CD55-deficient Protein-losing Enteropathy, CHAPLE
Conditions
Keywords
CD55-deficient PLE, complement hyperactivation, angiopathic thrombosis, protein-losing enteropathy (CHAPLE disease)
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
Interventions
DRUGPozelimab
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.
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Active Disease at Baseline Who Achieved Normalization of Serum Albumin and Improvement in Prespecified Clinical Outcomes at Week 24 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 | — |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Severity of TEAEs | From start of study drug administration up to approximately 144 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. |
| Number of Participants With Improvement in Most Bothersome Signs and Symptoms at Week 24 | 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. |
| 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 | 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. |
| 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 | 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. |
| Number of Participants With Abdominal Ascites at Week 24 | 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. |
| Absolute Value of Albumin at Specified Timepoints up to Week 24 | 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 albumin. Absolute value of albumin at specified timepoints was reported. |
| 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 | — |
| Absolute Values of Protein, and Immunoglobulin G (IgG) at Baseline and Week 24 | Baseline, 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. |
| Absolute Values of Immunoglobulin (Ig), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) at Baseline and Week 24 | Baseline, 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. |
| Absolute Values of Vitamin B12 at Baseline and Week 24 | Baseline, 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. |
| Absolute Values of Iron and Unsaturated Iron Binding Capacity at Baseline and Week 24 | Baseline, 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. |
| Absolute Values of Vitamin B9 up to Week 24 | Baseline up to Week 24 | Absolute Values of Vitamin B9 - Central Lab |
| Absolute Values of Ferritin at Baseline and Week 24 | Baseline, Week 24 | Blood samples were collected from participants at defined time points for the assessment of iron indices. Absolute values of ferritin was reported. |
| Absolute Values of Magnesium, Total Cholesterol, and Triglycerides at Week 24 | Baseline, 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. |
| 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 | Weeks 12 to 48; Weeks 12 to 144; Weeks 24 to 48; Weeks 48 to 96; Weeks 96 to 144 | 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 |
| Change From Baseline in Physician Assessment of Facial Edema Based on a 5-point Likert Rating Scale | Baseline and Week 144 | The physician assessment of facial edema is based on a 5-point Likert scale ranging from no edema (1) to very severe edema (5). |
| Change From Baseline in Physician Assessment of Peripheral Edema Based on a 5-point Likert Rating Scale | Baseline and Week 144 | The physician assessment of peripheral edema is based on a 5-point Likert scale ranging from no edema (1) to very severe edema (5). |
| Change From Baseline in Food and Drink Limitations as Assessed by the PedsQL™ GI Symptom Scales' Food and Drink Limits Sub-scale | Baseline and Week 144 | 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. |
| Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the PedsQL™ Generic Core Scales | Baseline and Week 144 | 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. |
| 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 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 | — |
| Change From Baseline in Ferritin Values | Baseline and 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 | Baseline and Week 144 | 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. |
| Change From Baseline in Height Z-Score | Baseline and Week 144 | 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. |
| 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 | — |
| Number of Participants Who Used Concomitant Medication | Baseline up to Week 144 | — |
Countries
Thailand, Turkey (Türkiye), United States
Participant flow
Pre-assignment details
A total of 11 participants were screened for this study. Of these, 1 participant did not meet inclusion/exclusion criteria, and 10 were assigned to study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Pozelimab Injection Participants received a single loading dose of pozelimab 30 mg/kg IV injection on day 1, followed by weekly SC injection as maintenance dosing of 125 mg for body weight \<10 kg, 200 mg for \>=10 kg and \<20 kg, 350 mg for \>=20 kg and \<40 kg, 500 mg for \>=40 kg and \<60 kg, and 800 mg for \>=60 kg over the treatment period. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Pozelimab Injection |
|---|---|
| Age, Continuous | 9.3 years STANDARD_DEVIATION 4.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 5 / 10 |
Outcome results
Primary
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
