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NCT01371825

Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Sebelipase Alfa in Children With Growth Failure Due to Lysosomal Acid Lipase Deficiency

Completed Phase 2, PHASE3 Results posted Last updated 30 January 2019
What this trial tests

Phase 2, PHASE3 trial testing Sebelipase alfa (SBC-102) in Lysosomal Acid Lipase Deficiency in 9 participants. Completed in 3 January 2018.

Timeline
4 May 2011
Primary endpoint
3 January 2018
3 January 2018

Quick facts

Lead sponsorAlexion Pharmaceuticals, Inc.
PhasePhase 2, PHASE3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment9
Start date4 May 2011
Primary completion3 January 2018
Estimated completion3 January 2018
Sites7 locations across France, Ireland, United Kingdom, United States, Egypt

Drugs / interventions tested

Conditions studied

Sponsor

Alexion Pharmaceuticals, Inc. — full company profile →

Who can join

Under 24 Months, any sex, with Lysosomal Acid Lipase Deficiency or Wolman Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age Primary · Month 12

The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.

GroupValue95% CI
Open-Label Sebelipase Alfa6729.9 – 92.5
Percentage Of Participants Surviving Beyond 12 Months Of Age Secondary · Baseline to Month 18, Month 24, Month 36, Month 48, and Month 60

The percentage of participants in the PES who survived to at least 18 months of age.

Survival Through 18 Months of Age
GroupValue95% CI
Open-Label Sebelipase Alfa5621.2 – 86.3
Survival Through 24 Months of Age
GroupValue95% CI
Open-Label Sebelipase Alfa5621.2 – 86.3
Survival Through 36 Months of Age
GroupValue95% CI
Open-Label Sebelipase Alfa5621.2 – 86.3
Survival Through 48 Months of Age
GroupValue95% CI
Open-Label Sebelipase Alfa5621.2 – 86.3
Survival Through 60 Months of Age
GroupValue95% CI
Open-Label Sebelipase Alfa439.9 – 81.6
Median Age At Death Secondary · Baseline to Week 260

Participants in the PES who died during the study, including 3 participants who died after having received between 1 and 4 infusions of sebelipase alfa and 1 participant who died after approximately 40 weeks on treatment.

GroupValue95% CI
Open-Label Sebelipase Alfa3.632.8 – 15.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles Secondary · Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60

Baseline is defined as the last measurement prior to the first infusion of sebelipase alfa.

Month 12
GroupValue95% CI
Open-Label Sebelipase Alfa7.4695.35 – 13.77
Month 24
GroupValue95% CI
Open-Label Sebelipase Alfa21.7870.91 – 30.37
Month 36
GroupValue95% CI
Open-Label Sebelipase Alfa14.037-0.35 – 89.00
Month 48
GroupValue95% CI
Open-Label Sebelipase Alfa15.7704.06 – 86.50
Month 60
GroupValue95% CI
Open-Label Sebelipase Alfa19.8697.36 – 71.39
Number Of Participants With Stunting, Wasting, Or Underweight Secondary · Baseline to Month 12, Month 24, Month 36, Month 48, and Month 60

The number of participants who met criteria for the following dichotomous indicators of under nutrition were reported. These indicators included the following: * Stunting was defined as at least 2 standard deviations below the median for length-for-age/height-for-age; * Wasting was defined as wasting at least 2 standard deviations below the median for weight-for-length/weight-for-height; and * Underweight was defined as at least 2 standard deviations below the median for WFA.

Stunting, Baseline
GroupValue95% CI
Open-Label Sebelipase Alfa4
Stunting, Month 12
GroupValue95% CI
Open-Label Sebelipase Alfa1
Stunting, Month 24
GroupValue95% CI
Open-Label Sebelipase Alfa0
Stunting, Month 36
GroupValue95% CI
Open-Label Sebelipase Alfa0
Stunting, Month 48
GroupValue95% CI
Open-Label Sebelipase Alfa0
Stunting, Month 60
GroupValue95% CI
Open-Label Sebelipase Alfa0
Wasting, Baseline
GroupValue95% CI
Open-Label Sebelipase Alfa2
Wasting, Month 12
GroupValue95% CI
Open-Label Sebelipase Alfa0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST) Secondary · Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60

