Open-Label Efficacy and Safety Study of Pozelimab in Patients With CD55-Deficient Protein-Losing Enteropathy (CHAPLE Disease)
Study Details
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2/Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Active PLE Patients aged 1 year and older with a clinical diagnosis of CD55-deficient PLE disease |
Drug: Pozelimab
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of patients with active disease at baseline achieving both normalization of serum albumin and clinical outcome improvement [Up to 24 weeks]
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) [Up to week 144]
TEAEs include adverse events (AEs), abnormal vital signs, height, weight, electrocardiograms (ECGs), and laboratory testing
- Improvement in each patient's most bothersome sign/symptom [Week 24]
Using a semi-structured concept elicitation interview
- Proportion of patients with active disease at baseline who maintain disease control [Week 48]
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 [Week 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
- Proportion of patients with inactive disease on eculizumab at baseline who maintain disease control [Week 24]
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 [Week 48]
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 [Week 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
- The number of bowel movements per day based on a 1-week average [Up to week 24]
Captured by e-diary
- The number of days/week with ≥1 bowel movement of loose/watery stool consistency [Up to week 24]
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 [Up to week 144]
Based on a 5-point Likert scale where 1 is strongly agree and 5 is strongly disagree
- Physician assessment of peripheral edema [Up to week 144]
Based on a 5-point Likert scale where 1 is strongly agree and 5 is strongly disagree
- Change in abdominal symptoms [Up to week 144]
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 [Up to week 144]
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 [Up to week 144]
A 5-point response scale where 0 is never a problem and 4 is almost always a problem
- Assessment of abdominal ascites [Up to week 24]
Assessed by measurement of abdominal circumference
- Frequency of albumin infusions [Up to week 144]
- Total albumin absolute value [Up to week 24]
- Total albumin absolute change from baseline [Up to week 144]
- Total albumin percent change [Up to week 144]
- Total albumin time to first normalization [Up to week 144]
- Total protein absolute value [Up to week 24]
- Total protein absolute change from baseline [Up to week 144]
- Total protein percent change [Up to week 144]
- Total protein time to first normalization [Up to week 144]
- Total Ig absolute value [Up to week 24]
- Total Ig absolute change from baseline [Up to week 144]
- Total Ig percent change [Up to week 144]
- Total Ig time to first normalization [Up to week 144]
- Total IgG absolute value [Up to week 24]
- Total IgG absolute change from baseline [Up to week 144]
- Total IgG percent change [Up to week 144]
- Total IgG time to first normalization [Up to week 144]
- Total IgM absolute value [Up to week 24]
- Total IgM absolute change from baseline [Up to week 144]
- Total IgM percent change [Up to week 144]
- Total IgM time to first normalization [Up to week 144]
- Total IgA absolute value [Up to week 24]
- Total IgA absolute change from baseline [Up to week 144]
- Total IgA percent change [Up to week 144]
- Total IgA time to first normalization [Up to week 144]
- Total Vitamin B12 absolute value [Up to week 24]
- Total Vitamin B12 change [Up to week 144]
- Total Vitamin B12 time to first normalization [Up to week 144]
- Total folate absolute value [Up to week 24]
- Total folate change [Up to week 144]
- Total folate time to first normalization [Up to week 144]
- Total iron absolute value [Up to week 24]
- Total iron change [Up to week 144]
- Total iron time to first normalization [Up to week 144]
- Total iron binding capacity absolute value [Up to week 24]
- Total iron binding capacity change [Up to week 144]
- Total iron binding capacity time to first normalization [Up to week 144]
- Total ferritin absolute value [Up to week 24]
- Total ferritin change [Up to week 144]
- Total ferritin time to first normalization [Up to week 144]
- Total magnesium absolute value [Up to week 24]
- Total magnesium change [Up to week 144]
- Total magnesium time to first normalization [Up to week 144]
- Total fasting cholesterol absolute value [Up to week 24]
- Total fasting cholesterol change [Up to week 144]
- Total fasting cholesterol time to first normalization [Up to week 144]
- Total fasting triglycerides absolute value [Up to week 24]
- Total fasting triglycerides change [Up to week 144]
- Total fasting triglycerides time to first normalization [Up to week 144]
- Change in alpha-1 antitrypsin levels in blood [Week 12]
- Change in alpha-1 antitrypsin levels in blood [Week 24]
- Change in alpha-1 antitrypsin levels in stool [Week 12]
- Change in alpha-1 antitrypsin levels in stool [Week 24]
- Number of participants use of conmeds [Up to week 144]
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 [Up to week 144]
- Body weight expressed as z score [Up to week 144]
- Height expressed as z score [Up to week 144]
- Concentrations of total pozelimab in serum [Up to week 144]
- Incidence of treatment-emergent anti-drug antibodies to pozelimab in patients [Up to week 144]
- Change from baseline of total complement activity CH50 assay [Up to week 144]
- Percent change from baseline of total complement activity CH50 assay [Up to week 144]
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Regeneron Research Site | Bethesda | Maryland | United States | 20892 |
| 2 | Regeneron Research Site | Pathum Wan | Bangkok | Thailand | 10330 |
| 3 | Regeneron Research Site | Istanbul | Turkey | 34890 |
Sponsors and Collaborators
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Trial Management, Regeneron Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R3918-PLE-1878