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Protocol Details

An Open-label Efficacy and Safety Study of Pozelimab in Patients with CD55 deficient Protein-losing Enteropathy (CHAPLE Disease)

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 3 Years
Max Age: N/A

Referral Letter Required


Population Exclusion(s)

Pregnant Women


Fully human monoclonal immunoglobin G4P antibody;
Polymorphic variations;
Serum albumin;
Complement protein C5

Recruitment Keyword(s)



CD55 deficient Protein-losing Enteropathy

Investigational Drug(s)

REGN3918 (Pozelimab)

Investigational Device(s)



Biological/Vaccine: REGN3918 (Pozelimab)

Supporting Site

National Institute of Allergy and Infectious Diseases


CHAPLE disease is a rare genetic condition that affects the immune system. People with CHAPLE disease have severe gastrointestinal problems, like abdominal pain and diarrhea. They are prone to lung infections and severe blood clots. They often have trouble absorbing nutrients in their diets. There is no drug to treat the disease. Researchers want to see if a new drug can help.


To see if pozelimab is safe for people with CHAPLE disease and if it can help treat the disease.


People age 1 and older with CHAPLE disease


Participants will be screened with:

Medical and medicine history

Blood tests

Pregnancy test (for some participants)

Electrocardiogram (to test heart function)

Physical exam.

Participants will have 25 study visits over approximately 3 years.

Participants will take pozelimab for approximately 3 years. They will get the first dose as an intravenous infusion. For this, a thin plastic tube is placed in an arm vein. They will get all other doses once a week as an injection under the skin with a needle.

At study visits, participants will have a checkup. They will give blood, urine, and fecal samples. They will talk about their health and complete questionnaires. They may have photographs taken of the face, stomach, or other areas of the body.

Participants may get vaccines. They will take antibiotics.

Participants will have 2 face-to-face interviews that will be audio-recorded. They will talk about living with CHAPLE disease, their study experience, and how pozelimab has affected their health and quality of life.

Between visits, participants will complete questionnaires about their health. For part of the study they will keep a stool diary. They may keep a medicine diary.

Participants may have a cheek swab.

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A patient must meet the following criteria to be eligible for inclusion in the study:

1. Male or female aged 1 year and older. The first 2 patients recruited must be aged 6 years or older.

2. Clinical diagnosis of CD55-deficient PLE/CHAPLE disease (based on a history of PLE), confirmed by biallelic CD55 loss-of-function mutation detected by genotype analysis (frameshift, nonsense mutations). In the case of missense or suspected splice site mutations, CD55-deficient PLE is to have been confirmed by flow cytometry of peripheral blood cells or western blot. These diagnostic tests can be performed as part of the study screening procedures, or as part of standard clinical evaluation prior to screening.

3. Patient either has:

a. Active disease, defined as:

i Hypoalbuminemia of less than or equal to 3.2 g/dL within the screening period, and

ii Within the last 6 months and attributable to CD55-deficient PLE, at least 7 days (which do not have to be consecutive) of at least one of the following symptoms or signs: diarrhea, vomiting, abdominal pain, peripheral or facial edema, or an episode of infection with concomitant hypogammaglobulinemia, or a new thromboembolic event

NOTE: The first 2 patients enrolled in the study must fall into inclusion criterion 3a.

b. Inactive disease on eculizumab therapy (and whose treating physician has the expectation of future access to renewed eculizumab treatment should this be required), and is willing to discontinue eculizumab during screening and start pozelimab at baseline with no eculizumab wash-out.

4. Willing and able to comply with clinic visits and study-related procedures.

5. Written informed consent from parent/guardian for minor patients.

6. Written assent from minor patients as appropriate (eg, above the age of 6 years or the applicable age per local regulatory requirements).

7. Patient either alone or with the help of their parents/legal guardians, as required, must be able to understand and complete study-related questionnaires.


A patient who meets any of the following criteria will be excluded from the study:

1. History of meningococcal infection.

2. No documented meningococcal vaccination within 3 years prior to screening and patient unwilling to undergo vaccination during the study (if fully available according to local practice).

3. No documented vaccination with Haemophilus influenzae and Streptococcus pneumoniae if applicable based on local practice or guidelines prior to screening and patient unwilling to undergo vaccination during the study if required per local practice or guidelines.

4. Presence of a concomitant disease that leads to hypoproteinemia at the time of starting pozelimab, including a urinary protein loss or a hepatic disease that affects production of proteins by liver.

5. A concomitant disease that leads to secondary intestinal lymphangiectasia such as a fontan procedure for congenital heart disease.

6. Recent infection requiring systemic treatment with antibiotics, antivirals, or antifungals (within 2 weeks of screening or during the screening period). If patient is appropriately treated and the 2-week window has passed, patient may be rescreened.