Change from Baseline to Months 12, 24, 36, 48, and 60 for alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

ALT, Month 12
GroupValue95% CI
Open-Label Sebelipase Alfa-13.50-121.00 – 12.00
ALT, Month 24
GroupValue95% CI
Open-Label Sebelipase Alfa-5.00-111.00 – 228.00
ALT, Month 36
GroupValue95% CI
Open-Label Sebelipase Alfa-4.00-100.00 – 107.0
ALT, Month 48
GroupValue95% CI
Open-Label Sebelipase Alfa-27.50-129.00 – -2.00
ALT, Month 60
GroupValue95% CI
Open-Label Sebelipase Alfa-27.00-122.00 – 2.00
AST, Month 12
GroupValue95% CI
Open-Label Sebelipase Alfa-43.50-62.00 – -29.00
AST, Month 24
GroupValue95% CI
Open-Label Sebelipase Alfa-30.00-49.00 – 67.00
AST, Month 36
GroupValue95% CI
Open-Label Sebelipase Alfa-33.00-49.00 – 86.00
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin Secondary · Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60

The median change in serum ferritin from Baseline to Months 12, 24, 36, 48, and 60 is presented.

Month 12
GroupValue95% CI
Open-Label Sebelipase Alfa-294.40-562.2 – -271.0
Month 24
GroupValue95% CI
Open-Label Sebelipase Alfa-239.00-298.0 – -235.0
Month 36
GroupValue95% CI
Open-Label Sebelipase Alfa-262.95-566.6 – -166.0
Month 48
GroupValue95% CI
Open-Label Sebelipase Alfa-268.00-278.0 – -179.0
Month 60
GroupValue95% CI
Open-Label Sebelipase Alfa-213.00-543.9 – -155.0
Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization [TFHN] Secondary · Baseline to Month 60

The number of participants achieving and maintaining TFHN are presented. For TFHN to be achieved, the participant must a) have had 2 post-baseline measurements of hemoglobin at least 4 weeks apart that were both above the age-adjusted lower limit of normal; b) have had no known additional measurements of hemoglobin that were below the age-adjusted lower limit of normal during the (minimum) 4-week period; and c) have had no transfusions during the (minimum) 4-week period, and also no transfusions for 2 weeks prior to the first hemoglobin measurement in the (minimum) 4-week period. For TFHN to

Achieved TFHN
GroupValue95% CI
Open-Label Sebelipase Alfa6
Maintained TFHN
GroupValue95% CI
Open-Label Sebelipase Alfa2

Adverse events — posted to ClinicalTrials.gov

Time frame: Week 260. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Open-Label Sebelipase Alfa
Serious: 9/9 (100%)
Deaths: 4/9

Serious adverse events (34 terms)

ReactionSystemOpen-Label Sebelipase Alfa
PyrexiaGeneral disorders
Catheter site infectionInfections and infestations
Device related infectionInfections and infestations
Viral infectionInfections and infestations
PallorVascular disorders
ChillsGeneral disorders
LymphadenopathyBlood and lymphatic system disorders
Cardiac arrestCardiac disorders
DiarrhoeaGastrointestinal disorders
Peritoneal haemorrhageGastrointestinal disorders
HyperthermiaGeneral disorders
Hepatic failureHepatobiliary disorders
Bacterial pyelonephritisInfections and infestations
Device related sepsisInfections and infestations
Respiratory tract infectionInfections and infestations
RoseolaInfections and infestations
Staphylococcal bacteraemiaInfections and infestations
Staphylococcal sepsisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Weight decreasedInvestigations
DehydrationMetabolism and nutrition disorders
Failure to thriveMetabolism and nutrition disorders
Food intoleranceMetabolism and nutrition disorders
Metabolic acidosisMetabolism and nutrition disorders
Poor venous accessVascular disorders
Other adverse events (187 terms — click to expand)

