Study of sebelipase alfa in a broad population of patients with Lysosomal Acid Lipase Deficiency (LALD).

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 20

Inclusion Criteria

1. Patient will be > 8 months of age at the time of dosing.
2. Confirmation of LALD diagnosis as determined by the central lab; a patient who received a liver or hematopoietic stem cell transplant who does not show evidence of LAL enzyme deficiency by DBS due to the effects of transplantation must have either:
a. Molecular genetic testing which confirms mutations in both
alleles of the LIPA gene; OR
b. Appropriately documented (based on consultation with the Sponsor) historical result of an enzyme test prior to hematopoietic or liver transplantation (performed in dry blood spots, leukocytes or fibroblasts).
3. Patients > 8 months but < 4 years of age at Screening will have at least 1 of the following documented clinical manifestations of LALD:
a. Dyslipidemia (defined as Screening LDL-C > 130 mg/dL; TG
> 200 mg/dL);
b. Elevated transaminases (ALT =1.5x ULN (based on the ageand
gender-specific normal ranges of the central laboratory performing the assay);
c. Impaired growth as defined as:
i. WFA or SFA less than the age- and gender appropriate 5th percentile on a standard WHO or CDC WFA or SFA chart for at least 3 months prior to study entry; OR
ii. Poor weight gain as evidenced by calculated weight
percentile decreasing across 2 major percentile lines on a standard WHO (patients < 24 months of age) or CDC (patients = 24 months and <4 years of age) WFA chart over a period of 6 months prior to study entry;
d. Suspected malabsorption with:
i. Persistent unexplained gastrointestinal symptoms such as nausea, diarrhea, abdominal pain, and bloating; OR
ii. Unexplained anemia, or other abnormalities suggestive of malabsorption (e.g., osteomalacia, hypoalbuminaemia, prolonged bleeding time due to vitamin K deficiency); AND
iii. Documented small intestinal disease involvement on
a small bowel biopsy performed within 1 year of Screening
e. Other clinical manifestation of LALD in the opinion of the
investigator and in consultation with the Sponsor (e.g.,
abnormal cardiac or pulmonary functions, or presence of
lymphadenopathy by imaging or palpation).
4. Patients = 4 years of age at Screening will have at least 1 of the
following documented clinical manifestations of LALD:
a. Evidence of advanced liver disease (e.g., cirrhosis confirmed
by imaging or biopsy, and Child-Pugh C) at Screening accompanied by:
i. Clinically significant portal hypertension as defined by a hepatic venous pressure gradient (HVPG) greater than or equal to 10 mmHg; OR
ii. Documented esophageal varices (historical or by
esophagogastroduodenoscopy (EGD) at Screening (unless medically contraindicated due to high risk of endoscopy-related bleeding based on presence of esophageal varices on endoscopy carried out within 3 months of assessment).
b. Histologically confirmed disease recurrence in patients with
past liver or hematopoietic transplants (e.g., re-accumulation
of lipid containing Kupffer cells, recurrence of fibrosis);
c. Persistent dyslipidemia (defined as LDL-C >130mg/dL, triglycerides >200mg/dL, or HDL-C <40mg/dL in males, and
<50mg/dL in females) that has persisted despite 3 or more
months of treatment with one or more lipid-lowering
therapies such as statins, cholesterol absorption inhibitors
(ezetimibe), combination therapies (single-pill;
ezetimibe/simvastatin, niacin/simvastatin), fibrates
(fenofibrate, gemfibrozil, fenofibric acid), niacin or bile acid
sequestrants (cholestyramine, colestipol, colesevelam);
d. Suspected ma

Exclusion Criteria

A patient who meets any of the following exclusion criteria will be ineligible for this study:
1. Patient meets eligibility criteria for another interventional study of sebelipase alfa in LALD that is open for enrollment in the region where the patient will receive treatment.
2. Patient has known causes of active liver disease other than LALD which have not been adequately treated (e.g., chronic viral hepatitis, autoimmune hepatitis, alcoholic liver disease).
3. Patient is unable or unwilling to comply with study procedures.
4. Patient received a hematopoietic stem cell or liver transplant <2 years from the time of dosing.
5. Females who are nursing or pregnant.
6. Patient with co-morbidities other than complications due to LALD which, in the opinion of the Investigator and in consultation with the Sponsor, are irreversible or associated with a high mortality risk within 6 months, or would interfere with study compliance or data interpretation (e.g. excessive alcohol consumption).
7. Exposure to any investigational product within 30 days of Screening for a small molecule and 60 days of Screening for a biologic.
8. Known hypersensitivity to eggs.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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