Cholesterol Ester Storage Disease(CESD)Phase 1/2NCT01307098
Safety, Tolerability and Pharmacokinetics of SBC-102 (Sebelipase Alfa) in Adult Participants With Lysosomal Acid Lipase Deficiency
A Phase 1/2 study testing Sebelipase alfa 0.35 mg/kg, Sebelipase alfa 1 mg/kg and Sebelipase alfa 3 mg/kg in people with Cholesterol Ester Storage Disease(CESD) and Lysosomal Acid Lipase Deficiency, run by Alexion Pharmaceuticals, Inc. at 7 sites in 4 countries.
Trial summary
This was the first clinical study of SBC-102 (sebelipase alfa) for the treatment of Lysosomal Acid Lipase (LAL) Deficiency. It was an open-label dose escalation study in adult participants with liver dysfunction due to LAL Deficiency and was designed to examine 3 doses of sebelipase alfa. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Cholesterol Ester Storage Disease(CESD), Lysosomal Acid Lipase Deficiency, LAL-Deficiency
- What is being tested?
- Sebelipase alfa 0.35 mg/kg, Sebelipase alfa 1 mg/kg and Sebelipase alfa 3 mg/kg
- 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 4 countries
- Study dates
- 25 Apr 2011to 6 Jan 2012
- Phase
- Phase 1/2
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants ≥ 18 and ≤ 65 years of age
- Documented decreased LAL activity
- Evidence of liver involvement
Who cannot join
- Clinically significant concurrent disease, serious inter-current illness, concomitant medications or other extenuating circumstances
- Clinically significant abnormal values on laboratory screening tests, other than liver function or lipid panel tests
- Aspartate aminotransferase and/or alanine aminotransferase persistently elevated > 3x upper limit of normal at screening
- Previous hemopoietic bone marrow or liver transplant
- Current history of alcohol abuse
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
United States3 sites
Study site
New York, New York, 10029
Study site
Pittsburgh, Pennsylvania, 15213
Study site
Stanford, California, 94305
United Kingdom2 sites
Study site
Cambridge, CB20QQ
Study site
Manchester, M139WL
About this study
Official title: An Open-Label Multicenter Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SBC-102 in Adult Participants With Liver Dysfunction Due to Lysosomal Acid Lipase Deficiency
This was the first clinical study of SBC-102 (sebelipase alfa) for the treatment of Lysosomal Acid Lipase (LAL) Deficiency. It was an open-label dose escalation study in adult participants with liver dysfunction due to LAL Deficiency and was designed to examine 3 doses of sebelipase alfa. The targeted number for this study was 9 evaluable participants.
Read the detailed description
The study was composed of a screening period, a treatment period, and a post-treatment follow-up period (including an End of Study visit). Participants who successfully completed screening assessments to determine study eligibility were allocated to 3 sequential cohorts (0.35, 1, or 3 milligrams/kilogram [mg/kg]). Within each cohort, one participant was initially dosed and, if sebelipase alfa was deemed safe and well tolerated in this participant (based on at least 24 hours of monitoring), dosing was allowed to be initiated for the remaining participants in the cohort. Initiation of dosing in the next cohort occurred only after all participants in the preceding cohort had been monitored for at least 5 days after the second infusion, without any evidence of significant safety signals, and an independent Safety Committee had reviewed the cumulative safety data and provided their recommendation on the acceptability of beginning dosing in the next cohort.
Cholesteryl Ester Storage Disease (CESD) is the late onset phenotype for LAL Deficiency, a lysosomal storage disorder, which also has an early onset phenotype known as Wolman disease that primarily affects infants. CESD can present in childhood but often goes unrecognized until adulthood when the underlying pathology is advanced. Many of the signs and symptoms are common to participants with other liver conditions.
CESD is an autosomal recessive genetic condition and is characterized by hepatomegaly, persistently abnormal liver function tests and type II hyperlipidemia. Splenomegaly and evidence of mild hypersplenism may affect some participants. Untreated, CESD may lead to fibrosis, cirrhosis, liver failure and death.
