Lysosomal Acid Lipase DeficiencyPhase 3ARISENCT01757184
Acid Lipase Replacement Investigating Safety and Efficacy (ARISE) in Participants With Lysosomal Acid Lipase Deficiency
A Phase 3 study testing Sebelipase Alfa in people with Lysosomal Acid Lipase Deficiency, run by Alexion Pharmaceuticals, Inc. at 40 sites in 15 countries.
Trial summary
This Phase 3 study evaluated the efficacy and safety of 1 milligram/kilogram (mg/kg) intravenous (IV) infusions of SBC-102 (sebelipase alfa) administered every other week (qow) in participants with late onset lysosomal acid lipase deficiency (LAL-D) (cholesteryl ester storage disease [CESD]). Read more about this study
- Who is it for?
- Ages 4 years 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?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 40 sitesin 15 countries
- Study dates
- 22 Jan 2013to 11 Dec 2018
- Phase
- Phase 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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Participant and/or participant's parent or legal guardian provided informed consent.
- Participant was ≥ 4 years of age on the date of informed consent.
- Deficiency of LAL enzyme activity confirmed by dried blood spot testing at screening.
- Alanine aminotransferase ≥ 1.5x upper limit of normal on 2 consecutive screening measurements obtained at least 1 week apart.
- Female participants of childbearing potential must not have been pregnant or breastfeeding and must have agreed to use a medically acceptable method of preventing contraception from screening until 4 weeks after the last dose of study drug.
- Participant receiving lipid-lowering therapies must have been on a stable dose of the medication for at least 6 weeks prior to randomization and was willing to remain on a stable dose for at least the first 32 weeks of treatment in the study.
- Participant receiving medications for the treatment of nonalcoholic fatty liver disease must have been on a stable dose for at least 16 weeks prior to randomization and was willing to remain on a stable dose for at least the first 32 weeks of treatment in the study.
Who cannot join
- Severe hepatic dysfunction (Child-Pugh Class C).
- Other medical conditions or comorbidities, which, in the opinion of the Investigator, would have interfered with study compliance or data interpretation.
- Previous hematopoietic or liver transplant procedure.
- Received treatment with high-dose corticosteroids (acute or chronic) within 26 weeks. (Note: Participants receiving maintenance therapy with low-dose oral, intranasal, topical, or inhaled corticosteroids were considered eligible for the study).
- Known hypersensitivity to eggs.
- Participated in a study employing an investigational medicinal product within 4 weeks prior to randomization.
Trial locations and contacts
40 sites in 15 countries.
40 sites in 15 countries
United States11 sites
Study site
Boston, Massachusetts, 02115
Study site
Buffalo, New York, 14222
Study site
Chicago, Illinois, 60611-2605
Study site
Cincinnati, Ohio, 45229
Study site
Manhasset, New York, 11030
Study site
New York, New York, 10029
Study site
Palo Alto, California, 94304
Study site
Philadelphia, Pennsylvania, 19104
Study site
San Francisco, California, 94143-0214
Study site
Tucson, Arizona, 85724
Study site
Wilmington, Delaware, 19803
Australia4 sites
Study site
Brisbane
Study site
New Lambton
Study site
Parkville
Study site
Perth
Germany3 sites
Study site
Freiburg im Breisgau
Study site
Mainz
Study site
Munich
United Kingdom3 sites
Study site
Cambridge
Study site
London
Study site
Plymouth
About this study
Official title: A Multicenter, Randomized, Placebo-controlled Study of SBC-102 in Patients With Lysosomal Acid Lipase Deficiency
This Phase 3 study evaluated the efficacy and safety of 1 milligram/kilogram (mg/kg) intravenous (IV) infusions of SBC-102 (sebelipase alfa) administered every other week (qow) in participants with late onset lysosomal acid lipase deficiency (LAL-D) (cholesteryl ester storage disease [CESD]).
