Hidradenitis Suppurativa
Conditions
Brief summary
This study is open to adults with moderate to severe hidradenitis suppurativa (HS). The purpose of this study is to find out whether a medicine called spesolimab helps people with HS. People who have previously taken specific medicines such as immunosuppressive biologics other than Tumor necrosis factor (TNF) inhibitors cannot take part. This study has 2 parts. In Part 1, participants are divided into 4 groups of almost equal size. 3 groups get different doses of spesolimab, 1 group gets placebo. All participants get injections into a vein or under the skin. Placebo injections look like spesolimab injections, but do not contain any medicine. Every participant has an equal chance of being in each group. In the beginning, participants get the study medicine every week and later every 2 weeks. After 4 months, participants in the placebo group switch to spesolimab treatment. In Part 2, participants are divided into 2 groups. One group gets a suitable dose of spesolimab that was found in Part 1 of the study. The other group gets placebo. After 4 months, participants in the placebo group switch to spesolimab treatment. Participants join only one of the two parts. They are in the study for about 1 year. During this time, they visit the study site in the beginning every week and later every 2 weeks. Some of the visits can be done at the participant's home instead of the study site. The doctors regularly check participants' HS symptoms. The results are compared between the groups to see whether spesolimab works. The doctors also regularly check participants' general health and take note of any unwanted effects.
Detailed description
Main endpoints for Part 2 will be supported by Part 1 results available at time of primary analysis.
Interventions
DRUGSpesolimab i.v.
Weekly dose of spesolimab via i.v. for 4 weeks.
DRUGSpesolimab s.c.
Weekly s.c. dose of spesolimab for 4 weeks (3 weeks for Placebo), and maintenance s.c. dose of spesolimab every two weeks until the end of the treatment.
DRUGPlacebo matching Spesolimab i.v.
Weekly dose of placebo via i.v. for 4 weeks.
DRUGPlacebo matching Spesolimab s.c.
Weekly s.c. dose of placebo for 4 weeks, and once every 2 weeks for the following 7 weeks.
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Of full age of consent at screening. 2. Signed and dated written informed consent in accordance with International Council on Harmonisation-Good clinical practice (ICH-GCP) and local legislation prior to admission to the trial. 3. Moderate to severe HS. 4. HS lesions in at least 2 distinct anatomic areas. 5. Biologic naive or Tumor Necrosis Factor inhibitor (TNFi)-exposed for HS. 6. For biologic naïve, inadequate response to an adequate course of appropriate oral antibiotics for treatment of HS in the last 1 year prior to the Baseline visit, as per investigator discretion. All participants must have previous exposure to antibiotics for HS. 7. Total AN count of greater than or equal to 5. 8. Total dT count of at least 1 at Baseline visit. Further inclusion criteria apply.
Exclusion criteria
1. Participants who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial. 2. Prior exposure to any immunosuppressive/immunomodulatory biologic other than TNFi for HS. 3. Prior exposure to Interleukin 36 receptor (IL-36R) inhibitors including spesolimab. 4. Treated with any investigational device or investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives of the drug, whichever is longer. 5. Women who are pregnant, nursing, or who plan to become pregnant while in the trial. 6. Participants with history of allergy/hypersensitivity to the systemically administered trial medication agent or its excipients. 7. Participants with a transplanted organ (with exception of a corneal transplant \>12 weeks prior to screening) or who has ever received stem cell therapy (e.g., Remestemcel-L). 8. Participants with any documented active or suspected malignancy or history of malignancy within 5 years prior to the screening visit, except appropriately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ carcinoma of uterine cervix. Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 8 | The MMRM model incorporates dT count from baseline (Week 0), Week 2, Week 4, Week 6 and Week 8. The data represent the Least Squares Means at Week 8. | Percent change from baseline in draining fistula/tunnel (dT) count at Week 8 is reported. Tunnel/fistula/sinus were counted as dT only if draining. Percent change was calculated as follows: (dT count at week 8 - dT count at baseline)/ dT at baseline. Least square means and standard errors were estimated by Mixed effect model for repeated measurements (MMRM). The MMRM included fixed categorical effects of treatment at each visit, Tumor Necrosis Factor inhibitor (TNFi) status at baseline, and categorical baseline dT count at each visit. Visit were treated as the repeated measure with an unstructured covariance structure used to model the within-trial participant measurements. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 16 | The MMRM model incorporates dT count from baseline (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14 and Week 16. The data represent the Least Squares Means at Week 16. | Percent change from baseline in draining fistula/tunnel (dT) count at Week 16 is reported. Tunnel/fistula/sinus were counted as dT only if draining. Least square means and standard errors were estimated by MMRM, which included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model. |
