021 affected22 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected38 at risk
EG0022 affected22 at risk
EG003
Pustulotic arthro-osteitis
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 affected43 at risk
EG0012 affected38 at risk
EG0020 affected22 at risk
EG003
Headache
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0001 affected43 at risk
EG0013 affected38 at risk
EG0022 affected22 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 24.0
Systematic Assessment
EG0003 affected43 at risk
EG0010 affected38 at risk
EG0021 affected22 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0021 affected22 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 affected43 at risk
EG0012 affected38 at risk
EG0021 affected22 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0002 affected43 at risk
EG0012 affected38 at risk
EG0026 affected22 at risk
EG003
Palmoplantar pustulosis
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0004 affected43 at risk
EG0010 affected38 at risk
EG0021 affected22 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 affected43 at risk
EG0011 affected38 at risk
EG0022 affected22 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected38 at risk
EG0022 affected22 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected43 at risk
EG0011 affected38 at risk
EG0020 affected22 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Kenward-Roger was used to estimate denominator degrees of freedom.
0.0883
Difference of adjusted means
-14.6
Standard Error of the Mean
8.5
2-Sided
95
-31.5
2.2
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG003
Mixed Models Analysis
Kenward-Roger was used to estimate denominator degrees of freedom.
0.1414
Difference of adjusted means
-12.6
Standard Error of the Mean
8.5
2-Sided
95
-29.4
4.3
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG004
Mixed Models Analysis
Kenward-Roger was used to estimate denominator degrees of freedom.
0.4514
Difference of adjusted means
-5.3
Standard Error of the Mean
7.0
2-Sided
95
-19.1
8.6
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod linear model fit
0.2120
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Emax model fit
Assumed 70% of the maximum effect was achieved at the "low dose" regimen.
0.1057
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Exponential model fit
Assumed 25% of the maximum effect was achieved at the "medium-low dose" regimen.
0.5241
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Logistic model fit
Assumed 20% of maximum effect was achieved at the "low dose", 95% of maximum effect was achieved at "medium high dose".
0.2773
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Sigmoid Emax model fit
Assumed 10% of the maximum effect was achieved at "low dose", 80% of the maximum effect was achieved at the "medium-high dose".
0.3867
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
OG002
Spesolimab 'Speso Medium-low'
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
OG003
Spesolimab 'Speso Medium-high'
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
OG004
Spesolimab 'Speso High'
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
Units
Counts
Participants
OG00038
OG00120
OG00221
OG00320
OG00441
Title
Denominators
Categories
Title
Measurements
OG000-9.3(-17.0 to -1.6)
OG001-15.4(-26.1 to -4.8)
OG002-14.7(-25.7 to -3.8)
OG003-12.8(-23.5 to -2.1)
OG004-18.7(-26.3 to -11.1)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Difference of adjusted means
-6.1
Standard Error of the Mean
6.7
2-Sided
95
-19.3
7.1
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG002
Difference of adjusted means
-5.4
Standard Error of the Mean
6.8
2-Sided
95
-18.8
8.0
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG003
Difference of adjusted means
-3.5
Standard Error of the Mean
6.6
2-Sided
95
-16.6
9.7
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG004
Difference of adjusted means
-9.4
Standard Error of the Mean
5.5
2-Sided
95
-20.3
1.4
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
OG002
Spesolimab 'Speso Medium-low'
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
OG003
Spesolimab 'Speso Medium-high'
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
OG004
Spesolimab 'Speso High'
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
Units
Counts
Participants
OG00038
OG00120
OG00221
OG00320
OG00441
Title
Denominators
Categories
Title
Measurements
OG000-14.7(-22.7 to -6.7)
OG001-18.7(-29.8 to -7.7)
OG002-13.8(-24.8 to -2.8)
OG003-18.9(-30.0 to -7.8)
OG004-22.4(-30.2 to -14.6)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Models Analysis
Kenward-Roger was used to estimate denominator degrees of freedom.
0.5595
Difference of adjusted means
-4.1
Standard Error of the Mean
6.9
2-Sided
95
-17.7
9.6
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG002
Mixed Models Analysis
Kenward-Roger was used to estimate denominator degrees of freedom.
0.8968
Difference of adjusted means
0.9
Standard Error of the Mean
6.9
2-Sided
95
-12.7
14.5
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG003
Mixed Models Analysis
Kenward-Roger was used to estimate denominator degrees of freedom.
0.5456
Difference of adjusted means
-4.2
Standard Error of the Mean
6.9
2-Sided
95
-17.9
9.5
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG004
Mixed Models Analysis
Kenward-Roger was used to estimate denominator degrees of freedom.
0.1762
Difference of adjusted means
-7.7
Standard Error of the Mean
5.7
2-Sided
95
-19.0
3.5
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod linear model fit
0.1726
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Emax model fit
Assumed 70% of the maximum effect was achieved at the "low dose" regimen.
0.2353
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Exponential model fit
Assumed 25% of the maximum effect was achieved at the "medium-low dose" regimen.
