Open-Label Efficacy and Safety Study of Pozelimab in Patients With CD55-Deficient Protein-Losing Enteropathy (CHAPLE Disease)
- Conditions
- CD55-deficient Protein-losing EnteropathyCHAPLE
- Interventions
- Registration Number
- NCT04209634
- Lead Sponsor
- Regeneron Pharmaceuticals
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 10
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Active PLE Pozelimab Patients aged 1 year and older with a clinical diagnosis of CD55-deficient PLE disease
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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 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 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 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 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 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 Change From Baseline in Ferritin Values Baseline and Week 144 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 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 Number of Participants Who Used Concomitant Medication Baseline up to 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 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.
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.
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.
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
Trial Locations
- Locations (1)
Regeneron Research Site
🇹🇷Istanbul, Turkey