| Part 1 - Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 8 | The MMRM model incorporates IHS4 value from baseline (Week 0), Week 2, Week 4, Week 6 and Week 8. The data represent the Least Squares Means at Week 8. | IHS4 is a validated, clinical scoring system for dynamic assessment of HS severity. The score was calculated as: (number of nodules x1) + (number of abscesses x2) + (number of draining tunnels \[fistulae/sinuses\] x4). The minimum is 0, the maximum depends on the count of nodules, abscesses, and draining tunnels. Scores 0-3 indicate mild HS, 4-10 moderate HS, ≥11 severe HS. Absolute change from baseline was calculated as follows: (IHS4 value at visit timepoints) - (IHS4 value at baseline). Least square means and standard errors were estimated by MMRM, which included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model. |
| Part 1 - Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 16 | The MMRM model incorporates IHS4 from baseline (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14 and Week 16. The data represent the Least Squares Means at Week 16. | IHS4 is a validated, clinical scoring system for dynamic assessment of HS severity. The score was calculated as: (number of nodules x1) + (number of abscesses x2) + (number of draining tunnels \[fistulae/sinuses\] x4). The minimum is 0, the maximum depends on the count of nodules, abscesses, and draining tunnels. Scores 0-3 indicate mild HS, 4-10 moderate HS, ≥11 severe HS. Absolute change from baseline was calculated as follows: (IHS4 value at visit timepoints) - (IHS4 value at baseline). Least square means and standard errors were estimated by MMRM, which included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model. |
| Part 1 - Occurrence of Treatment Emergent Adverse Events (TEAEs) | From first drug administration until end of exposure, plus residual effect period, up to approximately 68 weeks. | The occurrence of treatment emergent adverse events (TEAEs) is reported as the number of patients with TEAEs. |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Chile, China, Czechia, Denmark, Finland, France, Germany, Greece, Israel, Italy, Japan, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Philippines, Poland, Singapore, Slovakia, South Africa, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States, Vietnam
Participant flow
Recruitment details
This was an international, Phase IIb/III multi-center, double-blind, placebo-controlled, randomised trial assessing the efficacy and safety of spesolimab versus placebo in patients with moderate to severe Hidradenitis suppurativa.
Pre-assignment details
Subjects were screened for eligibility prior to participation and attended a specialist site which ensured that they 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. The trial was completed according to the protocol. However, part 2 was never initiated. The primary and interim analyses of part 1 (dose finding phase) didn't show signal to proceed with the confirmatory phase (part 2).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients with moderate to severe Hidradenitis suppurativa (HS) were administered an initial weekly dose of placebo via intravenous infusion (i.v.) (Week 0 to Week 3). Afterwards, patients were administered a subcutaneous injection (s.c.) dose of placebo once a week for 4 weeks (Week 4 to Week 7), and once every 2 weeks for the following 7 weeks (Week 8 to Week 14).
From Week 16 until the end of treatment (Week 48), patients were switched to the same s.c. dose of spesolimab administered to patients in the medium and high dose groups (starting with 3 loading s.c. doses of spesolimab every week and then maintenance s.c. dose of spesolimab every 2 weeks). | 53 |
| Spesolimab low dose group Patients with moderate to severe HS were administered an initial weekly low dose of spesolimab via i.v. (Week 0 to Week 3). Afterwards, patients were administered a lower weekly s.c. dose of spesolimab for 4 weeks (Week 4 to Week 7). Patients were then administered a maintenance s.c. dose of spesolimab every two weeks until the end of the treatment (Week 8 to Week 48).
From Week 16, if patients had inadequate clinical response defined as 25% increase in the ANdT count compared to baseline, the dose could be increased every two weeks to a pre-determined concentration. | 53 |
| Spesolimab medium dose group Patients with moderate to severe HS were administered an initial weekly medium dose of spesolimab via i.v. (Week 0 to Week 3). Afterwards, patients were administered a lower weekly s.c. dose of spesolimab for 4 weeks (Week 4 to Week 7). Patients were then administered a maintenance s.c. dose of spesolimab every two weeks until the end of the treatment (Week 8 to Week 48). | 52 |
| Spesolimab high dose group Patients with moderate to severe HS were administered an initial weekly high dose of spesolimab via i.v. (Week 0 to Week 3). Afterwards, patients were administered a lower weekly s.c. dose of spesolimab for 4 weeks (Week 4 to Week 7). Patients were then administered a maintenance s.c. dose of spesolimab every two weeks until the end of the treatment (Week 8 to Week 48). | 51 |
| Total | 209 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 4 | 5 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 | 0 | 1 |
| Overall Study | Other than listed | 0 | 2 | 2 | 0 |
| Overall Study | Study terminated by sponsor | 20 | 18 | 20 | 22 |
| Overall Study | Withdrawal by Subject | 11 | 7 | 6 | 6 |
Baseline characteristics
| Characteristic | Placebo | Spesolimab low dose group | Spesolimab medium dose group | Spesolimab high dose group | Total |
|---|---|---|---|---|---|
| Age, Continuous | 33.8 Years STANDARD_DEVIATION 8.8 | 37.0 Years STANDARD_DEVIATION 12.1 | 39.5 Years STANDARD_DEVIATION 13.9 | 39.2 Years STANDARD_DEVIATION 13.5 | 37.3 Years STANDARD_DEVIATION 12.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 7 Participants | 7 Participants | 7 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 44 Participants | 44 Participants | 42 Participants | 172 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 2 Participants | 1 Participants | 2 Participants | 10 Participants |
| Number of draining fistulas/tunnels (dT) | 5.2 Draining fistulas/tunnels STANDARD_DEVIATION 5.8 | 5.1 Draining fistulas/tunnels STANDARD_DEVIATION 5.1 | 7.0 Draining fistulas/tunnels STANDARD_DEVIATION 10.9 | 6.5 Draining fistulas/tunnels STANDARD_DEVIATION 6.7 | 5.9 Draining fistulas/tunnels STANDARD_DEVIATION 7.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 13 Participants | 13 Participants | 15 Participants | 63 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 2 Participants | 1 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) White | 23 Participants | 34 Participants | 35 Participants | 29 Participants | 121 Participants |
| Sex: Female, Male Female | 19 Participants | 22 Participants | 20 Participants | 20 Participants | 81 Participants |
| Sex: Female, Male Male | 34 Participants | 31 Participants | 32 Participants | 31 Participants | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 50 | 0 / 53 | 0 / 52 | 0 / 51 |
| other Total, other adverse events | 29 / 53 | 32 / 50 | 39 / 53 | 38 / 52 | 41 / 51 |
| serious Total, serious adverse events | 3 / 53 | 7 / 50 | 3 / 53 | 8 / 52 | 6 / 51 |
Outcome results
Primary
Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 8
Percent change from baseline in draining fistula/tunnel (dT) count at Week 8 is reported. Tunnel/fistula/sinus were counted as dT only if draining. Percent change was calculated as follows: (dT count at week 8 - dT count at baseline)/ dT at baseline. Least square means and standard errors were estimated by Mixed effect model for repeated measurements (MMRM). The MMRM included fixed categorical effects of treatment at each visit, Tumor Necrosis Factor inhibitor (TNFi) status at baseline, and categorical baseline dT count at each visit. Visit were treated as the repeated measure with an unstructured covariance structure used to model the within-trial participant measurements.
Time frame: The MMRM model incorporates dT count from baseline (Week 0), Week 2, Week 4, Week 6 and Week 8. The data represent the Least Squares Means at Week 8.
