Study of ATI-1777 in Adult Patients With Moderate or Severe Atopic Dermatitis
Condition: Atopic Dermatitis
MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema
Intervention: ATI-1777; Vehicle
Intervention description: ATI-1777 topical solution 2.0% w/w; Vehicle topical solution containing no ATI-1777
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, Double-blind, Vehicle-controlled, Parallel-group Study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This is a first-in-human, randomized, double-blind, parallel-group, vehicle-controlled study
      to evaluate the efficacy, safety, tolerability, and PK of ATI-1777 solution following
      twice-daily applications to target areas of participants with moderate or severe atopic
      dermatitis (AD).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Able to comprehend and willing to sign the IRB approved informed consent form (ICF)
             prior to administration of study-related procedures.

          2. Male patients or non-pregnant, non-nursing female patients 18 to 65 years old,
             inclusive, at the time of informed consent.

          3. Pregnancy and Contraception:

               -  Women of childbearing potential (WOCBP), must have a negative serum pregnancy
                  test at the Screening Visit, a negative urine pregnancy test immediately prior to
                  the first application of study medication on Day 1, and a negative urine
                  pregnancy test at each study visit thereafter.

               -  WOCBP must agree to use 2 forms of highly effective contraception, including 1
                  physical barrier (condom or diaphragm) plus another highly effective method, such
                  as adequate hormonal method (e.g., contraceptive implants, injectables, oral
                  contraceptives) or nonhormonal methods (e.g., intrauterine device, spermicidals)
                  throughout the Screening Period and until 30 days after the last administration
                  of study medication.

               -  Male patients with partners of childbearing potential may be enrolled if they
                  are:

                    -  Documented to be surgically sterile (vasectomy), or

                    -  Using 2 adequate forms of highly effective contraception, 1 of which should
                       be a physical barrier until 90 days after the last administration of study
                       medication.

          4. Have a diagnosis of AD fulfilling the specified diagnostic criteria of Hanifin and
             Rajka (Hanifin and Rajka 1980).

          5. Have at least a 6-month history of AD prior to the Screening Visit, and no significant
             AD flares for the 4 weeks prior to the Screening Visit.

          6. Have at least 1 lesion that measures at least 3 cm2 at the Screening Visit and on Day
             1 prior to the first dose of study medication. This lesion must be representative of
             the patient's disease state, but not located on the hands, feet, or genitalia.

          7. Have a stable diagnosis of moderate or severe (IGA score 3 or 4) AD at the Screening
             Visit.

          8. Have AD affecting 3% to 20% BSA (not including scalp, face, palms of hands, soles of
             feet, groin, and genitalia) at the Screening Visit.

          9. Willing to refrain from washing area of treatment or swimming for 6 hours after each
             study medication application.

         10. Willing to refrain from excessive sun exposure (e.g., sunbathing and/or tanning salon
             visits) and to minimize sun exposure (e.g., wear sun protective clothing, hat) as much
             as possible.

         11. Willing to refrain from use of moisturizers, emollients, and sunscreen on AD study
             treatment areas for duration of protocol therapy.

         12. Willing to refrain from participating in strenuous exercise that would cause profuse
             sweating for a period of 6 hours after each study medication application.

         13. Willing to return to the clinic, follow all study instructions, attend all study
             visits, and complete study procedures.

         14. In good general health and free of any known disease state or physical condition that,
             in the investigator's opinion, might impair evaluation of the patient or that might
             expose the patient to an unacceptable risk by study participation.

         15. Willing and capable of taking appropriate coronavirus disease 2019 (COVID-19) risk
             mitigation precautions (e.g., wearing a mask in public, adhering to social distancing,
             etc.) as recommended or required by local, state, or federal guidelines during
             participation in the study.

        Exclusion Criteria:

          1. Unstable course of AD (spontaneously improving or rapidly deteriorating) based on the
             patient history or as determined by the investigator during the Screening Period.

          2. Refractory AD (i.e., AD that required frequent hospitalizations and/or frequent
             intravenous treatment for skin infections within the year before the Screening Visit).

          3. AD of a severity (EASI >48) that the patient is not a candidate for a
             vehicle-controlled study.

          4. Any signs or symptoms associated with AD therapy (e.g., history of anaphylaxis,
             hypersensitivity reactions, skin atrophy, striae, pigmentary changes) that, in the
             investigator's opinion, might impair evaluation of the AD or which exposes the patient
             to unacceptable risk by study participation.

          5. Concomitant skin disease or clinically infected AD or presence of other skin disease
             in the area to be dosed that may interfere with study assessments.

          6. Use of any of the following treatments within the indicated washout period prior to
             Day 1:

               -  Phototherapy (ultraviolet A, ultraviolet B, or psoralen and ultraviolet A
                  therapy) within 4 weeks prior to Day 1.

               -  Systemic biologic immunosuppressant or immunomodulatory therapy (e.g.,
                  etanercept, alefacept, infliximab, dupilumab) within 12 weeks (or 5 half-lives of
                  the product, whichever is longer) prior to Day 1.

