Lysosomal Acid Lipase DeficiencyPhase 2NCT02112994
Safety and Efficacy Study of Sebelipase Alfa in Participants With Lysosomal Acid Lipase Deficiency
A Phase 2 study testing Sebelipase Alfa in people with Lysosomal Acid Lipase Deficiency, run by Alexion Pharmaceuticals, Inc. at 19 sites in 15 countries.
Trial summary
This study evaluated the safety and efficacy of sebelipase alfa in a broad population of participants with lysosomal acid lipase deficiency (LAL-D). Read more about this study
- Who is it for?
- Ages 8 months and older
- 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
- 31 participants
- Where
- 19 sitesin 15 countries
- Study dates
- 24 Jun 2014to 28 Dec 2017
- 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 8 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Participant was >8 months of age at the time of dosing.
- Confirmation of LAL-D diagnosis as determined by the central laboratory or, for participants with prior hematopoietic stem cell transplant or liver transplant, historical enzyme activity or molecular genetic testing confirming a diagnosis of LAL-D.
- Participants >8 months but <4 years of age at Screening had at least 1 of the following documented clinical manifestations of LAL-D:
- Dyslipidemia
- Elevated transaminases
- Impaired growth
Show all 14Show fewer
- Suspected malabsorption
- Other clinical manifestation of LAL-D
- Participants ≥4 years of age at Screening had at least 1 of the following documented clinical manifestations of LAL-D:
- Evidence of advanced liver disease
- Histologically confirmed disease recurrence in participants with past liver or hematopoietic transplant
- Persistent dyslipidemia
- Suspected malabsorption
- Other clinical manifestation of LAL-D
Who cannot join
- Participant had known causes of active liver disease other than LAL-D, which had not been adequately treated.
- Participant received a hematopoietic stem cell or liver transplant <2 years from the time of dosing.
- Participant with co-morbidities other than complications due to LAL-D, which were irreversible or associated with a high mortality risk within 6 months or would interfere with study compliance or data interpretation.
Trial locations and contacts
19 sites in 15 countries.
19 sites in 15 countries
United States3 sites
Study site
Chicago, Illinois, 60611
Study site
Cincinnati, Ohio, 45229
Study site
Shreveport, Louisiana, 71103
Spain3 sites
Study site
A Coruña, 15006
Study site
Barcelona, 08036
Study site
Madrid, 28046
About this study
Official title: A Multi-Center, Open-Label Study of Sebelipase Alfa in Patients With Lysosomal Acid Lipase Deficiency
This study evaluated the safety and efficacy of sebelipase alfa in a broad population of participants with lysosomal acid lipase deficiency (LAL-D).
Read the detailed description
The primary objective of this study was to evaluate the safety of intravenous (IV) infusions of sebelipase alfa in a more broad population of LAL-D participants than previously studied. Such participants may have been excluded from enrollment in other studies of LAL-D because of age, disease progression, previous treatment by hematopoietic stem cell or liver transplantation, less common disease manifestations, or disease characteristics that would preclude participation in a placebo-controlled study. This open-label study included infants >8 months, children, and adults. At least 4 participants in the study were to be between the age of 2 and 4 years. Eligible participants received sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) every other week (qow).
- Conditions
- Lysosomal Acid Lipase Deficiency
- Being tested
- Sebelipase Alfa
- Keywords
- Enzyme Replacement Therapy (ERT), Lysosomal Storage Disease, Late Onset Lysosomal Acid Lipase (LAL) Deficiency, Acid cholesteryl ester hydrolase deficiency, type 2, Acid lipase disease, Cholesterol ester hydrolase deficiency, LAL Deficiency, LIPA Deficiency, Wolman disease, Additional relevant MeSH terms:, Cholesterol Ester Storage Disease, Metabolic Diseases, Lipidoses, Lipid Metabolism, Inborn Errors, Metabolism, Inborn Errors, Genetic Diseases, Inborn, Lysosomal Storage Diseases, Lipid Metabolism Disorders, Infant, Newborn, Diseases
- Medical subject headings
- Wolman Disease, Lysosomal Storage Diseases, Cholesterol Ester Storage Disease, Metabolic Diseases, Lipidoses, Lipid Metabolism, Inborn Errors, Metabolism, Inborn Errors, Genetic Diseases, Inborn
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
IV infusion of sebelipase alfa
| Study group | Role | What they receive |
|---|---|---|
| Sebelipase Alfa | Experimental | Pediatric and adult participants initiated IV treatment with sebelipase alfa at a dose of 1 mg/kg qow. Participants were considered for a dose adjustment at the discretion of the Investigator and in consultation with the Sponsor. Dose escalation to 3 mg/kg qow was considered if pre-defined dose-escalation criteria were met. If these criteria continued to be met, a subsequent dose escalation to 3 mg/kg every week (qw) was considered. Dose decreases as low as 0.35 mg/kg qow were permitted based upon evidence of intolerance to sebelipase alfa treatment. Participants who completed the 96-week treatment period were permitted to continue receiving sebelipase alfa in an expanded treatment period for up to 48 weeks, pending local drug availability and study participation status. Receives: Drug: Sebelipase Alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 (AEs) information was obtained at each scheduled contact with the participant (or participant's parent or legal guardian). An AE was defined as any untoward medical occurrence that did not require a causal relationship with study drug administration. An AE could have been any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug. Pre-existing conditions that worsened in severity during the study were reported as AEs. A summary of all serious and other non-serious AEs regardless of causality is located in the Reported AE module. Severity assessed using Clinical Data Interchange Standards Consortium Study Data Tabulation Model standard terminology v3.1.1. Data presented only according to age group, not dose of study drug received.
