Open-Label Efficacy and Safety Study of Pozelimab in Patients With CD55-Deficient Protein-Losing Enteropathy (CHAPLE Disease)

An Open-Label Efficacy and Safety Study of Pozelimab in Patients With CD55-Deficient Protein-Losing Enteropathy (CHAPLE Disease)

The primary objective of the study is to determine the effect of pozelimab on active CD55-deficient protein-losing enteropathy (PLE; CHAPLE).

The secondary objectives of the study are:

• To evaluate the safety and tolerability of pozelimab in patients with CD55-deficient PLE disease
• To evaluate the effect of pozelimab on CD55-deficient PLE (both patients with active disease at baseline and those with inactive disease on eculizumab, switching to pozelimab)
• To determine the effects of pozelimab on albumin and other serum proteins (total protein, immunoglobulins)
• To determine the effects of pozelimab on ascites
• To determine the effects of pozelimab on stool consistency
• To determine the effect of pozelimab on health-related quality of life
• To determine the effect of pozelimab on lab abnormalities observed in CD55-deficient PLE such as hypertriglyceridemia, thrombocytosis, and hypovitaminosis B12
• To describe the effects of pozelimab on the sparing of concomitant medications and reduction in hospitalization days
• To determine the effects of pozelimab on growth
• To characterize the concentration of pozelimab in patients with CD55-deficient PLE
• To assess the incidence of treatment-emergent ADA for pozelimab in patients with CD55-deficient PLE disease

Study Overview

• Status: Completed
• Conditions: CD55-deficient Protein-losing Enteropathy; CHAPLE
• Intervention / Treatment: Drug: Pozelimab

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Thailand
  • Bangkok
    • Pathum Wan, Bangkok, Thailand, 10330
      • Regeneron Research Site
• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye), 34890
    • Regeneron Research Site
• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Regeneron Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• 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
• Active disease as defined by the protocol or 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

Key Exclusion Criteria:

• History of meningococcal infection
• No documented meningococcal vaccination within 3 years prior to screening and patient unwilling to undergo vaccination during the study
• No documented vaccination for 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
• Presence of a concomitant disease that leads to hypoproteinemia at the time of starting pozelimab
• A concomitant disease that leads to secondary intestinal lymphangiectasia such as a fontan procedure for congenital heart disease

Note: Other protocol-defined Inclusion/Exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active PLE; Patients aged 1 year and older with a clinical diagnosis of CD55-deficient PLE disease	Drug: Pozelimab; Single loading intravenous (IV) dose on day 1, then fixed doses sub-cutaneous (SC) (based on body weight) QW (±2 days) over the treatment period.; Other Names: REGN3918

