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

• ClinicalTrials.gov Identifier: NCT04209634
• Recruitment Status: Completed
• First Posted: December 24, 2019
• Results First Posted: October 30, 2023
• Last Update Posted: May 13, 2024
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

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

Condition or disease	Intervention/treatment	Phase
CD55-deficient Protein-losing Enteropathy; CHAPLE	Drug: Pozelimab	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Efficacy and Safety Study of Pozelimab in Patients With CD55-Deficient Protein-Losing Enteropathy (CHAPLE Disease)
• Actual Study Start Date: January 27, 2020
• Actual Primary Completion Date: November 9, 2021
• Actual Study Completion Date: May 2, 2024

Arms and Interventions

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 Name: REGN3918

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Active Disease at Baseline Who Achieved Normalization of Serum Albumin and Improvement in Prespecified Clinical Outcomes at Week 24 [ Time Frame: 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.

Secondary Outcome Measures :

1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Severity of TEAEs [ Time Frame: From start of study drug administration up to primary analysis cut-off date (24 May 2022) [i.e approximately 52 weeks]) ]
   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.
2. Number of Participants With Improvement in Most Bothersome Signs and Symptoms [ Time Frame: 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.
3. Proportion of Participants With Active Disease at Baseline Who Maintained Disease Control [ Time Frame: Week 12 to 48; Week 12 to 144; Week 24 to 48; Week 48 to 96; Week 96 to 144 ]
   Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
4. Proportion of Participants With Inactive Disease on Eculizumab at Baseline Who Maintained Disease Control [ Time Frame: Week 12 to 48; Week 12 to 144; Week 24 to 48; Week 48 to 96; Week 96 to 144 ]
   Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
5. Number of Bowel Movements Per Day Based on a 1-week Average [ Time Frame: 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 ]
   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.
6. Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 [ Time Frame: 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 ]
   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.
7. Physician Assessment of Facial Edema Based on a 5-point Likert Rating Scale [ Time Frame: Baseline up to Week 144 ]
   Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
8. Physician Assessment of Peripheral Edema Based on a 5-point Likert Rating Scale [ Time Frame: Baseline up to Week 144 ]
   Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
9. Change From Baseline in Abdominal Symptoms as Assessed by the PedsQL™ GI Symptom Scale Stomach Pain and Hurt Sub-scale and Food and Drink Limits Sub-scale [ Time Frame: Baseline up to Week 144 ]
   Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
10. Health-related Quality of Life (HRQoL) as Assessed by the PedsQL™ Generic Core Scales [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
11. HRQoL as Assessed by the PedsQL™ Generic Core Scales for About my Work/Studies and School Functioning Sub-scale [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
12. HRQoL as Assessed by the PedsQL™ Generic Core Scales for Physical Functioning Sub-scale [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
13. Number of Participants With Abdominal Ascites [ Time Frame: Baseline up to 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.
14. Number of Participants With Albumin Infusions [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
15. Absolute Value of Total Albumin at Specified Timepoints [ Time Frame: Baseline, Day 2, Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 ]
    Blood samples were collected from participants at defined time points for the assessment of total albumin. Absolute value of total albumin at specified timepoints was reported.
16. Change From Baseline in Total Albumin Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
17. Percentage Change From Baseline in Total Albumin Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
18. Time to First Normalization for Total Albumin Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
19. Absolute Values of Total Protein, and Immunoglobulin G (IgG) at Baseline and Week 24 [ Time Frame: Baseline, Week 24 ]
    Blood samples were collected from participants at defined time points for the assessment of total protein and IgG. Absolutes values of total protein and IgG measured as g/L at baseline and Week 24 was reported.
20. Absolute Values of Total Immunoglobulin (Ig), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) at Baseline and Week 24 [ Time Frame: Baseline, Week 24 ]
    Blood samples were collected from participants at defined time points for the assessment of total Ig, IgM and IgA. Absolute value of total Ig, IgM and IgA measured as mg/dL at baseline and Week 24 was reported.
21. Change From Baseline in Total Protein Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
22. Percent Change From Baseline in Total Protein Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
23. Time to First Normalization for Total Protein [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
24. Change From Baseline in Total Ig Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
25. Percent Change From Baseline in Total Ig Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
26. Time to First Normalization for Total Ig Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
27. Change From Baseline in Total IgG Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
28. Percent Change From Baseline in Total IgG Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
29. Time to First Normalization for Total IgG Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