Measured: Screening, Week 144
Secondary outcomes (4)
Percent Change In Serum Lipids From Baseline To Week 144
The effect of sebelipase alfa on lipid metabolism was evaluated by measuring the change from baseline to Week 144 in 4 serum lipids: low-density lipoprotein cholesterol (LDL-C); high-density lipoprotein cholesterol (HDL-C); non-HDL-C; triglycerides. Blood samples for these clinical laboratory tests were collected at scheduled time points and analyzed by a central laboratory.
Measured: Baseline, Week 144
Participants Testing Positive For Anti-drug Antibodies (ADAs)
The impact of ADAs on the safety and immunogenicity of sebelipase alfa was evaluated by testing for ADAs in participants who received sebelipase alfa in this open-label study. Blood samples for assessment were collected prior to study infusions at Week 2, Week 4, Week 8, Week 12, and every 12 weeks thereafter. Participants testing positive for ADAs were also tested for the presence of neutralizing antibodies that inhibited sebelipase alfa enzyme activity and/or cellular uptake. Any participant experiencing a moderate or severe infusion-associated reaction (IAR) was to have an additional assessment of ADAs at the next study visit (prior to study drug infusion); these participants were to also have serum samples collected at 1 to 2 hours after IAR onset and at the next study visit (prior to study drug infusion) for analysis of serum tryptase. The count of participants who became ADA positive and who tested positive for neutralizing antibodies are presented.
Measured: Week 144
Percent Change In Body Mass Index (BMI)-For-Age Percentile From Baseline To Week 144 In Pediatric Participants
To evaluate the effects of sebelipase alfa on growth parameters in pediatric participants (≤18 years old) presenting with evidence of growth delay, the percent change in the anthropometric parameter of BMI-for-age percentile from Baseline to Week 144 is reported. Anthropometric parameters were plotted on standard growth curves. When possible, historical data on growth parameters was also incorporated into the analyses. Percentiles and Z-scores for BMI-for-age were determined using standard growth charts appropriate to a participant's age on the date of the assessment: the World Health Organization standard growth chart for participants ≤2 years of age and the Centers for Disease Control standard growth chart for participants >2 years of age.
Measured: Baseline, Week 144
Shift In Child-Pugh Status From Baseline To Week 144
In order to evaluate the effects of sebelipase alfa on liver function, the number of participants with a shift in Child-Pugh status from Baseline to Week 144 is reported. The status is based on the Child-Pugh score, which is used in clinical practice to assess prognosis in individuals with chronic liver disease. Laboratory data were used in derivation of the score by summing individual scores (scored 1-3, with 3 indicating most severe) from clinical laboratory test results and physical examinations, including total serum bilirubin, serum albumin, prothrombin time, ascites, and hepatic encephalopathy. The total score was used to determine the Child-Pugh status, reported as Class A (score of 5 or 6), Class B (score of 7 to 9), or Class C (score of 10 to 15). Higher scores and higher categories represented a worse outcome. Data reported as 1 of 2 types of shifts in class: No Change from Baseline; Decline from Baseline.
Measured: Baseline, Week 144
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2014 (estimated)
- Study start24 Jun 2014
- Primary completion28 Dec 2017
- Study completion28 Dec 2017
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
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 31 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
- NCT02112994
- Sponsor's protocol ID
- LAL-CL06
- Other IDs
- 2011-004287-30
- Status last verified
- Nov 2019
- First submitted
- 20 Mar 2014
- Last updated
- 4 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Burton BK, Sanchez AC, Kostyleva M, Martins AM, Marulkar S, Abel F, Baric I. Long-Term Sebelipase Alfa Treatment in Children and Adults With Lysosomal Acid Lipase Deficiency. J Pediatr Gastroenterol Nutr. 2022 Jun 1;74(6):757-764. doi: 10.1097/MPG.0000000000003452. Epub 2022 Apr 19.
