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

Phase 1

• Conditions: ysosomal Acid Lipase Deficiency (LALD); MedDRA version: 19.1Level: HLTClassification code 10024579Term: Lysosomal storage disordersSystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2011-004287-30-DE
• Lead Sponsor: Alexion Pharmaceuitcals Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-05-13
• Last Update Posted: 4 December 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Subject will be > 8 months of age at the time of dosing.
2. Subject or subject's parent or legal guardian consents to participation in the study. If the subject is of minor age, he/she is willing to provide assent where required per local regulations, and if deemed able to do so.
3. Confirmation of LALD diagnosis as determined by the central lab; a subject 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 historical result of an enzyme test prior to hematopoietic or liver transplantation.
4. Subjects > 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);
c. Impaired growth as defined as:
i. WFA or SFA less than the age- and gender-appropriate 5th percentile on a standard WHO (subjects = 24 months of age) or CDC (subjects > 24 months and < 4 years of age) 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 (99th, 97th, 95th, 90th, 75th, 50th, 25th, 10th, 5th, 3rd, and 1st) lines on a standard WHO (subjects =24 months of age) or CDC subjects > 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; 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.
5. Subjects = 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 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 at Screening.
b. Disease recurrence in subjects with past liver or hematopoietic
transplants;
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 malabsorption based on the following manifestations:
i. Documented small intestinal involvement by small bowel biopsy
performed within 1 year of Screening; AND
ii. Unexplained iron deficiency, osteopenia, weight loss or chronic
diarrhea; OR
iii. Impaired growth in pediatric subjects defined as:
1. WFA or SFA less than the age- and gender-appropriate 5th percentileon a standard CDC WFA chart for at least 6 months prior to study e

Exclusion Criteria

1. Subject meets eligibility criteria for another interventional study of sebelipase alfa in LALD that is open for enrollment in the region where the subject will receive treatment.
2. Subject has known causes of active liver disease other than LALD
which have not been adequately treated
3. Subject is unable or unwilling to comply with study procedures.
4. Subject received a hematopoietic stem cell or liver transplant < 2
years from the time of dosing.
5. Females who are nursing or pregnant.
6. Subject 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.
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