0.1346
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Logistic model fit
Assumed 20% of maximum effect was achieved at the "low dose", 95% of maximum effect was achieved at "medium high dose".
0.1950
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Sigmoid Emax model fit
Assumed 10% of the maximum effect was achieved at "low dose", 80% of the maximum effect was achieved at the "medium-high dose".
0.1681
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
OG002
Spesolimab 'Speso Medium-low'
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
OG003
Spesolimab 'Speso Medium-high'
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
OG004
Spesolimab 'Speso High'
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
Units
Counts
Participants
OG00038
OG00120
OG00221
OG00320
OG00441
Title
Denominators
Categories
Title
Measurements
OG000-2.7(-3.4 to -2.0)
OG001-3.3(-4.3 to -2.4)
OG002-3.2(-4.2 to -2.3)
OG003-3.5(-4.4 to -2.5)
OG004-2.8(-3.4 to -2.1)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Models Analysis
Kenward-Roger was used to estimate denominator degrees of freedom.
0.2812
Difference of adjusted means
-0.7
Standard Error of the Mean
0.6
2-Sided
95
-1.8
0.5
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG002
Mixed Models Analysis
Kenward-Roger was used to estimate denominator degrees of freedom.
0.3357
Difference of adjusted means
-0.6
Standard Error of the Mean
0.6
2-Sided
95
-1.7
0.6
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG003
Mixed Models Analysis
Kenward-Roger was used to estimate denominator degrees of freedom.
0.1809
Difference of adjusted means
-0.8
Standard Error of the Mean
0.6
2-Sided
95
-2.0
0.4
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG004
Mixed Models Analysis
Kenward-Roger was used to estimate denominator degrees of freedom.
0.8322
Difference of adjusted means
-0.1
Standard Error of the Mean
0.5
2-Sided
95
-1.1
0.9
Difference was calculated as Speso - placebo.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod linear model fit
0.4035
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Emax model fit
Assumed 70% of the maximum effect was achieved at the "low dose" regimen.
0.2563
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Exponential model fit
Assumed 25% of the maximum effect was achieved at the "medium-low dose" regimen.
0.6810
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Logistic model fit
Assumed 20% of maximum effect was achieved at the "low dose", 95% of maximum effect was achieved at "medium high dose".
0.4665
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Sigmoid Emax model fit
Assumed 10% of the maximum effect was achieved at "low dose", 80% of the maximum effect was achieved at the "medium-high dose".
0.5565
Adjusted for multiplicity.
Other
Mixed-effects Model Repeated Measures (MMRM) estimates were used as input for the MCP-Mod. MMRM included'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
Spesolimab 'Speso Medium-low'
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
OG003
Spesolimab 'Speso Medium-high'
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
OG004
Spesolimab 'Speso High'
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
Units
Counts
Participants
OG00043
OG00122
OG00221
OG00322
OG00444
Title
Denominators
Categories
Title
Measurements
OG00012
OG0017
OG00210
OG00312
OG00418
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Risk Difference (RD)
0.042
2-Sided
95
-0.170
0.281
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG002
Risk Difference (RD)
0.195
2-Sided
95
-0.048
0.432
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG003
Risk Difference (RD)
0.270
2-Sided
95
0.020
0.496
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG004
Risk Difference (RD)
0.129
2-Sided
95
-0.067
0.314
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod linear model fit
0.0613
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Emax model fit
Assumed 70% of the maximum effect was achieved at the "low dose" regimen.
0.0628
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Exponential model fit
Assumed 25% of the maximum effect was achieved at the "medium-low dose" regimen.
0.1449
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Logistic model fit
Assumed 20% of maximum effect was achieved at the "low dose", 95% of maximum effect was achieved at "medium high dose".
0.0460
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Sigmoid Emax model fit
Assumed 10% of the maximum effect was achieved at "low dose", 80% of the maximum effect was achieved at the "medium-high dose".
0.0677
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
Spesolimab 'Speso Medium-low'
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
OG003
Spesolimab 'Speso Medium-high'
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
OG004
Spesolimab 'Speso High'
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
Units
Counts
Participants
OG00043
OG00122
OG00221
OG00322
OG00444
Title
Denominators
Categories
Title
Measurements
OG0003
OG0013
OG0026
OG0034
OG0049
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Risk Difference (RD)
0.063
2-Sided
95
-0.069
0.256
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG002
Risk Difference (RD)
0.188
2-Sided
95
0.018
0.405
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG003
Risk Difference (RD)
0.102
2-Sided
95
-0.042
0.303
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG004
Risk Difference (RD)
0.113
2-Sided
95
-0.018
0.250
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod linear model fit
0.0536
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Emax model fit
Assumed 70% of the maximum effect was achieved at the "low dose" regimen.
0.0476
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Exponential model fit
Assumed 25% of the maximum effect was achieved at the "medium-low dose" regimen.
0.1076
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Logistic model fit
Assumed 20% of maximum effect was achieved at the "low dose", 95% of maximum effect was achieved at "medium high dose".
0.0606
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Sigmoid Emax model fit
Assumed 10% of the maximum effect was achieved at "low dose", 80% of the maximum effect was achieved at the "medium-high dose".
0.0824
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG003
Spesolimab 'Speso Medium-high'
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
OG004
Spesolimab 'Speso High'
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
Units
Counts
Participants
OG00043
OG00122
OG00221
OG00322
OG00444
Title
Denominators
Categories
Title
Measurements
OG0002
OG0016
OG0024
OG0034
OG0049
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Risk Difference (RD)
0.211
2-Sided
95
0.040
0.422
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG002
Risk Difference (RD)
0.130
2-Sided
95
-0.018
0.339
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG003
Risk Difference (RD)
0.125
2-Sided
95
-0.022
0.328
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG004
Risk Difference (RD)
0.144
2-Sided
95
0.009
0.282
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod linear model fit
0.0333
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Emax model fit
Assumed 70% of the maximum effect was achieved at the "low dose" regime
0.0221
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Exponential model fit
Assumed 25% of the maximum effect was achieved at the "medium-low dose" regimen.
0.0707
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Logistic model fit
Assumed 20% of maximum effect was achieved at the "low dose", 95% of maximum effect was achieved at "medium high dose".
0.0578
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Sigmoid Emax model fit
Assumed 10% of the maximum effect was achieved at "low dose", 80% of the maximum effect was achieved at the "medium-high dose".
0.0771
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG003
Spesolimab 'Speso Medium-high'
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
OG004
Spesolimab 'Speso High'
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
Units
Counts
Participants
OG00043
OG00122
OG00221
OG00322
OG00444
Title
Denominators
Categories
Title
Measurements
OG0005
OG0017
OG0026
OG0038
OG00414
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Risk Difference (RD)
0.202
2-Sided
95
-0.005
0.427
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG002
Risk Difference (RD)
0.170
2-Sided
95
-0.032
0.401
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG003
Risk Difference (RD)
0.248
2-Sided
95
0.032
0.471
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG004
Risk Difference (RD)
0.202
2-Sided
95
0.024
0.367
Confidence intervals were calculated using the cumulative distribution function method of Reeve. Difference was calculated as Speso - placebo.
Other
Logistic regression with fixed classification effects included treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod linear model fit
0.0158
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Emax model fit
Assumed 70% of the maximum effect was achieved at the "low dose" regimen.
0.0120
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Exponential model fit
Assumed 25% of the maximum effect was achieved at the "medium-low dose" regimen.
0.0429
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Logistic model fit
Assumed 20% of maximum effect was achieved at the "low dose", 95% of maximum effect was achieved at "medium high dose".
0.0229
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
OG000
OG001
OG002
OG003
OG004
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).
MCP-Mod Sigmoid Emax model fit
Assumed 10% of the maximum effect was achieved at "low dose", 80% of the maximum effect was achieved at the "medium-high dose".
0.0300
Adjusted for multiplicity.
Other
Logistic regression estimates were used as input for the MCP-Mod, with fixed classification effects including treatment and region (Japan vs. Non-Japan). In case 0 event are observed a penalized regression based on the Firth's bias reduction method was used. The estimates from the logistic regression are on the logit scale, the difference in proportions were calculated as the difference between the predicted probabilities in the treatment groups on the original scale.
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
OG002
Spesolimab 'Speso Medium-low'
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
OG003
Spesolimab 'Speso Medium-high'
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
OG004
Spesolimab 'Speso High'
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
Units
Counts
Participants
OG00032
OG00119
OG00218
OG00317
OG00432
Title
Denominators
Categories
Title
Measurements
OG000-54.6(-65.8 to -43.3)
OG001-73.3(-87.9 to -58.6)
OG002-73.8(-89.1 to -58.6)
OG003-81.2(-96.4 to -66.1)
OG004-60.0(-70.9 to -49.2)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Difference of adjusted means
-18.7
Standard Error of the Mean
9.3
2-Sided
95
-37.2
-0.2
Difference was calculated as Speso - placebo.
Other
MMRM included 'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG002
Difference of adjusted means
-19.3
Standard Error of the Mean
9.6
2-Sided
95
-38.3
-0.2
Difference was calculated as Speso - placebo.
Other
MMRM included 'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG003
Difference of adjusted means
-26.6
Standard Error of the Mean
9.5
2-Sided
95
-45.5
-7.8
Difference was calculated as Speso - placebo.
Other
MMRM included 'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.
OG000
OG004
Difference of adjusted means
-5.4
Standard Error of the Mean
7.9
2-Sided
95
-21.1
10.2
Difference was calculated as Speso - placebo.
Other
MMRM included 'baseline' as a continuous covariate, and 'visit', 'treatment', 'region' (stratification according to Japan vs. non-Japan), 'visit*treatment' and 'visit*baseline' interaction as fixed effects as well as the random 'subject' effect. Covariance structure= Unstructured.