Lysosomal Acid Lipase DeficiencyPhase 2/3NCT01371825
Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Sebelipase Alfa in Children With Growth Failure Due to Lysosomal Acid Lipase Deficiency
A Phase 2/3 study testing Sebelipase alfa (SBC-102) in people with Lysosomal Acid Lipase Deficiency and Wolman Disease, run by Alexion Pharmaceuticals, Inc. at 7 sites in 5 countries.
Trial summary
This was an open-label, repeat-dose, intra-participant dose-escalation study of SBC-102 (sebelipase alfa) in children with growth failure due to lysosomal acid lipase (LAL) Deficiency. Eligible participants received once-weekly (qw) infusions of sebelipase alfa for up to 5 years. Read more about this study
- Who is it for?
- Ages Up to 24 months
- Conditions the study is for
- Lysosomal Acid Lipase Deficiency, Wolman Disease
- What is being tested?
- Sebelipase alfa (SBC-102)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 7 sitesin 5 countries
- Study dates
- 4 May 2011to 3 Jan 2018
- Phase
- Phase 2/3
- 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 24 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Participant's parent or legal guardian provided written informed consent/permission prior to any study procedures.
- Male or female child with documented decreased LAL activity relative to the normal range of the laboratory performing the assay or documented result of molecular genetic testing (2 mutations) confirming a diagnosis.
- Growth failure with onset before 6 months of age.
Who cannot join
- Clinically important concurrent disease or comorbidities.
- Had received an investigational product other than sebelipase alfa within 14 days prior to the first dose.
- Participant was older than 24 months of age.
- Myeloablative preparation, or other systemic pre-transplant conditioning, for hematopoietic stem cell or liver transplant.
- Previous hematopoietic stem cell or liver transplant.
- Known hypersensitivity to eggs.
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
United Kingdom2 sites
Study site
London, SE1 7EH
Study site
Manchester, M13 9WL
About this study
Official title: An Open Label, Multicenter, Dose Escalation Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of SBC-102 (Sebelipase Alfa) in Children With Growth Failure Due to Lysosomal Acid Lipase Deficiency
This was an open-label, repeat-dose, intra-participant dose-escalation study of SBC-102 (sebelipase alfa) in children with growth failure due to lysosomal acid lipase (LAL) Deficiency. Eligible participants received once-weekly (qw) infusions of sebelipase alfa for up to 5 years.
Read the detailed description
LAL Deficiency is a rare autosomal-recessive lipid storage disorder that is caused by a marked decrease or almost complete absence of LAL, leading to the accumulation of lipids, predominately cholesteryl esters and triglycerides, in various tissues and cell types. In the liver, accumulation of lipids leads to hepatomegaly, liver dysfunction, and hepatic failure. Although a single disease, LAL Deficiency presents as a clinical continuum with 2 major phenotypes, Cholesteryl Ester Storage Disease (CESD) and Wolman Disease.
Early-onset LAL Deficiency (Wolman Disease) is extremely rare, with an estimated incidence of less than 2 lives per million. It is characterized by profound malabsorption, growth failure, and hepatic failure, and is usually fatal in the first year of life.
- Conditions
- Lysosomal Acid Lipase Deficiency, Wolman Disease
- Being tested
- Sebelipase alfa (SBC-102)
- 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 alfa (SBC-102)Drug
Sebelipase alfa is a recombinant human lysosomal acid lipase enzyme. The investigational medicinal product is an enzyme replacement therapy intended for treatment of participants with LAL Deficiency. Dosing occurred qw for up to 5 years.
| Study group | Role | What they receive |
|---|---|---|
| Open-Label Sebelipase Alfa | Experimental | Participants received intravenous (IV) infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 milligrams (mg)/kilogram (kg) qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant's dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to an every other week (qow) dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow. Receives: Drug: Sebelipase alfa (SBC-102) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age
The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.
Measured: Month 12
Secondary outcomes (7)
Percentage Of Participants Surviving Beyond 12 Months Of Age
The percentage of participants in the PES who survived to at least 18 months of age.
Measured: Baseline to Month 18, Month 24, Month 36, Month 48, and Month 60
Median Age At Death
Participants in the PES who died during the study, including 3 participants who died after having received between 1 and 4 infusions of sebelipase alfa and 1 participant who died after approximately 40 weeks on treatment.
Measured: Baseline to Week 260
Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles
Baseline is defined as the last measurement prior to the first infusion of sebelipase alfa.
Measured: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Number Of Participants With Stunting, Wasting, Or Underweight
The number of participants who met criteria for the following dichotomous indicators of under nutrition were reported. These indicators included the following:
- Stunting was defined as at least 2 standard deviations below the median for length-for-age/height-for-age;
- Wasting was defined as wasting at least 2 standard deviations below the median for weight-for-length/weight-for-height; and
- Underweight was defined as at least 2 standard deviations below the median for WFA.
Measured: Baseline to Month 12, Month 24, Month 36, Month 48, and Month 60
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST)
Change from Baseline to Months 12, 24, 36, 48, and 60 for alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Measured: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin
The median change in serum ferritin from Baseline to Months 12, 24, 36, 48, and 60 is presented.
