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

Phase 2

Completed

Conditions: Hidradenitis Suppurativa

Interventions: Drug: Spesolimab - solution for infusion
Drug: Placebo matching spesolimab - solution for infusion
Drug: Spesolimab- solution for injection
Drug: Placebo matching to spesolimab- solution for injection

Registration Number: NCT04762277

Lead Sponsor: Boehringer Ingelheim

Brief Summary: This study is open to adults with a chronic inflammatory skin disease called hidradenitis suppurativa. The purpose of this study is to find out whether a medicine called spesolimab helps people with moderate to severe hidradenitis suppurativa.

Participants are put into 2 groups by chance. One group takes spesolimab. The other group takes placebo. Every participant has twice the chance of being in the spesolimab group than in the placebo group. Participants get spesolimab or placebo as an infusion into a vein every week for the first 3 weeks. Afterwards, they get spesolimab or placebo as injections under the skin every 2 weeks. Placebo infusions and injections look like spesolimab infusions and injections but do not contain any medicine.

Participants are treated in the study for about 3 months. During this time, they visit the study site about 9 times. After completing this part of the study, participants are offered to join another clinical study in which all participants get spesolimab. Participants who cannot join the other study, stay in this study for about 4 more months. During this time, participants do not take spesolimab nor placebo but they visit the study site 2 times to have their health checked.

At study visits, doctors thoroughly check the skin of participants to count lumps (nodules) and boils (abscesses). The results between the spesolimab group and the placebo group are compared after 3 months of treatment. The doctors also regularly check the general health of the participants.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 52

Inclusion Criteria

Male or female adult patients, 18 years of age or older
Signed and dated written informed consent in accordance with International Council on Harmonisation (ICH) Good Clinical Practice (GCP) and local legislation prior to the start of any screening procedures
Moderate to severe Hidradenitis suppurativa (HS), based on International Hidradenitis Suppurativa Severity Score System (IHS4) criteria, for at least 1 year prior to the baseline visit, as determined by the investigator through participant interview and/or review of the medical history. (If IHS4 scoring is not available, equivalent scoring based on scoring systems as HS-PGA or Hurley are acceptable based on documented investigator assessment)
HS lesions in at least 2 distinct anatomic area (right/left axillary, inguinal, inframammary, perineal)
Biologic naive or TNF inhibitor (TNFi)-failure for HS
Inadequate response to an adequate course of appropriate oral antibiotics for treatment of HS in the last 1 year, as per investigator discretion. This is not applicable for TNFi-failure patients
Total abscess and inflammatory nodule (AN) count of greater than or equal to 5
Total draining fistula count of less than or equal to 20 Further inclusion criteria apply

Exclusion Criteria

Presence of active skin lesions other than HS that interfere with the assessment of HS
Use of restricted medications as below:
- Topical corticosteroids over HS lesions within 1 week of Visit 2
- Systemic antibiotics within 4 weeks of visit 2
- Systemic non-biologic immunomodulatory and/or immunosuppressive agents use for HS within 4 weeks (or 5 half lives, whichever is longer) of visit 2
- Biologic agents use within 12 weeks or 5 half-lives, whichever is longer, prior to visit 2
- Opioid analgesics within 2 weeks of visit 2
- Live virus vaccine within 6 weeks of visit 2
Prior exposure to any immunosuppressive biologic other than TNFi for HS
Prior exposure to Interleukin 36 Receptor (IL-36R) inhibitors including spesolimab
Treatment 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, prior to visit 2
Women who are pregnant, nursing, or who plan to become pregnant while in the trial. Women who stop nursing before the study drug administration do not need to be excluded from participating
History of allergy/hypersensitivity to the systemically administered trial medication agent or its excipients
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., Remestemcel-L) Further exclusion criteria apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Spesolimab	Spesolimab - solution for infusion	-
Spesolimab	Spesolimab- solution for injection	-
Placebo	Placebo matching spesolimab - solution for infusion	-
Placebo	Placebo matching to spesolimab- solution for injection	-

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Total Abscess and Inflammatory Nodule Count at Week 12	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.	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.

Secondary Outcome Measures

Name	Time	Method
Occurrence of at Least One Flare at Week 12	At Week 12.	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.
Percent Change From Baseline in Draining Fistula Count at Week 12	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.	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.
Achievement of Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12	At baseline (Week 0) and at Week 12.	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.
Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 12	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.	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.
Absolute Change From Baseline in Hidradenitis Suppurativa Area and Severity Index (HASI) Score at Week 12	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.	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.
Achievement of Hidradenitis Suppurativa Physician Global Assessment (HS-PGA) Score of 0 or 1 at Week 12	At Week 12.	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.
Achievement of at Least 30% Reduction From Baseline in Numerical Rating Scale (NRS30) in Patient's Global Assessment of HS Pain at Week 12	At baseline (Week 0) and at Week 12.	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.
Occurrence of Complete Elimination of Draining Fistulas at Week 12	Baseline (Week 0) and at Week 12.	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.
Absolute Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 12	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.	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).
Absolute Change From Baseline in Hidradenitis Suppurativa Quality of Life (HiS-QoL) Total Score at Week 12	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.	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).
The Occurrence of Treatment Emergent Adverse Events (TEAEs)	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.	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)).

Trial Locations

Locations (25): Dermatology Research Associates
🇺🇸
Los Angeles, California, United States
Dawes Fretzin Clinical Research Group, LLC
🇺🇸
Indianapolis, Indiana, United States
University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Unity Clinical Research
🇺🇸
Oklahoma City, Oklahoma, United States
Universitätsklinikum Frankfurt
🇩🇪
Frankfurt am Main, Germany
Holdsworth House Medical Practice
🇦🇺
Sydney, New South Wales, Australia
ULB Hopital Erasme
🇧🇪
Bruxelles, Belgium
Dr. S. K. Siddha Medicine Professional Corporation
🇨🇦
Newmarket, Ontario, Canada
University Hospital Ostrava
🇨🇿
Ostrava, Czechia
CLI Reims Bezannes
🇫🇷
Bezannes, France
Katholisches Klinikum Bochum gGmbH
🇩🇪
Bochum, Germany
HOP Larrey
🇫🇷
Toulouse, France
Azienda Ospedaliera Universitaria Pisana
🇮🇹
Pisa, Italy
Erasmus Medisch Centrum
🇳🇱
Rotterdam, Netherlands
Ospedali Riuniti di Ancona
🇮🇹
Ancona, Italy
Haukeland Universitetssykehus
🇳🇴
Bergen, Norway
Nordlandssykehuset HF, Bodø
🇳🇴
Bodø, Norway
Non-Public Health Care Facility LABDERM
🇵🇱
Ossy, Poland
Cityclinic Medical and Psychological Clinic Matusiak Partnership
🇵🇱
Wroclaw, Poland
Hospital Santa Creu i Sant Pau
🇪🇸
Barcelona, Spain
Mayo Clinic, Rochester
🇺🇸
Rochester, Minnesota, United States
Royal Melbourne Hospital
🇦🇺
Parkville, Victoria, Australia
HOP Edouard Herriot
🇫🇷
Lyon, France
Städtisches Klinikum Dessau
🇩🇪
Dessau, Germany
Oslo Universitetssykehus HF, Rikshospitalet
🇳🇴
Oslo, Norway