ReactionSystemOpen-Label Sebelipase Alfa
VomitingGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
PyrexiaGeneral disorders
RhinitisInfections and infestations
NasopharyngitisInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
GastroenteritisInfections and infestations
Dermatitis diaperSkin and subcutaneous tissue disorders
TeethingGastrointestinal disorders
PharyngitisInfections and infestations
VaricellaInfections and infestations
Viral infectionInfections and infestations
Vitamin D deficiencyMetabolism and nutrition disorders
RashSkin and subcutaneous tissue disorders
UrticariaSkin and subcutaneous tissue disorders
EczemaSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
Ear infectionInfections and infestations
TachycardiaCardiac disorders
BradycardiaCardiac disorders
HydroceleCongenital, familial and genetic disorders
Ear painEar and labyrinth disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
HaematocheziaGastrointestinal disorders
Device related infectionInfections and infestations
Ear infection viralInfections and infestations
BronchiolitisInfections and infestations
Catheter site infectionInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
Blood albumin decreasedInvestigations
Protein total decreasedInvestigations
Iron deficiency anaemiaBlood and lymphatic system disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
ErythemaSkin and subcutaneous tissue disorders
Vitamin E deficiencyMetabolism and nutrition disorders
Vitamin K deficiencyMetabolism and nutrition disorders
Fungal skin infectionInfections and infestations
Hand-foot-and-mouth diseaseInfections and infestations

Most-reported serious reactions: Pyrexia, Catheter site infection, Device related infection, Viral infection, Pallor, Chills, Lymphadenopathy, Cardiac arrest.

Data from ClinicalTrials.gov NCT01371825 adverse events section.

Sponsor's own description

This was an open-label, repeat-dose, intra-participant dose-escalation study of SBC-102 (sebelipase alfa) in children with growth failure due to lysosomal acid lipase (LAL) Deficiency. Eligible participants received once-weekly (qw) infusions of sebelipase alfa for up to 5 years.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Survival in infants treated with sebelipase Alfa for lysosomal acid lipase deficiency: an open-label, multicenter, dose-escalation study.
    Jones SA, Rojas-Caro S, Quinn AG, Friedman M, et al · · 2017 · cited 63× · PMID 28179030 · DOI 10.1186/s13023-017-0587-3
  2. Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants.
    Jones SA, Valayannopoulos V, Schneider E, Eckert S, et al · · 2016 · cited 57× · PMID 26312827 · DOI 10.1038/gim.2015.108
  3. Long-term survival with sebelipase alfa enzyme replacement therapy in infants with rapidly progressive lysosomal acid lipase deficiency: final results from 2 open-label studies.
    Vijay S, Brassier A, Ghosh A, Fecarotta S, et al · · 2021 · cited 23× · PMID 33407676 · DOI 10.1186/s13023-020-01577-4
  4. The role of sebelipase alfa in the treatment of lysosomal acid lipase deficiency.
    Erwin AL. · · 2017 · cited 18× · PMID 28804516 · DOI 10.1177/1756283x17705775
  5. "Why them, why me, why us?" The experiences of parents of children with lysosomal acid lipase deficiency: an interpretative phenomenological analysis study.
    Hassall S, Smith DM, Rust S, Jones SA, et al · · 2022 · cited 8× · PMID 35550173 · DOI 10.1186/s13023-022-02335-4
  6. Enzyme replacement therapy in lysosomal acid lipase deficiency (LAL-D): a systematic literature review.
    Bashir A, Tiwari P, Duseja A. · · 2021 · cited 5× · PMID 37181111 · DOI 10.1177/26330040211026928
  7. Does Early Diagnosis and Treatment Alter the Clinical Course of Wolman Disease? Divergent Trajectories in Two Siblings and a Consideration for Newborn Screening.
    de Castro Lopez MJ, White FJ, Holmes V, Roberts J, et al · · 2025 · cited 4× · PMID 40136632 · DOI 10.3390/ijns11010017
  8. Long-Term Survival With Sebelipase Alfa Enzyme Replacement Therapy in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency Final Results From 2 Open-Label Studies
    Vijay S, Brassier A, Ghosh A, Fecarotta S, et al · · 2020 · cited 1× · DOI 10.21203/rs.3.rs-45422/v2

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