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Lysosomal Acid Lipase DeficiencyPhase 2NCT02193867

Clinical Study In Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency

A Phase 2 study testing Sebelipase Alfa in people with Lysosomal Acid Lipase Deficiency, run by Alexion Pharmaceuticals, Inc. at 5 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages Up to 8 months
Conditions the study is for
Lysosomal Acid Lipase Deficiency
What is being tested?
Sebelipase Alfa
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
5 sitesin 4 countries
Study dates
6 Jun 2014to 30 Oct 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 8 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Participant's parent or legal guardian (if applicable) consent to participation in the study
  • 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
  • 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

Who cannot join

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

Trial locations and contacts

5 sites in 4 countries.

5 sites in 4 countries

United Kingdom2 sites
  • Study site

    Birmingham

  • Study site

    Manchester

Other trials in United Kingdom

United States1 site
  • Study site

    Phoenix, Arizona, 85016

Other trials in United States

Finland1 site
  • Study site

    Kuopio

Other trials in Finland

Italy1 site
  • Study site

    Naples

Other trials in Italy

About this study

Official title: 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.

Read the 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.

Being tested
Sebelipase Alfa
Keywords
LIPA, Wolman Disease, Wolman Phenotype, Acid Lipase Deficiency, Acid Cholesteryl Hydrolase, Acid Lipase Disease Deficiency, type 2, Cholesteryl Ester Storage Disease (CESD), Cholesteryl Ester Hydrolase Deficiency, Early Onset Lysosomal Acid Lipase Deficiency (Wolman Disease), LAL Deficiency, Late Onset Lysosomal Acid Lipase Deficiency (CESD), Wolman Disease (early onset LAL Deficiency), Related Disorders:, Non-alcoholic Fatty Liver Disease (NAFLD), Non-alcoholic Steatohepatitis (NASH), Alcoholic Liver Disease, Cryptogenic Cirrhosis, Niemann-Pick Disease (NPD) Type C, Chanarin Dorfman Syndrome
Medical subject headings
Wolman Disease, Cholesterol Ester Storage Disease, Non-alcoholic Fatty Liver Disease, Liver Diseases, Alcoholic, Cirrhosis, Cryptogenic, Niemann-Pick Diseases, Chanarin-Dorfman Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sebelipase AlfaDrug

    Also called SBC-102

    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.

Study groups in NCT02193867
Study groupRoleWhat they receive
Open-Label Sebelipase AlfaExperimentalAll 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.
Receives: Drug: Sebelipase Alfa

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs)

    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.

    Measured: Screening through Month 37

Secondary outcomes (7)
  1. Percentage Of Participants Surviving To 12, 18, 24, And 36 Months Of Age

    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.

    Measured: Baseline through Month 12, Month 18, Month 24, and Month 36

  2. Median Age At Death

    Age at death for participants who died during the study. All deaths were assessed by the Investigator as unrelated to study drug.

    Measured: Baseline through Month 36

  3. Change From Baseline In Percentiles For Weight For Age (WFA) At 12, 24, And 36 Months

    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.

    Measured: Baseline, Month 12, Month 24, and Month 36

  4. Number Of Participants With Stunting, Wasting, Or Underweight At Baseline, 12, 24, And 36 Months

    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.

    Measured: Baseline to Month 12, Month 24, and Month 36

  5. Change From Baseline In Serum Transaminases (ALT And AST) At Month 12, 24, And 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).

    Measured: Baseline, Month 12, Month 24, and Month 36

  6. Change From Baseline In Serum Ferritin At Month 12, 24, And 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.

    Measured: Baseline, Month 12, Month 24, and Month 36

  7. Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization (TFHN)

    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).

    Measured: Baseline through Month 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jul 2014 (estimated)
  2. Study start6 Jun 2014
  3. Primary completion30 Oct 2018
  4. Study completion30 Oct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02193867
Sponsor's protocol ID
LAL-CL08
Status last verified
Oct 2019
First submitted
7 Jul 2014
Last updated
18 Nov 2019
Data monitoring committee
Yes

Publications

  • Balwani M, Breen C, Enns GM, Deegan PB, Honzik T, Jones S, Kane JP, Malinova V, Sharma R, Stock EO, Valayannopoulos V, Wraith JE, Burg J, Eckert S, Schneider E, Quinn AG. Clinical effect and safety profile of recombinant human lysosomal acid lipase in patients with cholesteryl ester storage disease. Hepatology. 2013 Sep;58(3):950-7. doi: 10.1002/hep.26289. Epub 2013 Mar 28.

    PubMed 23348766
  • Jones SA, Valayannopoulos V, Schneider E, Eckert S, Banikazemi M, Bialer M, Cederbaum S, Chan A, Dhawan A, Di Rocco M, Domm J, Enns GM, Finegold D, Gargus JJ, Guardamagna O, Hendriksz C, Mahmoud IG, Raiman J, Selim LA, Whitley CB, Zaki O, Quinn AG. Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants. Genet Med. 2016 May;18(5):452-8. doi: 10.1038/gim.2015.108. Epub 2015 Aug 27.

    PubMed 26312827
  • Jones SA, Rojas-Caro S, Quinn AG, Friedman M, Marulkar S, Ezgu F, Zaki O, Gargus JJ, Hughes J, Plantaz D, Vara R, Eckert S, Arnoux JB, Brassier A, Le Quan Sang KH, Valayannopoulos V. Survival in infants treated with sebelipase Alfa for lysosomal acid lipase deficiency: an open-label, multicenter, dose-escalation study. Orphanet J Rare Dis. 2017 Feb 8;12(1):25. doi: 10.1186/s13023-017-0587-3.

    PubMed 28179030

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sebelipase Alfa in people with Lysosomal Acid Lipase Deficiency, run by Alexion Pharmaceuticals, Inc. at 5 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United Kingdom, United States, Finland, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs) (time frame: Screening through Month 37). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02193867, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2019.

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