Screening for Lysosomal Acid Lipase Deficiency

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)

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.

Study Overview

• Status: Terminated
• Conditions: Lysosomal Acid Lipase Deficiency
• Intervention / Treatment: Other: There is no intervention in the study

• Study Type: Observational
• Enrollment (Actual): 22

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children's Healthcare of Atlanta
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital, Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 16 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

1. 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.)
2. 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.
3. 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:

1. Patient has a confirmed cause of liver disease other than LAL-D.
2. Patient has genetically confirmed heterozygous familial hypercholesteremia or other secondary causes of hypercholesterolemia.
3. Patient has current evidence of neurological dysfunction and/or a history of neurological dysfunction within one year prior to the date of informed consent.
4. 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.
5. Patient is currently receiving treatment with sebelipase alfa (Kanuma) or has previously participated in a clinical study with sebelipase alfa (Kanuma).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Entire Study Population; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (ACTUAL): June 5, 2017
• Study Completion (ACTUAL): June 5, 2017

Study Registration Dates

• First Submitted: October 4, 2016
• First Submitted That Met QC Criteria: October 5, 2016
• First Posted (ESTIMATE): October 6, 2016

Study Record Updates

• Last Update Posted (ACTUAL): June 16, 2017
• Last Update Submitted That Met QC Criteria: June 14, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Screening; Pediatric Patients; Hepatic Injury
• Additional Relevant MeSH Terms: Metabolic Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Lipidoses; Lipid Metabolism, Inborn Errors; Cholesterol Ester Storage Disease; Wolman Disease
• Other Study ID Numbers: ALX-LAL-502

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO