A Placebo-Controlled Study of the Safety of INCB054707 in Participants With Hidradenitis Suppurativa

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of INCB054707 over an 8-week treatment period in men and women with moderate to severe hidradenitis suppurativa.

Official Title
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A Phase 2, Dose-Escalation, Placebo-Controlled Study of the Safety of INCB054707 in Participants With Hidradenitis Suppurativa

Conditions
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Hidradenitis Suppurativa

Intervention / Treatment
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* Drug: INCB054707
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of HS (confirmed by a dermatologist) with a disease duration of at least 6 months before screening. Stable course of HS for at least 90 days before screening, as determined by the investigator. HS lesions present in at least 2 distinct anatomic areas, 1 of which must be Hurley Stage II or Hurley Stage III at screening. Total AN count of at least 3 at screening and baseline. Willingness to avoid pregnancy or fathering children. Exclusion Criteria: Women who are currently pregnant or lactating. Presence of > 20 draining fistulas at screening and baseline. Participants with protocol-defined concurrent conditions or history of other diseases. Prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF), defined as ≥ 450 msec. Positive test result for tuberculosis from the QuantiFERON-TB Gold test, or T-SPOT.TB test at screening. A history of active tuberculosis (treated or untreated) or a history of untreated latent tuberculosis. Positive serology test results for HIV, hepatitis B surface antigen, hepatitis B virus core antibody, or hepatitis C virus (HCV antibody with positive HCV-RNA) at screening. Decreased blood cell counts at screening per protocol-defined criteria. Severely impaired liver function (Child-Pugh Class C) or alanine aminotransferase or aspartate aminotransferase levels ≥ 1.5 × upper limit of normal at screening. Impaired renal function with serum creatinine > 1.5 mg/dL at screening. Use of protocol-prohibited medications. Known or suspected allergy to INCB054707 or any component of the study drug. Known history of clinically significant drug or alcohol abuse in the last year before baseline.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>INCB054707 at the Cohort 1 dose or placebo. | Drug: INCB054707<br>* INCB054707 tablet administered orally once daily at the protocol-defined dose.<br>* Other names: Povorcitinib;Drug: Placebo<br>* Placebo tablet administered orally once daily.<br>|
| Experimental: Cohort 2<br>INCB054707 at the Cohort 2 dose or placebo. | Drug: INCB054707<br>* INCB054707 tablet administered orally once daily at the protocol-defined dose.<br>* Other names: Povorcitinib;Drug: Placebo<br>* Placebo tablet administered orally once daily.<br>|
| Experimental: Cohort 3<br>INCB054707 at the Cohort 3 dose or placebo. | Drug: INCB054707<br>* INCB054707 tablet administered orally once daily at the protocol-defined dose.<br>* Other names: Povorcitinib;Drug: Placebo<br>* Placebo tablet administered orally once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment-emergent Adverse Events (TEAEs) | TEAE is defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. Grading was performed using guidance from the CTCAE v 4.03. A grade 3 and above would constitute as severe. | Up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apparent Oral Clearance of INCB054707 | To determine the systemic exposure to INCB054707. Dependent upon the final compartmental model describing INCB054707. | Predose Day 1, Week 4, and 8, Postdose Day1, week 2,4,6, and 8 | 
| Apparent Oral Volume of Distribution of INCB054707 | To determine the systemic exposure to INCB054707. Dependent upon the final compartmental model describing INCB054707. | Predose Day 1, Week 4, and 8, Postdose Day1, week 2,4,6, and 8 | 
| Proportion of Participants Achieving a Hidradenitis Suppurativa Clinical Response (HiSCR) at Each Visit | HiSCR defined as at least 50% reduction in abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to baseline. | Weeks 1, 2, 4, 6, 8, Early Termination and Follow-up (Up to 3 months) | 
| Proportion of Participants Achieving an AN Count of 0 to 2 at Each Visit | AN defined as abscess and inflammatory nodule count. | Baseline,Weeks 1, 2, 4, 6, 8, Early Termination and Follow-up (Up to 3 months) | 