- Being tested
- Sebelipase alfa 0.35 mg/kg, Sebelipase alfa 1 mg/kg, Sebelipase alfa 3 mg/kg
- 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
- Medical subject headings
- Cholesterol Ester Storage Disease, Wolman Disease, Lysosomal Storage Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sebelipase alfa 0.35 mg/kgDrug
Also called Kanuma, SBC-102
Sebelipase alfa is a recombinant human lysosomal acid lipase.
Sebelipase alfa 1 mg/kgDrug
Also called Kanuma, SBC-102
Sebelipase alfa is a recombinant human lysosomal acid lipase.
Sebelipase alfa 3 mg/kgDrug
Also called Kanuma, SBC-102
Sebelipase alfa is a recombinant human lysosomal acid lipase.
| Study group | Role | What they receive |
|---|---|---|
| Sebelipase alfa 0.35 mg/kg | Experimental | Cohort 1: Participants were administered once weekly (qw) infusions of 0.35 mg/kg sebelipase alfa. Receives: Drug: Sebelipase alfa 0.35 mg/kg |
| Sebelipase alfa 1 mg/kg | Experimental | Cohort 2: Participants were administered qw infusions of 1 mg/kg sebelipase alfa. Receives: Drug: Sebelipase alfa 1 mg/kg |
| Sebelipase alfa 3 mg/kg | Experimental | Cohort 3: Participants were administered qw infusions of 3 mg/kg sebelipase alfa. Receives: Drug: Sebelipase alfa 3 mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number Of Participants Reporting TEAEs And Infusion-Related Reactions (IRRs)
Safety and tolerability of sebelipase alfa was primarily assessed by monitoring the number of participants reporting treatment-emergent adverse events (TEAEs), including serious adverse events, and infusion-related reactions (IRRs). The number of participants who discontinued from the study due to a TEAE is also presented. An IRR was defined as any adverse event that occurred between the start of the infusion and 4 hours after completion of the infusion and was assessed by the Investigator as at least possibly related to study drug. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Measured: Screening up to Day 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2011 (estimated)
- Study start25 Apr 2011
- Primary completion6 Jan 2012
- Study completion6 Jan 2012
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 Cholesterol Ester Storage Disease(CESD)Studies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- 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
- NCT01307098
- Sponsor's protocol ID
- LAL-CL01
- Status last verified
- Dec 2018
- First submitted
- 1 Mar 2011
- Last updated
- 11 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
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
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Multicenter Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SBC-102 in Adult Participants With Liver Dysfunction Due to Lysosomal Acid Lipase Deficiency
- ClinicalTrials.gov ID
- NCT01307098
- Acronym / sponsor ID
- LAL-CL01
- 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 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 25 Apr 2011 (actual)
- Primary completion
- 6 Jan 2012 (actual)
- Study completion
- 6 Jan 2012 (actual)
- First posted
- 2 Mar 2011 (estimated)
- Results
- Posted 11 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was the first clinical study of SBC-102 (sebelipase alfa) for the treatment of Lysosomal Acid Lipase (LAL) Deficiency. It was an open-label dose escalation study in adult participants with liver dysfunction due to LAL Deficiency and was designed to examine 3 doses of sebelipase alfa. The targeted number for this study was 9 evaluable participants.
Detailed description
The study was composed of a screening period, a treatment period, and a post-treatment follow-up period (including an End of Study visit). Participants who successfully completed screening assessments to determine study eligibility were allocated to 3 sequential cohorts (0.35, 1, or 3 milligrams/kilogram [mg/kg]). Within each cohort, one participant was initially dosed and, if sebelipase alfa was deemed safe and well tolerated in this participant (based on at least 24 hours of monitoring), dosing was allowed to be initiated for the remaining participants in the cohort. Initiation of dosing in the next cohort occurred only after all participants in the preceding cohort had been monitored for at least 5 days after the second infusion, without any evidence of significant safety signals, and an independent Safety Committee had reviewed the cumulative safety data and provided their recommendation on the acceptability of beginning dosing in the next cohort.
