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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
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.
Regeneron Research Site
Bethesda, Maryland, United States
Regeneron Research Site
Pathum Wan, Bangkok, Thailand
Regeneron Research Site
Istanbul, Turkey (Türkiye)
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.
Time frame: At Week 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.
Time frame: 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.
Time frame: 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.
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
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.
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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline, Week 24
Absolute Values of Vitamin B9 up to Week 24
Absolute Values of Vitamin B9 - Central Lab
Time frame: 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.
Time frame: 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.
Time frame: Baseline, Week 24
Change From Baseline in Alpha-1 Antitrypsin Levels in Stool at Week 12 and Week 24
Time frame: Week 12, Week 24
Change From Baseline in Alpha-1 Antitrypsin Levels in Blood at Week 12 and Week 24
Time frame: 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
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: Baseline and Week 144
Number of Participants With Albumin Infusion by 24 Week Periods
Time frame: 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
Time frame: Baseline and Week 144
Percentage Change From Baseline in Albumin Values
Time frame: Baseline and Week 144
Time to First Normalization for Albumin Values
Time frame: Baseline up to Week 144
Change From Baseline in Protein Values
Time frame: Baseline and Week 144
Time to First Normalization for Total Protein
Time frame: Baseline up to Week 144
Change From Baseline in Immunoglobulin (Ig) Values
Time frame: Baseline and Week 144
Time to First Normalization for Ig Values
Time frame: Baseline up to Week 144
Change From Baseline in IgG Values
Time frame: Baseline and Week 144
Time to First Normalization for IgG Values
Time frame: Baseline up to Week 144
Change From Baseline in IgM Values
Time frame: Baseline and Week 144
Time to First Normalization for IgM Values
Time frame: Baseline up to Week 44
Change From Baseline in IgA Values
Time frame: Baseline and Week 144
Time to First Normalization for IgA Values
Time frame: Baseline up to Week 144
Change From Baseline in Vitamin B12 Values
Time frame: Baseline and Week 144
Time to First Normalization for Vitamin B12 Values
Time frame: Baseline up to Week 144
Change From Baseline in Vitamin B9 (Folate) Values
Time frame: Baseline and Week 144
Time to First Normalization for Vitamin B9 (Folate) Values
Time frame: Baseline up to Week 144
Change From Baseline in Iron Values
Time frame: Baseline and Week 144
Time to First Normalization for Iron Values
Time frame: Baseline up to Week 144
Change From Baseline in Unsaturated Iron Binding Capacity
Time frame: Baseline and Week 144
Time to First Normalization for Unsaturated Iron Binding Capacity
Time frame: Baseline up to Week 144
Change From Baseline in Ferritin Values
Time frame: Baseline and Week 144
Time to First Normalization for Ferritin Values
Time frame: Baseline up to Week 144
Change From Baseline in Magnesium Values
Time frame: Baseline and Week 144
Time to First Normalization for Magnesium Values
Time frame: Baseline up to Week 144
Change From Baseline in Fasting Cholesterol Values
Time frame: Baseline and Week 144
Time to First Normalization for Fasting Cholesterol Values
Time frame: Baseline up to Week 144
Change From Baseline in Fasting Triglycerides Values
Time frame: Baseline and Week 144
Time to First Normalization for Fasting Triglycerides Values
Time frame: Baseline up to Week 144
Number of Participants Who Used Concomitant Medication
Time frame: Baseline up to Week 144
Number of Hospitalization Days by 24 Week Period
Time frame: 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.
Time frame: 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.
Time frame: Baseline and Week 144
Change From Baseline in Total Complement Activity Complement Hemolytic Assay (CH50)
Time frame: Baseline and Week 144
Concentrations of Total Pozelimab in Serum
Time frame: Baseline up to Week 164
Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Pozelimab
Time frame: Baseline up to Week 164
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