30. Change From Baseline in Total IgM Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
31. Percent Change From Baseline in Total IgM Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
32. Time to First Normalization for Total IgM Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
33. Change From Baseline in Total IgA Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
34. Percent Change From Baseline in Total IgA Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
35. Time to First Normalization for Total IgA Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
36. Absolute Values of Total Vitamin B12 at Baseline and Week 24 [ Time Frame: Baseline, Week 24 ]
    Blood samples were collected from participants at defined time points for the assessment of total vitamin B12. Absolute values of total vitamin B12 at baseline and Week 24 was reported.
37. Change From Baseline in Total Vitamin B12 Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
38. Time to First Normalization for Total Vitamin B12 Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
39. Absolute Values of Vitamin B9 [ Time Frame: Baseline up to Week 24 ]
    Absolute Values of Vitamin B9 - Central Lab
40. Change From Baseline in Total Folate Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
41. Time to First Normalization for Total Folate Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
42. Absolute Values of Total Iron and Iron Binding Capacity at Baseline and Week 24 [ Time Frame: Baseline, Week 24 ]
    Blood samples were collected from participants at defined time points for the assessment of iron indices. Absolute values of total iron and iron binding capacity measured as micromoles per liter (mcmol/L) at baseline and Week 24 was reported.
43. Change From Baseline in Total Iron Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
44. Time to First Normalization for Total Iron Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
45. Change From Baseline in Total Iron Binding Capacity [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
46. Time to First Normalization for Total Iron Binding Capacity [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
47. Absolute Values of Total Ferritin at Baseline and Week 24 [ Time Frame: Baseline, Week 24 ]
    Blood samples were collected from participants at defined time points for the assessment of iron indices. Absolute values of total ferritin was reported.
48. Change From Baseline in Total Ferritin Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
49. Time to First Normalization for Total Ferritin Levels [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
50. Absolute Values of Total Magnesium, Total Cholesterol, and Triglycerides [ Time Frame: Baseline, Week 24 ]
    Blood samples were collected from participants at defined time points for the assessment of total magnesium, total cholesterol, and triglycerides. Absolute values of total magnesium, total cholesterol, and triglycerides measured as mmol/L at baseline and Week 24 was reported.
51. Change From Baseline in Total Magnesium Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
52. Time to First Normalization for Total Magnesium Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
53. Change From Baseline in Total Fasting Cholesterol Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
54. Time to First Normalization for Total Fasting Cholesterol Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
55. Change From Baseline in Total Fasting Triglycerides Values [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
56. Time to First Normalization for Total Fasting Triglycerides Value [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
57. Change From Baseline in Alpha-1 Antitrypsin Levels in Stool [ Time Frame: Week 12, Week 24 ]
58. Change From Baseline in Alpha-1 Antitrypsin Levels in Blood [ Time Frame: Week 12, Week 24 ]
59. Number of Participants Who Used Concomitant Medication [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
60. Number of Hospitalization Days [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
61. Change From Baseline in Body Weight Z-Score [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
62. Change From Baseline in Height Z-Scores [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
63. Concentrations of Total Pozelimab in Serum [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
64. Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Pozelimab [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
65. Change From Baseline of Total Complement Activity Complement Hemolytic Assay (CH50) [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).
66. Percent Change From Baseline of Total Complement Activity CH50 Assay [ Time Frame: Baseline up to Week 144 ]
    Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025).

Eligibility Criteria

• Ages Eligible for Study: 1 Year and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Maryland

Regeneron Research Site

Bethesda, Maryland, United States, 20892

Thailand

Regeneron Research Site

Pathum Wan, Bangkok, Thailand, 10330

Turkey

Regeneron Research Site

Istanbul, Turkey, 34890

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Regeneron Pharmaceuticals:

Study Protocol  [PDF] February 1, 2022

Statistical Analysis Plan  [PDF] June 23, 2022

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04209634
• Other Study ID Numbers: R3918-PLE-1878
• First Posted: December 24, 2019
• Results First Posted: October 30, 2023
• Last Update Posted: May 13, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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).
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Regeneron Pharmaceuticals:

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

Additional relevant MeSH terms:

Intestinal Diseases; Protein-Losing Enteropathies; Gastrointestinal Diseases; Digestive System Diseases