Screening for Lysosomal Acid Lipase Deficiency

NCT02926872 | Terminated

• 1 other identifier: ALX-LAL-502
• Study Type: observational
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Lysosomal Acid Lipase Deficiency

Keywords

Screening; Hepatic Injury; Pediatric Patients

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• LIPA gene mutations for LAL-D diagnosed patients

  Confirmed LAL-D diagnosed patients, for a period extending up to a maximum of 6 months after the date of diagnosis

Study Arms (1)

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

Interventions

There is no intervention in the study OTHER

Entire Study Population

Eligibility Criteria

• Age: 2 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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

You may qualify if:

• 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.)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (2)

Children's Healthcare of Atlanta

Atlanta, Georgia, 30342, United States

Location

Texas Children's Hospital, Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

A stored (Dried Blood Spot) DBS card is collected for future assay development may be used irrespective of a patient's DBS LAL enzyme activity result.

MeSH Terms

Conditions

Wolman Disease

Condition Hierarchy (Ancestors)

Cholesterol Ester Storage Disease; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Infant, Newborn, Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2016
• First Posted: October 6, 2016
• Study Start: November 1, 2016
• Primary Completion: June 5, 2017
• Study Completion: June 5, 2017
• Last Updated: June 16, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)