Clinical Study In Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency

October 29, 2019 updated by: Alexion Pharmaceuticals

A Phase 2, Open Label, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Sebelipase Alfa in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency

This was an open-label, repeat-dose, study of sebelipase alfa in infants with rapidly progressive lysosomal acid lipase deficiency (LAL-D). Eligible participants received once-weekly infusions of sebelipase alfa for up to 3 years.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Lysosomal acid lipase deficiency is a rare autosomal recessive lipid storage disorder that is caused by a marked decrease or complete absence of the LAL enzyme, leading to the accumulation of lipids, predominately cholesteryl esters and triglycerides, in various tissues and cell types. In the liver, accumulation of lipids in hepatocytes and macrophages leads to hepatomegaly, fibrosis, cirrhosis, liver dysfunction, and hepatic failure. In the small intestine, lipid-laden macrophage accumulation in the lamina propria leads to profound malabsorption.

Lysosomal acid lipase deficiency presenting in infancy is an extremely rare form of the disease characterized by profound malabsorption, growth failure, and hepatic failure that is usually fatal within the first 6 months of life.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 8 months (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Participant's parent or legal guardian (if applicable) consent to participation in the study
  2. Confirmation of documented decreased LAL activity relative to the normal range of the lab performing the assay or confirmation of LAL-D diagnosis as determined by a Sponsor-approved central laboratory

  3. Substantial clinical concerns, in the opinion of Investigator and Sponsor, of rapid disease progression requiring urgent medical intervention including, but not restricted to the following:

    • Marked abdominal distension and hepatomegaly
    • Failure to thrive
    • Disturbance of coagulation
    • Severe anemia
    • Sibling with rapidly progressive course of LAL-D

Exclusion Criteria:

  1. Clinically important concurrent disease
  2. Participant was > 8 months of age at the time of first dosing
  3. Participant received an investigational medicinal product other than sebelipase alfa within 14 days prior to the first dose of sebelipase alfa in this study
  4. Myeloablative preparation, or other systemic pre-transplant conditioning, for hematopoietic stem cell or liver transplantation
  5. Previous hematopoietic stem cell or liver transplant
  6. Known hypersensitivity to eggs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Open-Label Sebelipase Alfa
All participants initiated once weekly (qw) intravenous (IV) infusions with sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) qw. A participant who met protocol defined dose escalation criteria at a dose of 1 mg/kg qw could be considered for a dose escalation to 3 mg/kg qw. If a participant continued to meet dose escalation criteria after at least 4 infusions at a dose of 3 mg/kg qw, the participant could be considered for a further dose escalation to 5 mg/kg qw. Under country-specific provisions (United Kingdom only), participants could be considered for a further dose escalation to 7.5 mg/kg qw if a thorough case review indicated that a participant continued to have evidence of disease progression at a dose of 5 mg/kg qw. All dose escalations were contingent upon acceptable safety and tolerability of preceding infusions and were undertaken by mutual agreement of the Investigator and Sponsor and after approval by an independent safety committee.
Drug: Sebelipase Alfa
Sebelipase alfa is a recombinant human lysosomal acid lipase. The investigational medicinal product is an enzyme replacement therapy intended for treatment of participants with LAL-D. Dosing occurred once weekly for up to 3 years.
Other Names:
  • SBC-102

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs)
Time Frame: Screening through Month 37
The number of participants experiencing severe TEAEs is presented for participants who received sebelipase alfa in this open-label study. Adverse events were obtained through spontaneous reporting or elicited by specific questioning or examination of the participant's parent or legal guardian. An adverse event was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant, whether or not causally related to administration of study drug. Adverse event severity was graded by the Investigator as mild, moderate, or severe based on definitions developed from Clinical Data Interchange Standards Consortium Study Data Tabulation Model standard terminology v3.1.1. Adverse events reporting was from the date of informed consent until completion of the follow-up visit at approximately 30 days after the last dose of study drug. A summary of all serious and other nonserious AEs regardless of causality is located in the Reported AE module.
Screening through Month 37