Late-onset LAL-D is an underappreciated cause of cirrhosis, liver failure and dyslipidemia. There is currently no standard treatment for LAL-D other than supportive care. Enzyme replacement therapy may be a potential new treatment option for LAL-D participants.
Read the detailed description
Lysosomal acid lipase deficiency (LAL-D) is a genetic disease characterized by abnormal lipid accumulation in many parts of the body due to a marked decrease in activity of the enzyme lysosomal acid lipase (LAL).
The LAL-D disease spectrum ranges from a presentation in infants that is rapidly progressive to a presentation that occurs in childhood, adolescence, or less frequently, in adulthood in which the rate of disease progression is more variable. Irrespective of where a patient is on the disease spectrum, LAL-D is associated with significant burden of disease and a shortened life expectancy in some patients.
The non-infantile onset form of the disease, also known as CESD, occurs in both children and adults and is an under-appreciated cause of fatty liver with prominent microvesicular steatosis, fibrosis, and cirrhosis. Although the natural history of the disease has not been well studied, serious complications are frequently described, including early death, liver transplantation, or cardiovascular accidents. Other complications include premature atherosclerosis (hardening of arteries) associated with high levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, often called the "bad" cholesterol. The levels of triglycerides can also be high and the levels of high-density lipoprotein (HDL) cholesterol (the "good" cholesterol) are typically low.
In the past, treatments mainly focused on control of the lipid abnormalities through diet and the use of lipid-lowering medications, which only address some aspects of the disease, while progression to fibrosis and cirrhosis may still occur. In preclinical studies and clinical studies in participants with LAL-D, treatment with SBC-102 (sebelipase alfa, Kanuma®) has been shown to produce improvements in markers of liver damage and in the lipid abnormalities. The purpose of this study was to examine the effects of using SBC-102 to treat LAL-D through a placebo-controlled, randomized, double-blinded study in children and adults.
This multicenter, randomized, double-blind, placebo-controlled study involving 66 participants evaluated the safety and efficacy of enzyme-replacement therapy with sebelipase alfa (administered intravenously at a dose of 1 mg/kg of body weight qow). The study included a 20-week placebo-controlled period followed by open-label treatment periods for all participants. The primary end-point was normalization of the alanine aminotransferase level. Secondary end-points included additional disease-related efficacy and safety assessments.
Final study results have not been published in a peer-reviewed journal.
- Conditions
- Lysosomal Acid Lipase Deficiency
- Being tested
- Sebelipase Alfa, Placebo
- Keywords
- Enzyme replacement therapy (ERT), Lysosomal storage disease, Late-onset lysosomal acid lipase deficiency (LAL-D), Acid cholesteryl ester hydrolase deficiency, type 2, Acid lipase disease, Cholesterol ester hydrolase deficiency, LAL-D, LIPA deficiency, Wolman disease, Cholesterol ester storage disease (CESD)
- Medical subject headings
- Wolman Disease, Lysosomal Storage Diseases, Cholesterol Ester Storage Disease
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 infusions of sebelipase alfa
PlaceboDrug
IV infusions of matched placebo
| Study group | Role | What they receive |
|---|---|---|
| Double-blind Sebelipase Alfa | Experimental | Double-blind Period: IV infusions of sebelipase alfa at a dose of 1 mg/kg administered qow for 20 weeks. Receives: Drug: Sebelipase Alfa |
| Double-blind Placebo | Placebo comparator | Double-blind Period: IV infusions of matched placebo administered qow for 20 weeks. Receives: Drug: Placebo |
| Open-label Sebelipase Alfa/Sebelipase Alfa | Experimental | Participants who were randomized to receive sebelipase alfa during the Double-blind Period and received sebelipase alfa in the Open-label Period. All participants received sebelipase alfa at a dose of 1 mg/kg qow, irrespective of treatment received in the Double-blind Period. Dose modifications were permitted during the Open-label Period. Receives: Drug: Sebelipase Alfa |
| Open-label Placebo/Sebelipase Alfa | Experimental | Participants who were randomized to receive placebo during the Double-blind Period and received sebelipase alfa in the Open-label Period. All participants received sebelipase alfa at a dose of 1 mg/kg qow, irrespective of treatment received in the Double-blind Period. Dose modifications were permitted during the Open-label Period. Receives: Drug: Sebelipase Alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Of Participants Achieving Alanine Aminotransferase Normalization
Alanine aminotransferase (ALT) normalization was defined as an abnormal baseline value (ALT > the age- and gender-specific upper limit of normal [ULN] provided by the central laboratory performing the assay) that becomes normal (< ULN). Alanine aminotransferase normalization was evaluated at the end of the Double-blind Period (the last double-blind assessment) and at the end of the Open-label Period (last open-label assessment). Baseline for the Open-label Period was defined relative to the first infusion of sebelipase alfa, which occurred at Week 0 for participants in the sebelipase alfa/sebelipase alfa group and Week 22 for participants in the placebo/sebelipase alfa group. The last open-label assessment varied by participant, depending on whether a participant completed treatment through Week 256 or discontinued prior to this timepoint to transition out of clinical study settings.
