A Phase 2/3 interventional study of Sebelipase alfa (SBC-102) in Lysosomal Acid Lipase Deficiency and Wolman Disease, sponsored by Alexion Pharmaceuticals, Inc.. Completed at 7 sites in 5 countries. Open to participants aged Up to 24 Months. Per ClinicalTrials.gov, last updated 2019-01-30.
Sponsored by Alexion Pharmaceuticals, Inc. (part of AstraZeneca) · Phase 2/3, Interventional, and Treatment
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.
LAL Deficiency is a rare autosomal-recessive lipid storage disorder that is caused by a marked decrease or almost complete absence of LAL, leading to the accumulation of lipids, predominately cholesteryl esters and triglycerides, in various tissues and cell types. In the liver, accumulation of lipids leads to hepatomegaly, liver dysfunction, and hepatic failure. Although a single disease, LAL Deficiency presents as a clinical continuum with 2 major phenotypes, Cholesteryl Ester Storage Disease (CESD) and Wolman Disease.
Early-onset LAL Deficiency (Wolman Disease) is extremely rare, with an estimated incidence of less than 2 lives per million. It is characterized by profound malabsorption, growth failure, and hepatic failure, and is usually fatal in the first year of life.
33 studies on the registry are indexed under Wolman Disease; 5 are open to participants now.
This study's enrollment of 9 is below the median of 31 across 16 interventional studies indexed under Wolman Disease.
Browse Wolman Disease studies →Alexion Pharmaceuticals, Inc. is the lead sponsor of 255 studies on the registry; 23 are open to participants now.
Of its 101 completed or terminated interventional studies of FDA-regulated products, 75 (74%) have results posted.
First submitted before Alexion Pharmaceuticals, Inc. became part of AstraZeneca.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants received intravenous (IV) infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 milligrams (mg)/kilogram (kg) qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant's dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to an every other week (qow) dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.
Drug: Sebelipase alfa (SBC-102)
Sebelipase alfa is a recombinant human lysosomal acid lipase enzyme. The investigational medicinal product is an enzyme replacement therapy intended for treatment of participants with LAL Deficiency. Dosing occurred qw for up to 5 years.
Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age
The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.
Time frame: Month 12
Percentage Of Participants Surviving Beyond 12 Months Of Age
The percentage of participants in the PES who survived to at least 18 months of age.
Time frame: Baseline to Month 18, Month 24, Month 36, Month 48, and Month 60
Median Age At Death
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.
Time frame: Baseline to Week 260
Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles
Baseline is defined as the last measurement prior to the first infusion of sebelipase alfa.
Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Number Of Participants With Stunting, Wasting, Or Underweight
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.
Time frame: Baseline to Month 12, Month 24, Month 36, Month 48, and Month 60
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST)
Change from Baseline to Months 12, 24, 36, 48, and 60 for alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin
The median change in serum ferritin from Baseline to Months 12, 24, 36, 48, and 60 is presented.
Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization [TFHN]
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 be maintained, the participant must have been transfusion-free beginning at Week 6 and had all hemoglobin assessments above the lower limit of normal beginning in Week 8 and lasting at least 13 weeks.
Time frame: Baseline to Month 60
A total of 8 centers participated in this study in the United Kingdom (UK), United States (US), France, Turkey, Ireland, and Egypt.
| Milestone | Open-Label Sebelipase Alfa |
|---|---|
| Started | 9 |
| Received at least 1 dose of study drug | 9 |
| Completed | 5 |
| Not completed | 4 |
| Withdrew: Death | 4 |
The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.
| Percentage of participants | Open-Label Sebelipase Alfa |
|---|---|
| Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age | 67 (29.9 to 92.5) |
The percentage of participants in the PES who survived to at least 18 months of age.
| Percentage of participants | Open-Label Sebelipase Alfa |
|---|---|
| Survival Through 18 Months of Age | 56 (21.2 to 86.3) |
| Survival Through 24 Months of Age | 56 (21.2 to 86.3) |
| Survival Through 36 Months of Age | 56 (21.2 to 86.3) |
| Survival Through 48 Months of Age | 56 (21.2 to 86.3) |
| Survival Through 60 Months of Age | 43 (9.9 to 81.6) |
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.
| months | Open-Label Sebelipase Alfa |
|---|---|
| Median Age At Death | 3.63 (2.8 to 15.0) |
Baseline is defined as the last measurement prior to the first infusion of sebelipase alfa.
| WFA Percentile | Open-Label Sebelipase Alfa |
|---|---|
| Month 12 | 7.469 (5.35 to 13.77) |
| Month 24 | 21.787 (0.91 to 30.37) |
| Month 36 | 14.037 (-0.35 to 89.00) |
| Month 48 | 15.770 (4.06 to 86.50) |
| Month 60 | 19.869 (7.36 to 71.39) |
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.
| Participants | Open-Label Sebelipase Alfa |
|---|---|
| Stunting, Baseline | 4 |
| Stunting, Month 12 | 1 |
| Stunting, Month 24 | 0 |
| Stunting, Month 36 | 0 |
| Stunting, Month 48 | 0 |
| Stunting, Month 60 | 0 |
| Wasting, Baseline | 2 |
| Wasting, Month 12 | 0 |
| Wasting, Month 24 | 0 |
| Wasting, Month 36 | 0 |
| Wasting, Month 48 | 0 |
| Wasting, Month 60 | 0 |
| Underweight, Baseline | 2 |
| Underweight, Month 12 | 0 |
| Underweight, Month 24 | 1 |
| Underweight, Month 36 | 0 |
| Underweight, Month 48 | 0 |
| Underweight, Month 60 | 0 |
| No Stunting, Wasting, or Underweight, Baseline | 4 |
| No Stunting, Wasting, or Underweight, Month 12 | 3 |
| No Stunting, Wasting, or Underweight, Month 24 | 4 |
| No Stunting, Wasting, or Underweight, Month 36 | 5 |
| No Stunting, Wasting, or Underweight, Month 48 | 5 |
| No Stunting, Wasting, or Underweight, Month 60 | 5 |
Change from Baseline to Months 12, 24, 36, 48, and 60 for alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
| units/Liter (U/L) | Open-Label Sebelipase Alfa |
|---|---|
| ALT, Month 12 | -13.50 (-121.00 to 12.00) |
| ALT, Month 24 | -5.00 (-111.00 to 228.00) |
| ALT, Month 36 | -4.00 (-100.00 to 107.0) |
| ALT, Month 48 | -27.50 (-129.00 to -2.00) |
| ALT, Month 60 | -27.00 (-122.00 to 2.00) |
| AST, Month 12 | -43.50 (-62.00 to -29.00) |
| AST, Month 24 | -30.00 (-49.00 to 67.00) |
| AST, Month 36 | -33.00 (-49.00 to 86.00) |
| AST, Month 48 | -51.00 (-67.00 to -31.00) |
| AST, Month 60 | -40.00 (-84.00 to -17.00) |
The median change in serum ferritin from Baseline to Months 12, 24, 36, 48, and 60 is presented.
| micrograms/Liter (µg/L) | Open-Label Sebelipase Alfa |
|---|---|
| Month 12 | -294.40 (-562.2 to -271.0) |
| Month 24 | -239.00 (-298.0 to -235.0) |
| Month 36 | -262.95 (-566.6 to -166.0) |
| Month 48 | -268.00 (-278.0 to -179.0) |
| Month 60 | -213.00 (-543.9 to -155.0) |
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 be maintained, the participant must have been transfusion-free beginning at Week 6 and had all hemoglobin assessments above the lower limit of normal beginning in Week 8 and lasting at least 13 weeks.
| Participants | Open-Label Sebelipase Alfa |
|---|---|
| Achieved TFHN | 6 |
| Maintained TFHN | 2 |
Collected over Week 260. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Open-Label Sebelipase Alfa | 4/9 (44.4%) | 9/9 (100%) | 9/9 (100%) |
| Event | Open-Label Sebelipase Alfa |
|---|---|
| PyrexiaGeneral disorders | 3/9 |
| Catheter site infectionInfections and infestations | 2/9 |
| Device related infectionInfections and infestations | 2/9 |
| Viral infectionInfections and infestations | 2/9 |
| PallorVascular disorders | 1/9 |
| ChillsGeneral disorders | 1/9 |
| LymphadenopathyBlood and lymphatic system disorders | 1/9 |
| Cardiac arrestCardiac disorders | 1/9 |
| DiarrhoeaGastrointestinal disorders | 1/9 |
| Peritoneal haemorrhageGastrointestinal disorders | 1/9 |
| Event | Open-Label Sebelipase Alfa |
|---|---|
| VomitingGastrointestinal disorders | 6/9 |
| DiarrhoeaGastrointestinal disorders | 6/9 |
| PyrexiaGeneral disorders | 5/9 |
| RhinitisInfections and infestations | 5/9 |
| NasopharyngitisInfections and infestations | 5/9 |
| CoughRespiratory, thoracic and mediastinal disorders | 5/9 |
| AnaemiaBlood and lymphatic system disorders | 4/9 |
| GastroenteritisInfections and infestations | 4/9 |
| Dermatitis diaperSkin and subcutaneous tissue disorders | 4/9 |
| TeethingGastrointestinal disorders | 3/9 |
| Age, Categorical(Participants) | Open-Label Sebelipase Alfa |
|---|---|
| <=18 years | 9 |
| Between 18 and 65 years | 0 |
| >=65 years | 0 |
| Age, Continuous(months) | Open-Label Sebelipase Alfa |
|---|---|
| Mean | 3.41 (1.1 to 5.8) |
| Sex: Female, Male(Participants) | Open-Label Sebelipase Alfa |
|---|---|
| Female | 4 |
| Male | 5 |
| Ethnicity (NIH/OMB)(Participants) | Open-Label Sebelipase Alfa |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 6 |
| Unknown or Not Reported | 3 |
| Race (NIH/OMB)(Participants) | Open-Label Sebelipase Alfa |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 1 |
| White | 4 |
| More than one race | 0 |
| Unknown or Not Reported | 3 |
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Studies of the drug tested here: Sebelipase alfa
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