               -  Non-biologic immunosuppressants (e.g., methotrexate, retinoids, calcineurin
                  inhibitors, cyclosporine, hydroxycarbamide [hydroxyurea], azathioprine) within 4
                  weeks prior to Day 1.

               -  Janus kinase (JAK) inhibitors (systemic and topical) within 4 weeks prior to Day
                  1.

               -  Systemic corticosteroids within 2 weeks prior to Day 1 (intranasal, inhaled, and
                  topical ocular corticosteroids are allowed).

               -  Cytostatic agents within 4 weeks prior to Day 1.

               -  Crisaborole within 2 weeks prior to Day 1.

               -  Systemic antibiotics within 30 days prior to Day 1.

               -  Topical treatments for AD (corticosteroids, calcineurin inhibitors, topical H1
                  and H2 antihistamines, topical antimicrobials, and other medicated topical
                  agents) within 2 weeks prior to Day 1.

               -  Live attenuated vaccine treatment within 12 weeks prior to Day 1.

               -  Other investigational product within 30 days or 5 half-lives (whichever is
                  longer) prior to Day 1.

          7. Previous failure to respond to prior therapy with JAK inhibitors (systemic or
             topical), as determined by the investigator.

          8. Current use of an oral H1 antihistamine (e.g., diphenhydramine, terfenadine) unless
             the patient is on a stable dose for at least 14 days prior to the Screening Visit.

          9. Medical marijuana unless the patient is on a stable dose for at least 14 days prior to
             the Screening Visit.

         10. Clinically significant laboratory abnormalities at the Screening Visit that, in the
             opinion of the investigator, could affect interpretation of study data or the safety
             of the patient's participation in the study.

         11. Clinical laboratory values:

               -  White blood cell count <2×109/L

               -  Absolute neutrophil count (ANC) <1800/mL

               -  Platelet count <130,000/mL

               -  Hemoglobin <8g/dL

               -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2× the upper
                  limit of normal

               -  Lymphocyte count <0.5×109/L

         12. Investigator-assessed history of, or current physical findings of, severe,
             progressive, or uncontrolled immunologic, hepatic, gastrointestinal, pulmonary,
             cardiovascular, genitourinary (renal), hematological, neurologic or cerebral
             disorders, infectious disease or coagulation disorders that, as determined by the
             investigator, could affect the safety of the patient's participation in the study or
             would preclude participation in and completion of study assessments.

         13. History of, current, or suspected systemic or cutaneous malignancy and/or
             lymphoproliferative disease within the last 5 years, other than patients with a
             history of adequately treated and well healed and completely cleared nonmelanoma skin
             cancers (i.e., basal or squamous cell carcinoma) or cervical carcinoma in situ treated
             successfully at least 1 year prior to the Screening Visit 1 with no evidence of
             disease.

         14. Evidence of active, chronic, or latent infections at the time of enrollment or a
             systemic infection including but not limited to a history of treated infection (e.g.,
             pneumonia, septicemia) within 3 months prior to Day 1.

         15. Patient has a known active or history of incompletely treated or untreated active
             tuberculosis. Patients with a history of active tuberculosis must have documented
             adequate treatment verified by the investigator. Patients who demonstrate evidence of
             latent tuberculosis infection (positive QuantiFERON® Tuberculosis Gold Test) will only
             be allowed to participate in the study if there is documented evidence of a completed
             adequate treatment course for latent tuberculosis and if active tuberculosis is
             excluded per the investigator's judgment.

         16. History of a serious local skin infection (e.g., cellulitis, abscess) within 5 years
             of the Screening Visit.

         17. Positive serological test for human immunodeficiency virus (HIV) (antibody), hepatitis
             C virus (antibody), hepatitis B surface antigen, or hepatitis B core antigen antibody.

         18. Known significant exposure (close contact [<6 feet] for ≥15 minutes) to an individual
             with a confirmed diagnosis of coronavirus disease 2019 (COVID-19) at any time during
             the Screening Period.

         19. Herpes zoster or cytomegalovirus infection that resolved less than 2 months prior to
             the Screening Visit. Patients with a history of frequent outbreaks of herpes simplex
             virus (defined as 4 or more outbreaks a year).

         20. Clinically significant electrocardiogram (ECG) findings such as, but not limited to,
             baseline mean QTcF >450 msec for males or >470 msec for females (use of the ECG
             algorithm is acceptable for this purpose).

         21. Known allergy to any of the inactive ingredients in the study drug.

         22. Female patients who are pregnant, nursing, or planning to become pregnant during the
             study.

         23. Legal incapacity or limited legal capacity.

         24. Major surgery within 3 months of the Screening Visit.

         25. Any other condition that precludes adequate understanding, cooperation, and compliance
             with study procedures or any condition that could pose a risk to the patient's safety,
             as per the investigator's judgment.