Safety, tolerability, and preliminary efficacy of soquelitinib in participants with moderate to severe AD

A Phase 1, Randomized, Blinded, Placebo-controlled, Dose Escalation and Expansion Study to Investigate the Safety, Tolerability, and Preliminary Efficacy of ITK Inhibitor Soquelitinib in Participants with Moderate to Severe Atopic Dermatitis

Inclusion Criteria:

1. Adult male or female, ≥18 years of age at Screening.

2. Atopic dermatitis, according to Hanifin and Rajka criteria and confirmed by a dermatologist.

3. Moderate to severe disease defined by EASI ≥16; body surface area ≥10; and vIGA ≥3.

4. Documented history of inadequate response or intolerance to one or more topical therapies (including but not limited to corticosteroids, immune modulators, PDE-4 inhibitors) and/or systemic therapies (including but not limited to, dupilumab, cyclosporine, mycophenolate, azathioprine, oral corticosteroids or a JAK inhibitor, e.g., tofacitinib, baricitinib, and ruxolitinib).

5. A male participant must agree to use contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period.

6. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

   1. Not a woman of childbearing potential (WOCBP) OR
   2. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after last dose of study treatment

Exclusion Criteria:

1. Are currently experiencing or have a history of other concomitant skin conditions (e.g., psoriasis, cutaneous lupus, previous burns, or extensive tattoos) that would interfere with evaluations of the effect of study medication on AD.

2. Other active skin diseases or skin infections (bacterial, fungal, or viral) requiring systemic treatment within 4 weeks of the Baseline visit or would interfere with the appropriate assessment of AD lesions.

3. Administration of oral prednisone or its equivalent within 2 weeks of starting the trial or receiving corticosteroids parenterally within 4 weeks of Screening.

4. Administration of oral or injectable immunosuppressive medications such as methotrexate, mycophenolate, azathioprine, cyclosporine, dupixent, a janus kinase inhibitor or tacrolimus (except that topical is allowed) within 4 weeks of Screening.

5. Active use of phototherapy, attending a tanning booth, or extended sun exposure which could affect judging disease activity.

6. Female participant who is pregnant, breastfeeding or is considering becoming pregnant during the study or for approximately 120 days after the last dose of study intervention.

7. Male participant who is considering fathering a child or donating sperm during the study or for approximately 120 days after the last dose of study intervention.

8. History of immunosuppression not related to medication (such as common variable hypogammaglobulinemia), history of clinically significant medical conditions (such as anemia, neutropenia, thrombocytopenia, abnormal renal function, or abnormal liver function), planned surgical procedures, or any other reason which in the opinion of the investigator or Sponsor would interfere with the participant's participation in this study, would make the participant an unsuitable candidate to receive study intervention, or would put the participant at risk by participating in the protocol; or permanently wheelchair-bound or bedridden or very poor functional status which prevents the ability to perform self-care.

9. Have an unstable or uncontrolled illness, including but not limited to cerebrocardiovascular (e.g., unstable angina, unstable arterial hypertension, moderate to severe heart failure [New York Heart Association Class III/IV]), respiratory, gastrointestinal, endocrine, hematologic, or neurologic disorders that would potentially affect participant safety within the study or confound efficacy and safety assessments.

10. Participants with renal function which is moderately or severely impaired, defined as an estimated glomerular filtration rate (eGFR) ≤59 ml/minute.

11. Participants with abnormal liver function as recognized by the FDA and as defined by the Child-Pugh criteria. Specifically, participants must show no signs of encephalopathy, have no ascites, have a serum bilirubin ≤2.0 mg/dL, have a serum albumin ≥3.5 g/dL, and have a prothrombin time prolonged by no more than 4 seconds.

12. Any of the following laboratory values would preclude participation in this trial:

    • Hematocrit <30%
    • Neutrophil count <2000/μl
    • Liver enzymes ≥2 × upper limit of normal (ULN)
    • Platelet count <100,000/μl

13. Participants who cannot ingest medications orally or who have malabsorption.

Blinded Placebo-Controlled