A Study to Evaluate the Efficacy and Safety of Povorcitinib (INCB054707) in Participants With Moderate to Severe Hidradenitis Suppurativa

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of Povorcitinib (INCB054707) in participants with moderate to severe Hidradenitis Suppurativa (HS) over a 12-week placebo controlled period, followed by a 42-week extension period.

Official Title
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A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Efficacy and Safety Study of Povorcitinib (INCB054707) in Participants With Moderate to Severe Hidradenitis Suppurativa

Conditions
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Hidradenitis Suppurativa (HS)

Intervention / Treatment
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* Drug: Povorcitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of moderate to severe HS for at least 3 months prior to the screening visit. Total abscess and inflammatory nodule count of at least 5 at both the screening and baseline visits HS lesions in at least 2 distinct anatomical areas (examples include but are not limited to left and right axilla or left and right inguinocrural fold), 1 of which must be at least Hurley Stage II or Hurley Stage III, at both the screening and baseline visits Documented history of inadequate response to at least a 3-month course of at least 1 conventional systemic therapy (oral antibiotic or biologic drug) for HS (or demonstrated intolerance to, or have a contraindication to, a conventional systemic therapy for treatment of their HS). Agreement to NOT use topical and systemic antibiotics for treatment of HS during the placebo-controlled period. Agreement to NOT use a diluted bleach bath or topical antiseptic washes containing chlorhexidine gluconate or benzoyl peroxide on the areas affected by HS lesions during the placebo-controlled period. Note: Over-the-counter soap and water is allowed. Agreement to use contraception Willing and able to comply with the study protocol and procedures. Further inclusion criteria apply. Exclusion Criteria: Presence of > 20 draining tunnels (fistulas) at either the screening or baseline visit. Women who are pregnant (or who are considering pregnancy) or breastfeeding. Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, Q-wave interval abnormalities, current or history of certain infections, cancer, lymphoproliferative disorders and other medical conditions at the discretion of the investigator. Laboratory values outside of the protocol-defined ranges. Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized 1:1:1 to Povorcitinib Dose A, Povorcitinib Dose B, or placebo once a day (QD); participants who complete the placebo controlled (PC) 12-week period may continue to a 42-week extension(EXT) period with Povorcitinib (Dose A or Dose B) QD.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Povorcitinib Dose A<br>Participants will receive Povorcitinib Dose A for 54 weeks. | Drug: Povorcitinib<br>* Oral; Tablet<br>* Other names: INCB054707;|
| Experimental: Povorcitinib Dose B<br>Participants will receive Povorcitinib Dose B for 54 weeks. | Drug: Povorcitinib<br>* Oral; Tablet<br>* Other names: INCB054707;|
| Placebo Comparator: Placebo<br>Participants will receive Placebo for 12 weeks, followed by Povorcitinib (Dose A or Dose B) for 42 weeks. | Drug: Placebo<br>* Oral; Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who achieve Hidradenitis Suppurativa Clinical Response (HiSCR) | HiSCR is defined as at least a 50% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who achieve Hidradenitis Suppurativa Clinical Response 75 (HiSCR75) | HiSCR75 is defined as at least a 75% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count. | Week 12 | 
| Proportion of participants with flare | Participants who experience at least 1 flare over 12 weeks; flare is defined as at least a 25% increase in the total abscess and inflammatory nodule count with a minimum increase of 2 relative to baseline. | 12 weeks | 
| Proportion of participants with a ≥ 3-point decrease in Skin Pain Numeric Rating Scale (NRS) score among participants with baseline Skin Pain NRS score ≥ 3. | Participants with a Skin Pain score of at least 3 at baseline and who experience at least a 3-point decrease in Skin Pain score at Week 12, relative to baseline. Skin Pain is an 11 point NRS, ranging from 0 (no skin pain) to 10 (worst skin pain). | Week 12 | 
| Proportion of participants who achieve Skin Pain NRS30 among participants with baseline Skin Pain NRS score ≥ 3. | Participants with a Skin Pain score of at least 3 at baseline and who achieve at Week 12 Skin Pain NRS30, defined as at least a 30% reduction and at least 1-unit reduction from baseline in the Skin Pain NRS. | Week 12 | 
| Proportion of participants with a ≥ 4-point increase from baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT F) score | Participants with a baseline FACIT-F score ≤ 48 and who experience at least a 4-point increase in FACIT-F score at Week 12, relative to baseline. The FACIT-F scale is a 13-item questionnaire that assesses self reported fatigue and its impact upon daily activities and function over the past 7 days, with scores ranging from 0 (worst fatigue) to 52 (no fatigue). | Week 12 | 
| Mean change from baseline in Dermatology Life Quality Index (DLQI) score at each visit | The DLQI is a skin disease specific questionnaire aimed at the evaluation of how symptoms and treatment affect participants' health-related quality of life (QoL). The DLQI total score ranges from 0 to 30, with higher scores indicating lower skin health related QoL. | 54 weeks | 
| Mean change from baseline in abscess count at each visit. | Defined as mean change of Abscess count relative to baseline. | 54 weeks | 
| Percentage change from baseline in abscess count at every visit | Percent change from baseline in number of abscess(es) | 54 weeks | 
| Mean change from baseline in inflammatory nodule count at each visit | Defined as mean change of inflammatory nodule count relative to baseline. | 54 weeks | 
| Percentage change from baseline in inflammatory nodule count at each visit. | Defined as percent change from baseline in number of inflammatory nodule(s) | 54 weeks | 
| Mean change from baseline in draining tunnel count at each visit. | Defined as mean change of draining tunnel count relative to baseline. | 54 weeks | 
| Percentage change from baseline in draining tunnel count at each visit. | Defined as percent change from baseline in number of draining tunnel(s) | 54 weeks | 
| Extension Period: Proportion of participants who achieve HiSCR | HiSCR is defined as at least a 50% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count. | Week 24 | 
| Extension Period: Proportion of participants who achieve HiSCR75 | HiSCR75 is defined as at least a 75% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count. | Week 24 | 
| Extension Period: Proportion of participants with flare | Participants who experience at least 1 flare over the period under assessment; flare is defined as at least a 25% increase in the total abscess and inflammatory nodule count with a minimum increase of 2 relative to baseline. | From Week 12 through Week 24 | 
| Extension Period: Proportion of participants who achieved Skin Pain NRS30 among participants with baseline Skin Pain NRS score ≥ 3 | Skin Pain NRS30 defined as at least a 30% reduction and at least 1-unit reduction from baseline in the Skin Pain NRS. | Week 24 | 
| Extension Period: Proportion of participants who achieve HiSCR | HiSCR is defined as at least a 50% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count | Week 54 | 
| Extension Period: Proportion of participants who achieve HiSCR75 | HiSCR75 is defined as at least a 75% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count. | Week 54 | 
| Extension Period : Proportion of participants with flare | Participants who experience at least 1 flare over the period under assessment; flare is defined as at least a 25% increase in the total abscess and inflammatory nodule count with a minimum increase of 2 relative to baseline. | From Week 12 through Week 54 | 
| Extension Period: Proportion of participants who achieved Skin Pain NRS30 among participants with baseline Skin Pain NRS score ≥ 3. | Participants with a Skin Pain score of at least 3 at baseline and who achieve at Week 24 Skin Pain NRS30, defined as at least a 30% reduction and at least 1-unit reduction from baseline in the Skin Pain NRS. | Week 54 | 
| Extension Period:Proportion of participants who achieve maintenance of HiSCR or greater response at each visit | Maintenance of response defined as participants who achieve HiSCR at Week 12 and maintain it or achieve greater response at each visit during the EXT period. | From Week 12 through Week 54 | 
| Extension Period : Proportion of participants who achieve maintenance of HiSCR75 or greater response at each visit | Maintenance of response defined as participants who achieve HiSCR75 at Week 12 and maintain it or achieve greater response at each visit during the EXT period. | From Week 12 through Week 54 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hidradenitis Suppurativa, Hidradenitis, Acne inversa, HS, INCB054707, Povorcitinib