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

Study Overview
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Brief Summary
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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

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

Conditions
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CD55-deficient Protein-losing Enteropathy, CHAPLE

Intervention / Treatment
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* Drug: Pozelimab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active PLE<br>Patients aged 1 year and older with a clinical diagnosis of CD55-deficient PLE disease | Drug: Pozelimab<br>* 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.<br>* Other names: REGN3918;|

What is the study measuring?
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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 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 primary analysis cut-off date (24 May 2022) [i.e approximately 52 weeks]) | 
| Number of Participants With Improvement in Most Bothersome Signs and Symptoms | 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 | 
| Proportion of Participants With Active Disease at Baseline Who Maintained Disease Control | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Week 12 to 48; Week 12 to 144; Week 24 to 48; Week 48 to 96; Week 96 to 144 | 
| Proportion of Participants With Inactive Disease on Eculizumab at Baseline Who Maintained Disease Control | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Week 12 to 48; Week 12 to 144; Week 24 to 48; Week 48 to 96; Week 96 to 144 | 
| Number of Bowel Movements Per Day Based on a 1-week Average | 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 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 | 
| Physician Assessment of Facial Edema Based on a 5-point Likert Rating Scale | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Physician Assessment of Peripheral Edema Based on a 5-point Likert Rating Scale | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| 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 | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Health-related Quality of Life (HRQoL) as Assessed by the PedsQL™ Generic Core Scales | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| HRQoL as Assessed by the PedsQL™ Generic Core Scales for About my Work/Studies and School Functioning Sub-scale | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| HRQoL as Assessed by the PedsQL™ Generic Core Scales for Physical Functioning Sub-scale | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Number of Participants With Abdominal Ascites | 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 | 
| Number of Participants With Albumin Infusions | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Absolute Value of Total Albumin at Specified Timepoints | 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. | Baseline, Day 2, Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 | 
| Change From Baseline in Total Albumin Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Percentage Change From Baseline in Total Albumin Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Time to First Normalization for Total Albumin Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Absolute Values of Total Protein, and Immunoglobulin G (IgG) at Baseline and 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. | Baseline, Week 24 | 
| Absolute Values of Total 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 total Ig, IgM and IgA. Absolute value of total Ig, IgM and IgA measured as mg/dL at baseline and Week 24 was reported. | Baseline, Week 24 | 
| Change From Baseline in Total Protein Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Percent Change From Baseline in Total Protein Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Time to First Normalization for Total Protein | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Change From Baseline in Total Ig Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Percent Change From Baseline in Total Ig Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Time to First Normalization for Total Ig Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Change From Baseline in Total IgG Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Percent Change From Baseline in Total IgG Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Time to First Normalization for Total IgG Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Change From Baseline in Total IgM Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Percent Change From Baseline in Total IgM Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Time to First Normalization for Total IgM Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Change From Baseline in Total IgA Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Percent Change From Baseline in Total IgA Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Time to First Normalization for Total IgA Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Absolute Values of Total Vitamin B12 at Baseline and 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. | Baseline, Week 24 | 
| Change From Baseline in Total Vitamin B12 Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Time to First Normalization for Total Vitamin B12 Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Absolute Values of Vitamin B9 | Absolute Values of Vitamin B9 - Central Lab | Baseline up to Week 24 | 
| Change From Baseline in Total Folate Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Time to First Normalization for Total Folate Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Absolute Values of Total Iron and 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 total iron and iron binding capacity measured as micromoles per liter (mcmol/L) at baseline and Week 24 was reported. | Baseline, Week 24 | 
| Change From Baseline in Total Iron Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Time to First Normalization for Total Iron Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Change From Baseline in Total Iron Binding Capacity | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Time to First Normalization for Total Iron Binding Capacity | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Absolute Values of Total 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 total ferritin was reported. | Baseline, Week 24 | 
| Change From Baseline in Total Ferritin Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Time to First Normalization for Total Ferritin Levels | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Absolute Values of Total Magnesium, Total Cholesterol, and Triglycerides | 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. | Baseline, Week 24 | 
| Change From Baseline in Total Magnesium Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Time to First Normalization for Total Magnesium Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Change From Baseline in Total Fasting Cholesterol Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Time to First Normalization for Total Fasting Cholesterol Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Change From Baseline in Total Fasting Triglycerides Values | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Time to First Normalization for Total Fasting Triglycerides Value | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Change From Baseline in Alpha-1 Antitrypsin Levels in Stool |  | Week 12, Week 24 | 
| Change From Baseline in Alpha-1 Antitrypsin Levels in Blood |  | Week 12, Week 24 | 
| Number of Participants Who Used Concomitant Medication | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Number of Hospitalization Days | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Change From Baseline in Body Weight Z-Score | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Change From Baseline in Height Z-Scores | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Concentrations of Total Pozelimab in Serum | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Pozelimab | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Change From Baseline of Total Complement Activity Complement Hemolytic Assay (CH50) | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 
| Percent Change From Baseline of Total Complement Activity CH50 Assay | Data for this outcome measure will be reported at the time of final results posting (i.e. August 2025). | Baseline up to Week 144 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD55-deficient PLE, complement hyperactivation, angiopathic thrombosis, protein-losing enteropathy (CHAPLE disease)