Population: The FAS included all enrolled participants who received the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Injection | Percentage of Participants With Active Disease at Baseline Who Achieved Normalization of Serum Albumin and Improvement in Prespecified Clinical Outcomes at Week 24 | 100 percentage of participants |
Secondary
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
Population: FAS included all enrolled participants who received the study drug. Here, number analyzed signifies those participants who were evaluable for specified timepoints in categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Baseline | 2.160 g/dL | Standard Deviation 0.5296 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Day 2 | 2.267 g/dL | Standard Deviation 0.4 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Week 1 | 3.311 g/dL | Standard Deviation 0.4485 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Week 2 | 3.589 g/dL | Standard Deviation 0.4428 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Week 3 | 4.025 g/dL | Standard Deviation 0.3955 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Week 4 | 4.167 g/dL | Standard Deviation 0.3841 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Week 6 | 4.411 g/dL | Standard Deviation 0.7026 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Week 8 | 4.188 g/dL | Standard Deviation 0.3137 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Week 10 | 4.322 g/dL | Standard Deviation 0.2279 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Week 12 | 4.288 g/dL | Standard Deviation 0.2748 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Week 14 | 4.363 g/dL | Standard Deviation 0.2615 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Week 16 | 4.367 g/dL | Standard Deviation 0.3674 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Week 18 | 4.344 g/dL | Standard Deviation 0.2555 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Week 20 | 4.449 g/dL | Standard Deviation 0.2539 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Week 22 | 4.422 g/dL | Standard Deviation 0.2906 |
| Pozelimab Injection | Absolute Value of Albumin at Specified Timepoints up to Week 24 | Week 24 | 4.544 g/dL | Standard Deviation 0.2603 |
Secondary
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
Population: The safety analysis set included all enrolled participants who received the study drug. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pozelimab Injection | Absolute Values of Ferritin at Baseline and Week 24 | Baseline | 10.0 microgram per liter (mcg/L) | Standard Deviation 5.9 |
| Pozelimab Injection | Absolute Values of Ferritin at Baseline and Week 24 | Week 24 | 12.0 microgram per liter (mcg/L) | Standard Deviation 7.86 |
Secondary
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
Population: The safety analysis set included all enrolled participants who received the study drug. Here, number analyzed signifies those participants who were evaluable for specified timepoints in categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pozelimab Injection | Absolute Values of Immunoglobulin (Ig), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) at Baseline and Week 24 | Ig at Baseline | 318.2 mg/dL | Standard Deviation 113.36 |
| Pozelimab Injection | Absolute Values of Immunoglobulin (Ig), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) at Baseline and Week 24 | Ig at Week 24 | 1430.1 mg/dL | Standard Deviation 263.36 |
| Pozelimab Injection | Absolute Values of Immunoglobulin (Ig), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) at Baseline and Week 24 | IgM at Baseline | 52.9 mg/dL | Standard Deviation 28.36 |
| Pozelimab Injection | Absolute Values of Immunoglobulin (Ig), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) at Baseline and Week 24 | IgM at Week 24 | 180.3 mg/dL | Standard Deviation 74.81 |
| Pozelimab Injection | Absolute Values of Immunoglobulin (Ig), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) at Baseline and Week 24 | IgA at Baseline | 47.0 mg/dL | Standard Deviation 18.51 |
| Pozelimab Injection | Absolute Values of Immunoglobulin (Ig), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) at Baseline and Week 24 | IgA at Week 24 | 119.8 mg/dL | Standard Deviation 52.46 |
Secondary
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
Population: The safety analysis set included all enrolled participants who received the study drug. Here, number analyzed signifies those participants who were evaluable for specified timepoints in categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pozelimab Injection | Absolute Values of Iron and Unsaturated Iron Binding Capacity at Baseline and Week 24 | Iron at Baseline | 3.40 mcmol/L | Standard Deviation 1.478 |
| Pozelimab Injection | Absolute Values of Iron and Unsaturated Iron Binding Capacity at Baseline and Week 24 | Iron at Week 24 | 7.38 mcmol/L | Standard Deviation 5.036 |
| Pozelimab Injection | Absolute Values of Iron and Unsaturated Iron Binding Capacity at Baseline and Week 24 | Unsaturated Binding Capacity at Baseline | 38.24 mcmol/L | Standard Deviation 12.357 |
| Pozelimab Injection | Absolute Values of Iron and Unsaturated Iron Binding Capacity at Baseline and Week 24 | Unsaturated Iron Binding Capacity at Week 24 | 73.95 mcmol/L | Standard Deviation 12.049 |
