Evaluating Ruxolitinib for Hair Regrowth in APECED-Associated Alopecia Areata

* INCLUSION CRITERIA:

For participants with APECED-associated AA:

1. Participant must be able to understand and provide informed consent.
2. Aged \>=12 to \<=75 years.
3. Patients with APECED (genetic or clinical diagnosis) and severe AA (defined as having \>=50% total scalp loss at screening per the SALT score).
4. Duration of hair loss greater than 6 months.
5. No present evidence of hair regrowth.
6. Is na(SqrRoot) ve or unresponsive to other treatments for AA.
7. No treatment for alopecia in the past 2 months prior to study enrollment.
8. Willingness to use valacyclovir prophylaxis for the prevention of herpes viral reactivation.
9. Vaccinations should be up to date in agreement with current CDC immunization guidelines prior to start of ruxolitinib.
10. Proficient in written English.
11. Participants who can get pregnant or impregnate their partner must agree to use at least one highly effective method of contraception when engaging in sexual activities that can result in pregnancy, starting at screening until 12 weeks after the last dose. Highly effective contraceptive measures include:

    1. Stable use of combined (estrogen- and progestogen-containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) starting 1 month prior to screening.
    2. Intrauterine device; intrauterine hormone-releasing system.
    3. Two barrier methods (eg, condom with spermicide, diaphragm with spermicide, or cervical cap and spermicide). Internal and external condoms may not be used together.
    4. Bilateral tubal ligation.

Periodic abstinence (calendar, symptothermal, and post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception.

For family members or household contacts:

1. Aged \>=18 years.
2. Lives with the participant.
3. Proficient in written English.

EXCLUSION CRITERIA:

For participants with APECED-associated AA:

1. Known history of hypersensitivity to ruxolitinib or other JAK inhibitors.
2. History of or active skin disease on the scalp other than AA, such as psoriasis or seborrheic dermatitis.
3. Diagnosis of AA is in question or the pattern of hair loss is such that quantification of hair loss and assessment of regrowth is difficult, eg, patients with androgenic alopecia.
4. Treated within the last 2 months with intralesional steroids, systemic steroids, anthralin, squaric acid, diphenylcyclopropenone, tacrolimus, minoxidil, or other medication that, in the opinion of the investigator, may affect hair regrowth.
5. Current or recent use of any investigational drug (within 3 months or 5 half-lives, whichever is longer, prior to screening).
6. Scheduled to participate in another clinical study involving an investigational drug during the course of this study.
7. Use of systemic immunosuppressive or immune-modulating agents within 3 months prior to screening, except systemic steroids 10 mg of prednisone equivalent per day.
8. Current use of systemic steroids with daily dose \>10 mg of prednisone equivalent for any reason or steroid burst for \>3 days within 1 month of screening.
9. History of alcohol or drug abuse within 6 months prior to screening.
10. Presence of one or more of the following clinically significant laboratory abnormalities:

    1. Serum ALT\>=3 times upper limit of normal (ULN).
    2. Serum total bilirubin \>=2 times ULN.
    3. ANC\<=1000 cells/microliter.
    4. Hemoglobin \<=9.0 g/dL.
    5. Platelet count \<=100,000/microliter.
    6. Serum creatinine \>=2 times ULN.
11. Planned or anticipated major surgical procedure during the study.
12. Plans to receive any live vaccines within 1 month of the anticipated first dose of ruxolitinib.
13. Known or suspected immunodeficiency disorder besides APECED.
14. History of untreated invasive opportunistic infections (eg, tuberculosis, non-tuberculous mycobacterial infections, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis pneumonia, aspergillosis) despite infection resolution or otherwise recurrent infections of

    abnormal frequency or prolonged infections suggesting an immune-compromised status as judged by the investigator.
15. Untreated latent tuberculosis infection.
16. Infection with HIV.
17. Untreated infection with hepatitis B or C.
18. History of serious bacterial infection within the last 3 months prior to screening, unless treated and resolved with antibiotics, or any chronic bacterial infection (eg, chronic pyelonephritis, osteomyelitis).
19. History of unprovoked DVT, PE, arterial thrombosis, or other thrombotic events.
20. History of stroke, heart attack, or heart failure.
21. History of herpes zoster or cytomegalovirus infection that resolved within 2 months prior to screening.
22. History of basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix, unless the participant is in remission and curative therapy was completed at least 12 months prior to screening.
23. History of other malignancies, unless the participant is in remission and curative therapy was completed at least 5 years prior to screening.
24. Planned or anticipated use of any prohibited medications and procedures during the study.
25. Current pregnancy or breastfeeding.
26. Past or current medical problems or findings from physical examination, EKG, or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant s ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

There are no exclusion criteria for family members or household contacts.