Measured: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256)
Secondary outcomes (8)
Percent Change From Baseline In Low-density Lipoprotein Cholesterol (LDL-C)
Relative reduction (percentage change from baseline) in LDL-C, as assessed by laboratory measurements was evaluated at the end of the Double-blind Period and at the end of the Open-label Period. Baseline for the Open-label Period was defined relative to the first infusion of sebelipase alfa, which occurred at Week 0 for participants in the sebelipase alfa/sebelipase alfa group and Week 22 for participants in the placebo/sebelipase alfa group. The last open-label assessment varied by participant, depending on whether a participant completed treatment through Week 256 or discontinued prior to this timepoint to transition out of clinical study settings.
Measured: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256).
Percent Change From Baseline In Non-high Density Lipoprotein Cholesterol (Non-HDL-C)
Relative reduction (percent change from baseline) in non-HDL-C, as assessed by laboratory measurements, was evaluated at the end of the Double-blind Period and the Open-label Period. Baseline for the Open-label Period was defined relative to the first infusion of sebelipase alfa, which occurred at Week 0 for participants in the sebelipase alfa/sebelipase alfa group and Week 22 for participants in the placebo/sebelipase alfa group. The last open-label assessment varied by participant, depending on whether a participant completed treatment through Week 256 or discontinued prior to this timepoint to transition out of clinical study settings.
Measured: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256).
Percentage Of Participants Achieving Aspartate Aminotransferase Normalization
Aspartate aminotransferase (AST) normalization was defined as an abnormal baseline value (AST > the age- and gender-specific ULN provided by the central laboratory performing the assay) that becomes normal (< ULN). AST normalization was evaluated at the end of the Double-blind Period (the last Double-blind assessment) and at the end of the Open-label Period (last open-label assessment).
Baseline for the Open-label Period was defined relative to the first infusion of sebelipase alfa, which occurred at Week 0 for participants in the sebelipase alfa/sebelipase alfa group and Week 22 for participants in the placebo/sebelipase alfa group. The last open-label assessment varied by participant, depending on whether a participant completed treatment through Week 256 or discontinued prior to this timepoint to transition out of clinical study settings.
Measured: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256).
Percent Change From Baseline In Triglycerides
Relative reduction (percent change from baseline) in triglycerides, as assessed by laboratory measurements, was evaluated at the end of the Double-blind Period and the Open-label Period. Baseline for the Open-label Period was defined relative to the first infusion of sebelipase alfa, which occurred at Week 0 for participants in the sebelipase alfa/sebelipase alfa group and Week 22 for participants in the placebo/sebelipase alfa group. The last open-label assessment varied by participant, depending on whether a participant completed treatment through Week 256 or discontinued prior to this timepoint to transition out of clinical study settings.
Measured: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256).
Percent Change From Baseline In High-density Lipoprotein Cholesterol (HDL-C)
Relative increase (percent change from baseline) in HDL-C, assessed by laboratory measurements, was evaluated at the end of the Double-blind Period and the Open-label Period. Baseline for the Open-label Period was defined relative to the first infusion of sebelipase alfa, which occurred at Week 0 for participants in the sebelipase alfa/sebelipase alfa group and Week 22 for participants in the placebo/sebelipase alfa group. The last open-label assessment varied by participant, depending on whether a participant completed treatment through Week 256 or discontinued prior to this timepoint to transition out of clinical study settings.
Measured: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256).
Percent Change From Baseline In Liver Fat Content
Decrease in liver fat content, as assessed by magnetic resonance imaging (MRI), was evaluated in participants for whom imaging was performed. Baseline for the Open-label Period was defined relative to the first infusion of sebelipase alfa, which occurred at Week 0 for participants in the sebelipase alfa/sebelipase alfa group and Week 22 for participants in the placebo/sebelipase alfa group. The last open-label assessment varied by participant, depending on whether a participant completed treatment through Week 256 or discontinued prior to this timepoint to transition out of clinical study settings.
Measured: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256).
Participants With Improvement In Liver Histopathology (Decrease Of > 5% In Hepatic Steatosis Score)
The number of participants who had an improvement in hepatic histopathology (defined as a decrease of > 5% in hepatic steatosis score, assessed by morphometry), as determined by blinded central pathologist review, in the participants for whom liver biopsy was performed. Baseline for the Open-label Period was defined relative to the first infusion of sebelipase alfa, which occurred at Week 0 for participants in the sebelipase alfa/sebelipase alfa group and Week 22 for participants in the placebo/sebelipase alfa group.
Measured: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline up to Week 52.
Percent Change From Baseline In Liver Volume
Relative reduction (percent change from baseline) in liver volume, as assessed by MRI, was evaluated in participants for whom imaging was performed. Baseline for the Open-label Period was defined relative to the first infusion of sebelipase alfa, which occurred at Week 0 for participants in the sebelipase alfa/sebelipase alfa group and Week 22 for participants in the placebo/sebelipase alfa group. The last open-label assessment varied by participant, depending on whether a participant completed treatment through Week 256 or discontinued prior to this timepoint to transition out of clinical study settings.
Measured: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2012 (estimated)
- Study start22 Jan 2013
- Primary completion30 May 2014
- Study completion11 Dec 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 (4)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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Florian Abel, MD, Study director, Alexion Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01757184
- Sponsor's protocol ID
- LAL-CL02
- Acronym
- ARISE
- Status last verified
- Dec 2020
- First submitted
- 17 Dec 2012
- Last updated
- 29 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Wilson DP, Friedman M, Marulkar S, Hamby T, Bruckert E. Sebelipase alfa improves atherogenic biomarkers in adults and children with lysosomal acid lipase deficiency. J Clin Lipidol. 2018 May-Jun;12(3):604-614. doi: 10.1016/j.jacl.2018.02.020. Epub 2018 Mar 9.
PubMed 29628368Burton BK, Balwani M, Feillet F, Baric I, Burrow TA, Camarena Grande C, Coker M, Consuelo-Sanchez A, Deegan P, Di Rocco M, Enns GM, Erbe R, Ezgu F, Ficicioglu C, Furuya KN, Kane J, Laukaitis C, Mengel E, Neilan EG, Nightingale S, Peters H, Scarpa M, Schwab KO, Smolka V, Valayannopoulos V, Wood M, Goodman Z, Yang Y, Eckert S, Rojas-Caro S, Quinn AG. A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency. N Engl J Med. 2015 Sep 10;373(11):1010-20. doi: 10.1056/NEJMoa1501365.
PubMed 26352813Burton BK, Feillet F, Furuya KN, Marulkar S, Balwani M. Sebelipase alfa in children and adults with lysosomal acid lipase deficiency: Final results of the ARISE study. J Hepatol. 2022 Mar;76(3):577-587. doi: 10.1016/j.jhep.2021.10.026. Epub 2021 Nov 10.