Secondary
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
Population: The safety analysis set included all enrolled participants who received the study drug. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable for specified timepoints in categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pozelimab Injection | Absolute Values of Magnesium, Total Cholesterol, and Triglycerides at Week 24 | Magnesium at Baseline | 0.793 mmol/L | Standard Deviation 0.0381 |
| Pozelimab Injection | Absolute Values of Magnesium, Total Cholesterol, and Triglycerides at Week 24 | Magnesium at Week 24 | 0.858 mmol/L | Standard Deviation 0.0245 |
| Pozelimab Injection | Absolute Values of Magnesium, Total Cholesterol, and Triglycerides at Week 24 | Total Cholesterol at Baseline | 3.819 mmol/L | Standard Deviation 0.8786 |
| Pozelimab Injection | Absolute Values of Magnesium, Total Cholesterol, and Triglycerides at Week 24 | Total Cholesterol at Week 24 | 3.604 mmol/L | Standard Deviation 0.3118 |
| Pozelimab Injection | Absolute Values of Magnesium, Total Cholesterol, and Triglycerides at Week 24 | Triglycerides at Baseline | 2.033 mmol/L | Standard Deviation 0.7946 |
| Pozelimab Injection | Absolute Values of Magnesium, Total Cholesterol, and Triglycerides at Week 24 | Triglycerides at Week 24 | 1.094 mmol/L | Standard Deviation 0.3745 |
Secondary
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
Population: The safety analysis set included all enrolled participants who received the study drug. Here, number analyzed signifies those participants who were evaluable for specified timepoints in categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pozelimab Injection | Absolute Values of Protein, and Immunoglobulin G (IgG) at Baseline and Week 24 | Protein at Baseline | 37.50 g/L | Standard Deviation 6.996 |
| Pozelimab Injection | Absolute Values of Protein, and Immunoglobulin G (IgG) at Baseline and Week 24 | Protein at Week 24 | 72.22 g/L | Standard Deviation 4.969 |
| Pozelimab Injection | Absolute Values of Protein, and Immunoglobulin G (IgG) at Baseline and Week 24 | IgG at Baseline | 2.183 g/L | Standard Deviation 0.9103 |
| Pozelimab Injection | Absolute Values of Protein, and Immunoglobulin G (IgG) at Baseline and Week 24 | IgG at Week 24 | 11.301 g/L | Standard Deviation 2.0503 |
Secondary
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
Population: The safety analysis set included all enrolled participants who received the study drug. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pozelimab Injection | Absolute Values of Vitamin B12 at Baseline and Week 24 | Baseline | 158.5 picomoles per liter (pmol/L) | Standard Deviation 52.32 |
| Pozelimab Injection | Absolute Values of Vitamin B12 at Baseline and Week 24 | Week 24 | 383.1 picomoles per liter (pmol/L) | Standard Deviation 102.73 |
Secondary
Absolute Values of Vitamin B9 up to Week 24
Absolute Values of Vitamin B9 - Central Lab
Time frame: Baseline up to Week 24
Population: Number of participants based on the total in the safety analysis set (SAF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pozelimab Injection | Absolute Values of Vitamin B9 up to Week 24 | Week 1 | 17.80 nanomoles per liter (nmol/L) | Standard Deviation 15.017 |
| Pozelimab Injection | Absolute Values of Vitamin B9 up to Week 24 | Week 4 | 22.07 nanomoles per liter (nmol/L) | Standard Deviation 14.342 |
| Pozelimab Injection | Absolute Values of Vitamin B9 up to Week 24 | Week 8 | 17.32 nanomoles per liter (nmol/L) | Standard Deviation 8.042 |
| Pozelimab Injection | Absolute Values of Vitamin B9 up to Week 24 | Week 12 | 17.89 nanomoles per liter (nmol/L) | Standard Deviation 9.646 |
| Pozelimab Injection | Absolute Values of Vitamin B9 up to Week 24 | Week 16 | 18.01 nanomoles per liter (nmol/L) | Standard Deviation 10.61 |
| Pozelimab Injection | Absolute Values of Vitamin B9 up to Week 24 | Week 20 | 19.91 nanomoles per liter (nmol/L) | Standard Deviation 15.436 |
| Pozelimab Injection | Absolute Values of Vitamin B9 up to Week 24 | Week 24 | 18.93 nanomoles per liter (nmol/L) | Standard Deviation 6.538 |
Secondary
Change From Baseline in Albumin Values
Time frame: Baseline and Week 144
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Albumin Values | 2.400 grams per deciliter (g/dL) | Standard Deviation 0.6103 |
Secondary
Change From Baseline in Alpha-1 Antitrypsin Levels in Blood at Week 12 and Week 24
Time frame: Week 12, Week 24
Population: Number of participants based on the total in the safety analysis set (SAF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Alpha-1 Antitrypsin Levels in Blood at Week 12 and Week 24 | Change from Baseline to Week 12 | -57.8 mg/dL | Standard Deviation 33.15 |
| Pozelimab Injection | Change From Baseline in Alpha-1 Antitrypsin Levels in Blood at Week 12 and Week 24 | Change from Baseline to Week 24 | -43.4 mg/dL | Standard Deviation 35.89 |
Secondary
Change From Baseline in Alpha-1 Antitrypsin Levels in Stool at Week 12 and Week 24
Time frame: Week 12, Week 24