7. PLE previously refractory to eculizumab, with the exception of patients with the Arg885His variant in the C5 gene.

8. Known hereditary complement deficiency other than CD55 deficiency.

9. Documented history of active, ongoing systemic autoimmune diseases.

10. Known or suspected infectious colitis at screening. Once this has resolved, patient may be rescreened.

11. Patients with an estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m2 (according to Chronic Kidney Disease - Epidemiology Collaboration equation 2009 [adults] or creatinine-based Schwartz equation [pediatric patients]).

12. Recent, unstable medical conditions, excluding PLE and related complications, within the past 3 months prior to screening visit. Option to rescreen after 3 months has elapsed.

13. Known sensitivity to doxycycline or to any of the components of the pozelimab formulation or drug product. Doxycycline sensitivity history should be a clear history of significant allergic reaction.

14. Any clinically significant abnormality identified at the time of screening that in the judgment of the investigator or any sub-investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases, or patients with short life expectancy.

15. Participation in another interventional clinical study or use of any experimental therapy within 30 days before screening visit or within 5 half-lives of that investigational product, whichever is greater, with the exception of complement inhibitors

16. Considered by the investigator or any sub-investigator as inappropriate for this study for any reason, eg:

--Deemed unable to meet specific protocol requirements, such as scheduled visits and/or

--Deemed unable to tolerate long-term injections as per the patient, the investigator, sub-investigator, pharmacist, study coordinator, other study staff, or relative thereof directly involved in the conduct of the study, etc. and/or

--Presence of any other conditions (eg, geographic, social, etc.), actual or anticipated, that the investigator feels would restrict or limit the patient s participation for the duration of the study

17. Patients who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

18. Women who are pregnant, breastfeeding, or who have a positive pregnancy test at screening visit or day 1

19. Pregnant or breastfeeding women

20. Women of childbearing potential* and girls beyond menarche (and not sexually abstinent) who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 21 weeks after the last

dose. Highly effective contraceptive measures include:

a. Stable use of combined (estrogen and progestogen-containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening

b. Intrauterine device (IUD); intrauterine hormone-releasing system (IUS)

c. Bilateral tubal ligation

d. Vasectomized partner

e. And/or sexual abstinence

--Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

--Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient

--Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.

21. Known chronic infection with hepatitis B or C, defined as a testing history showing a currently positive status for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus DNA, or hepatitis C virus RNA (HCV RNA).

22. Documented history of unresolved tuberculosis (TB), or evidence of active or latent tuberculosis infection (LTBI) during screening period. Assessment for active TB and LTBI should accord with local practice or guidelines, including those pertaining to risk assessment, and the use of tuberculin skin test or T-cell interferon-gamma release assay.

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Ozen A, Comrie WA, Ardy RC, Dom(SqrRoot)(NotEqual)nguez Conde C, Dalgic B, Beser (SqrRoot) F, Morawski AR, Karakoc-Aydiner E, Tutar E, Baris S, Ozcay F, Serwas NK, Zhang Y, Matthews HF, Pittaluga S, Folio LR, Unlusoy Aksu A, McElwee JJ, Krolo A, Kiykim A, Baris Z, Gulsan M, Ogulur I, Snapper SB, Houwen RHJ, Leavis HL, Ertem D, Kain R, Sari S, Erkan T, Su HC, Boztug K, Lenardo MJ. CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis. N Engl J Med. 2017 Jul 6;377(1):52-61. doi: 10.1056/NEJMoa1615887. Epub 2017 Jun 28. PMID: 28657829; PMCID: PMC6690356.

Kurolap A, Eshach Adiv O, Hershkovitz T, Tabib A, Karbian N, Paperna T, Mory A, Vachyan A, Slijper N, Steinberg R, Zohar Y, Mevorach D, Baris Feldman H. Eculizumab Is Safe and Effective as a Long-term Treatment for Protein-losing Enteropathy Due to CD55 Deficiency. J Pediatr Gastroenterol Nutr. 2019 Mar;68(3):325-333. doi: 10.1097/MPG.0000000000002198. PMID: 30418410.

Kurolap A, Eshach-Adiv O, Hershkovitz T, Paperna T, Mory A, Oz-Levi D, Zohar Y, Mandel H, Chezar J, Azoulay D, Peleg S, Half EE, Yahalom V, Finkel L, Weissbrod O, Geiger D, Tabib A, Shaoul R, Magen D, Bonstein L, Mevorach D, Baris HN. Loss of CD55 in Eculizumab-Responsive Protein-Losing Enteropathy. N Engl J Med. 2017 Jul 6;377(1):87-89. doi: 10.1056/NEJMc1707173. Epub 2017 Jun 28. PMID: 28657861.

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Principal Investigator

Referral Contact

For more information:

Michael J. Lenardo, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 11N311
10 Center Drive
Bethesda, Maryland 20892
(301) 496-6754

Helen F. Matthews
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 5-3940
10 Center Drive
Bethesda, Maryland 20892
(301) 443-8080

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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