A Study to Test Whether Spesolimab Helps People With a Skin Disease Called Hidradenitis Suppurativa

Percent change from baseline in total abscess and inflammatory nodule count at Week 12= \[(Total Abscess at Week 12 + Total Inflammatory Nodule at Week 12) - (Total Abscess at baseline + Total Inflammatory Nodule at baseline)\] \*100/ (Total Abscess at baseline + Total Inflammatory Nodule at baseline). Percent change from baseline in total abscess and inflammatory nodule count at Week 12 was modelled using mixed effects model for repeated measures (MMRM) accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to tumor necrosis factor inhibitor (TNFi)-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit (Weeks 1, 2, 4, 6, 8, 10, and 12). The Least Squares Mean (Standard Error) at Week 12 is reported.

Time frame: MMRM included measurements from baseline (Week 0) and at Weeks 1, 2, 4, 6, 8, 10, and 12 after first drug administration. MMRM estimates of percent change from baseline to Week 12 is reported.

Population: Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug. Data up to use of rescue therapy were included for analysis, and data post the use were censored. Only patients with non-missing endpoint data were included.

The DLQI is a patient-administered, ten-question, quality of life questionnaire that covers six domains: 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). DLQI total score is calculated by summing the scores of each question resulting in a range of 0 to 30 with higher scores indicating greater health-related quality of life impairment. Absolute change from baseline in DLQI score at Week 12 was modelled using MMRM accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to tumor necrosis factor inhibitor (TNFi)-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit (Weeks 1, 4, 8, and 12).

Time frame: MMRM included measurements at baseline (Week 0) and at Weeks 1, 4, 8, and 12 after first drug administration. MMRM estimates of absolute change in DLQI from baseline to Week 12 is reported.

Population: Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug. Data up to use of rescue therapy were included for analysis, and data post the use were censored. Only patients with non-missing endpoint data were included.

HASI includes four domains to assess the severity of HS disease activity, which are erythema, induration, open ulcer and draining fistula and scored on a Likert scale 0 (none) to 3 (severe/extensive) for each predetermined body region. For body surface area (BSA) assessment, the number of palms (one palm indicates 1% of the patient's BSA) involved for each body region (head, right axilla, left axilla, anterior chest, back, anterior bathing trunk, posterior bathing trunk, other) is assessed and converted to a percentage of that region. An area score was assigned to each region using the approach (0 = none, 1 = 1-9%, 2 = 10-29%, 3 = 30-49%, 4 = 50-69%, 5 = 70-89%, 6 = 90- 100%). Scores for the four domains of HS are summed and adjusted for the area affected, and the score of each area are summed to calculate the total HASI score, which ranges from 0 (no disease) to 72 (severe disease). The Least Squares Mean (Standard Error (SE)) derive from MMRM.

Time frame: MMRM included measurements at baseline (Week 0) and at Weeks 1, 2, 4, 6, 8, 10, and 12 after first drug administration. MMRM estimates of absolute change from baseline in HASI score at Week 12 is reported in the table below.

Population: Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug. Data up to use of rescue therapy were included for analysis, and data post the use were censored. Only patients with non-missing endpoint data were included.

HiS-QoL is a patient-administered, 17-item instrument to measure HS-specific quality of life in clinical trials with a 7-day recall period. The 17-item HiS-QoL included four symptom items, eight activity-adaptation items and five psychosocial items. The item scores are summed to create a total ranging from 0 to 68, with higher scores indicating more severe impact on health-related quality of life. Absolute change from baseline in HiS-QoL total score at Week 12 was modelled using MMRM accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to tumor necrosis factor inhibitor (TNFi)-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit (Weeks 1, 4, 8, and 12).

Time frame: MMRM included measurements at baseline (Week 0) and at Weeks 1, 4, 8, and 12 after first drug administration. MMRM estimates of absolute change in HiS-QoL from baseline to Week 12 is reported.

Population: Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug. Data up to use of rescue therapy were included for analysis, and data post the use were censored. Only patients with non-missing endpoint data were included.

The IHS4 assesses the hidradenitis suppurativa (HS) severity and the resulting IHS4 score is arrived at by= number of nodules \* 1 + number of abscesses \* 2 + number of draining fistula \* 4. A total score of 3 or less signifies mild, 4-10 signifies moderate and 11 or higher signifies severe disease. Absolute change from baseline in IHS4 value at Week 12 was modelled using mixed effects model for repeated measures (MMRM) accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to tumor necrosis factor inhibitor (TNFi)-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit (Weeks 1, 2, 4, 6, 8, 10, and 12). The Least Squares Mean (Standard Error) at Week 12 is reported.

Time frame: MMRM included measurements at baseline (Week 0) and at Weeks 1, 2, 4, 6, 8, 10, and 12 after first drug administration. MMRM estimates of absolute change in IHS4 from baseline to Week 12 is reported.

Population: Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug. Data up to use of rescue therapy were included for analysis, and data post the use were censored. Only patients with non-missing endpoint data were included.