Population: The FAS included all enrolled participants who received the study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Alpha-1 Antitrypsin Levels in Stool at Week 12 and Week 24 | Change from Baseline to Week 12 | -527.80 milligrams per deciliter (mg/dL) | Standard Deviation 318.818 |
| Pozelimab Injection | Change From Baseline in Alpha-1 Antitrypsin Levels in Stool at Week 12 and Week 24 | Change from Baseline to Week 24 | -463.71 milligrams per deciliter (mg/dL) | Standard Deviation 204.25 |
Secondary
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
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Body Weight Z-Score | 0.924 z-score | Standard Deviation 0.7529 |
Secondary
Change From Baseline in Fasting Cholesterol Values
Time frame: Baseline and Week 144
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Fasting Cholesterol Values | -0.072 mmol/L | Standard Deviation 0.7299 |
Secondary
Change From Baseline in Fasting Triglycerides Values
Time frame: Baseline and Week 144
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Fasting Triglycerides Values | -0.710 mmol/L | Standard Deviation 0.9086 |
Secondary
Change From Baseline in Ferritin Values
Time frame: Baseline and Week 144
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Ferritin Values | 32.0 microgram per liter (ug/L) | Standard Deviation 23.67 |
Secondary
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
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at this time point for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Food and Drink Limitations as Assessed by the PedsQL™ GI Symptom Scales' Food and Drink Limits Sub-scale | 47.40 score on a scale | Standard Deviation 36.653 |
Secondary
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
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at this time point for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the PedsQL™ Generic Core Scales | Week 144 Change from Baseline Total score of PedsQL Core Score | 26.55 score on a scale | Standard Deviation 17.023 |
| Pozelimab Injection | Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the PedsQL™ Generic Core Scales | Week 144 Change from Baseline Subscale score: Physical functioning | 14.45 score on a scale | Standard Deviation 39.9 |
| Pozelimab Injection | Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the PedsQL™ Generic Core Scales | Week 144 Change from Baseline Subscale score: Emotional functioning | 26.3 score on a scale | Standard Deviation 28.88 |
| Pozelimab Injection | Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the PedsQL™ Generic Core Scales | Week 144 Change from Baseline Subscale score: Social functioning | 30.6 score on a scale | Standard Deviation 20.43 |
| Pozelimab Injection | Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the PedsQL™ Generic Core Scales | Week 144 Change from Baseline Subscale score: School functioning | 41.43 score on a scale | Standard Deviation 19.518 |
Secondary
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
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Height Z-Score | 1.079 z-score | Standard Deviation 0.6469 |
Secondary
Change From Baseline in IgA Values
Time frame: Baseline and Week 144
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in IgA Values | 96.7 mg/dL | Standard Deviation 28.78 |
Secondary
Change From Baseline in IgG Values
Time frame: Baseline and Week 144
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in IgG Values | 10.626 g/L | Standard Deviation 2.2486 |
Secondary
Change From Baseline in IgM Values
Time frame: Baseline and Week 144
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in IgM Values | 112.0 mg/dL | Standard Deviation 51.21 |
Secondary
Change From Baseline in Immunoglobulin (Ig) Values
Time frame: Baseline and Week 144
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Immunoglobulin (Ig) Values | 1271.2 mg/dL | Standard Deviation 261.91 |
Secondary
Change From Baseline in Iron Values
Time frame: Baseline and Week 144
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Iron Values | 7.82 micromole/liter (umol/L) | Standard Deviation 4.091 |
Secondary
Change From Baseline in Magnesium Values
Time frame: Baseline and Week 144
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Magnesium Values | 0.083 millimoles per liter (mmol/L) | Standard Deviation 0.0606 |
Secondary
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
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Physician Assessment of Facial Edema Based on a 5-point Likert Rating Scale | -1.7 score on a scale | Standard Deviation 0.87 |
Secondary
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
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Physician Assessment of Peripheral Edema Based on a 5-point Likert Rating Scale | -1.7 score on a scale | Standard Deviation 0.71 |
Secondary
Change From Baseline in Protein Values
Time frame: Baseline and Week 144
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at this time point for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Protein Values | 37.13 grams per liter (g/L) | Standard Deviation 10.789 |
Secondary
Change From Baseline in Total Complement Activity Complement Hemolytic Assay (CH50)
Time frame: Baseline and Week 144
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Total Complement Activity Complement Hemolytic Assay (CH50) | -241.6 international units/milliliter (IU/mL) | Standard Deviation 39.79 |