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Active Disease at Baseline Who Achieved Normalization of Serum Albumin and Improvement in Prespecified Clinical Outcomes at Week 24	Normalization of serum albumin was defined as serum albumin within the normal range at least 70 percent (%) of measurements between weeks 12 and 24, and no single albumin measurement of <2.5 grams per deciliter (g/dL) between weeks 12 and 24, and no requirement for albumin infusion between weeks 12 and 24. Improvement in the following 4 prespecified clinical outcomes that were evaluable for improvement at baseline, without worsening of the others: Daily bowel movement frequency, the presence and severity of facial edema (physician-reported), the presence and severity of peripheral edema (physician-reported), and the participant/caregiver assessment of frequency of problematic abdominal pain. Percentage of participants with active disease at baseline who achieved normalization of serum albumin and improvement in prespecified clinical outcomes at Week 24 were reported.	At Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24	The number of days per week with >=1 loose/watery bowel movement, is calculated each week of the study as the sum of the number of days with >=1 loose/watery bowel movement in a given week divided by the number of days with non-missing stool consistency data and then multiplied by 7, is presented. If more than 3 days of stool consistency data was missing in a given week, stool consistency data was considered missing for that week.	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Severity of TEAEs	TEAEs are defined as AEs that developed or worsened during the on-treatment period. The on-treatment period is defined as the time from first dose of investigational product up to 21 weeks after the last dose of investigational product. Severity of TEAEs was graded according to the following scale: Mild: Does not interfere in a significant manner with the patient's normal functioning level, Moderate: Produces some impairment of functioning but is not hazardous to health and Severe: Produces significant impairment of functioning or incapacitation and is a definite hazard to the participants health.	From start of study drug administration up to approximately 144 weeks
Number of Participants With Improvement in Most Bothersome Signs and Symptoms at Week 24	Improvement in most bothersome sign/symptom determined using semi-structured concept elicitation interview, from 'core' clinical endpoints of frequency of bowel movements, peripheral edema, facial edema, abdominal pain frequency, nausea, vomiting, stool consistency.	At Week 24
Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24	Daily bowel movements captured by e-diary. The number of bowel movements per day was calculated each week of the study. It was based on a 1-week average and calculated as the sum of the number of bowel movements in a given week divided by the number of days with non-missing bowel movement frequency data. If more than 3 days of bowel movement data was missing in a given week, bowel movement frequency data was considered missing for that week.	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24
Number of Participants With Abdominal Ascites at Week 24	The measurement of abdominal ascites (excess abdominal fluid) was based on abdominal circumference. Abdominal circumference was measured regardless of the physician's assessment of the presence or absence of ascites.	Baseline up to Week 24
Absolute Value of Albumin at Specified Timepoints up to Week 24	Blood samples were collected from participants at defined time points for the assessment of albumin. Absolute value of albumin at specified timepoints was reported.	Baseline, Day 2, Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24
Absolute Values of Protein, and Immunoglobulin G (IgG) at Baseline and Week 24	Blood samples were collected from participants at defined time points for the assessment of protein and IgG. Absolutes values of protein and IgG measured as g/L at baseline and Week 24 was reported.	Baseline, Week 24
Absolute Values of Immunoglobulin (Ig), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) at Baseline and Week 24	Blood samples were collected from participants at defined time points for the assessment of Ig, IgM and IgA. Absolute value of Ig, IgM and IgA measured as mg/dL at baseline and Week 24 was reported.	Baseline, Week 24
Absolute Values of Vitamin B12 at Baseline and Week 24	Blood samples were collected from participants at defined time points for the assessment of vitamin B12. Absolute values of vitamin B12 at baseline and Week 24 was reported.	Baseline, Week 24
Absolute Values of Iron and Unsaturated Iron Binding Capacity at Baseline and Week 24	Blood samples were collected from participants at defined time points for the assessment of iron indices. Absolute values of unsaturated iron and unsaturated iron binding capacity measured as micromoles per liter (mcmol/L) at baseline and Week 24 was reported.	Baseline, Week 24
Absolute Values of Vitamin B9 up to Week 24	Absolute Values of Vitamin B9 - Central Lab	Baseline up to Week 24
Absolute Values of Ferritin at Baseline and Week 24	Blood samples were collected from participants at defined time points for the assessment of iron indices. Absolute values of ferritin was reported.	Baseline, Week 24
Absolute Values of Magnesium, Total Cholesterol, and Triglycerides at Week 24	Blood samples were collected from participants at defined time points for the assessment of magnesium, total cholesterol, and triglycerides. Absolute values of magnesium, total cholesterol, and triglycerides measured as mmol/L at baseline and Week 24 was reported.	Baseline, Week 24
Change From Baseline in Alpha-1 Antitrypsin Levels in Stool at Week 12 and Week 24		Week 12, Week 24
Change From Baseline in Alpha-1 Antitrypsin Levels in Blood at Week 12 and Week 24		Week 12, Week 24
Percentage of Participants With Active Disease at Baseline Who Maintained Disease Control	Measured by normalization of serum albumin, no worsening of facial or peripheral edema, increase in bowel movement, or increase in abdominal pain frequency, no increase in dose of permitted concomitant medication for the treatment of PLE at any time as described in the protocol	Weeks 12 to 48; Weeks 12 to 144; Weeks 24 to 48; Weeks 48 to 96; Weeks 96 to 144
Change From Baseline in Physician Assessment of Facial Edema Based on a 5-point Likert Rating Scale	The physician assessment of facial edema is based on a 5-point Likert scale ranging from no edema (1) to very severe edema (5).	Baseline and Week 144
Change From Baseline in Physician Assessment of Peripheral Edema Based on a 5-point Likert Rating Scale	The physician assessment of peripheral edema is based on a 5-point Likert scale ranging from no edema (1) to very severe edema (5).	Baseline and Week 144
Change From Baseline in Food and Drink Limitations as Assessed by the PedsQL™ GI Symptom Scales' Food and Drink Limits Sub-scale	Frequency of limitations is assessed on a 5-point Likert response scale, ranging from never a problem (0) to almost always a problem (4). Items were reverse scored and linearly transformed to a 0 to 100 scale, where lower scores indicate more frequent problems with food and drink limitations.	Baseline and Week 144
Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the PedsQL™ Generic Core Scales	Physical functioning, emotional functioning, social functioning, and school/work/studies functioning is assessed using a 5-point Likert scale, ranging from never a problem (0) to almost always a problem (4). Items were reverse-scored and linearly transformed to a 0 to 100 scale, with higher scores indicating better HRQoL. The total scale score is computed as the sum of all the items over the number of items answered on individual scales. Subscale score is calculated as the sum of the items in the scale divided by the number of items answered in the scale.	Baseline and Week 144
Number of Participants With Albumin Infusion by 24 Week Periods		Weeks 0 to 24; Weeks 24 to 48; Weeks 48 to 72; Weeks 72 to 96; Weeks 96 to 120; Weeks 120 to 144
Change From Baseline in Albumin Values		Baseline and Week 144
Percentage Change From Baseline in Albumin Values		Baseline and Week 144
Time to First Normalization for Albumin Values		Baseline up to Week 144
Change From Baseline in Protein Values		Baseline and Week 144
Time to First Normalization for Total Protein		Baseline up to Week 144
Change From Baseline in Immunoglobulin (Ig) Values		Baseline and Week 144
Time to First Normalization for Ig Values		Baseline up to Week 144
Change From Baseline in IgG Values		Baseline and Week 144
Time to First Normalization for IgG Values		Baseline up to Week 144
Change From Baseline in IgM Values		Baseline and Week 144
Time to First Normalization for IgM Values		Baseline up to Week 44
Change From Baseline in IgA Values		Baseline and Week 144
Time to First Normalization for IgA Values		Baseline up to Week 144
Change From Baseline in Vitamin B12 Values		Baseline and Week 144
Time to First Normalization for Vitamin B12 Values		Baseline up to Week 144
Change From Baseline in Vitamin B9 (Folate) Values		Baseline and Week 144
Time to First Normalization for Vitamin B9 (Folate) Values		Baseline up to Week 144
Change From Baseline in Iron Values		Baseline and Week 144
Time to First Normalization for Iron Values		Baseline up to Week 144
Change From Baseline in Unsaturated Iron Binding Capacity		Baseline and Week 144
Time to First Normalization for Unsaturated Iron Binding Capacity		Baseline up to Week 144
Change From Baseline in Ferritin Values		Baseline and Week 144
Time to First Normalization for Ferritin Values		Baseline up to Week 144
Change From Baseline in Magnesium Values		Baseline and Week 144
Time to First Normalization for Magnesium Values		Baseline up to Week 144
Change From Baseline in Fasting Cholesterol Values		Baseline and Week 144
Time to First Normalization for Fasting Cholesterol Values		Baseline up to Week 144
Change From Baseline in Fasting Triglycerides Values		Baseline and Week 144
Time to First Normalization for Fasting Triglycerides Values		Baseline up to Week 144
Number of Participants Who Used Concomitant Medication		Baseline up to Week 144
Number of Hospitalization Days by 24 Week Period		Weeks 0 to 24; Weeks 24 to 48; Weeks 48 to 72; Weeks 72 to 96; Weeks 96 to 120; Weeks 120 to 144
Change From Baseline in Body Weight Z-Score	Weight-for-age z-score compares a participant's weight to children of the same age and sex from a healthy reference population. A z-score reflects an individual score as compared to a population mean and is expressed in units of standard deviation above (positive values) and below (negative values). Body weight z-score, regardless of magnitude, represents catch-up growth.	Baseline and Week 144
Change From Baseline in Height Z-Score	Height-for-age z-score compares a participant's height to children of the same age and sex from a healthy reference population. A z-score reflects an individual score as compared to a population mean and is expressed in units of standard deviation above (positive values) and below (negative values). Any increase in height z-score, regardless of magnitude, represents catch-up growth.	Baseline and Week 144
Change From Baseline in Total Complement Activity Complement Hemolytic Assay (CH50)		Baseline and Week 144
Concentrations of Total Pozelimab in Serum		Baseline up to Week 164
Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Pozelimab		Baseline up to Week 164

