Lysosomal Acid Lipase (LAL) Deficiency Registry (ALX-LALD-501)

• ClinicalTrials.gov Identifier: NCT01633489
• Recruitment Status: Recruiting
• First Posted: July 4, 2012
• Last Update Posted: July 29, 2022
• Sponsor: Alexion
• Information provided by (Responsible Party): Alexion

Tracking Information

• First Submitted Date: June 29, 2012
• First Posted Date: July 4, 2012
• Last Update Posted Date: July 29, 2022
• Actual Study Start Date: December 31, 2012
• Estimated Primary Completion Date: June 30, 2029 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 13, 2013): Understanding of the variability, progression, identification and natural history of LAL Deficiency. [ Time Frame: Ongoing ]
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Lysosomal Acid Lipase (LAL) Deficiency Registry
• Official Title: An Observational Disease and Clinical Outcomes Registry of Patients With Lysosomal Acid Lipase (LAL) Deficiency
• Brief Summary: This is an observational, multi-center, international disease registry designed to collect longitudinal data and create a knowledge base that will be utilized to improve the care and treatment of patients with LAL Deficiency. Participation in the Registry by both physicians and patients is voluntary.

Detailed Description

Lysosomal Acid Lipase (LAL) Deficiency is a rare autosomal recessive lysosomal storage disorder (LSD) that is caused by a marked decrease of lysosomal acid lipase (LAL), the enzyme that breaks down cholesteryl esters and triglycerides in the lysosomes.

Lysosomal Acid Lipase Deficiency presenting in infants (historically called Wolman Disease) is a medical emergency with rapid disease progression over a period of weeks that is typically fatal within the first 6 months of life. More commonly, LAL Deficiency presents in children and adults and this presentation has been historically called Cholesteryl Ester Storage Disease (CESD). In general, data on the prevalence of LAL Deficiency are limited, and the overall prevalence of the disease in the population is unclear.

For all presentations, LAL Deficiency is associated with significant morbidity and mortality. Deficient LAL enzyme activity results in the lysosomal accumulation of cholesteryl esters and triglycerides. In the liver, this accumulation leads to hepatomegaly, increased hepatic fat content, transaminase elevation signaling chronic liver injury, and progression to fibrosis, cirrhosis, and complications of end stage liver disease. In the spleen, LAL Deficiency results in splenomegaly, anemia, and thrombocytopenia. Lipid accumulation in the intestinal wall leads to malabsorption and growth failure. Dyslipidemia is common with elevated low density lipoprotein (LDL) and triglycerides and low high density lipoprotein (HDL), associated with increased liver fat content and transaminase elevations. In addition to liver disease, patients with LAL Deficiency experience increased risk for cardiovascular disease and accelerated atherosclerosis.

The LAL Deficiency Registry is a global registry, established to help improve care for patients through improved understanding of the disease and long-term effectiveness of therapeutic interventions including sebelipase alfa.

As with other registries, which are becoming increasingly valuable for collecting information in large, heterogeneous, 'real world' populations, the LAL Deficiency Registry aims to provide evidence to help support patient care and inform clinical practice. This Registry is also being conducted, in part, to fulfill post-marketing commitments and requirements agreed to by the Sponsor as a condition for sebelipase alfa approval in the EU and the USA.

• Study Type: Observational [Patient Registry]
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: 10 Years
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: All patients with a diagnosis of LAL Deficiency.

Condition

• Lysosomal Acid Lipase Deficiency
• Cholesterol Ester Storage Disease
• Wolman Disease
• Acid Cholesteryl Ester Hydrolase Deficiency, Type 2
• Acid Lipase Deficiency
• LIPA Deficiency
• LAL-Deficiency

• Intervention: Not Provided

Study Groups/Cohorts

LAL Deficiency patients

Patients are those with a diagnosis of LAL Deficiency (living and deceased), irrespective of treatment status or treatment choice.

• Publications *: Soll D, Spira D, Hollstein T, Haberbosch L, Demuth I, Steinhagen-Thiessen E, Bobbert T, Spranger J, Kassner U. Clinical outcome of a patient with lysosomal acid lipase deficiency and first results after initiation of treatment with Sebelipase alfa: A case report. Mol Genet Metab Rep. 2019 Jun 18;20:100479. doi: 10.1016/j.ymgmr.2019.100479. eCollection 2019 Sep.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 3, 2012): 1000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2029
• Estimated Primary Completion Date: June 30, 2029 (Final data collection date for primary outcome measure)

Eligibility Criteria

Patients must have a confirmed diagnosis of LAL Deficiency. An Informed Consent and Authorization must be obtained prior to patient enrollment where required under applicable laws and regulations, or a waiver must be obtained by the Institutional Review Board/Independent Ethics Committee.

Patients cannot be currently participating in an Alexion-sponsored clinical trial. Patients who have concluded participation in an Alexion-sponsored sebelipase alfa clinical trial are eligible to enroll in this Registry, and enrollment in the Registry will not exclude a patient from enrolling in a future clinical trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No

Contacts

Contact: Alexion Pharmaceuticals, Inc.; clinicaltrials@alexion.com

• Listed Location Countries: Australia, Belgium, Brazil, Canada, Croatia, Czechia, Denmark, France, Germany, Greece, Ireland, Israel, Italy, Mexico, Netherlands, Poland, Portugal, Saudi Arabia, Slovenia, Spain, United Kingdom, United States
• Removed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT01633489
• Other Study ID Numbers: ALX-LALD-501
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Alexion
• Original Responsible Party: Same as current
• Current Study Sponsor: Alexion
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Alexion Pharmaceuticals; Sponsor GmbH

• PRS Account: Alexion
• Verification Date: July 2022