Secondary
Change From Baseline in Unsaturated Iron Binding Capacity
Time frame: Baseline and Week 144
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Unsaturated Iron Binding Capacity | 16.20 umol/L | Standard Deviation 13.811 |
Secondary
Change From Baseline in Vitamin B12 Values
Time frame: Baseline and Week 144
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Vitamin B12 Values | 138.8 picomoles per liter (pmol/L) | Standard Deviation 56.07 |
Secondary
Change From Baseline in Vitamin B9 (Folate) Values
Time frame: Baseline and Week 144
Population: All enrolled participants who received the study drug and consented to Protocol Amendment 6 and who were evaluable at both time points for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Change From Baseline in Vitamin B9 (Folate) Values | 2.92 nanomole per liter (nmol/L) | Standard Deviation 10.241 |
Secondary
Concentrations of Total Pozelimab in Serum
Time frame: Baseline up to Week 164
Population: The Pharmacokinetic Analysis Set (PKAS) includes all treated participants who received any amount of study drug and had at least 1 non-missing total pozelimab measurement following the first dose of study drug. The PKAS is based on the actual treatment received (as treated) rather than as randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 145 | NA mg/L | — |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 1 | 182 mg/L | Standard Deviation 68.9 |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 2 | 185 mg/L | Standard Deviation 103 |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 4 | 227 mg/L | Standard Deviation 110 |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 6 | 268 mg/L | Standard Deviation 106 |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 8 | 306 mg/L | Standard Deviation 111 |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 12 | 341 mg/L | Standard Deviation 115 |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 16 | 402 mg/L | Standard Deviation 141 |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 20 | 418 mg/L | Standard Deviation 136 |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 24 | 421 mg/L | Standard Deviation 129 |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 36 | 467 mg/L | Standard Deviation 127 |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 48 | 517 mg/L | Standard Deviation 142 |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 72 | 492 mg/L | Standard Deviation 131 |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 96 | 461 mg/L | Standard Deviation 115 |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 144 | 430 mg/L | Standard Deviation 134 |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 146 | NA mg/L | — |
| Pozelimab Injection | Concentrations of Total Pozelimab in Serum | Week 164 | 410 mg/L | Standard Deviation 104 |
Secondary
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
Population: FAS included all enrolled participants who received the study drug. Here, number analyzed signifies those participants who were evaluable for specified timepoints in categories.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Baseline | 1.64 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 1 | 1.13 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 2 | 1.36 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 3 | 1.43 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 4 | 1.50 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 5 | 1.57 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 6 | 1.21 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 7 | 1.21 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 8 | 1.07 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 9 | 1.00 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 10 | 1.00 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 11 | 1.00 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 12 | 0.79 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 13 | 0.93 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 14 | 0.93 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 15 | 1.07 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 16 | 1.10 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 17 | 1.13 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 18 | 1.00 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 19 | 1.00 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 20 | 0.83 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 21 | 1.00 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 22 | 0.83 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 23 | 0.86 Bowel movements per day |
| Pozelimab Injection | Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 | Week 24 | 0.90 Bowel movements per day |
Secondary
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
