A Phase 2, Open-Label, Single-Arm Study of the Safety of INCB054707 in Participants With Hidradenitis Suppurativa

Inclusion Criteria

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Men and women aged 18 to 75 years at the time of consent.
• 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 (ie, recurrent abscessed with tract formation and cicatrization; single or multiple, widely separated lesions) or Hurley Stage III (ie, diffuse, or near diffuse involvement or multiple interconnected tracts and abscesses across the entire area) at screening and baseline.
• Total AN count of at least 3 at screening and baseline.
• Agreement to use contraception, as follows:

a. Male participants must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through 90 days after the last dose of study drug. Male participants must also refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participant and his understanding confirmed.

Exclusion Criteria**

Participants are excluded from the study if any of the following criteria apply:

• Women of childbearing potential or who are currently pregnant or lactating.

Note: Nonchildbearing potential is defined as surgically sterile with a hysterectomy and/or bilateral oophorectomy OR postmenopausal (defined as amenorrhea at least 12 months before screening, confirmed by FSH levels at screening).

• Presence of > 20 draining fistulas at screening and baseline.
• Participants with concurrent conditions or history of other diseases, as follows:

a. Any clinically significant medical condition other than HS, as determined by the investigator, that is not adequately controlled with appropriate treatment.

b. Any other active skin disease or condition (eg, bacterial, fungal, or viral infection) that may interfere with the course, severity, or assessments of HS.

c. Active systemic viral infection or any active viral infection that, based on the investigator's clinical assessment, make the participant an unsuitable candidate for the study.

d. Current herpes zoster infection, a history of recurrent herpes zoster, a history of disseminated herpes simplex, or a history of herpes zoster.

e. History of malignancy, including lymphoma and leukemia within 5 years before baseline, other than a successfully treated nonmetastatic cutaneous squamous cell carcinoma, basal cell carcinoma, or localized carcinoma in situ of the cervix.

f. Albinism.

• Prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF), defined as ≥ 450 msec.

Note: Prolonged QTcF values of ≥ 450 msec at screening are to be confirmed by performing 2 additional ECGs and averaging the results to determine if the averaged value meets the exclusion criterion.

• Positive test result for TB from the QuantiFERON-TB Gold test, or equivalent, at screening (or, if 2 indeterminate tests or not available, then as evaluated by a purified protein derivative test with a result of < 5 mm of induration within 3 months of screening) or a history of active TB.

Note: If the participant has possible evidence of a latent TB infection, the participant must have documented completion of an adequate course of therapy for latent TB and provide recent (within 3 months) posteroanterior and lateral views chest x-ray without changes suggestive of active or latent TB, prior to baseline.

• Positive serology test results for HIV, HBsAg, HBV core antibody, or HCV (HCV-antibody with positive HCV-RNA) at screening.
• Decreased blood cell counts at screening, defined as follows:

a. Leukocytes < 3.0 × 109/L (< 2.5 × 109/L for participants who are African- American).

b. ANC < 1.5× 109/L.

c. Lymphocytes < 0.8 × 109/L.

d. Hemoglobin < 10 g/dL.

e. Platelets < 150 × 109/L.

• Severely impaired liver function (Child-Pugh Class C) or ALT or AST levels ≥ 1.5 × ULN.
• Impaired renal function with serum creatinine > 1.5 mg/dL.
• Use of the following medications:

a. Previous use of JAK inhibitors, systemic or topical (eg, ruxolitinib, tofacitinib, baricitinib, filgotinib, lestaurtinib, and pacritinib).

b. Previous use of adalimumab or any other TNF-α treatment, investigational, or any experimental treatments within 12 weeks or 5 half-lives (whichever is longer) before baseline.

c. Systemic immunosuppressive or immunomodulating drugs (eg, oral or injectable corticosteroids, methotrexate, cyclosporine, and azathioprine) within 4 weeks or 5 half-lives (whichever is longer) before baseline.

d. Other systemic therapies for HS (eg, retinoids and antiandrogens) with potential therapeutic impact for HS within 4 weeks or 5 half-lives (whichever is longer) before baseline.

e. Surgical, laser, or IPL intervention in area with HS lesion within 4 weeks before baseline.

f. Systemic anti-infectives (eg, antibiotics, antivirals, antifungals) within 4 weeks or topical anti-infectives on HS lesions (eg, antibiotics, antivirals, antifungals) within 2 weeks before baseline.

g. Received live vaccine within 6 weeks before baseline or planning to receive live vaccine during the course of the study or within 6 weeks after EOT.

h. Topical antiseptic washes, creams, soaps, ointments, gels, and liquids containing antibacterial agents to treat HS, except those listed in Sections 6.6.2.3 and 6.6.2.4, within 2 weeks before baseline.

i. Potent systemic CYP3A4 inhibitors and inducers (see Appendix B) or fluconazole within 2 weeks or 5 half-lives (whichever is longer) before baseline.

Note: Topical agents with limited systemic availability are permitted.

• 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 prior to baseline.
• For participants consenting to biopsies only:

a. Participant has a history of an allergic reaction or significant sensitivity to lidocaine or other local anesthetics.

b. Participant has a history of hypertrophic scarring or keloid formation in scars or suture sites.

c. Participant is taking anticoagulant medication, such as heparin, low molecular weight-heparin, warfarin, and antiplatelets (nonsteroidal anti- inflammatory drugs and low-dose aspirin ≤ 81 mg will not be considered antiplatelets), or has a contraindication to skin biopsies.

• Inability or unlikeliness of the participant to comply with the dose schedule and study evaluations, in the opinion of the investigator.
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
• Inability of the participant (or parent, guardian, or legally authorized representative) to comprehend or unwilling to sign the ICF.