Back to resultsOpen-Label Efficacy and Safety Study of Pozelimab in Patients With CD55-Deficient Protein-Losing Enteropathy (CHAPLE Disease)
Primary Purpose
CD55-deficient Protein-losing Enteropathy, CHAPLE
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pozelimab
Sponsored by
About this trial
This is an interventional treatment trial for CD55-deficient Protein-losing Enteropathy focused on measuring CD55-deficient PLE, complement hyperactivation, angiopathic thrombosis, protein-losing enteropathy (CHAPLE disease)
Eligibility Criteria
Key Inclusion Criteria:
- Clinical diagnosis of CD55-deficient PLE/CHAPLE disease (based on a history of PLE), confirmed by biallelic CD55 loss-of-function mutation detected by genotype analysis
- Active disease as defined by the protocol or inactive disease on eculizumab therapy (and whose treating physician has the expectation of future access to renewed eculizumab treatment should this be required), and is willing to discontinue eculizumab during screening and start pozelimab at baseline with no eculizumab wash-out
Key Exclusion Criteria:
- History of meningococcal infection
- No documented meningococcal vaccination within 3 years prior to screening and patient unwilling to undergo vaccination during the study
- No documented vaccination for Haemophilus influenzae and Streptococcus pneumoniae if applicable based on local practice or guidelines prior to screening and patient unwilling to undergo vaccination during the study if required per local practice or guidelines
- Presence of a concomitant disease that leads to hypoproteinemia at the time of starting pozelimab
- A concomitant disease that leads to secondary intestinal lymphangiectasia such as a fontan procedure for congenital heart disease
Note: Other protocol-defined Inclusion/Exclusion criteria apply.
Sites / Locations
- Regeneron Research Site
- Regeneron Research Site
- Regeneron Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Active PLE
Arm Description
Patients aged 1 year and older with a clinical diagnosis of CD55-deficient PLE disease
Outcomes
Primary Outcome Measures
Proportion of patients with active disease at baseline achieving both normalization of serum albumin and clinical outcome improvement
Normalization of serum albumin defined as intra-patient mean serum albumin within the normal range.
Clinical Outcomes:
The number of bowel movements per day captured by e-diary
Physician assessment of facial edema (based on a 5-point Likert scale)
Physician assessment of peripheral edema (based on a 5-point Likert scale)
Patient/caregiver assessment of abdominal pain as assessed by the Stomach pain and hurt sub-scale of the PedsQL™ GI Symptom Scale
Secondary Outcome Measures
Incidence and severity of treatment-emergent adverse events (TEAEs)
TEAEs include adverse events (AEs), abnormal vital signs, height, weight, electrocardiograms (ECGs), and laboratory testing
Improvement in each patient's most bothersome sign/symptom
Using a semi-structured concept elicitation interview
Proportion of patients with active disease at baseline who maintain 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
Proportion of patients with active disease at baseline who maintain 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
Proportion of patients with inactive disease on eculizumab at baseline who maintain 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
Proportion of patients with inactive disease on eculizumab at baseline who maintain 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
Proportion of patients with inactive disease on eculizumab at baseline who maintain 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
The number of bowel movements per day based on a 1-week average
Captured by e-diary
The number of days/week with ≥1 bowel movement of loose/watery stool consistency
As captured by e- diary and measured by the
Bristol Stool Form Scale (BSFS) from 1 to 7 where 1 is separate hard lumps and 7 is entirely liquid
modified BSFS from 1 to 5 where 1 is separate hard lumps and 5 is watery, no solid pieces
or the Brussels Infant and Toddler Stool Scale (BIFSS) from 1 to 4 where 1 is hard stools and 4 is watery
Physician assessment of facial edema
Based on a 5-point Likert scale where 1 is strongly agree and 5 is strongly disagree
Physician assessment of peripheral edema
Based on a 5-point Likert scale where 1 is strongly agree and 5 is strongly disagree
Change in abdominal symptoms
As assessed by the Stomach pain and hurt sub-scale and food and drink limits sub-scale of the PedsQL™ GI Symptom Scale 5-point scale where 0 is never a problem and 4 is almost always a problem
Health-related quality of life as assessed by the PedsQL™ Generic Core Scales for about my work/studies and school functioning sub-scale
A 5-point response scale where 0 is never a problem and 4 is almost always a problem
Health-related quality of life as assessed by the PedsQL™ Generic Core Scales for physical functioning sub-scale
A 5-point response scale where 0 is never a problem and 4 is almost always a problem
Assessment of abdominal ascites
Assessed by measurement of abdominal circumference
Frequency of albumin infusions
Total albumin absolute value
Total albumin absolute change from baseline
Total albumin percent change