Population: FAS included all enrolled participants who received any study drug. Here, number analyzed signifies those participants who were evaluable for specified timepoints in categories.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Baseline | 2.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 1 | 0.50 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 2 | 0.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 3 | 0.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 4 | 0.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 5 | 0.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 6 | 1.20 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 7 | 0.50 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 8 | 0.50 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 9 | 0.50 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 10 | 0.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 11 | 1.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 12 | 0.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 13 | 0.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 14 | 1.58 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 15 | 1.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 16 | 0.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 17 | 1.28 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 18 | 0.50 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 19 | 0.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 20 | 0.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 21 | 0.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 22 | 0.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 23 | 0.00 Days per week |
| Pozelimab Injection | Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 | Week 24 | 0.00 Days per week |
Secondary
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
Population: All enrolled participants who received the study drug. 1 participant was consented to Protocol Amendment 5 and completed the study at week 104. The remaining 9 participants were consented to Protocol Amendment 6 and completed the study at week 144.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pozelimab Injection | Number of Hospitalization Days by 24 Week Period | Weeks 96 to 120 | 0.0 days |
| Pozelimab Injection | Number of Hospitalization Days by 24 Week Period | Weeks 0 to 24 | 0.0 days |
| Pozelimab Injection | Number of Hospitalization Days by 24 Week Period | Weeks 24 to 48 | 0.0 days |
| Pozelimab Injection | Number of Hospitalization Days by 24 Week Period | Weeks 48 to 72 | 0.0 days |
| Pozelimab Injection | Number of Hospitalization Days by 24 Week Period | Weeks 72 to 96 | 0.0 days |
| Pozelimab Injection | Number of Hospitalization Days by 24 Week Period | Weeks 120 to 144 | 0.0 days |
Secondary
Number of Participants Who Used Concomitant Medication
Time frame: Baseline up to Week 144
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pozelimab Injection | Number of Participants Who Used Concomitant Medication | 10 Participants |
Secondary
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
Population: FAS included all enrolled participants who received any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pozelimab Injection | Number of Participants With Abdominal Ascites at Week 24 | 1 Participants |
Secondary
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
Population: All enrolled participants who received the study drug. 1 participant was consented to Protocol Amendment 5, and completed the study at week 104. The remaining 9 participants were consented to Protocol Amendment 6 and completed the study at week 144.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pozelimab Injection | Number of Participants With Albumin Infusion by 24 Week Periods | Weeks 0 to 24 | 1 Participants |
| Pozelimab Injection | Number of Participants With Albumin Infusion by 24 Week Periods | Weeks 24 to 48 | 0 Participants |
| Pozelimab Injection | Number of Participants With Albumin Infusion by 24 Week Periods | Weeks 48 to 72 | 0 Participants |
| Pozelimab Injection | Number of Participants With Albumin Infusion by 24 Week Periods | Weeks 72 to 96 | 0 Participants |
| Pozelimab Injection | Number of Participants With Albumin Infusion by 24 Week Periods | Weeks 96 to 120 | 0 Participants |
| Pozelimab Injection | Number of Participants With Albumin Infusion by 24 Week Periods | Weeks 120 to 144 | 0 Participants |
Secondary
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
Population: FAS included all enrolled participants who received the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pozelimab Injection | Number of Participants With Improvement in Most Bothersome Signs and Symptoms at Week 24 | 10 Participants |
Secondary
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
Population: The safety analysis set included all enrolled participants who received the study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pozelimab Injection | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Severity of TEAEs | Participants with TEAEs | 10 Participants |
| Pozelimab Injection | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Severity of TEAEs | Participants with mild severity | 3 Participants |
| Pozelimab Injection | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Severity of TEAEs | Participants with moderate severity | 5 Participants |
| Pozelimab Injection | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Severity of TEAEs | Participants with severe severity | 2 Participants |
Secondary
Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Pozelimab