PubMed 34774639Valayannopoulos V, Malinova V, Honzik T, Balwani M, Breen C, Deegan PB, Enns GM, Jones SA, Kane JP, Stock EO, Tripuraneni R, Eckert S, Schneider E, Hamilton G, Middleton MS, Sirlin C, Kessler B, Bourdon C, Boyadjiev SA, Sharma R, Twelves C, Whitley CB, Quinn AG. Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency. J Hepatol. 2014 Nov;61(5):1135-42. doi: 10.1016/j.jhep.2014.06.022. Epub 2014 Jun 30.
PubMed 24993530
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Placebo-controlled Study of SBC-102 in Patients With Lysosomal Acid Lipase Deficiency
- ClinicalTrials.gov ID
- NCT01757184
- Acronym / sponsor ID
- ARISE / LAL-CL02
- Conditions
- Lysosomal Acid Lipase Deficiency
- Keywords
- Enzyme replacement therapy (ERT), Lysosomal storage disease, Late-onset lysosomal acid lipase deficiency (LAL-D), Acid cholesteryl ester hydrolase deficiency, type 2, Acid lipase disease, Cholesterol ester hydrolase deficiency, LAL-D, LIPA deficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Jan 2013 (actual)
- Primary completion
- 30 May 2014 (actual)
- Study completion
- 11 Dec 2018 (actual)
- First posted
- 28 Dec 2012 (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 Phase 3 study evaluated the efficacy and safety of 1 milligram/kilogram (mg/kg) intravenous (IV) infusions of SBC-102 (sebelipase alfa) administered every other week (qow) in participants with late onset lysosomal acid lipase deficiency (LAL-D) (cholesteryl ester storage disease [CESD]).
Late-onset LAL-D is an underappreciated cause of cirrhosis, liver failure and dyslipidemia. There is currently no standard treatment for LAL-D other than supportive care. Enzyme replacement therapy may be a potential new treatment option for LAL-D participants.
Detailed description
Lysosomal acid lipase deficiency (LAL-D) is a genetic disease characterized by abnormal lipid accumulation in many parts of the body due to a marked decrease in activity of the enzyme lysosomal acid lipase (LAL).
The LAL-D disease spectrum ranges from a presentation in infants that is rapidly progressive to a presentation that occurs in childhood, adolescence, or less frequently, in adulthood in which the rate of disease progression is more variable. Irrespective of where a patient is on the disease spectrum, LAL-D is associated with significant burden of disease and a shortened life expectancy in some patients.
The non-infantile onset form of the disease, also known as CESD, occurs in both children and adults and is an under-appreciated cause of fatty liver with prominent microvesicular steatosis, fibrosis, and cirrhosis. Although the natural history of the disease has not been well studied, serious complications are frequently described, including early death, liver transplantation, or cardiovascular accidents. Other complications include premature atherosclerosis (hardening of arteries) associated with high levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, often called the "bad" cholesterol. The levels of triglycerides can also be high and the levels of high-density lipoprotein (HDL) cholesterol (the "good" cholesterol) are typically low.
In the past, treatments mainly focused on control of the lipid abnormalities through diet and the use of lipid-lowering medications, which only address some aspects of the disease, while progression to fibrosis and cirrhosis may still occur. In preclinical studies and clinical studies in participants with LAL-D, treatment with SBC-102 (sebelipase alfa, Kanuma®) has been shown to produce improvements in markers of liver damage and in the lipid abnormalities. The purpose of this study was to examine the effects of using SBC-102 to treat LAL-D through a placebo-controlled, randomized, double-blinded study in children and adults.