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Litcher-Kelly L, Ozen A, Ollis S, Feldman HB, Yaworsky A, Medrano P, Chongsrisawat V, Perlee L, Walker M, Pradeep S, Turner-Bowker DM, Kurolap A, Adiv OE, Lenardo MJ, Harari OA, Jalbert JJ. The patient experience of CHAPLE disease: results from interviews conducted as part of a clinical trial for an ultra-rare condition. Orphanet J Rare Dis. 2025 Feb 11;20(1):68. doi: 10.1186/s13023-024-03436-y.
• Litcher-Kelly L, Ozen A, Ollis S, Feldman HB, Yaworsky A, Medrano P, Chongsrisawa V, Brackin T, Perlee L, Walker M, Pradeep S, Lenardo MJ, Harari OA, Jalbert JJ. Pozelimab for CHAPLE disease: results from in-trial interviews and clinical outcome assessments. Orphanet J Rare Dis. 2024 Aug 8;19(1):290. doi: 10.1186/s13023-024-03277-9.
• Ozen A, Chongsrisawat V, Sefer AP, Kolukisa B, Jalbert JJ, Meagher KA, Brackin T, Feldman HB, Baris S, Karakoc-Aydiner E, Ergelen R, Fuss IJ, Moorman H, Suratannon N, Suphapeetiporn K, Perlee L, Harari OA, Yancopoulos GD, Lenardo MJ; Pozelimab CHAPLE Working Group. Evaluating the efficacy and safety of pozelimab in patients with CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy disease: an open-label phase 2 and 3 study. Lancet. 2024 Feb 17;403(10427):645-656. doi: 10.1016/S0140-6736(23)02358-9. Epub 2024 Jan 23.

Helpful Links

• A Plain Language Summary is available on TrialSummaries.com

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2020
• Primary Completion (Actual): November 9, 2021
• Study Completion (Actual): May 2, 2024

Study Registration Dates

• First Submitted: December 20, 2019
• First Submitted That Met QC Criteria: December 20, 2019
• First Posted (Actual): December 24, 2019

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: CD55-deficient PLE; complement hyperactivation, angiopathic thrombosis, protein-losing enteropathy (CHAPLE disease)
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Protein-Losing Enteropathies
• Other Study ID Numbers: R3918-PLE-1878

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, EMA, PMDA, etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No