A Study to Test Whether BI 655130 (Spesolimab) Prevents Flare-ups in Patients With Generalized Pustular Psoriasis

A GPP flare was defined as increase in Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score by ≥ 2 from baseline and the pustular component of GPPGA ≥ 2) up to week 48. Use of rescue medication, or investigator-prescribed Standard of Care (SoC) for GPP worsening, was considered to represent a GPP flare onset. 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.

Time frame: GPPGA was regularly assessed at baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Patients could come to site for flare confirmation anytime as unscheduled visit. Visit window was ±7 days.

Population: Randomized Set (EM-PM): This patient set includes all randomized patients. EM: Primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator-prescribed SoC for GPP worsening is considered as GPP flare. PM: Primary method for censoring, which is made at the earliest date of End of Study (EoS), Day 351 if no intercurrent event.

Proportion of patients with at least one GPP flare up to Week 48 is reported. Proportions were rounded up to three decimal places. A GPP flare was defined as increase in Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score by ≥ 2 from baseline and the pustular component of GPPGA ≥ 2. Any use of rescue medication, or investigator-prescribed SoC for GPP worsening, prior to week 48 was considered to represent the onset of a GPP flare. Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) relied on the clinical assessment of GPP patient's skin presentation. The total score is calculated by taking the mean of the three subscores: 1) erythema; 2) pustules and 3) scaling/crusting which were assessed using a scale score 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). The final GPPGA score: 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.

Time frame: GPPGA was regularly assessed at baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Patients could come to site for flare confirmation anytime as unscheduled visit. Visit window was ±7 days.

Population: Randomized Set (EM-MI): This patient set includes all randomized patients. EM:primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator - prescribed SoC for GPP worsening is considered as GPP flare. MI: multiple imputation method using sequential logistic regression method.

Proportion of patients with sustained remission at all visits up to Week 48. Proportions were rounded up to three decimal places. Remission was defined as a patient with a GPPGA score of 0 or 1 (clear or almost clear) at all visits up to week 48, without intake of rescue medication, or investigator-prescribed SoC for GPP worsening. 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.

Time frame: GPPGA was regularly assessed at baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Patients could come to site for flare confirmation anytime as unscheduled visit. Visit window was ±7 days.

Population: Randomized Set (EM-MI): This patient set includes all randomized patients. EM:primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator-prescribed SoC for GPP worsening is considered as GPP flare. MI: multiple imputation method using sequential logistic regression method.

Percentage of patients with treatment emergent adverse events (TEAEs) is reported. Percentages were rounded up to one decimal places. Time Frame: Placebo, Spesolimab (Speso) SC low, medium, high: From randomized study treatment start until the first use of rescue medication with IV spesolimab or until last dose + 16 weeks, up to 62 weeks. Speso IV SD and Speso IV DD: From first use of rescue medication with IV spesolimab until OL maintenance spesolimab SC or until last dose of spesolimab IV + 16 weeks, up to 17 weeks. Speso OL SC: From the first dose of OL spesolimab SC treatment until last dose + 16 weeks, up to 62 weeks.

Time frame: Up to 62 weeks (for detailed timeframe see description).

Population: Arms Placebo, Speso SC Low, medium, high:Safety Set (SAF)-This patient set included all patients who were randomized and received at least one dose of study drug. One patient who was randomized to placebo arm but received active spesolimab dose is reported under the arm Spesolimab SC low instead of Placebo.~Arms Speso IV SD, Speso IV SD: Safety Analysis set for flare rescue treatment period (SAF-FT).~Arm Speso OL SC: Safety Analysis set for OL maintenance treatment period (SAF-MT).

Worsening of DLQI up to week 48 was defined as a 4-point increase in total score from baseline. Intake of rescue medication, or investigator-prescribed SoC for GPP worsening, was considered as onset of a worsening. The DLQI is a patient-administered, ten-question, quality of life questionnaire that covers six domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Response categories include not relevant (score of 0), not at all (score of 0), a little (score of 1), a lot (score of 2) and very much (score of 3). Question 7 is a yes/ no question where yes is scored as 3. DLQI total score is calculated by summing the scores of each question resulting in a range of 0 (no effect on patient's life) to 30 (extremely large effect on patient's life).

Time frame: DLQI assessments were performed at: Baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 24, 36 and 48). Visit window was ±7 days. Time window for Week 48 was from Week 46 to Week 50.

Population: Randomized Set (EM-PM): This patient set includes all randomized patients. EM:primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator-prescribed SoC for GPP worsening is considered as GPP flare. PM: primary method for censoring, which is made at the earliest date of End of Study (EoS), Day 351 if no intercurrent event.

Worsening of Psoriasis Symptom Scale (PSS) was defined as a 4-point increase in total score from baseline. Intake of rescue medication, or investigator-prescribed SoC for GPP worsening, was considered as onset of a worsening. The PSS is a 4-item patient-reported outcome (PRO) instrument that was developed to assess the severity of 4 psoriasis symptoms in patients with moderate to severe psoriasis. The symptoms included are: pain, redness, itching, and burning. Current symptom severity is assessed using a 5-point scale ranging from 0 (none) to 4 (very severe). The symptom scores are added to an unweighted total score (range: 0 (no symptoms) to 16 (severe symptoms)).

Time frame: PSS assessments were performed at: Baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Visit window was ±7 days.

Population: Randomized Set (EM-PM): This patient set includes all randomized patients. EM:primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator-prescribed SoC for GPP worsening is considered as GPP flare. PM: primary method for censoring, which is made at the earliest date of End of Study (EoS), Day 351 if no intercurrent event.