A Phase 2 Randomized Stepped Wedge Study of Emapalumab in APECED Enteritis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Averaged changes in APECED ES from baseline.
研究概览
简要总结
Background:
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.
Objective:
To test a drug (emapalumab) in people with enteritis caused by APECED.
Eligibility:
People aged 2 to 75 years with APECED and enteritis. They must also be enrolled in protocol 11-I-0187.
Design:
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.
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详细描述
Study Description:
This is a phase 2 randomized stepped wedge open-label study to evaluate the efficacy and safety of the anti-interferon-gamma (IFN-gamma) monoclonal antibody, emapalumab, in autoimmune polyendocrinopathycandidiasis-ectodermal dystrophy (APECED) enteritis. Qualifying participants will be randomized to initiate emapalumab at 0, 2, 4, or 6 months post-baseline visit. They will be admitted for up to 10 days for an inpatient visit to start receiving emapalumab in 2 intravenous (IV) infusions 3 days apart. Thereafter, participants will receive 5 additional monthly IV infusions of emapalumab followed by an additional in-person visit 1 month after the final dose of emapalumab. All participants will be followed for an additional 6 months after this via virtual visits every 2 months and an in-person visit at the end of this 6-month period. Throughout the study, participants will be monitored for adverse events (AEs) and will complete patient-reported outcome (PRO) metrics to track their symptoms and general wellbeing as well as have blood draws for safety labs and research.
Primary Objective:
To evaluate the efficacy of emapalumab on gastrointestinal (GI) symptoms as measured by the APECED enteritis score (APECED ES) in participants with APECED enteritis.
Secondary Objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •Participant must be able to understand and provide informed consent.
- •Aged >= 2 to <= 75 years.
- •Currently co-enrolled on NIH protocol 11-I-0187, "The Natural History and Pathogenesis of Human Fungal Infections."
- •Patients with APECED (genetic or clinical diagnosis) and enteritis (with APECED ES > 50 at screening).
- •Duration of enteritis greater than 6 months.
- •Is naive or unresponsive to other treatments for enteritis.
- •Willingness to use acyclovir or valacyclovir prophylaxis for the prevention of herpes viral reactivation.
- •Willingness to use entecavir prophylaxis against hepatitis B virus reactivation, if applicable.
- •Vaccinations should be up to date in agreement with current Centers for Disease Control and Prevention immunization guidelines prior to start of emapalumab.
- •Proficient in written English.
- •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.
排除标准
- •Known history of hypersensitivity to emapalumab.
- •History of active intestinal disease other than enteritis such as inflammatory bowel disease.
- •Current or recent use of any investigational drug (within 3 months or 5 half-lives, whichever is longer, prior to screening).
- •Scheduled to participate in another clinical study involving an investigational drug during the course of this study.
- •History of alcohol or drug abuse within 6 months prior to screening.
- •Presence of one or more of the following clinically significant laboratory abnormalities:
- •Serum ALT >= 3 times upper limit of normal (ULN).
- •Serum total bilirubin >= 2 times ULN.
- •Serum creatinine >= 2 times ULN.
- •Planned or anticipated major surgical procedure during the study.
- •Plans to receive any live or live attenuated vaccines within 1 month of the anticipated first dose of emapalumab.
- •Known or suspected immunodeficiency disorder besides APECED.
- •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.
- •Untreated latent tuberculosis infection.
- •Infection with HIV.
- •Untreated infection with hepatitis B or C.
- •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).
- •Current pregnancy or breastfeeding.
- •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.
研究组 & 干预措施
Group 1
No observation period prior to start of study drug.
干预措施: Emapalumab (Drug)
Group 2
2 month observation period prior to start of study drug.
干预措施: Emapalumab (Drug)
Group 3
4 month observation period prior to start of study drug.
干预措施: Emapalumab (Drug)
Group 4
6 month observation period prior to start of study drug.
干预措施: Emapalumab (Drug)
结局指标
主要结局
Averaged changes in APECED ES from baseline.
时间窗: Duration of study
To evaluate the efficacy of emapalumab on gastrointestinal (GI) symptoms as measured by the APECED enteritis score (APECED ES) in participants with APECED enteritis.
次要结局
- Incidence of serious adverse events (SAEs), AEs requiring study drug discontinuation, and other AEs during the 6 months of emapalumab treatment.(Duration of study)
- Change from baseline in APECED ES at 6 months after emapalumab initiation.(Duration of study)
- Averaged changes in irritable bowel syndrome (IBS) QOL score from baseline and change from baseline in IBS QOL score at 6 months after emapalumab initiation.(Duration of study)
- Averaged changes in scores for 36-Item Short Form Health Survey (SF-36) for adult participants or Pediatric Quality of Life Inventory (PedsQL) for pediatric participants from baseline and changes from baseline in SF-36 (adults) or PedsQL (pediat...(Duration of study)
- Averaged changes in serum zinc from baseline in participants with decreased zinc at baseline and changes from baseline in serum zinc at 6 months after emapalumab initiation in participants with decreased zinc at baseline.(Duration of study)
- Change from baseline in 48-hour fecal fat at 6 months after emapalumab initiation in participants with elevated fecal fat at baseline.(Duration of study)
- Change from baseline in histologic and immunologic abnormalities of duodenal tissue after 6 months of treatment.(Duration of study)
- Averaged changes in serum CXCL9 from baseline and change from baseline in serum CXCL9 at 6 months after emapalumab initiation.(Duration of study)