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug. The use of treatment policy approach disregards the intercurrent event and uses the value of the variable regardless of the occurrence of the intercurrent event.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 8 | -21.5 Percentage change | Standard Error 7.7 |
| Spesolimab low dose group | Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 8 | -41.9 Percentage change | Standard Error 7.8 |
| Spesolimab medium dose group | Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 8 | -39.3 Percentage change | Standard Error 7.9 |
| Spesolimab high dose group | Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 8 | -25.8 Percentage change | Standard Error 7.9 |
Comparison: The MMRM included fixed categorical effects of treatment at each visit, Tumor Necrosis Factor inhibitor (TNFi) status at baseline, and categorical baseline dT count at each visit. Visit were treated as the repeated measure with an unstructured covariance structure used to model the within-trial participant measurements.95% CI: [-41.9, 1.1]
Comparison: The MMRM included fixed categorical effects of treatment at each visit, Tumor Necrosis Factor inhibitor (TNFi) status at baseline, and categorical baseline dT count at each visit. Visit were treated as the repeated measure with an unstructured covariance structure used to model the within-trial participant measurements.95% CI: [-39.5, 3.9]
Comparison: The MMRM included fixed categorical effects of treatment at each visit, Tumor Necrosis Factor inhibitor (TNFi) status at baseline, and categorical baseline dT count at each visit. Visit were treated as the repeated measure with an unstructured covariance structure used to model the within-trial participant measurements.95% CI: [-26, 17.5]
Comparison: Multiple comparison and modelling techniques (MCPMod) was used to evaluate several possible dose response models (patterns: Linear, Exponential, Emax, SigEmax, BetaMod), and to identify the best-fitting model or subset of models.p-value: 0.697MCPMod Linear model
Comparison: Multiple comparison and modelling techniques (MCPMod) was used to evaluate several possible dose response models (patterns: Linear, Exponential, Emax, SigEmax, BetaMod), and to identify the best-fitting model or subset of models.p-value: 0.844MCPMod Exponential: model
Comparison: Multiple comparison and modelling techniques (MCPMod) was used to evaluate several possible dose response models (patterns: Linear, Exponential, Emax, SigEmax, BetaMod), and to identify the best-fitting model or subset of models.p-value: 0.256MCPMod Emax model
Comparison: Multiple comparison and modelling techniques (MCPMod) was used to evaluate several possible dose response models (patterns: Linear, Exponential, Emax, SigEmax, BetaMod), and to identify the best-fitting model or subset of models.p-value: 0.571MCPMod SigEmax model
Comparison: Multiple comparison and modelling techniques (MCPMod) was used to evaluate several possible dose response models (patterns: Linear, Exponential, Emax, SigEmax, BetaMod), and to identify the best-fitting model or subset of models.p-value: 0.232MCPMod BetaMod model
Secondary
Part 1 - Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 16
IHS4 is a validated, clinical scoring system for dynamic assessment of HS severity. The score was calculated as: (number of nodules x1) + (number of abscesses x2) + (number of draining tunnels \[fistulae/sinuses\] x4). The minimum is 0, the maximum depends on the count of nodules, abscesses, and draining tunnels. Scores 0-3 indicate mild HS, 4-10 moderate HS, ≥11 severe HS. Absolute change from baseline was calculated as follows: (IHS4 value at visit timepoints) - (IHS4 value at baseline). Least square means and standard errors were estimated by MMRM, which included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model.
Time frame: The MMRM model incorporates IHS4 from baseline (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14 and Week 16. The data represent the Least Squares Means at Week 16.
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug. The use of treatment policy approach disregards the intercurrent event and uses the value of the variable regardless of the occurrence of the intercurrent event.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Part 1 - Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 16 | -11.8 Units on a scale | Standard Error 3.8 |
| Spesolimab low dose group | Part 1 - Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 16 | -7.2 Units on a scale | Standard Error 3.9 |
| Spesolimab medium dose group | Part 1 - Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 16 | -17.0 Units on a scale | Standard Error 3.9 |
| Spesolimab high dose group | Part 1 - Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 16 | -4.2 Units on a scale | Standard Error 4 |
Comparison: The MMRM included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model.95% CI: [-6.1, 15.3]
Comparison: The MMRM included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model.95% CI: [-15.9, 5.5]
Comparison: The MMRM included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model.95% CI: [-3.3, 18.5]
Secondary
Part 1 - Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 8
IHS4 is a validated, clinical scoring system for dynamic assessment of HS severity. The score was calculated as: (number of nodules x1) + (number of abscesses x2) + (number of draining tunnels \[fistulae/sinuses\] x4). The minimum is 0, the maximum depends on the count of nodules, abscesses, and draining tunnels. Scores 0-3 indicate mild HS, 4-10 moderate HS, ≥11 severe HS. Absolute change from baseline was calculated as follows: (IHS4 value at visit timepoints) - (IHS4 value at baseline). Least square means and standard errors were estimated by MMRM, which included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model.
Time frame: The MMRM model incorporates IHS4 value from baseline (Week 0), Week 2, Week 4, Week 6 and Week 8. The data represent the Least Squares Means at Week 8.
