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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01757184




Registration number
NCT01757184
Ethics application status
Date submitted
17/12/2012
Date registered
28/12/2012
Date last updated
29/12/2020

Titles & IDs
Public title
Acid Lipase Replacement Investigating Safety and Efficacy (ARISE) in Participants With Lysosomal Acid Lipase Deficiency
Scientific title
A Multicenter, Randomized, Placebo-controlled Study of SBC-102 in Patients With Lysosomal Acid Lipase Deficiency
Secondary ID [1] 0 0
LAL-CL02
Universal Trial Number (UTN)
Trial acronym
ARISE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lysosomal Acid Lipase Deficiency 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sebelipase Alfa
Treatment: Drugs - Placebo

Experimental: Double-blind Sebelipase Alfa - Double-blind Period: IV infusions of sebelipase alfa at a dose of 1 mg/kg administered qow for 20 weeks.

Placebo comparator: Double-blind Placebo - Double-blind Period: IV infusions of matched placebo administered qow for 20 weeks.

Experimental: Open-label Sebelipase Alfa/Sebelipase Alfa - 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.

Experimental: Open-label Placebo/Sebelipase Alfa - 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.


Treatment: Drugs: Sebelipase Alfa
IV infusions of sebelipase alfa

Treatment: Drugs: Placebo
IV infusions of matched placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage Of Participants Achieving Alanine Aminotransferase Normalization
Timepoint [1] 0 0
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 outcome [1] 0 0
Percent Change From Baseline In Low-density Lipoprotein Cholesterol (LDL-C)
Timepoint [1] 0 0
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 outcome [2] 0 0
Percent Change From Baseline In Non-high Density Lipoprotein Cholesterol (Non-HDL-C)
Timepoint [2] 0 0
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 outcome [3] 0 0
Percentage Of Participants Achieving Aspartate Aminotransferase Normalization
Timepoint [3] 0 0
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 outcome [4] 0 0
Percent Change From Baseline In Triglycerides
Timepoint [4] 0 0
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 outcome [5] 0 0
Percent Change From Baseline In High-density Lipoprotein Cholesterol (HDL-C)
Timepoint [5] 0 0
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 outcome [6] 0 0
Percent Change From Baseline In Liver Fat Content
Timepoint [6] 0 0
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 outcome [7] 0 0
Participants With Improvement In Liver Histopathology (Decrease Of > 5% In Hepatic Steatosis Score)
Timepoint [7] 0 0
Double-blind Period: Baseline to the end of the Double-blind Period (Week 20). Open-label Period: Baseline up to Week 52.
Secondary outcome [8] 0 0
Percent Change From Baseline In Liver Volume
Timepoint [8] 0 0
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).

Eligibility
Key inclusion criteria
* 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.
Minimum age
4 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/01/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/12/2018
Sample size
Target
Accrual to date
Final
66
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Brisbane
Recruitment hospital [2] 0 0
- New Lambton
Recruitment hospital [3] 0 0
- Parkville
Recruitment hospital [4] 0 0
- Perth
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
- New Lambton
Recruitment postcode(s) [3] 0 0
- Parkville
Recruitment postcode(s) [4] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Delaware
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
Argentina
State/province [9] 0 0
Córdoba
Country [10] 0 0
Croatia
State/province [10] 0 0
Zagreb
Country [11] 0 0
Czechia
State/province [11] 0 0
Olomouc
Country [12] 0 0
Czechia
State/province [12] 0 0
Prague
Country [13] 0 0
France
State/province [13] 0 0
Paris
Country [14] 0 0
France
State/province [14] 0 0
Vandoeuvre les Nancy
Country [15] 0 0
Germany
State/province [15] 0 0
Freiburg
Country [16] 0 0
Germany
State/province [16] 0 0
Mainz
Country [17] 0 0
Germany
State/province [17] 0 0
Munich
Country [18] 0 0
Italy
State/province [18] 0 0
Bergamo
Country [19] 0 0
Italy
State/province [19] 0 0
Genoa
Country [20] 0 0
Italy
State/province [20] 0 0
Padova
Country [21] 0 0
Japan
State/province [21] 0 0
Tokyo
Country [22] 0 0
Japan
State/province [22] 0 0
Tottori
Country [23] 0 0
Mexico
State/province [23] 0 0
Mexico City
Country [24] 0 0
Poland
State/province [24] 0 0
Warsaw
Country [25] 0 0
Russian Federation
State/province [25] 0 0
Moscow
Country [26] 0 0
Spain
State/province [26] 0 0
Elche
Country [27] 0 0
Spain
State/province [27] 0 0
Madrid
Country [28] 0 0
Spain
State/province [28] 0 0
Oviedo
Country [29] 0 0
Turkey
State/province [29] 0 0
Ankara
Country [30] 0 0
Turkey
State/province [30] 0 0
Izmir
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Cambridge
Country [32] 0 0
United Kingdom
State/province [32] 0 0
London
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Plymouth

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Alexion Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 \[CESD\]).

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.
Trial website
https://clinicaltrials.gov/study/NCT01757184
Trial related presentations / 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.
Burton 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.
Burton 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.
Valayannopoulos 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.
Public notes

Contacts
Principal investigator
Name 0 0
Florian Abel, MD
Address 0 0
Alexion Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01757184