This multicenter, randomized, double-blind, placebo-controlled study involving 66 participants evaluated the safety and efficacy of enzyme-replacement therapy with sebelipase alfa (administered intravenously at a dose of 1 mg/kg of body weight qow). The study included a 20-week placebo-controlled period followed by open-label treatment periods for all participants. The primary end-point was normalization of the alanine aminotransferase level. Secondary end-points included additional disease-related efficacy and safety assessments.
Final study results have not been published in a peer-reviewed journal.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Double-blind Sebelipase Alfa | Experimental | Drug: Sebelipase AlfaDouble-blind Period: IV infusions of sebelipase alfa at a dose of 1 mg/kg administered qow for 20 weeks. |
| Double-blind Placebo | Placebo comparator | Drug: PlaceboDouble-blind Period: IV infusions of matched placebo administered qow for 20 weeks. |
| Open-label Sebelipase Alfa/Sebelipase Alfa | Experimental | Drug: Sebelipase AlfaParticipants who were randomized to receive sebelipase alfa during the Double-blind Period and received sebelipase alfa in the Open-label Period. All participants received sebelipase alfa at a dose of 1 mg/kg qow, irrespective of treatment received in the Double-blind Period. Dose modifications were permitted during the Open-label Period. |
| Open-label Placebo/Sebelipase Alfa | Experimental | Drug: Sebelipase AlfaParticipants who were randomized to receive placebo during the Double-blind Period and received sebelipase alfa in the Open-label Period. All participants received sebelipase alfa at a dose of 1 mg/kg qow, irrespective of treatment received in the Double-blind Period. Dose modifications were permitted during the Open-label Period. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Participant and/or participant's parent or legal guardian provided informed consent.
- Participant was ≥ 4 years of age on the date of informed consent.
- Deficiency of LAL enzyme activity confirmed by dried blood spot testing at screening.
- Alanine aminotransferase ≥ 1.5x upper limit of normal on 2 consecutive screening measurements obtained at least 1 week apart.
- Female participants of childbearing potential must not have been pregnant or breastfeeding and must have agreed to use a medically acceptable method of preventing contraception from screening until 4 weeks after the last dose of study drug.
Key exclusion criteria (6 listed)
- Severe hepatic dysfunction (Child-Pugh Class C).
- Other medical conditions or comorbidities, which, in the opinion of the Investigator, would have interfered with study compliance or data interpretation.
- Previous hematopoietic or liver transplant procedure.
- Received treatment with high-dose corticosteroids (acute or chronic) within 26 weeks. (Note: Participants receiving maintenance therapy with low-dose oral, intranasal, topical, or inhaled corticosteroids were considered eligible for the study).
- Known hypersensitivity to eggs.
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 infusions of sebelipase alfa | Drug | Double-blind Sebelipase Alfa, Open-label Placebo/Sebelipase Alfa, Open-label Sebelipase Alfa/Sebelipase Alfa |
| PlaceboIV infusions of matched placebo | Drug | Double-blind Placebo |
Primary outcome
Percentage Of Participants Achieving Alanine Aminotransferase Normalization
Time frame: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256)
Alanine aminotransferase (ALT) normalization was defined as an abnormal baseline value (ALT > the age- and gender-specific upper limit of normal [ULN] provided by the central laboratory performing the assay) that becomes normal (< ULN). Alanine aminotransferase normalization was evaluated at the end of the Double-blind Period (the last double-blind assessment) and at the end of the Open-label Period (last open-label assessment). Baseline for the Open-label Period was defined relative to the first infusion of sebelipase alfa, which occurred at Week 0 for participants in the sebelipase alfa/sebelipase alfa group and Week 22 for participants in the placebo/sebelipase alfa group. The last open-label assessment varied by participant, depending on whether a participant completed treatment through Week 256 or discontinued prior to this timepoint to transition out of clinical study settings.
8 secondary outcomes
Percent Change From Baseline In Low-density Lipoprotein Cholesterol (LDL-C)
Time frame: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256).
Percent Change From Baseline In Non-high Density Lipoprotein Cholesterol (Non-HDL-C)
Time frame: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256).