PubMed 35442238
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Open-Label Study of Sebelipase Alfa in Patients With Lysosomal Acid Lipase Deficiency
- ClinicalTrials.gov ID
- NCT02112994
- Acronym / sponsor ID
- LAL-CL06
- Conditions
- Lysosomal Acid Lipase Deficiency
- Keywords
- Enzyme Replacement Therapy (ERT), Lysosomal Storage Disease, Late Onset Lysosomal Acid Lipase (LAL) Deficiency, Acid cholesteryl ester hydrolase deficiency, type 2, Acid lipase disease, Cholesterol ester hydrolase deficiency, LAL Deficiency, LIPA Deficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 24 Jun 2014 (actual)
- Primary completion
- 28 Dec 2017 (actual)
- Study completion
- 28 Dec 2017 (actual)
- First posted
- 14 Apr 2014 (estimated)
- Results
- Posted 15 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluated the safety and efficacy of sebelipase alfa in a broad population of participants with lysosomal acid lipase deficiency (LAL-D).
Detailed description
The primary objective of this study was to evaluate the safety of intravenous (IV) infusions of sebelipase alfa in a more broad population of LAL-D participants than previously studied. Such participants may have been excluded from enrollment in other studies of LAL-D because of age, disease progression, previous treatment by hematopoietic stem cell or liver transplantation, less common disease manifestations, or disease characteristics that would preclude participation in a placebo-controlled study. This open-label study included infants >8 months, children, and adults. At least 4 participants in the study were to be between the age of 2 and 4 years. Eligible participants received sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) every other week (qow).
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sebelipase Alfa | Experimental | Drug: Sebelipase AlfaPediatric and adult participants initiated IV treatment with sebelipase alfa at a dose of 1 mg/kg qow. Participants were considered for a dose adjustment at the discretion of the Investigator and in consultation with the Sponsor. Dose escalation to 3 mg/kg qow was considered if pre-defined dose-escalation criteria were met. If these criteria continued to be met, a subsequent dose escalation to 3 mg/kg every week (qw) was considered. Dose decreases as low as 0.35 mg/kg qow were permitted based upon evidence of intolerance to sebelipase alfa treatment. Participants who completed the 96-week treatment period were permitted to continue receiving sebelipase alfa in an expanded treatment period for up to 48 weeks, pending local drug availability and study participation status. |
Who may qualify
- Ages
- 8 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Participant was >8 months of age at the time of dosing.
- Confirmation of LAL-D diagnosis as determined by the central laboratory or, for participants with prior hematopoietic stem cell transplant or liver transplant, historical enzyme activity or molecular genetic testing confirming a diagnosis of LAL-D.
- Participants >8 months but <4 years of age at Screening had at least 1 of the following documented clinical manifestations of LAL-D:
- Participants ≥4 years of age at Screening had at least 1 of the following documented clinical manifestations of LAL-D:
Key exclusion criteria (3 listed)
- Participant had known causes of active liver disease other than LAL-D, which had not been adequately treated.
- Participant received a hematopoietic stem cell or liver transplant <2 years from the time of dosing.
- Participant with co-morbidities other than complications due to LAL-D, which were irreversible or associated with a high mortality risk within 6 months or would interfere with study compliance or data interpretation.
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 AlfaAlso: SBC-102IV infusion of sebelipase alfa | Drug | Sebelipase Alfa |
Primary outcome
Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs)
Time frame: Screening, Week 144
The number of participants experiencing severe TEAEs is presented for participants who received sebelipase alfa in this open-label study. Adverse events (AEs) information was obtained at each scheduled contact with the participant (or participant's parent or legal guardian). An AE was defined as any untoward medical occurrence that did not require a causal relationship with study drug administration. An AE could have been any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug. Pre-existing conditions that worsened in severity during the study were reported as AEs. A summary of all serious and other non-serious AEs regardless of causality is located in the Reported AE module. Severity assessed using Clinical Data Interchange Standards Consortium Study Data Tabulation Model standard terminology v3.1.1. Data presented only according to age group, not dose of study drug received.
4 secondary outcomes
Percent Change In Serum Lipids From Baseline To Week 144
Time frame: Baseline, Week 144
Participants Testing Positive For Anti-drug Antibodies (ADAs)
Time frame: Week 144
Percent Change In Body Mass Index (BMI)-For-Age Percentile From Baseline To Week 144 In Pediatric Participants
Time frame: Baseline, Week 144
Shift In Child-Pugh Status From Baseline To Week 144
Time frame: Baseline, Week 144
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35442238Burton BK, Sanchez AC, Kostyleva M, Martins AM, Marulkar S, Abel F, Baric I. Long-Term Sebelipase Alfa Treatment in Children and Adults With Lysosomal Acid Lipase Deficiency. J Pediatr Gastroenterol Nutr. 2022 Jun 1;74(6):757-764. doi: 10.1097/MPG.0000000000003452. Epub 2022 Apr 19.
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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.
19 sites in 15 countries: see every site and its status.
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 19 sites in 15 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 14 inclusion and 3 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 4 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, Spain, Australia, Belgium, Brazil and 10 more countries. 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 15 Jan 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, Week 144). 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 NCT02112994, 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 4 Dec 2019; AzTrials last refreshed its copy on 8 Nov 2026.