Time frame: Baseline up to Week 164
Population: The Anti-Drug Antibody Analysis Set (AAS) includes all treated participants who received any amount of study drug and had at least 1 non-missing ADA result following the first dose of study drug. The AAS is based on the actual treatment received (as treated) rather than as randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pozelimab Injection | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Pozelimab | 0 Participants |
Secondary
Percentage Change From Baseline in Albumin Values
Time frame: Baseline and Week 144
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Injection | Percentage Change From Baseline in Albumin Values | 127.489 percentage of change | Standard Deviation 81.0666 |
Secondary
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
Population: All enrolled participants who received the study drug. 1 participant was consented to Protocol Amendment 5, and completed the study at week 104. The remaining 9 participants were consented to Protocol Amendment 6 and completed the study at week 144.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pozelimab Injection | Percentage of Participants With Active Disease at Baseline Who Maintained Disease Control | Weeks 12 to 48 | 100 percentage of participants |
| Pozelimab Injection | Percentage of Participants With Active Disease at Baseline Who Maintained Disease Control | Weeks 12 to 144 | 100 percentage of participants |
| Pozelimab Injection | Percentage of Participants With Active Disease at Baseline Who Maintained Disease Control | Weeks 24 to 48 | 100 percentage of participants |
| Pozelimab Injection | Percentage of Participants With Active Disease at Baseline Who Maintained Disease Control | Weeks 48 to 96 | 100 percentage of participants |
| Pozelimab Injection | Percentage of Participants With Active Disease at Baseline Who Maintained Disease Control | Weeks 96 to 144 | 100 percentage of participants |
Secondary
Time to First Normalization for Albumin Values
Time frame: Baseline up to Week 144
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Injection | Time to First Normalization for Albumin Values | 15.5 days |
Secondary
Time to First Normalization for Fasting Cholesterol Values
Time frame: Baseline up to Week 144
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Injection | Time to First Normalization for Fasting Cholesterol Values | 1 days |
Secondary
Time to First Normalization for Fasting Triglycerides Values
Time frame: Baseline up to Week 144
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Injection | Time to First Normalization for Fasting Triglycerides Values | 4 days |
Secondary
Time to First Normalization for Ferritin Values
Time frame: Baseline up to Week 144
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Injection | Time to First Normalization for Ferritin Values | 28 days |
Secondary
Time to First Normalization for IgA Values
Time frame: Baseline up to Week 144
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Injection | Time to First Normalization for IgA Values | 1 days |
Secondary
Time to First Normalization for IgG Values
Time frame: Baseline up to Week 144
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Injection | Time to First Normalization for IgG Values | 29.0 days |
Secondary
Time to First Normalization for IgM Values
Time frame: Baseline up to Week 44
Population: All enrolled participants who received the study drug who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Injection | Time to First Normalization for IgM Values | 1 days |
Secondary
Time to First Normalization for Ig Values
Time frame: Baseline up to Week 144
Population: All enrolled participants with available Ig lab reference ranges.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Injection | Time to First Normalization for Ig Values | 341 days |
Secondary
Time to First Normalization for Iron Values
Time frame: Baseline up to Week 144
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Injection | Time to First Normalization for Iron Values | 97.5 days |
Secondary
Time to First Normalization for Magnesium Values
Time frame: Baseline up to Week 144
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Injection | Time to First Normalization for Magnesium Values | 1 days |
Secondary
Time to First Normalization for Total Protein
Time frame: Baseline up to Week 144
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Injection | Time to First Normalization for Total Protein | 22.0 days |
Secondary
Time to First Normalization for Unsaturated Iron Binding Capacity
Time frame: Baseline up to Week 144
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Injection | Time to First Normalization for Unsaturated Iron Binding Capacity | 1 days |
Secondary
Time to First Normalization for Vitamin B12 Values
Time frame: Baseline up to Week 144
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Injection | Time to First Normalization for Vitamin B12 Values | 8 days |
Secondary
Time to First Normalization for Vitamin B9 (Folate) Values
Time frame: Baseline up to Week 144
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Injection | Time to First Normalization for Vitamin B9 (Folate) Values | 1 days |