Safety and Efficacy Study of Sebelipase Alfa in Participants With Lysosomal Acid Lipase Deficiency

Alexion Pharmaceuticals, Inc.31 enrolled

Overview

This study evaluated the safety and efficacy of sebelipase alfa in a broad population of participants with lysosomal acid lipase deficiency (LAL-D).

The primary objective of this study was to evaluate the safety of intravenous (IV) infusions of sebelipase alfa in a more broad population of LAL-D participants than previously studied. Such participants may have been excluded from enrollment in other studies of LAL-D because of age, disease progression, previous treatment by hematopoietic stem cell or liver transplantation, less common disease manifestations, or disease characteristics that would preclude participation in a placebo-controlled study. This open-label study included infants \>8 months, children, and adults. At least 4 participants in the study were to be between the age of 2 and 4 years. Eligible participants received sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) every other week (qow).

Study Type

INTERVENTIONAL

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Lysosomal Acid Lipase Deficiency

Interventions

Sebelipase AlfaDRUG

IV infusion of sebelipase alfa

Eligibility

Sex: ALLMin age: 8 Months

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Participant was \>8 months of age at the time of dosing. 2. Confirmation of LAL-D diagnosis as determined by the central laboratory or, for participants with prior hematopoietic stem cell transplant or liver transplant, historical enzyme activity or molecular genetic testing confirming a diagnosis of LAL-D. 3. Participants \>8 months but \<4 years of age at Screening had at least 1 of the following documented clinical manifestations of LAL-D: * Dyslipidemia * Elevated transaminases * Impaired growth * Suspected malabsorption * Other clinical manifestation of LAL-D 4. Participants ≥4 years of age at Screening had at least 1 of the following documented clinical manifestations of LAL-D: * Evidence of advanced liver disease * Histologically confirmed disease recurrence in participants with past liver or hematopoietic transplant * Persistent dyslipidemia * Suspected malabsorption * Other clinical manifestation of LAL-D Key Exclusion Criteria: 1. Participant had known causes of active liver disease other than LAL-D, which had not been adequately treated. 2. Participant received a hematopoietic stem cell or liver transplant \<2 years from the time of dosing. 3. Participant with co-morbidities other than complications due to LAL-D, which were irreversible or associated with a high mortality risk within 6 months or would interfere with study compliance or data interpretation.

Locations (19)

Unnamed facility

Chicago, Illinois, United States

Unnamed facility

Shreveport, Louisiana, United States

Unnamed facility

Cincinnati, Ohio, United States

Outcomes

Primary Outcomes

Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs)

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.

Time frame: Screening, Week 144

Secondary Outcomes

Percent Change In Serum Lipids From Baseline To 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.

Time frame: Baseline, Week 144

Participants Testing Positive For Anti-drug Antibodies (ADAs)

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.

Data from ClinicalTrials.gov

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