Safety and Efficacy Study of Sebelipase Alfa in Participants With Lysosomal Acid Lipase Deficiency
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|ClinicalTrials.gov Identifier: NCT02112994|
Recruitment Status : Completed
First Posted : April 14, 2014
Results First Posted : January 15, 2019
Last Update Posted : December 4, 2019
|Condition or disease||Intervention/treatment||Phase|
|Lysosomal Acid Lipase Deficiency||Drug: Sebelipase Alfa||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||31 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multi-Center, Open-Label Study of Sebelipase Alfa in Patients With Lysosomal Acid Lipase Deficiency|
|Actual Study Start Date :||June 24, 2014|
|Actual Primary Completion Date :||December 28, 2017|
|Actual Study Completion Date :||December 28, 2017|
Experimental: Sebelipase Alfa
Pediatric and adult participants initiated IV treatment with sebelipase alfa at a dose of 1 mg/kg qow. Participants were considered for a dose adjustment at the discretion of the Investigator and in consultation with the Sponsor. Dose escalation to 3 mg/kg qow was considered if pre-defined dose-escalation criteria were met. If these criteria continued to be met, a subsequent dose escalation to 3 mg/kg every week (qw) was considered. Dose decreases as low as 0.35 mg/kg qow were permitted based upon evidence of intolerance to sebelipase alfa treatment. Participants who completed the 96-week treatment period were permitted to continue receiving sebelipase alfa in an expanded treatment period for up to 48 weeks, pending local drug availability and study participation status.
Drug: Sebelipase Alfa
IV infusion of sebelipase alfa
Other Name: SBC-102
- Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Screening, Week 144 ]The number of participants experiencing severe TEAEs is presented for participants who received sebelipase alfa in this open-label study. Adverse events (AEs) information was obtained at each scheduled contact with the participant (or participant's parent or legal guardian). An AE was defined as any untoward medical occurrence that did not require a causal relationship with study drug administration. An AE could have been any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug. Pre-existing conditions that worsened in severity during the study were reported as AEs. A summary of all serious and other non-serious AEs regardless of causality is located in the Reported AE module. Severity assessed using Clinical Data Interchange Standards Consortium Study Data Tabulation Model standard terminology v3.1.1. Data presented only according to age group, not dose of study drug received.
- Percent Change In Serum Lipids From Baseline To Week 144 [ Time Frame: Baseline, Week 144 ]The effect of sebelipase alfa on lipid metabolism was evaluated by measuring the change from baseline to Week 144 in 4 serum lipids: low-density lipoprotein cholesterol (LDL-C); high-density lipoprotein cholesterol (HDL-C); non-HDL-C; triglycerides. Blood samples for these clinical laboratory tests were collected at scheduled time points and analyzed by a central laboratory.
- Participants Testing Positive For Anti-drug Antibodies (ADAs) [ Time Frame: Week 144 ]The impact of ADAs on the safety and immunogenicity of sebelipase alfa was evaluated by testing for ADAs in participants who received sebelipase alfa in this open-label study. Blood samples for assessment were collected prior to study infusions at Week 2, Week 4, Week 8, Week 12, and every 12 weeks thereafter. Participants testing positive for ADAs were also tested for the presence of neutralizing antibodies that inhibited sebelipase alfa enzyme activity and/or cellular uptake. Any participant experiencing a moderate or severe infusion-associated reaction (IAR) was to have an additional assessment of ADAs at the next study visit (prior to study drug infusion); these participants were to also have serum samples collected at 1 to 2 hours after IAR onset and at the next study visit (prior to study drug infusion) for analysis of serum tryptase. The count of participants who became ADA positive and who tested positive for neutralizing antibodies are presented.
- Percent Change In Body Mass Index (BMI)-For-Age Percentile From Baseline To Week 144 In Pediatric Participants [ Time Frame: Baseline, Week 144 ]To evaluate the effects of sebelipase alfa on growth parameters in pediatric participants (≤18 years old) presenting with evidence of growth delay, the percent change in the anthropometric parameter of BMI-for-age percentile from Baseline to Week 144 is reported. Anthropometric parameters were plotted on standard growth curves. When possible, historical data on growth parameters was also incorporated into the analyses. Percentiles and Z-scores for BMI-for-age were determined using standard growth charts appropriate to a participant's age on the date of the assessment: the World Health Organization standard growth chart for participants ≤2 years of age and the Centers for Disease Control standard growth chart for participants >2 years of age.
- Shift In Child-Pugh Status From Baseline To Week 144 [ Time Frame: Baseline, Week 144 ]In order to evaluate the effects of sebelipase alfa on liver function, the number of participants with a shift in Child-Pugh status from Baseline to Week 144 is reported. The status is based on the Child-Pugh score, which is used in clinical practice to assess prognosis in individuals with chronic liver disease. Laboratory data were used in derivation of the score by summing individual scores (scored 1-3, with 3 indicating most severe) from clinical laboratory test results and physical examinations, including total serum bilirubin, serum albumin, prothrombin time, ascites, and hepatic encephalopathy. The total score was used to determine the Child-Pugh status, reported as Class A (score of 5 or 6), Class B (score of 7 to 9), or Class C (score of 10 to 15). Higher scores and higher categories represented a worse outcome. Data reported as 1 of 2 types of shifts in class: No Change from Baseline; Decline from Baseline.
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02112994
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, Louisiana|
|Shreveport, Louisiana, United States, 71103|
|United States, Ohio|
|Cincinnati, Ohio, United States, 45229|
|Westmead, Australia, NSW 2145|
|Brussels, Belgium, 1200|
|Sao Paulo, Brazil, 04024-002|
|Canada, Nova Scotia|
|Halifax, Nova Scotia, Canada, B3H 1V7|
|Zagreb, Croatia, 10000|
|Copenhagen, Denmark, 2100|
|Freiburg, Germany, 79106|
|Padova, Italy, 35128|
|Mexico City, Mexico, 06720|
|Amsterdam, Netherlands, 1105|
|Moscow, Russian Federation, 117997|
|A Coruna, Spain, 15006|
|Barcelona, Spain, 08036|
|Madrid, Spain, 28046|
|Balcali, Turkey, 01300|
|Birmingham, United Kingdom, B4 6NH|