The HS Pain Numerical Rating Scale (NRS) is an endpoint for the assessment of HS-related pain severity. Recall period is 24 hours and response is given by an 11-point scale ranging from 0 (no pain) to 10 (worst possible pain). For the analysis of pain, weekly average of daily assessment was calculated for each visit based on values prior to the visit. Missing daily values within a week were ignored if there are at least 4 reported values. Proportion of patients with achievement of at least 30% reduction from baseline in NRS30 in Patient's Global Assessment of HS Pain at Week 12. Proportion of patients with achievement of at least 30% reduction from baseline in NRS30 in Patient's Global Assessment of HS Pain at Week 12 was calculated as: number of patients with achievement of at least 30% reduction from baseline in NRS30 in Patient's Global Assessment of HS Pain at Week 12/number of patients analyzed. Proportions were rounded up to three decimal places.

Time frame: At baseline (Week 0) and at Week 12.

Population: Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug. Any binary data collected after use of any rescue therapy was censored and then imputed using the no response imputation (NRI) method as described in the statistical analysis plan.

HiSCR is defined as at least a 50% reduction in the total abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to baseline. Proportion of patients with achievement of Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12 is reported. Proportion of patients with achievement of HiSCR at Week 12 was calculated as: number of patients with achievement of HiSCR at Week 12/number of patients analyzed. Proportions were rounded up to three decimal places.

Time frame: At baseline (Week 0) and at Week 12.

Population: Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug. Any binary data collected after use of any rescue therapy was censored and then imputed using the no response imputation (NRI) method as described in the statistical analysis plan.

HS-PGA documents the physician's assessment of the patient's HS at a given timepoint. The HS-PGA score ranges from 0 to 5, where: 0=clear - no abscesses, draining fistula, inflammatory nodules or noninflammatory nodules); 1=minimal - no abscesses, draining fistula or inflammatory nodules and the presence of noninflammatory nodules); 2=mild - no abscesses or draining fistula and 1-4 inflammatory nodules, or 1 abscess or draining tunnel and no inflammatory nodules); 3=moderate - no abscesses or draining fistula and ≥5 inflammatory nodules, or 1 abscess or draining fistula and ≥1 inflammatory nodule, or 2-5 abscesses or draining fistula and \<10 inflammatory nodules); 4=severe - 2-5 abscesses or draining fistula and ≥10 inflammatory nodules); 5=very severe - \>5 abscesses or draining fistula). Proportion of patients with achievement of HS-PGA score of 0 or 1 at Week 12 was calculated as: number of patients with achievement of HS-PGA score of 0 or 1 at Week 12/number of patients analyzed.

Time frame: At Week 12.

Population: Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug. Any binary data collected after use of any rescue therapy was censored and then imputed using the no response imputation (NRI) method as described in the statistical analysis plan.

Proportion of patients with occurrence of at least one flare at Week 12. Flare was defined as at least 25 % increase in abscess and inflammatory nodule count with a minimum increase of 2 relative to baseline. Proportion of patients with occurrence of at least one flare at Week 12 was calculated as: number of patients with occurrence of at least one flare at Week 12/number of patients analyzed. Proportions were rounded up to three decimal places.

Time frame: At Week 12.

Population: Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug. Any binary data collected after use of any rescue therapy was censored and then imputed using the no response imputation (NRI) method as described in the statistical analysis plan.

Proportion of patients with occurrence of complete elimination of draining fistulas at Week 12 is reported. Proportion of patients with occurrence of complete elimination of draining fistulas at Week 12 was calculated as: number of patients with occurrence of complete elimination of draining fistulas at Week 12/number of patients analyzed. Proportions were rounded up to three decimal places.

Time frame: Baseline (Week 0) and at Week 12.

Population: Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug. Any binary data collected after use of any rescue therapy was censored and then imputed using the no response imputation (NRI) method as described in the statistical analysis plan. Only patients with baseline draining fistulas \>= 1 and non-missing endpoint data were included.

Percent change from baseline in draining fistula at Week 12 was calculated as: \[(total draining fistula at Week 12) - (total draining fistula at baseline)\] \* 100 %/ (total draining fistula at baseline). Percent change from baseline in draining fistula count at Week 12 was modelled using mixed effects model for repeated measures (MMRM) accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to tumor necrosis factor inhibitor (TNFi)-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit (Weeks 1, 2, 4, 6, 8, 10, and 12). The Least Squares Mean (Standard Error) at Week 12 is reported.

Time frame: MMRM included measurements from baseline (Week 0) and at Weeks 1, 2, 4, 6, 8, 10, and 12 after first drug administration. MMRM estimates of percent change in draining fistula from baseline to Week 12 is reported.

Population: Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug. Data up to use of rescue therapy were included for analysis, and data post the use were censored. Only patients with baseline draining fistulas \>=1 and non-missing endpoint data were included.

Percentage of patients with occurrence of Treatment Emergent Adverse Events (TEAEs) is reported. Percentage of patients with occurrence of Treatment Emergent Adverse Events (TEAEs) was calculated as: number of patients with occurrence of TEAEs / number of patients analyzed. Percentages were rounded to one decimal place. Time Frame: From first drug administration until 16 weeks after last drug administration, up to 28 weeks for patients who did not to roll-over to the open-label extension (OLE) trial (trial number 1368-0067 (NCT04876391)). From first drug administration until Week 12 for patients who did roll-over to the open-label extension (OLE) trial (trial number 1368-0067 (NCT04876391)).

Time frame: Up to 12 weeks for patients who did roll-over to the open-label extension (OLE) trial (trial number 1368-0067 (NCT04876391)) and up to 28 weeks who did not roll-over to the OLE trial. For details please see description.

Population: Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug. One patient randomised to receive placebo took spesolimab during the study, therefore was considered in spesolimab arm instead for safety reporting.