Phase 3
N=10
Open-Label Efficacy and Safety Study of Pozelimab in Patients With CD55-Deficient Protein-Losing Enteropathy (CHAPLE Disease)
CD55-deficient Protein-losing Enteropathy · CHAPLE
Bottom Line
View on ClinicalTrials.gov: NCT04209634 ↗Enrolled (actual)
10
Serious AEs
50.0%
Results posted
Oct 2023
Primary outcome: Primary: 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
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Pozelimab (Drug)
- Age
- Pediatric, Adult, Older Adult · 1+ yrs
- Sex
- All
- Sponsor
- Regeneron Pharmaceuticals
- Primary completion
- Nov 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Active Disease at Baseline Who Achieved Normalization of Serum Albumin and Improvement in Prespecified Clinical Outcomes at Week 24 |
100 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Severity of TEAEs |
10; 3; 5; 2 | — |
| SECONDARY Number of Participants With Improvement in Most Bothersome Signs and Symptoms at Week 24 |
10 | — |
| SECONDARY Number of Bowel Movements Per Day Based on a 1-week Average up to Week 24 |
1.64; 1.13; 1.36; 1.43; 1.50; 1.57 | — |
| SECONDARY Number of Days Per Week With >=1 Bowel Movement of Loose/Watery Stool Consistency at Week 24 |
2.00; 0.50; 0.00; 0.00; 0.00; 0.00 | — |
| SECONDARY Number of Participants With Abdominal Ascites at Week 24 |
1 | — |
| SECONDARY Absolute Value of Albumin at Specified Timepoints up to Week 24 |
2.160; 2.267; 3.311; 3.589; 4.025; 4.167 | — |
| SECONDARY Absolute Values of Protein, and Immunoglobulin G (IgG) at Baseline and Week 24 |
37.50; 72.22; 2.183; 11.301 | — |
| SECONDARY Absolute Values of Immunoglobulin (Ig), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) at Baseline and Week 24 |
318.2; 1430.1; 52.9; 180.3; 47.0; 119.8 | — |
| SECONDARY Absolute Values of Vitamin B12 at Baseline and Week 24 |
158.5; 383.1 | — |
| SECONDARY Absolute Values of Iron and Unsaturated Iron Binding Capacity at Baseline and Week 24 |
3.40; 7.38; 38.24; 73.95 | — |
| SECONDARY Absolute Values of Vitamin B9 up to Week 24 |
17.80; 22.07; 17.32; 17.89; 18.01; 19.91 | — |
| SECONDARY Absolute Values of Ferritin at Baseline and Week 24 |
10.0; 12.0 | — |
| SECONDARY Absolute Values of Magnesium, Total Cholesterol, and Triglycerides at Week 24 |
0.793; 0.858; 3.819; 3.604; 2.033; 1.094 | — |
| SECONDARY Change From Baseline in Alpha-1 Antitrypsin Levels in Stool at Week 12 and Week 24 |
-527.80; -463.71 | — |
| SECONDARY Change From Baseline in Alpha-1 Antitrypsin Levels in Blood at Week 12 and Week 24 |
-57.8; -43.4 | — |
| SECONDARY Percentage of Participants With Active Disease at Baseline Who Maintained Disease Control |
100; 100; 100; 100; 100 | — |
| SECONDARY Change From Baseline in Physician Assessment of Facial Edema Based on a 5-point Likert Rating Scale |
-1.7 | — |
| SECONDARY Change From Baseline in Physician Assessment of Peripheral Edema Based on a 5-point Likert Rating Scale |
-1.7 | — |
| SECONDARY Change From Baseline in Food and Drink Limitations as Assessed by the PedsQL™ GI Symptom Scales' Food and Drink Limits Sub-scale |
47.40 | — |
| SECONDARY Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the PedsQL™ Generic Core Scales |
26.55; 14.45; 26.3; 30.6; 41.43 | — |
| SECONDARY Number of Participants With Albumin Infusion by 24 Week Periods |
1; 0; 0; 0; 0; 0 | — |
| SECONDARY Change From Baseline in Albumin Values |
2.400 | — |
| SECONDARY Percentage Change From Baseline in Albumin Values |
127.489 | — |
| SECONDARY Time to First Normalization for Albumin Values |
15.5 | — |
| SECONDARY Change From Baseline in Protein Values |
37.13 | — |
| SECONDARY Time to First Normalization for Total Protein |
22.0 | — |
| SECONDARY Change From Baseline in Immunoglobulin (Ig) Values |
1271.2 | — |
| SECONDARY Time to First Normalization for Ig Values |
341 | — |
| SECONDARY Change From Baseline in IgG Values |
10.626 | — |
| SECONDARY Time to First Normalization for IgG Values |
29.0 | — |
| SECONDARY Change From Baseline in IgM Values |
112.0 | — |
| SECONDARY Time to First Normalization for IgM Values |
1 | — |
| SECONDARY Change From Baseline in IgA Values |
96.7 | — |
| SECONDARY Time to First Normalization for IgA Values |
1 | — |
| SECONDARY Change From Baseline in Vitamin B12 Values |
138.8 | — |
| SECONDARY Time to First Normalization for Vitamin B12 Values |
8 | — |
| SECONDARY Change From Baseline in Vitamin B9 (Folate) Values |
2.92 | — |
| SECONDARY Time to First Normalization for Vitamin B9 (Folate) Values |
1 | — |
| SECONDARY Change From Baseline in Iron Values |
7.82 | — |
| SECONDARY Time to First Normalization for Iron Values |
97.5 | — |
| SECONDARY Change From Baseline in Unsaturated Iron Binding Capacity |
16.20 | — |
| SECONDARY Time to First Normalization for Unsaturated Iron Binding Capacity |
1 | — |
| SECONDARY Change From Baseline in Ferritin Values |
32.0 | — |
| SECONDARY Time to First Normalization for Ferritin Values |
28 | — |
| SECONDARY Change From Baseline in Magnesium Values |
0.083 | — |
| SECONDARY Time to First Normalization for Magnesium Values |
1 | — |
| SECONDARY Change From Baseline in Fasting Cholesterol Values |
-0.072 | — |
| SECONDARY Time to First Normalization for Fasting Cholesterol Values |
1 | — |
| SECONDARY Change From Baseline in Fasting Triglycerides Values |
-0.710 | — |
| SECONDARY Time to First Normalization for Fasting Triglycerides Values |
4 | — |
| SECONDARY Number of Participants Who Used Concomitant Medication |
10 | — |
| SECONDARY Number of Hospitalization Days by 24 Week Period |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Change From Baseline in Body Weight Z-Score |
0.924 | — |
| SECONDARY Change From Baseline in Height Z-Score |
1.079 | — |
| SECONDARY Change From Baseline in Total Complement Activity Complement Hemolytic Assay (CH50) |
-241.6 | — |
| SECONDARY Concentrations of Total Pozelimab in Serum |
182; 185; 227; 268; 306; 341 | — |
| SECONDARY Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Pozelimab |
— | — |
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.
Data sourced from ClinicalTrials.gov (NCT04209634). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.