Cholesteryl Ester Storage Disease (CESD) is the late onset phenotype for LAL Deficiency, a lysosomal storage disorder, which also has an early onset phenotype known as Wolman disease that primarily affects infants. CESD can present in childhood but often goes unrecognized until adulthood when the underlying pathology is advanced. Many of the signs and symptoms are common to participants with other liver conditions.
CESD is an autosomal recessive genetic condition and is characterized by hepatomegaly, persistently abnormal liver function tests and type II hyperlipidemia. Splenomegaly and evidence of mild hypersplenism may affect some participants. Untreated, CESD may lead to fibrosis, cirrhosis, liver failure and death.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sebelipase alfa 0.35 mg/kg | Experimental | Drug: Sebelipase alfa 0.35 mg/kgCohort 1: Participants were administered once weekly (qw) infusions of 0.35 mg/kg sebelipase alfa. |
| Sebelipase alfa 1 mg/kg | Experimental | Drug: Sebelipase alfa 1 mg/kgCohort 2: Participants were administered qw infusions of 1 mg/kg sebelipase alfa. |
| Sebelipase alfa 3 mg/kg | Experimental | Drug: Sebelipase alfa 3 mg/kgCohort 3: Participants were administered qw infusions of 3 mg/kg sebelipase alfa. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male or female participants ≥ 18 and ≤ 65 years of age
- Documented decreased LAL activity
- Evidence of liver involvement
Key exclusion criteria (5 listed)
- Clinically significant concurrent disease, serious inter-current illness, concomitant medications or other extenuating circumstances
- Clinically significant abnormal values on laboratory screening tests, other than liver function or lipid panel tests
- Aspartate aminotransferase and/or alanine aminotransferase persistently elevated > 3x upper limit of normal at screening
- Previous hemopoietic bone marrow or liver transplant
- Current history of alcohol abuse
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 0.35 mg/kgAlso: Kanuma, SBC-102Sebelipase alfa is a recombinant human lysosomal acid lipase. | Drug | Sebelipase alfa 0.35 mg/kg |
| Sebelipase alfa 1 mg/kgAlso: Kanuma, SBC-102Sebelipase alfa is a recombinant human lysosomal acid lipase. | Drug | Sebelipase alfa 1 mg/kg |
| Sebelipase alfa 3 mg/kgAlso: Kanuma, SBC-102Sebelipase alfa is a recombinant human lysosomal acid lipase. | Drug | Sebelipase alfa 3 mg/kg |
Primary outcome
Number Of Participants Reporting TEAEs And Infusion-Related Reactions (IRRs)
Time frame: Screening up to Day 52
Safety and tolerability of sebelipase alfa was primarily assessed by monitoring the number of participants reporting treatment-emergent adverse events (TEAEs), including serious adverse events, and infusion-related reactions (IRRs). The number of participants who discontinued from the study due to a TEAE is also presented. An IRR was defined as any adverse event that occurred between the start of the infusion and 4 hours after completion of the infusion and was assessed by the Investigator as at least possibly related to study drug. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23348766Balwani 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.
- WebsiteLink provided by the sponsor.
- 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 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sebelipase alfa 0.35 mg/kg, Sebelipase alfa 1 mg/kg and Sebelipase alfa 3 mg/kg in people with Cholesterol Ester Storage Disease(CESD) and Lysosomal Acid Lipase Deficiency, run by Alexion Pharmaceuticals, Inc. at 7 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 3 inclusion and 5 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 11 Dec 2018. 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 United States, United Kingdom, Czechia, France. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 11 Dec 2018). 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?
Number Of Participants Reporting TEAEs And Infusion-Related Reactions (IRRs) (time frame: Screening up to Day 52). 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 NCT01307098, 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 11 Dec 2018.