Total albumin time to first normalization
Total protein absolute value
Total protein absolute change from baseline
Total protein percent change
Total protein time to first normalization
Total Ig absolute value
Total Ig absolute change from baseline
Total Ig percent change
Total Ig time to first normalization
Total IgG absolute value
Total IgG absolute change from baseline
Total IgG percent change
Total IgG time to first normalization
Total IgM absolute value
Total IgM absolute change from baseline
Total IgM percent change
Total IgM time to first normalization
Total IgA absolute value
Total IgA absolute change from baseline
Total IgA percent change
Total IgA time to first normalization
Total Vitamin B12 absolute value
Total Vitamin B12 change
Total Vitamin B12 time to first normalization
Total folate absolute value
Total folate change
Total folate time to first normalization
Total iron absolute value
Total iron change
Total iron time to first normalization
Total iron binding capacity absolute value
Total iron binding capacity change
Total iron binding capacity time to first normalization
Total ferritin absolute value
Total ferritin change
Total ferritin time to first normalization
Total magnesium absolute value
Total magnesium change
Total magnesium time to first normalization
Total fasting cholesterol absolute value
Total fasting cholesterol change
Total fasting cholesterol time to first normalization
Total fasting triglycerides absolute value
Total fasting triglycerides change
Total fasting triglycerides time to first normalization
Change in alpha-1 antitrypsin levels in blood
Change in alpha-1 antitrypsin levels in blood
Change in alpha-1 antitrypsin levels in stool
Change in alpha-1 antitrypsin levels in stool
Number of participants use of conmeds
List of conmeds:
Corticosteroids
IV or SC immunoglobulin
IV albumin
Biologic immunomodulators (anti-TNF, vedolizumab)
Small molecule immunomodulators (eg, azathioprine, mesalazine) micronutrients
Enteral or parenteral supplementation
Anti-coagulants (eg, low-molecular-weight heparin)
Antibiotics (with the exception of those used for the purpose of Neisserial prophylaxis)
Anti-platelet agents (eg, low-dose aspirin)
Percentage of days hospitalized
Body weight expressed as z score
Height expressed as z score
Concentrations of total pozelimab in serum
Incidence of treatment-emergent anti-drug antibodies to pozelimab in patients
Change from baseline of total complement activity CH50 assay
Percent change from baseline of total complement activity CH50 assay
Full Information
NCT ID
NCT04209634
First Posted
December 20, 2019
Last Updated
July 7, 2023
Sponsor
Regeneron Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04209634
Brief Title
Open-Label Efficacy and Safety Study of Pozelimab in Patients With CD55-Deficient Protein-Losing Enteropathy (CHAPLE Disease)
Official Title
An Open-Label Efficacy and Safety Study of Pozelimab in Patients With CD55-Deficient Protein-Losing Enteropathy (CHAPLE Disease)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 27, 2020 (Actual)
Primary Completion Date
November 9, 2021 (Actual)
Study Completion Date
May 2, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of the study is to determine the effect of pozelimab on active CD55-deficient protein-losing enteropathy (PLE; CHAPLE).
The secondary objectives of the study are:
To evaluate the safety and tolerability of pozelimab in patients with CD55-deficient PLE disease
To evaluate the effect of pozelimab on CD55-deficient PLE (both patients with active disease at baseline and those with inactive disease on eculizumab, switching to pozelimab)
To determine the effects of pozelimab on albumin and other serum proteins (total protein, immunoglobulins)
To determine the effects of pozelimab on ascites
To determine the effects of pozelimab on stool consistency
To determine the effect of pozelimab on health-related quality of life
To determine the effect of pozelimab on lab abnormalities observed in CD55-deficient PLE such as hypertriglyceridemia, thrombocytosis, and hypovitaminosis B12
To describe the effects of pozelimab on the sparing of concomitant medications and reduction in hospitalization days
To determine the effects of pozelimab on growth
To characterize the concentration of pozelimab in patients with CD55-deficient PLE
To assess the incidence of treatment-emergent ADA for pozelimab in patients with CD55-deficient PLE disease
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CD55-deficient Protein-losing Enteropathy, CHAPLE
Keywords
CD55-deficient PLE, complement hyperactivation, angiopathic thrombosis, protein-losing enteropathy (CHAPLE disease)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active PLE
Arm Type
Experimental
Arm Description
Patients aged 1 year and older with a clinical diagnosis of CD55-deficient PLE disease
Intervention Type
Drug
Intervention Name(s)
Pozelimab
Other Intervention Name(s)
REGN3918
Intervention Description
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.
Primary Outcome Measure Information:
Title
Proportion of patients with active disease at baseline achieving both normalization of serum albumin and clinical outcome improvement
Description
Normalization of serum albumin defined as intra-patient mean serum albumin within the normal range.