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug. The use of treatment policy approach disregards the intercurrent event and uses the value of the variable regardless of the occurrence of the intercurrent event.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Part 1 - Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 8 | -13.5 Units on a scale | Standard Error 2.5 |
| Spesolimab low dose group | Part 1 - Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 8 | -11.1 Units on a scale | Standard Error 2.5 |
| Spesolimab medium dose group | Part 1 - Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 8 | -14.1 Units on a scale | Standard Error 2.5 |
| Spesolimab high dose group | Part 1 - Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 8 | -10.5 Units on a scale | Standard Error 2.5 |
Comparison: The MMRM included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model.95% CI: [-4.5, 9.4]
Comparison: The MMRM included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model.95% CI: [-7.5, 6.3]
Comparison: The MMRM included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model.95% CI: [-3.9, 10]
Comparison: Multiple comparison and modelling techniques (MCPMod) was used to evaluate several possible dose response models (patterns: Linear, Exponential, Emax, SigEmax, BetaMod), and to identify the best-fitting model or subset of models.p-value: 0.887MCPMod Linear model
Comparison: Multiple comparison and modelling techniques (MCPMod) was used to evaluate several possible dose response models (patterns: Linear, Exponential, Emax, SigEmax, BetaMod), and to identify the best-fitting model or subset of models.p-value: 0.902MCPMod Exponential: model
Comparison: Multiple comparison and modelling techniques (MCPMod) was used to evaluate several possible dose response models (patterns: Linear, Exponential, Emax, SigEmax, BetaMod), and to identify the best-fitting model or subset of models.p-value: 0.866MCPMod Emax model
Comparison: Multiple comparison and modelling techniques (MCPMod) was used to evaluate several possible dose response models (patterns: Linear, Exponential, Emax, SigEmax, BetaMod), and to identify the best-fitting model or subset of models.p-value: 0.825MCPMod SigEmax model
Comparison: Multiple comparison and modelling techniques (MCPMod) was used to evaluate several possible dose response models (patterns: Linear, Exponential, Emax, SigEmax, BetaMod), and to identify the best-fitting model or subset of models.p-value: 0.634MCPMod BetaMod model
Secondary
Part 1 - Occurrence of Treatment Emergent Adverse Events (TEAEs)
The occurrence of treatment emergent adverse events (TEAEs) is reported as the number of patients with TEAEs.
Time frame: From first drug administration until end of exposure, plus residual effect period, up to approximately 68 weeks.
Population: Safety Analysis Set (SAF): all subjects who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Part 1 - Occurrence of Treatment Emergent Adverse Events (TEAEs) | 44 Participants |
| Spesolimab low dose group | Part 1 - Occurrence of Treatment Emergent Adverse Events (TEAEs) | 47 Participants |
| Spesolimab medium dose group | Part 1 - Occurrence of Treatment Emergent Adverse Events (TEAEs) | 51 Participants |
| Spesolimab high dose group | Part 1 - Occurrence of Treatment Emergent Adverse Events (TEAEs) | 47 Participants |
Secondary
Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 16
Percent change from baseline in draining fistula/tunnel (dT) count at Week 16 is reported. Tunnel/fistula/sinus were counted as dT only if draining. Least square means and standard errors were estimated by MMRM, which included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model.
Time frame: The MMRM model incorporates dT count from baseline (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14 and Week 16. The data represent the Least Squares Means at Week 16.
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug. The use of treatment policy approach disregards the intercurrent event and uses the value of the variable regardless of the occurrence of the intercurrent event.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 16 | -14.0 Percentage change | Standard Error 10.6 |
| Spesolimab low dose group | Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 16 | -23.5 Percentage change | Standard Error 10.7 |
| Spesolimab medium dose group | Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 16 | -36.2 Percentage change | Standard Error 10.8 |
| Spesolimab high dose group | Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 16 | -22.7 Percentage change | Standard Error 11.2 |
Comparison: The MMRM included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model.95% CI: [-39.2, 20.1]
Comparison: The MMRM included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model.95% CI: [-52, 7.6]
Comparison: The MMRM included fixed categorical effects of treatment at each visit, TNFi status at baseline, categorical baseline dT count and fixed continuous effect of baseline of outcome measures at each visit. Visit was treated as repeated measure with an unstructured covariance matrix for the within trial participant variability and all visits with planned measurements of the outcome variable as well as all dose groups were included in the model.95% CI: [-39.1, 21.6]