Screening for Lysosomal Acid Lipase Deficiency

Study Overview
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Brief Summary
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The primary outcome of this study is the development of a clinical profile of pediatric patients with LAL-D, which will enable the Sponsor to provide more focused guidance to the medical community as to which pediatric patients should be tested for LAL-D.

Official Title
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SCREENING FOR LYSOSOMAL ACID LIPASE DEFICIENCY AS THE UNDERLYING SOURCE OF HEPATIC INJURY IN PEDIATRIC PATIENTS WITH EVIDENCE OF ABNORMAL CLINICAL OR BIOCHEMICAL TESTS (DETECT)

Conditions
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Lysosomal Acid Lipase Deficiency

Intervention / Treatment
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* Other: There is no intervention in the study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patient is ≥ 2 to ≤ 16 years of age at the date of informed consent. (Note: Female patients who are of childbearing potential or are pregnant may participate in this study.) Patient or patient's parent or legal guardian (if applicable) consents to participation in the study. If the patient is of minor age, he/she is willing to provide assent where required per local regulations, and if deemed able to do so. Patient meets all components of Criterion A and/or Criterion B below. Criterion A: Patient has dyslipidemia, defined as having at least one of the following lipid abnormalities based on a local laboratory result obtained within 3 months prior to the date of informed consent (or at the screening visit, as applicable): LDL-c ≥ 130 mg/dL HDL c ≤ 40 mg/dL (male patients) or ≤ 50 mg/dL (female patients) Note: For patients receiving a lipid-lowering medication (LLM), the patient must have been on a stable dose of the LLM for at least 4 weeks prior to the serum lipid result. AND Patient has at least one of the following liver or spleen abnormalities: Hepatomegaly, as determined by the investigator based on a physical examination or imaging procedure; Splenomegaly, as determined by the investigator based on a physical examination or imaging procedure; ALT >75 U/L or ALT >1.5x the upper limit of normal (ULN) (based on age- and gender-specific normal ranges of the local laboratory performing the assay) within 3 months prior to the date of informed consent (or at the screening visit, as applicable). Criterion B: Patient has steatosis (microvesicular or mixed macro/microvesicular), hepatic fibrosis, and/or cirrhosis of unknown etiology, as determined from a liver biopsy performed within the previous 3 years. (Note: For patients who have received a liver transplantation, the liver biopsy results must have been obtained prior to the date of the liver transplantation.) Exclusion Criteria: Patient has a confirmed cause of liver disease other than LAL-D. Patient has genetically confirmed heterozygous familial hypercholesteremia or other secondary causes of hypercholesterolemia. Patient has current evidence of neurological dysfunction and/or a history of neurological dysfunction within one year prior to the date of informed consent. Patient has been previously screened for LAL-D and found to have normal enzyme activity based on the reference range of the laboratory performing the assay. Patient is currently receiving treatment with sebelipase alfa (Kanuma) or has previously participated in a clinical study with sebelipase alfa (Kanuma).

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Entire Study Population<br>Male or female patients who are between 2 and 16 years of age (inclusive) will be eligible for the study if they meet all components of Criterion A and/or Criterion B below, provided that these abnormalities are of unknown or unconfirmed etiology and the patient has not previously had a normal LAL enzyme activity result, has not received treatment with sebelipase alfa (Kanuma), and has no evidence of neurological dysfunction within the past year. (Note: Female patients who are of childbearing potential or are pregnant may participate in this study.) | Other: There is no intervention in the study<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eligibility Criteria for LAL-D diagnosed patients | Eligibility criteria will be summarized descriptively by LAL-D diagnostic status. Statistical differences in the distributions of eligibility criteria by diagnostic status will be assessed with t test for continuous variables (e.g., lab values) and chi-square test/Fishers exact test for categorical variables (e.g., presence of hepatomegaly). Among those with confirmed LAL-D, demographic data (e.g., age, sex, race/ethnicity, and country of origin) and clinical data (i.e., laboratory values, imaging and biopsy data, medications, physical exam findings, medical history, and family medical history) will be summarized as appropriate | Confirmed LAL-D diagnosed patients, for a period extending up to a maximum of 6 months after the date of diagnosis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LIPA gene mutations for LAL-D diagnosed patients | Among patients with a confirmed diagnosis of LAL-D, specific LIPA gene mutations and type of mutation will be summarized. Listings will present patient characteristics, including signs, symptoms, and laboratory values by mutation. Patient (e.g., age) and clinical features (e.g., laboratory values, signs, and symptoms) will be summarized by genetic mutation to assess associations between phenotypes and genetic variants. | Confirmed LAL-D diagnosed patients, for a period extending up to a maximum of 6 months after the date of diagnosis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Screening, Hepatic Injury, Pediatric Patients