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage Of Participants Surviving To 12, 18, 24, And 36 Months Of Age
Time Frame: Baseline through Month 12, Month 18, Month 24, and Month 36
The percentage of participants in the FAS who survived to 12, 18, 24, and 36 months of age. The exact confidence interval was calculated using the Clopper-Pearson method. Participants with unknown survival status at the age specified in the analysis were excluded. At 36 months, there were 2 participants who were alive and still on study who had not yet reached the age specified in the analysis. As such, these participants were excluded from the calculation of percent surviving.
Baseline through Month 12, Month 18, Month 24, and Month 36
Median Age At Death
Time Frame: Baseline through Month 36
Age at death for participants who died during the study. All deaths were assessed by the Investigator as unrelated to study drug.
Baseline through Month 36
Change From Baseline In Percentiles For Weight For Age (WFA) At 12, 24, And 36 Months
Time Frame: Baseline, Month 12, Month 24, and Month 36
This outcome measure evaluated the effects of sebelipase alfa on growth by measuring the changes from baseline in percentiles for WFA. Percentiles for WFA were summarized as observed values by visit. Baseline was defined as the last available assessment prior to the first infusion of sebelipase alfa.
Baseline, Month 12, Month 24, and Month 36
Number Of Participants With Stunting, Wasting, Or Underweight At Baseline, 12, 24, And 36 Months
Time Frame: Baseline to Month 12, Month 24, and Month 36

The number of participants who met criteria for the following 3 dichotomous indicators of under nutrition were reported. These indicators included the following:

  1. Stunting was defined as at least 2 standard deviations below the median for length-for-age/height-for-age.
  2. Wasting was defined as wasting at least 2 standard deviations below the median for weight-for-length/weight-for-height.
  3. Underweight was defined as at least 2 standard deviations below the median for WFA.
Baseline to Month 12, Month 24, and Month 36
Change From Baseline In Serum Transaminases (ALT And AST) At Month 12, 24, And 36
Time Frame: Baseline, Month 12, Month 24, and Month 36
This outcome measure evaluated the effects of sebelipase alfa on liver function by measuring the change from baseline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at months 12, 24, and 36. Results are reported in units/liter (U/L).
Baseline, Month 12, Month 24, and Month 36
Change From Baseline In Serum Ferritin At Month 12, 24, And 36
Time Frame: Baseline, Month 12, Month 24, and Month 36
The median change in the inflammatory marker serum ferritin from Baseline to Months 12, 24, and 36 is presented. The number of participants analyzed reflects only those from the FAS who had both a baseline value and a value at the indicated timepoint (Months 12, 24, and 36). Results are reported in micrograms (ug)/L.
Baseline, Month 12, Month 24, and Month 36
Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization (TFHN)
Time Frame: Baseline through Month 36

The number of participants achieving and maintaining TFHN are presented. For TFHN to be achieved, the participant had to meet the following criteria:

  1. Two post baseline measurements of hemoglobin, at least 4 weeks apart, were above the age-adjusted lower limit of normal (LLN);
  2. No known additional measurements of hemoglobin were below the age-adjusted LLN during the (minimum) 4 week period;
  3. No transfusions were administered to the participant during the (minimum) 4 week period, or for 2 weeks prior to the first hemoglobin measurement in the (minimum) 4 week period. If all 3 criteria were met, a participant was considered to have achieved TFHN on the date of the first hemoglobin assessment in the 4 week period. A participant was considered to have maintained TFHN if he/she was transfusion free at Week 6 and had no abnormally low hemoglobin levels (levels below the age adjusted LLN) beginning at Week 8 of the study and continuing for at least 13 weeks (3 months).
Baseline through Month 36

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexion Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 6, 2014

Primary Completion (ACTUAL)

October 30, 2018

Study Completion (ACTUAL)

October 30, 2018

Study Registration Dates

First Submitted

July 7, 2014

First Submitted That Met QC Criteria

July 16, 2014

First Posted (ESTIMATE)

July 18, 2014

Study Record Updates

Last Update Posted (ACTUAL)

November 18, 2019

Last Update Submitted That Met QC Criteria

October 29, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LAL-CL08

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lysosomal Acid Lipase Deficiency

Clinical Trials on Sebelipase Alfa

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kuwait

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe