To Assess the Efficacy and Safety of INCB054707 in Participants With Hidradenitis Suppurativa

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of INCB054707 in participants with hidradenitis suppurativa over a 16-week placebo-controlled treatment period followed by a 36-week open-label extension period. All eligible participants will be invited to continue treatment for an additional 48-week Long-term extension period (also open label).

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of the Efficacy and Safety of INCB054707 in Participants With Hidradenitis Suppurativa

Conditions
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Hidradenitis Suppurativa, Acne Inversa

Intervention / Treatment
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* Drug: INCB054707
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HS disease duration of at least 3 months before screening. Willingness to avoid pregnancy or fathering children. Active HS in at least 2 distinct anatomical areas. Participants agree NOT to use topical antiseptics on the areas affected by HS lesions during the placebo-controlled 16-week treatment period Exclusion Criteria: Draining fistula count of > 20 at screening or baseline. Women who are pregnant (or who are considering pregnancy) or lactating. 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. History of failure to treatment of inflammatory diseases with JAK inhibitors. Have evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis. Participants known to be infected with HIV, Hepatitis B, or Hepatitis C. Laboratory values outside of the protocol-defined ranges.

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: INCB054707 15 mg<br>Participants will receive INCB054707 15 milligrams (mg) for 16 weeks in the Placebo-controlled Treatment Period, followed by INCB054707 75 mg for 36 weeks in the Open-label Extension Period. Participants will have the option to continue open-label treatment for an additional 48 weeks. | Drug: INCB054707<br>* Oral; Tablet<br>* Other names: Povorcitinib;|
| Experimental: INCB054707 45 mg<br>Participants will receive INCB054707 45 mg for 16 weeks in the Placebo-controlled Treatment Period, followed by INCB054707 75 mg for 36 weeks in the Open-label Extension Period. Participants will have the option to continue open-label treatment for an additional 48 weeks. | Drug: INCB054707<br>* Oral; Tablet<br>* Other names: Povorcitinib;|
| Experimental: INCB054707 75 mg<br>Participants will receive INCB054707 75 mg for 52 weeks in the Placebo-controlled Treatment Period (16 weeks) plus the Open-label Extension Period (36 weeks). Participants will have the option to continue open-label treatment for an additional 48 weeks. | Drug: INCB054707<br>* Oral; Tablet<br>* Other names: Povorcitinib;|
| Placebo Comparator: Placebo followed by INCB054707 75 mg<br>Participants will receive placebo for 16 weeks in the Placebo-controlled Treatment Period, followed by INCB054707 75 mg for 36 weeks in the Open-label Extension Period. Participants will have the option to continue open-label treatment for an additional 48 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 |
| --- | --- | --- |
| Mean Change From Baseline in Abscess and Inflammatory Nodule (AN) Count at Week 16 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The mixed model repeated measure (MMRM) included the fixed effects of treatment group (placebo and INCB054707 15, 45, and 75 mg), stratification factors (disease severity [Hurley Stage I, II, and III] and geographical region [North America and outside of North America]), visit (Weeks 2, 4, 6, 8, 12, and 16), treatment by visit interaction, and covariates of Baseline measurement and Baseline measurement by visit interaction. The variance-covariance matrix of the within-participant errors in MMRM are modeled as unstructured. | Baseline; Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 16 | HiSCR, the key secondary endpoint, was defined as at least a 50% decrease from Baseline in AN count with no increase in the number of abscesses or draining fistulas. | Baseline; Week 16 | 
| Percentage of Participants Who Achieved a HiSCR at Weeks 2 Through 12 | HiSCR was defined as at least a 50% decrease from Baseline in AN count with no increase in the number of abscesses or draining fistulas. | Baseline; Weeks 2, 4, 6, 8, and 12 | 
| Percentage of Participants Who Achieved HiSCR75 From Weeks 2 to 16 | HiSCR75 was defined as at least a 75% decrease from Baseline in AN count with no increase in the number of abscesses or draining fistulas. | Baseline; Weeks 2, 4, 6, 8, 12, and 16 | 
| Mean Change From Baseline in the Severity of the Disease, as Assessed by the International Hidradenitis Suppurativa Severity Score System (IHS4) Score, From Weeks 2 to 16 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The IHS4 is a composite, dynamic score and validated tool used to determine Hidradenitis Suppurativa severity. It employs a weighted scale using the number of inflammatory nodules, the number of abscesses, and the number of draining tunnels (fistulas or sinuses), with respective weight factors of 1, 2, and 4. Scores: mild=0-3; moderate=4-10; severe ≥11. MMRM included the fixed effects of treatment group (placebo and INCB054707 15, 45, and 75 mg), stratification factors (disease severity [Hurley Stage I, II, and III] and geographical region [North America and outside of North America]), visit (Weeks 2, 4, 6, 8, 12, and 16), treatment by visit interaction, and covariates of Baseline measurement and Baseline measurement by visit interaction. The variance-covariance matrix of the within-participant errors in MMRM are modeled as unstructured. | Baseline; Weeks 2, 4, 6, 8, 12, and 16 | 
| Percentage of Participants Who Achieved AN50, AN75, AN90, and AN100 From Weeks 2 to 16 | AN50, AN75, AN90, and AN100 were defined as at least a 50%, 75%, 90%, and 100% decrease, respectively, from Baseline in AN count. | Baseline; Weeks 2, 4, 6, 8, 12, and 16 | 
| Mean Change From Baseline in AN Count at Weeks 2 to 12 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. MMRM included the fixed effects of treatment group (placebo and INCB054707 15, 45, and 75 mg), stratification factors (disease severity [Hurley Stage I, II, and III] and geographical region [North America and outside of North America]), visit (Weeks 2, 4, 6, 8, 12, and 16), treatment by visit interaction, and covariates of Baseline measurement and Baseline measurement by visit interaction. The variance-covariance matrix of the within-participant errors in MMRM are modeled as unstructured. | Baseline; Weeks 2, 4, 6, 8, and 12 | 
| Percentage of Participants With a Total AN Count of 0 to 2 From Weeks 2 to 16 | Total AN count was assessed throughout the study. | Weeks 2, 4, 6, 8, 12, and 16 | 
| Mean Change From Baseline in Draining Fistula Count From Weeks 2 to 16 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline; Weeks 2, 4, 6, 8, 12, and 16 | 
| Mean Change From Baseline in Abscess, Inflammatory Nodule (IN), and Draining Fistula (DF) (ANF) Count From Weeks 2 to 16 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. MMRM included the fixed effects of treatment group (placebo and INCB054707 15, 45, and 75 mg), stratification factors (disease severity [Hurley Stage I, II, and III] and geographical region [North America and outside of North America]), visit (Weeks 2, 4, 6, 8, 12, and 16), treatment by visit interaction, and covariates of Baseline measurement and Baseline measurement by visit interaction. The variance-covariance matrix of the within-participant errors in MMRM are modeled as unstructured. | Baseline; Weeks 2, 4, 6, 8, 12, and 16 | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until the end of the safety follow-up. | up to Week 16 |