| Mean Change From Baseline in the Hidradenitis Suppurativa Pain Numeric Rating Scale (HS Pain NRS) Scores at Each Visit | An 11-point scale used to assess the worst skin pain and the average skin pain due to HS. Skin pain ranges from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). | Baseline,Weeks 1, 2, 4, 6, 8, Early Termination and Follow-up (Up to 3 months) | 
| Mean Change From Baseline in the Modified Sartorius Scale Score | The Sartorius Scale is used to quantify the severity of HS. Points are awarded for 12 body areas (left and right axillae, left and right sub/inframammary areas, intermammary area, left and right buttocks, left and right inguino-crural folds, perianal area, perineal area, and other). For each area, points are awarded for nodules (2 points for each); abscesses (4 points); fistulas (4 points); scars (1 point); longest distance between two lesions (2-6 points, 0 if no lesions); and if lesions are separated buy normal skin (yes-0 point; no-6 points). The total Sartorius Scale score is the sum of the 12 regional scores. Scale scores range from 0 to infinite, with larger scores representing higher severity of HS. | From baseline up to week 8 | 
| Mean Change From Baseline in the Number of Draining Fistulas Count at Each Visit. | Defined as fistulas that drain serous or purulent fluid, either spontaneously or by gentle palpation. | Baseline,Weeks 1, 2, 4, 6, 8 and Follow-up (Up to 3 months) | 
| Proportion of Participants at Each Category of Hurley Stage | The Hurley classification is a static score and was originally designed for selection of the appropriate treatment modality in a certain body region. The assessor determines the Hurley stage in each affected anatomical region. If more than 1 stage is present in the same region, the worst stage in that region is documented. The participant will be assigned an overall Hurley stage classification corresponding to the stage of the worst involved anatomical region. The definition of each Hurley stage is as follows: Stage I : Abscess formation, single or multiple, without sinus tracts and cicatrization (scarring). Stage II : One or more widely separated recurrent abscesses with tract formation and cicatrization (scarring). Stage III : Multiple interconnected tracts and abscesses across the entire area, with diffuse or near diffuse involvement. | Baseline and Week 8 | 
| Proportions of Participants in Each HS Patient Global Impression of Change (PGIC) Category During the Treatment Period | The HS-PGIC consists of 1 self-administered item that assesses change in the severity of skin in the HS area. The participant will answer the following: Since your last visit, your HS is: (1) very much improved, (2) much improved, (3) minimally improved, (4) no change, (5) minimally worse, (6) much worse, or (7) very much worse. | Up to 12 weeks | 
| Actual Measurements in HS-PGIC at Each Visit | The HS-PGIC consists of 1 self-administered item that assesses change in the severity of skin in the HS area. The participant will answer the following: Since your last visit, your HS is: (1) very much improved, (2) much improved, (3) minimally improved, (4) no change, (5) minimally worse, (6) much worse, or (7) very much worse. | Up to 12 weeks | 
| Proportion of Participants With Change From Baseline Hurley Stage | The Hurley classification is a static score and was originally designed for selection of the appropriate treatment modality in a certain body region. The assessor determines the Hurley stage in each affected anatomical region. If more than 1 stage is present in the same region, the worst stage in that region is documented. The participant will be assigned an overall Hurley stage classification corresponding to the stage of the worst involved anatomical region. The definition of each Hurley stage is as follows: Stage I : Abscess formation, single or multiple, without sinus tracts and cicatrization (scarring). Stage II : One or more widely separated recurrent abscesses with tract formation and cicatrization (scarring). Stage III : Multiple interconnected tracts and abscesses across the entire area, with diffuse or near diffuse involvement. | Baseline and Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hidradenitis suppurativa, Janus kinase (JAK) inhibitor, skin disease