ATI-501 Oral Suspension Compared to Placebo in Subjects With Alopecia Areata, Alopecia Universalis or Alopecia Totalis

This Phase 2, multicenter, randomized study will evaluate the safety, tolerability and efficacy of ATI-501 for the treatment of Alopecia Areata (AA), Alopecia Universalis (AU) or Alopecia Totalis (AT) in adult subjects.

This Phase 2, multicenter, randomized study will evaluate the safety, tolerability and efficacy of ATI-501 for the treatment of Alopecia Areata (AA), Alopecia Universalis (AU) or Alopecia Totalis (AT) in adult subjects. Subjects will be required to have a clinical diagnosis of stable AA, AU, or AT. A total of approximately 80 subjects will be randomized.

Eligibility Criteria:
Inclusion Criteria:

Subjects must meet the following criteria to be eligible for participation in the study:

1. Able to comprehend and willing to sign an Informed Consent Form (ICF).
2. Male or non-pregnant, non-nursing female ≥ 18 years old at the time of informed consent.
3. Have a clinical diagnosis of stable Alopecia Areata (AA), Alopecia Universalis (AU), or Alopecia Totalis (AT).
4. If the subject is a woman of childbearing potential (WOCBP), she must have:

   * Negative urine and serum pregnancy tests at Screening (Visit 1); and
   * A negative urine pregnancy test at Baseline (Visit 2); and
   * Agree to not be planning a pregnancy during the study duration and use a highly effective method of contraception for the duration of the study and 30 days after the last dose of study medication. (Refer to Section 8.4.2).
5. Be in good general health and free of any known disease state or physical condition which, in the investigator's opinion, might impair evaluation of the subject or which might expose the subject to an unacceptable risk by study participation.
6. Be willing to maintain the same hair style and hair dyeing throughout the study period.
7. Subjects taking hormonal replacement therapies must be on stable doses for 6 months prior to enrollment and remain on a maintenance dose throughout the study.
8. Subjects taking thyroid replacement medication must be on stable doses for 6 months prior to enrollment and remain on a maintenance dose throughout the study.
9. Sexually active male subjects whose partner is a WOCBP must agree to use a barrier method of contraception from the first dose of study medication to at least 30 days after the last dose of study medication.

Exclusion Criteria:

Subjects are excluded from this study if any 1 or more of the following criteria is met:

1. Females who are nursing, pregnant, or planning to become pregnant for the duration of the study and up to 30 days after the last dose of study medication.
2. Diffuse AA or a history of an atypical pattern of AA.
3. Concomitant hair loss disorder (by history or physical exam) such as androgenetic alopecia (AGA) or scarring alopecia.
4. Active skin disease on the scalp or a history of skin disease on the scalp that in the opinion of the investigator would interfere with study assessments of efficacy or safety.
5. Active scalp trauma or other condition affecting the scalp that, in the investigator's opinion, may affect the course of AA, AU or AT or interfere with the study conduct or evaluations.
6. The presence of a permanent or difficult to remove hairpiece or wig that will, in the opinion of the investigator, interfere with study assessments if not removed at each visit.
7. History of, or current, severe, progressive or uncontrolled autoimmune, metabolic, hepatic, endocrine, renal, gastrointestinal, pulmonary, cardiovascular, genitourinary, or hematological disease, neurologic or cerebral disorders, or coagulation disorders that, as determined by the Investigator, would preclude participation in and completion of study assessments.
8. History of, current or suspected systemic or cutaneous malignancy and /or lymphoproliferative disease, other than subjects with a history of adequately treated and well healed and completely cleared non-melanoma skin cancers (e.g. basal or squamous cell carcinoma) treated successfully at least 1 year prior to study entry with no evidence of disease.
9. Evidence of active or latent bacterial (including tuberculosis) or viral infections at the time of enrollment, or history of incompletely treated or untreated tuberculosis. Subjects who have completed therapy for latent tuberculosis may participate.
10. History of serious local infection (e.g., cellulitis, abscess) or systemic infection including but not limited to a history of treated infection (e.g., pneumonia, septicemia) within 3 months prior to Baseline. Subjects on an antibiotic for a nonserious, acute local infection must complete the course prior to enrollment into the study.
11. Positive for HIV, Hepatitis B or C. Subjects with serologic evidence of Hepatitis B vaccination (HepB surface Ab without the presence of Hep B surface Ag will be allowed to participate).
12. History of recurrent herpes zoster (more than one episode) or disseminated herpes zoster (a single episode) or disseminated herpes simplex (single episode) or cytomegalovirus (CMV) that resolved less than 2 months before study enrollment. Subjects with a history of frequent outbreaks of Herpes Simplex Virus (defined as 4 or more outbreaks a year).
13. Subjects who have received any of the following treatments for the timeframes specified below:

    * Disease Modifying Anti-Rheumatic Drugs (DMARDS), Biologics or immunosuppressants, including but not limited to: anakinra, adalimumab, azathioprine, corticosteroids, cyclosporine, etanercept, infliximab, methotrexate, TNF inhibitors, ustekinumab within 1 month or 5 half-lives (whichever is greater) of Baseline (Visit 2).
    * Plaquenil within 2 months of Baseline (Visit 2).
    * Janus kinase (JAK) inhibitors (oral or topical) within 6 months of Baseline (Visit 2).
    * Intralesional steroids or platelet rich plasma injections in the scalp within 1 month of Baseline (Visit 2).
    * Topical treatments on the scalp with anthralin, bimatoprost, corticosteroids, diphencyprone, diphenylcyclopropenone (DPCP), squaric acid dibutylester (SADBE), minoxidil, pimecrolimus, or tacrolimus within 1 month of Baseline (Visit 2).
    * Phototherapy (narrow band Ultraviolet B \[NB UVB\] or broadband therapy) within 4 weeks of Baseline (Visit 2).
14. Participation in an investigational drug or device trial in which administration of an investigational drug or device occurred within 30 days or 5 half-lives (whichever is longer) of Baseline (Visit 2).
15. Any condition possibly affecting oral drug absorption, e.g., gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass. Procedures such as gastric banding are not exclusionary.
16. Unwillingness to refrain from weaves, hair extensions, or shaving of the scalp for at least two weeks prior to a study visit, at the discretion of the investigator, based on the ability to assess hair growth.
17. Vaccination with a live or attenuated vaccine within 6 weeks prior to Baseline (Visit 2) or planned vaccination with these vaccines at any time during treatment or within 6 weeks following discontinuation of study medication.