Clinical Outcomes:
The number of bowel movements per day captured by e-diary
Physician assessment of facial edema (based on a 5-point Likert scale)
Physician assessment of peripheral edema (based on a 5-point Likert scale)
Patient/caregiver assessment of abdominal pain as assessed by the Stomach pain and hurt sub-scale of the PedsQL™ GI Symptom Scale
Time Frame
Up to 24 weeks
Secondary Outcome Measure Information:
Title
Incidence and severity of treatment-emergent adverse events (TEAEs)
Description
TEAEs include adverse events (AEs), abnormal vital signs, height, weight, electrocardiograms (ECGs), and laboratory testing
Time Frame
Up to week 144
Title
Improvement in each patient's most bothersome sign/symptom
Description
Using a semi-structured concept elicitation interview
Time Frame
Week 24
Title
Proportion of patients with active disease at baseline who maintain disease control
Description
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
Week 48
Title
Proportion of patients with active disease at baseline who maintain disease control
Description
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
Week 144
Title
Proportion of patients with inactive disease on eculizumab at baseline who maintain disease control
Description
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
Week 24
Title
Proportion of patients with inactive disease on eculizumab at baseline who maintain disease control
Description
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
Week 48
Title
Proportion of patients with inactive disease on eculizumab at baseline who maintain disease control
Description
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
Week 144
Title
The number of bowel movements per day based on a 1-week average
Description
Captured by e-diary
Time Frame
Up to week 24
Title
The number of days/week with ≥1 bowel movement of loose/watery stool consistency
Description
As captured by e- diary and measured by the
Bristol Stool Form Scale (BSFS) from 1 to 7 where 1 is separate hard lumps and 7 is entirely liquid
modified BSFS from 1 to 5 where 1 is separate hard lumps and 5 is watery, no solid pieces
or the Brussels Infant and Toddler Stool Scale (BIFSS) from 1 to 4 where 1 is hard stools and 4 is watery
Time Frame
Up to week 24
Title
Physician assessment of facial edema
Description
Based on a 5-point Likert scale where 1 is strongly agree and 5 is strongly disagree
Time Frame
Up to week 144
Title
Physician assessment of peripheral edema
Description
Based on a 5-point Likert scale where 1 is strongly agree and 5 is strongly disagree
Time Frame
Up to week 144
Title
Change in abdominal symptoms
Description
As assessed by the Stomach pain and hurt sub-scale and food and drink limits sub-scale of the PedsQL™ GI Symptom Scale 5-point scale where 0 is never a problem and 4 is almost always a problem
Time Frame
Up to week 144
Title
Health-related quality of life as assessed by the PedsQL™ Generic Core Scales for about my work/studies and school functioning sub-scale
Description
A 5-point response scale where 0 is never a problem and 4 is almost always a problem
Time Frame
Up to week 144
Title
Health-related quality of life as assessed by the PedsQL™ Generic Core Scales for physical functioning sub-scale
Description
A 5-point response scale where 0 is never a problem and 4 is almost always a problem
Time Frame
Up to week 144
Title
Assessment of abdominal ascites
Description
Assessed by measurement of abdominal circumference
Time Frame
Up to week 24
Title
Frequency of albumin infusions
Time Frame
Up to week 144
Title
Total albumin absolute value
Time Frame
Up to week 24
Title
Total albumin absolute change from baseline
Time Frame
Up to week 144
Title
Total albumin percent change
Time Frame
Up to week 144
Title
Total albumin time to first normalization
Time Frame
Up to week 144
Title
Total protein absolute value
Time Frame
Up to week 24
Title
Total protein absolute change from baseline
Time Frame
Up to week 144
Title
Total protein percent change
Time Frame
Up to week 144
Title
Total protein time to first normalization
Time Frame
Up to week 144
Title
Total Ig absolute value
Time Frame
Up to week 24
Title
Total Ig absolute change from baseline
Time Frame
Up to week 144
Title
Total Ig percent change
Time Frame
Up to week 144
Title
Total Ig time to first normalization
Time Frame
Up to week 144
Title
Total IgG absolute value
Time Frame
Up to week 24
Title
Total IgG absolute change from baseline
Time Frame
Up to week 144
Title
Total IgG percent change
Time Frame
Up to week 144
Title
Total IgG time to first normalization
Time Frame
Up to week 144
Title
Total IgM absolute value
Time Frame
Up to week 24
Title
Total IgM absolute change from baseline
Time Frame
Up to week 144
Title
Total IgM percent change
Time Frame
Up to week 144
Title
Total IgM time to first normalization
Time Frame
Up to week 144
Title
Total IgA absolute value
Time Frame
Up to week 24
Title
Total IgA absolute change from baseline
Time Frame
Up to week 144
Title
Total IgA percent change
Time Frame
Up to week 144
Title
Total IgA time to first normalization
Time Frame
