This study is currently recruiting participants.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as Autoimmune polyendocrine syndrome type-1 (APS-1), is a disease that causes the immune system to attack parts of a person s body. In some people, APECED attacks the small intestine; this causes an illness called enteritis.
To test a drug (emapalumab) in people with enteritis caused by APECED.
People aged 2 to 75 years with APECED and enteritis. They must also be enrolled in protocol 11-I-0187.
Participants will have 10-13 study visits in an 18-month period.
Participants will be screened. They will have a physical exam with blood tests. These tests will be repeated at every study visit. They will have a test of their heart function. This will be at screening and prior to drug administration.
Other tests are optional: Participants may have imaging exams and a test of lung function. They may have an endoscopy, which is an exam of their digestive tract. Participants may provide samples of urine, stool, nail clippings, saliva, vaginal fluid, or skin. Photos may be taken of their skin or scalp. These tests may be repeated at some visits.
Emapalumab is given through a tube attached to a needle inserted into a vein. All participants will receive 7 doses: 2 on their first study visit; then 1 each at 30-day intervals. Some participants will have an observation period before they begin taking the drug; in those situations, they will either be seen in person or via video visit every 2 months before starting emapalumab to see how their symptoms change over time.
Participants will have a follow-up visit 1 month after their last dose. Then they will have 2 telehealth visits at 30-day intervals. They will have a final clinic visit 1 year after their first dose.
INCLUSION CRITERIA:
1. Participant must be able to understand and provide informed consent.
2. Aged >= 2 to <= 75 years.
3. Currently co-enrolled on NIH protocol 11-I-0187, "The Natural History and Pathogenesis of Human Fungal Infections."
4. Patients with APECED (genetic or clinical diagnosis) and enteritis (with APECED ES > 50 at screening).
5. Duration of enteritis greater than 6 months.
6. Is naive or unresponsive to other treatments for enteritis.
7. Willingness to use acyclovir or valacyclovir prophylaxis for the prevention of herpes viral reactivation.
8. Willingness to use entecavir prophylaxis against hepatitis B virus reactivation, if applicable.
9. Vaccinations should be up to date in agreement with current Centers for Disease Control and Prevention immunization guidelines prior to start of emapalumab.
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:
-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.
- Intrauterine device (IUD); intrauterine hormone-releasing system.
-Two barrier methods (e.g., condom with spermicide, diaphragm with spermicide, or cervical cap and spermicide). Internal and external condoms may not be used together.
-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.
EXCLUSION CRITERIA:
1. Known history of hypersensitivity to emapalumab.
2. History of active intestinal disease other than enteritis such as inflammatory bowel disease.
3. Current or recent use of any investigational drug (within 3 months or 5 half-lives, whichever is longer, prior to screening).
4. Scheduled to participate in another clinical study involving an investigational drug during the course of this study.
5. History of alcohol or drug abuse within 6 months prior to screening.
6. Presence of one or more of the following clinically significant laboratory abnormalities:
a. Serum ALT >= 3 times upper limit of normal (ULN).
b. Serum total bilirubin >= 2 times ULN.
c. Serum creatinine >= 2 times ULN.
7. Planned or anticipated major surgical procedure during the study.
8. Plans to receive any live or live attenuated vaccines within 1 month of the anticipated first dose of emapalumab.
9. Known or suspected immunodeficiency disorder besides APECED.
10. History of untreated invasive opportunistic infections (e.g., 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.
11. Untreated latent tuberculosis infection.
12. Infection with HIV.
13. Untreated infection with hepatitis B or C.
14. History of serious bacterial infection within the last 3 months prior to screening, unless treated and resolved with antibiotics, or any chronic bacterial infection (e.g., chronic pyelonephritis, osteomyelitis).
15. Current pregnancy or breastfeeding.
16. 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.