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

NCT04209634 | Completed Phase 2 Results FDA Drug

• 1 other identifier: R3918-PLE-1878
• Study Type: interventional
• Target: 10
• Locations: 3 countries
• Sites: 3

Brief Summary

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

Conditions

CD55-deficient Protein-losing Enteropathy; CHAPLE

Keywords

CD55-deficient PLE; complement hyperactivation, angiopathic thrombosis, protein-losing enteropathy (CHAPLE disease)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (57)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Severity of TEAEs

  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

  At Week 24

• Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24

  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 Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24

  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

  Baseline up to Week 24

Study Arms (1)

Active PLE

EXPERIMENTAL

Patients aged 1 year and older with a clinical diagnosis of CD55-deficient PLE disease

Drug: Pozelimab

Interventions

Pozelimab DRUG

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.

Also known as: REGN3918

Active PLE

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (3)

Regeneron Research Site

Bethesda, Maryland, 20892, United States

Location

Regeneron Research Site

Pathum Wan, Bangkok, 10330, Thailand

Location

Regeneron Research Site

Istanbul, 34890, Turkey (Türkiye)

Location

Related Publications (3)

• 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.

  PMID: 39934837 DERIVED

• 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.

  PMID: 39118150 DERIVED

• 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.

  PMID: 38278170 DERIVED

Related Links

• A Plain Language Summary is available on TrialSummaries.com

MeSH Terms

Conditions

Protein-Losing Enteropathies

Condition Hierarchy (Ancestors)

Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

844-734-6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: December 24, 2019
• Study Start: January 27, 2020
• Primary Completion: November 9, 2021
• Study Completion: May 2, 2024
• Last Updated: August 29, 2025
• Results First Posted: October 30, 2023

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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.
• 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).

Locations

TH (1); TU (1); US (1)