Up to week 144
Title
Total Vitamin B12 absolute value
Time Frame
Up to week 24
Title
Total Vitamin B12 change
Time Frame
Up to week 144
Title
Total Vitamin B12 time to first normalization
Time Frame
Up to week 144
Title
Total folate absolute value
Time Frame
Up to week 24
Title
Total folate change
Time Frame
Up to week 144
Title
Total folate time to first normalization
Time Frame
Up to week 144
Title
Total iron absolute value
Time Frame
Up to week 24
Title
Total iron change
Time Frame
Up to week 144
Title
Total iron time to first normalization
Time Frame
Up to week 144
Title
Total iron binding capacity absolute value
Time Frame
Up to week 24
Title
Total iron binding capacity change
Time Frame
Up to week 144
Title
Total iron binding capacity time to first normalization
Time Frame
Up to week 144
Title
Total ferritin absolute value
Time Frame
Up to week 24
Title
Total ferritin change
Time Frame
Up to week 144
Title
Total ferritin time to first normalization
Time Frame
Up to week 144
Title
Total magnesium absolute value
Time Frame
Up to week 24
Title
Total magnesium change
Time Frame
Up to week 144
Title
Total magnesium time to first normalization
Time Frame
Up to week 144
Title
Total fasting cholesterol absolute value
Time Frame
Up to week 24
Title
Total fasting cholesterol change
Time Frame
Up to week 144
Title
Total fasting cholesterol time to first normalization
Time Frame
Up to week 144
Title
Total fasting triglycerides absolute value
Time Frame
Up to week 24
Title
Total fasting triglycerides change
Time Frame
Up to week 144
Title
Total fasting triglycerides time to first normalization
Time Frame
Up to week 144
Title
Change in alpha-1 antitrypsin levels in blood
Time Frame
Week 12
Title
Change in alpha-1 antitrypsin levels in blood
Time Frame
Week 24
Title
Change in alpha-1 antitrypsin levels in stool
Time Frame
Week 12
Title
Change in alpha-1 antitrypsin levels in stool
Time Frame
Week 24
Title
Number of participants use of conmeds
Description
List of conmeds:
Corticosteroids
IV or SC immunoglobulin
IV albumin
Biologic immunomodulators (anti-TNF, vedolizumab)
Small molecule immunomodulators (eg, azathioprine, mesalazine) micronutrients
Enteral or parenteral supplementation
Anti-coagulants (eg, low-molecular-weight heparin)
Antibiotics (with the exception of those used for the purpose of Neisserial prophylaxis)
Anti-platelet agents (eg, low-dose aspirin)
Time Frame
Up to week 144
Title
Percentage of days hospitalized
Time Frame
Up to week 144
Title
Body weight expressed as z score
Time Frame
Up to week 144
Title
Height expressed as z score
Time Frame
Up to week 144
Title
Concentrations of total pozelimab in serum
Time Frame
Up to week 144
Title
Incidence of treatment-emergent anti-drug antibodies to pozelimab in patients
Time Frame
Up to week 144
Title
Change from baseline of total complement activity CH50 assay
Time Frame
Up to week 144
Title
Percent change from baseline of total complement activity CH50 assay
Time Frame
Up to week 144
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Clinical diagnosis of CD55-deficient PLE/CHAPLE disease (based on a history of PLE), confirmed by biallelic CD55 loss-of-function mutation detected by genotype analysis
Active disease as defined by the protocol or inactive disease on eculizumab therapy (and whose treating physician has the expectation of future access to renewed eculizumab treatment should this be required), and is willing to discontinue eculizumab during screening and start pozelimab at baseline with no eculizumab wash-out
Key Exclusion Criteria:
History of meningococcal infection
No documented meningococcal vaccination within 3 years prior to screening and patient unwilling to undergo vaccination during the study
No documented vaccination for Haemophilus influenzae and Streptococcus pneumoniae if applicable based on local practice or guidelines prior to screening and patient unwilling to undergo vaccination during the study if required per local practice or guidelines
Presence of a concomitant disease that leads to hypoproteinemia at the time of starting pozelimab
A concomitant disease that leads to secondary intestinal lymphangiectasia such as a fontan procedure for congenital heart disease
Note: Other protocol-defined Inclusion/Exclusion criteria apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Regeneron Research Site
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Regeneron Research Site
City
Pathum Wan
State/Province
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Regeneron Research Site
City
Istanbul
ZIP/Postal Code
34890
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
IPD Sharing Time Frame
Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
IPD Sharing Access Criteria
Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, EMA, PMDA, etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
IPD Sharing URL
https://vivli.org/
Learn more about this trial
Open-Label Efficacy and Safety Study of Pozelimab in Patients With CD55-Deficient Protein-Losing Enteropathy (CHAPLE Disease)
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