Measured: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
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 must a) have had 2 post-baseline measurements of hemoglobin at least 4 weeks apart that were both above the age-adjusted lower limit of normal; b) have had no known additional measurements of hemoglobin that were below the age-adjusted lower limit of normal during the (minimum) 4-week period; and c) have had no transfusions during the (minimum) 4-week period, and also no transfusions for 2 weeks prior to the first hemoglobin measurement in the (minimum) 4-week period.
For TFHN to be maintained, the participant must have been transfusion-free beginning at Week 6 and had all hemoglobin assessments above the lower limit of normal beginning in Week 8 and lasting at least 13 weeks.
Measured: Baseline to Month 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2011 (estimated)
- Study start4 May 2011
- Primary completion3 Jan 2018
- Study completion3 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lysosomal Acid Lipase DeficiencyStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01371825
- Sponsor's protocol ID
- LAL-CL03
- Status last verified
- Jan 2019
- First submitted
- 9 Jun 2011
- Last updated
- 30 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Multicenter, Dose Escalation Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of SBC-102 (Sebelipase Alfa) in Children With Growth Failure Due to Lysosomal Acid Lipase Deficiency
- ClinicalTrials.gov ID
- NCT01371825
- Acronym / sponsor ID
- LAL-CL03
- Conditions
- Lysosomal Acid Lipase Deficiency, Wolman Disease
- 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
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 4 May 2011 (actual)
- Primary completion
- 3 Jan 2018 (actual)
- Study completion
- 3 Jan 2018 (actual)
- First posted
- 13 Jun 2011 (estimated)
- Results
- Posted 18 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was an open-label, repeat-dose, intra-participant dose-escalation study of SBC-102 (sebelipase alfa) in children with growth failure due to lysosomal acid lipase (LAL) Deficiency. Eligible participants received once-weekly (qw) infusions of sebelipase alfa for up to 5 years.
Detailed description
LAL Deficiency is a rare autosomal-recessive lipid storage disorder that is caused by a marked decrease or almost complete absence of LAL, leading to the accumulation of lipids, predominately cholesteryl esters and triglycerides, in various tissues and cell types. In the liver, accumulation of lipids leads to hepatomegaly, liver dysfunction, and hepatic failure. Although a single disease, LAL Deficiency presents as a clinical continuum with 2 major phenotypes, Cholesteryl Ester Storage Disease (CESD) and Wolman Disease.
Early-onset LAL Deficiency (Wolman Disease) is extremely rare, with an estimated incidence of less than 2 lives per million. It is characterized by profound malabsorption, growth failure, and hepatic failure, and is usually fatal in the first year of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open-Label Sebelipase Alfa | Experimental | Drug: Sebelipase alfa (SBC-102)Participants received intravenous (IV) infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 milligrams (mg)/kilogram (kg) qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant's dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to an every other week (qow) dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow. |
Who may qualify
- Ages
- Up to 24 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Participant's parent or legal guardian provided written informed consent/permission prior to any study procedures.
- Male or female child with documented decreased LAL activity relative to the normal range of the laboratory performing the assay or documented result of molecular genetic testing (2 mutations) confirming a diagnosis.
- Growth failure with onset before 6 months of age.
Key exclusion criteria (6 listed)
- Clinically important concurrent disease or comorbidities.
- Had received an investigational product other than sebelipase alfa within 14 days prior to the first dose.
- Participant was older than 24 months of age.
- Myeloablative preparation, or other systemic pre-transplant conditioning, for hematopoietic stem cell or liver transplant.
- Previous hematopoietic stem cell or liver transplant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sebelipase alfa (SBC-102)Sebelipase alfa is a recombinant human lysosomal acid lipase enzyme. The investigational medicinal product is an enzyme replacement therapy intended for treatment of participants with LAL Deficiency. Dosing occurred qw for up to 5 years. | Drug | Open-Label Sebelipase Alfa |
Primary outcome
Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age
Time frame: Month 12
The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.
7 secondary outcomes
Percentage Of Participants Surviving Beyond 12 Months Of Age
Time frame: Baseline to Month 18, Month 24, Month 36, Month 48, and Month 60
Median Age At Death
Time frame: Baseline to Week 260
Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles
Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Number Of Participants With Stunting, Wasting, Or Underweight
Time frame: Baseline to Month 12, Month 24, Month 36, Month 48, and Month 60
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST)
Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin
Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization [TFHN]
Time frame: Baseline to Month 60
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28179030Jones 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Sebelipase alfa (SBC-102) in people with Lysosomal Acid Lipase Deficiency and Wolman Disease, run by Alexion Pharmaceuticals, Inc. at 7 sites in 5 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 3 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: finished, as of the sponsor's last update on 30 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in France, United Kingdom, United States, Egypt, Ireland. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Apr 2016). 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?
Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age (time frame: Month 12). 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 NCT01371825, which also lists 1 linked publication.
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 30 Jan 2019.