Clinical trial NCT04209634: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: CD55-deficient Protein-losing Enteropathy
CHAPLE
Keywords: CD55-deficient PLE
complement hyperactivation, angiopathic thrombosis, protein-losing enteropathy (CHAPLE disease)
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-12-24
Enrollment: 10
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Percentage of Participants With Active Disease at Baseline Who Achieved Normalization of Serum Albumin and Improvement in Prespecified Clinical Outcomes at Week 24
timeFrame: At Week 24
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Severity of TEAEs
timeFrame: From start of study drug administration up to approximately 144 weeks
measure: Number of Participants With Improvement in Most Bothersome Signs and Symptoms at Week 24
timeFrame: At Week 24
measure: Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24
timeFrame: 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
measure: Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24
timeFrame: 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
measure: Number of Participants With Abdominal Ascites at Week 24
timeFrame: Baseline up to Week 24
measure: Absolute Value of Albumin at Specified Timepoints up to Week 24
timeFrame: Baseline, Day 2, Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24
measure: Absolute Values of Protein, and Immunoglobulin G (IgG) at Baseline and Week 24
timeFrame: Baseline, Week 24
measure: Absolute Values of Immunoglobulin (Ig), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) at Baseline and Week 24
timeFrame: Baseline, Week 24
measure: Absolute Values of Vitamin B12 at Baseline and Week 24
timeFrame: Baseline, Week 24
measure: Absolute Values of Iron and Unsaturated Iron Binding Capacity at Baseline and Week 24
timeFrame: Baseline, Week 24
measure: Absolute Values of Vitamin B9 up to Week 24
timeFrame: Baseline up to Week 24
measure: Absolute Values of Ferritin at Baseline and Week 24
timeFrame: Baseline, Week 24
measure: Absolute Values of Magnesium, Total Cholesterol, and Triglycerides at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Alpha-1 Antitrypsin Levels in Stool at Week 12 and Week 24
timeFrame: Week 12, Week 24
measure: Change From Baseline in Alpha-1 Antitrypsin Levels in Blood at Week 12 and Week 24
timeFrame: Week 12, Week 24
measure: Percentage of Participants With Active Disease at Baseline Who Maintained Disease Control
timeFrame: Weeks 12 to 48; Weeks 12 to 144; Weeks 24 to 48; Weeks 48 to 96; Weeks 96 to 144
measure: Change From Baseline in Physician Assessment of Facial Edema Based on a 5-point Likert Rating Scale
timeFrame: Baseline and Week 144
measure: Change From Baseline in Physician Assessment of Peripheral Edema Based on a 5-point Likert Rating Scale
timeFrame: Baseline and Week 144
measure: Change From Baseline in Food and Drink Limitations as Assessed by the PedsQL™ GI Symptom Scales' Food and Drink Limits Sub-scale
timeFrame: Baseline and Week 144
measure: Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the PedsQL™ Generic Core Scales
timeFrame: Baseline and Week 144
measure: Number of Participants With Albumin Infusion by 24 Week Periods
timeFrame: Weeks 0 to 24; Weeks 24 to 48; Weeks 48 to 72; Weeks 72 to 96; Weeks 96 to 120; Weeks 120 to 144
measure: Change From Baseline in Albumin Values
timeFrame: Baseline and Week 144
measure: Percentage Change From Baseline in Albumin Values
timeFrame: Baseline and Week 144
measure: Time to First Normalization for Albumin Values
timeFrame: Baseline up to Week 144
measure: Change From Baseline in Protein Values
timeFrame: Baseline and Week 144
measure: Time to First Normalization for Total Protein
timeFrame: Baseline up to Week 144
measure: Change From Baseline in Immunoglobulin (Ig) Values
timeFrame: Baseline and Week 144
measure: Time to First Normalization for Ig Values
timeFrame: Baseline up to Week 144
measure: Change From Baseline in IgG Values
timeFrame: Baseline and Week 144
measure: Time to First Normalization for IgG Values
timeFrame: Baseline up to Week 144
measure: Change From Baseline in IgM Values
timeFrame: Baseline and Week 144
measure: Time to First Normalization for IgM Values
timeFrame: Baseline up to Week 44
measure: Change From Baseline in IgA Values
timeFrame: Baseline and Week 144
measure: Time to First Normalization for IgA Values
timeFrame: Baseline up to Week 144
measure: Change From Baseline in Vitamin B12 Values
timeFrame: Baseline and Week 144
measure: Time to First Normalization for Vitamin B12 Values
timeFrame: Baseline up to Week 144
measure: Change From Baseline in Vitamin B9 (Folate) Values
timeFrame: Baseline and Week 144
measure: Time to First Normalization for Vitamin B9 (Folate) Values
timeFrame: Baseline up to Week 144
measure: Change From Baseline in Iron Values
timeFrame: Baseline and Week 144
measure: Time to First Normalization for Iron Values
timeFrame: Baseline up to Week 144
measure: Change From Baseline in Unsaturated Iron Binding Capacity
timeFrame: Baseline and Week 144
measure: Time to First Normalization for Unsaturated Iron Binding Capacity
timeFrame: Baseline up to Week 144
measure: Change From Baseline in Ferritin Values
timeFrame: Baseline and Week 144
measure: Time to First Normalization for Ferritin Values
timeFrame: Baseline up to Week 144
measure: Change From Baseline in Magnesium Values
timeFrame: Baseline and Week 144
measure: Time to First Normalization for Magnesium Values
timeFrame: Baseline up to Week 144
measure: Change From Baseline in Fasting Cholesterol Values
timeFrame: Baseline and Week 144
measure: Time to First Normalization for Fasting Cholesterol Values
timeFrame: Baseline up to Week 144
measure: Change From Baseline in Fasting Triglycerides Values
timeFrame: Baseline and Week 144
measure: Time to First Normalization for Fasting Triglycerides Values
timeFrame: Baseline up to Week 144
measure: Number of Participants Who Used Concomitant Medication
timeFrame: Baseline up to Week 144
measure: Number of Hospitalization Days by 24 Week Period
timeFrame: Weeks 0 to 24; Weeks 24 to 48; Weeks 48 to 72; Weeks 72 to 96; Weeks 96 to 120; Weeks 120 to 144
measure: Change From Baseline in Body Weight Z-Score
timeFrame: Baseline and Week 144
measure: Change From Baseline in Height Z-Score
timeFrame: Baseline and Week 144
measure: Change From Baseline in Total Complement Activity Complement Hemolytic Assay (CH50)
timeFrame: Baseline and Week 144
measure: Concentrations of Total Pozelimab in Serum
timeFrame: Baseline up to Week 164
measure: Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Pozelimab
timeFrame: Baseline up to Week 164
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Regeneron Research Site
state: Maryland
city: Pathum Wan
country: Thailand
facility: Regeneron Research Site
state: Bangkok
city: Istanbul
country: Turkey
facility: Regeneron Research Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: