Effisayil™ 1: A Study to Test Spesolimab (BI 655130) in Patients With a Flare-up of a Skin Disease Called Generalized Pustular Psoriasis

The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) relies on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The investigator (or qualified site personnel) scored the erythema, pustules, and scaling of all GPP lesions from 0 to 4. The GPPGA pustulation subscore ranges from 0 to 4 where: 0 = clear; 1. = almost clear; 2. = mild: 3. = moderate; 4. = severe. A lower GPPGA pustulation subscore indicates a better outcome. A GPPGA pustulation subscore of 0 means no visible pustules. The proportion of patients who achieved a GPPGA pustulation subscore of 0 at Week 1 is reported.

Time frame: At Week 1.

Population: Randomized Set (RS) (via estimand EN-NRI): This patient set included all randomized patients. EN = Any assessments after death, or any use of escape medication due to disease worsening (defined as worsening of clinical status or GPP skin and/or systemic symptoms as defined by the investigator) prior to Week 1 were considered to represent a non-response. NRI = Non-response imputation for any missing data.

The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Each items is scored from 0 to 4. Score range is 0 (extreme fatigue)-52 (no fatigue). Change from baseline=FACIT Fatigue score at Week 4- FACIT-Fatigue score at baseline. Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR). NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is s (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3.

Time frame: Baseline and at Week 4.

Population: Randomized Set (RS) (via estimand EN-LOCF): This patient set included all randomized patients. EN = Any assessments after death, or any use of escape medication before or after Day 8, open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8 were considered to represent a non-response and assigned with the worst possible outcomes in rank analysis. LOCF = last observation carried forward imputation for any missing data.

The pain Visual Analogue Scale (VAS) is a participant-administered single-item scale designed to measure skin pain intensity from generalized pustular psoriasis (GPP) using a 100 millimeter (mm) horizontal VAS. Overall severity of participant's skin pain from GPP is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no pain) to 100 mm (pain as bad as one can imagine). Change from baseline was calculated by subtracting the VAS score at baseline from the VAS score at Week 4. A negative change indicates an improvement from baseline. Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR). NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3.

Time frame: Baseline and at Week 4.

Population: Randomized Set (RS) (via estimand EN-LOCF): This patient set included all randomized patients. EN = Death or any use of escape medication before or after Day 8, open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8 were considered to represent a non-response and assigned with the worst possible outcomes in rank analysis. LOCF = last observation carried forward imputation for any missing data.

PSS is a 4-item patient-reported outcome instrument that assesses the severity of psoriasis symptoms in moderate to severe psoriasis patients. The symptoms included are: pain, redness, itching, and burning. The symptom severity was assessed using a 5 point scale ranging from 0 to 4 where 0=none, 1=mild, 2=moderate, 3=severe, 4=very severe. The symptom scores are added to an unweighted total score (range: 0 to 16). A lower PSS score indicates a better outcome. Change from baseline =PSS score at Week 4 - PSS score at baseline. Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR). NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3.

Time frame: Baseline and at Week 4.

Population: Randomized Set (RS) (via estimand EN-LOCF): This patient set included all randomized patients. EN = Any assessments after death, or any use of escape medication before or after Day 8, open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8 were considered to represent a non-response and assigned with the worst possible outcomes in rank analysis. LOCF = last observation carried forward imputation for any missing data.

GPPGA relied on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The GPPGA total score was calculated by taking the mean of the erythema subscore, pustules subscore and scaling/crusting subscore. The severity of each subscore was assessed using a 5 point scale score ranging from 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). The final GPPGA score is assigned as follows: * 0, if scores for all three subscores are 0, * 1, if 0 \< mean \< 1.5, * 2, if 1.5 ≤ mean \< 2.5, * 3, if 2.5 ≤ mean \< 3.5, * 4, if mean ≥ 3.5. A lower GPPGA score indicates a better outcome, with 0 being clear and 1 being almost clear. The proportion of patients with a GPPGA score of 0 or 1 at Week 1 is reported.

Time frame: At Week 1.

Population: Randomized Set (RS) (via estimand EN-NRI): This patient set included all randomized patients. EN =Any assessments after death, or any use of escape medication due to disease worsening (defined as worsening of clinical status or GPP skin and/or systemic symptoms as defined by the investigator) prior to Week 1 were considered to represent a non-response. NRI = Non-response imputation for any missing data.

TEAEs were all Adverse Events (AEs) occurring between start of treatment and Day 8 (Day 8 excluded). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'.

Time frame: From start of treatment until Day 7, up to 7 days.

Population: Safety Analysis set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug on Day 1. Patients were analyzed according to the actual treatment received.

TEAEs were all Adverse Events (AEs) occurring between start of treatment and end of the residual effect period (REP) (16 weeks). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'.

Time frame: From start of treatment until end of the residual effect period (REP) but censored at any use of open label spesolimab, up to 16 weeks.

Population: Safety Analysis set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug on Day 1. Patients were analyzed according to the actual treatment received.

TEAEs were all Adverse Events (AEs) occurring between start of treatment and Day 8 (Day 8 excluded). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'. The exposure-adjusted incidence rate was calculated as: Incidence rate \[1/100 patients-years\] = 100 × number of patients with AE / Total AE specific time at risk \[patient-years\] where: Time at risk \[patient-years\] = (date of onset of TEAE - study drug start date + 1) /365.25

Time frame: From start of treatment until Day 7, up to 7 days.

Population: Safety Analysis set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug on Day 1. Patients were analyzed according to the actual treatment received.

TEAEs were all Adverse Events (AEs) occurring between start of treatment and end of the residual effect period (REP) (16 weeks). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'. The exposure-adjusted incidence rate was calculated as: Incidence rate \[1/100 patients-years\] = 100 × number of patients with AE / Total AE specific time at risk \[patient-years\] where Time at risk where: Time at risk \[patient-years\] = (date of onset of TEAE - study drug start date + 1) /365.25 If, for a patient, the selected TEAE did not occur then the time at risk was censored at min * Date of death * For patients who did not roll over into the Open Label Extension (OLE) study: last contact date Visit14/15 * For patients who rolled over into the OLE study: the 1st dose in the OLE study * Drug stop date + 112 days * Date of Day 8 if OL spesolimab was given * Date of rescue medication if spesolimab was given.

Time frame: From start of treatment until end of the residual effect period (REP) but censored at any use of open label spesolimab, up to 16 weeks.

Population: Safety Analysis set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug on Day 1. Patients were analyzed according to the actual treatment received.

Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). A higher score indicates a worse disease state, while a score of 0 indicates no disease. The percent change from baseline at Week 1 is calculated as: % GPPASI change from baseline = (GPPASI at Week 1 - GPPASI at baseline) \*100/GPPASI at baseline. If % GPPASI change from baseline is positive, it means the disease is becoming worse.

Time frame: At Week 1.

Population: Randomized Set (RS) (via estimand EN-LOCF): This patient set included all randomized patients. EN = Any assessments after death, or any use of escape medication before or after Day 8, open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8 were considered to represent a non-response and assigned with the worst possible outcomes in rank analysis. LOCF = last observation carried forward imputation for any missing data.

GPPASI provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 (no disease) to 72 (worse disease state). It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). %GPPASI change from baseline=(GPPASI at Week 4-GPPASI at baseline) \*100/(GPPASI at baseline). Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR).NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3. Planned statistical analysis were not performed due to lack of valid data.

Time frame: Baseline and at Week 4.

Population: Randomized Set (RS) (via estimand EN-LOCF): This patient set included all randomized patients. EN = Any assessments after death, or any use of escape medication before or after Day 8, open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8 were considered to represent a non-response and assigned with the worst possible outcomes in rank analysis. LOCF = last observation carried forward imputation for any missing data.

Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). A higher score indicates a worse disease state, while a score of 0 indicates no disease. GPPASI 50 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 50 % reduction. Proportion of patients with GPPASI 50 at Week 1 is reported.

Time frame: At Week 1.

Population: Randomized Set (RS) (via estimand EN-NRI): This patient set included all randomized patients. EN = Any assessments after death, or the use of escape medication (before or after Day 8), or open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8, was considered a failure to achieve the endpoint outcome (i.e. non-response). NRI = Non-response imputation for any missing data.

Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). A higher score indicates a worse disease state, while a score of 0 indicates no disease. GPPASI 50 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 50 % reduction. Proportion of patients with GPPASI 50 at Week 4 is reported.

Time frame: At Week 4.

Population: Randomized Set (RS) (via estimand EN-NRI): This patient set included all randomized patients. EN = Any assessments after death, or the use of escape medication (before or after Day 8), or open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8, was considered a failure to achieve the endpoint outcome (i.e. non-response). NRI = Non-response imputation for any missing data.

The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) relies on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The investigator (or qualified site personnel) scores the erythema, pustules, and scaling of all GPP lesions from 0 to 4. The GPPGA pustulation subscore ranges from 0 to 4 where: 0 = clear; 1. = almost clear; 2. = mild: 3. = moderate; 4. = severe. A lower GPPGA pustulation subscore indicates a better outcome. The proportion of patients who achieved a GPPGA pustulation subscore of 0 at Week 1 is reported.

Time frame: At Week 4.

Population: Randomized Set (RS) (via estimand EN-NRI): This patient set included all randomized patients. EN = Any assessments after death, or the use of escape medication (before or after Day 8), or open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8, was considered a failure to achieve the endpoint outcome (i.e. non-response). NRI = Non-response imputation for any missing data.

GPPGA relied on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The GPPGA total score is calculated by taking the mean of the erythema subscore, pustules subscore and scaling/crusting subscore. The severity of each subscore was assessed using a 5 point scale score ranging from 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). The final GPPGA score is assigned as follows: * 0, if scores for all three scores are 0, * 1, if 0 \< mean \< 1.5, * 2, if 1.5 ≤ mean \< 2.5, * 3, if 2.5 ≤ mean \< 3.5, * 4, if mean ≥ 3.5. A lower GPPGA score indicates a better outcome, with 0 being clear and 1 being almost clear. The proportion of participants with a GPPGA score of 0 or 1 at Week 4 is reported.

Time frame: At Week 4.

Population: Randomized Set (RS) (via estimand EN-NRI): This patient set included all randomized patients. EN = Any assessments after death, or the use of escape medication (before or after Day 8), or open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8, was considered a failure to achieve the endpoint outcome (i.e. non-response). NRI = Non-response imputation for any missing data.

Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). A higher score indicates a worse disease state, while a score of 0 indicates no disease. GPPASI 75 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 75% reduction. Proportion of patients with GPPASI 75 at Week 4 is reported.

Time frame: At Week 4.

Population: Randomized Set (RS) (via estimand EN-NRI): This patient set included all randomized patients. EN = Any assessments after death, or any use of escape medication before or after Day 8, open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8 were considered to represent a non-response. NRI = Non-response imputation for any missing data.