Percentage Of Participants Achieving Aspartate Aminotransferase Normalization
Time frame: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256).
Percent Change From Baseline In Triglycerides
Time frame: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256).
Percent Change From Baseline In High-density Lipoprotein Cholesterol (HDL-C)
Time frame: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256).
Percent Change From Baseline In Liver Fat Content
Time frame: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256).
Participants With Improvement In Liver Histopathology (Decrease Of > 5% In Hepatic Steatosis Score)
Time frame: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline up to Week 52.
Percent Change From Baseline In Liver Volume
Time frame: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29628368Wilson DP, Friedman M, Marulkar S, Hamby T, Bruckert E. Sebelipase alfa improves atherogenic biomarkers in adults and children with lysosomal acid lipase deficiency. J Clin Lipidol. 2018 May-Jun;12(3):604-614. doi: 10.1016/j.jacl.2018.02.020. Epub 2018 Mar 9.
- Background: PubMed 26352813Burton BK, Balwani M, Feillet F, Baric I, Burrow TA, Camarena Grande C, Coker M, Consuelo-Sanchez A, Deegan P, Di Rocco M, Enns GM, Erbe R, Ezgu F, Ficicioglu C, Furuya KN, Kane J, Laukaitis C, Mengel E, Neilan EG, Nightingale S, Peters H, Scarpa M, Schwab KO, Smolka V, Valayannopoulos V, Wood M, Goodman Z, Yang Y, Eckert S, Rojas-Caro S, Quinn AG. A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency. N Engl J Med. 2015 Sep 10;373(11):1010-20. doi: 10.1056/NEJMoa1501365.
- Derived from this study: PubMed 34774639Burton BK, Feillet F, Furuya KN, Marulkar S, Balwani M. Sebelipase alfa in children and adults with lysosomal acid lipase deficiency: Final results of the ARISE study. J Hepatol. 2022 Mar;76(3):577-587. doi: 10.1016/j.jhep.2021.10.026. Epub 2021 Nov 10.
- Derived from this study: PubMed 24993530Valayannopoulos V, Malinova V, Honzik T, Balwani M, Breen C, Deegan PB, Enns GM, Jones SA, Kane JP, Stock EO, Tripuraneni R, Eckert S, Schneider E, Hamilton G, Middleton MS, Sirlin C, Kessler B, Bourdon C, Boyadjiev SA, Sharma R, Twelves C, Whitley CB, Quinn AG. Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency. J Hepatol. 2014 Nov;61(5):1135-42. doi: 10.1016/j.jhep.2014.06.022. Epub 2014 Jun 30.
Related trials for Lysosomal Acid Lipase Deficiency
Enrolling by invitationObservational study
ScreenPlus: A Comprehensive, Flexible, Multi-disorder Newborn Screening Program
Acid Sphingomyelinase Deficiency, Ceroid Lipofuscinosis, Neuronal, 2
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
RecruitingObservational study
Registry of Patients Diagnosed With Lysosomal Storage Diseases
Mucopolysaccharidosis I, Mucopolysaccharidosis II
RecruitingPhase 1
PEARL (PrEnAtal Enzyme Replacement Therapy for Lysosomal Storage Disorders)
MPS I, MPS II
RecruitingObservational study
Lysosomal Acid Lipase (LAL) Deficiency Registry
Lysosomal Acid Lipase Deficiency, Cholesterol Ester Storage Disease
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.
Florian Abel, MD study director
Alexion Pharmaceuticals, Inc.
40 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sebelipase Alfa in people with Lysosomal Acid Lipase Deficiency, run by Alexion Pharmaceuticals, Inc. at 40 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 7 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 29 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States, Australia, Germany, Italy, Spain 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. Some participants in this study may receive a placebo. 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 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 Achieving Alanine Aminotransferase Normalization (time frame: Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline to the last Open-label assessment (up to Week 256)). 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 NCT01757184, which also lists 4 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 29 Dec 2020.