Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of SBC-102 (Sebelipase Alfa) in Adult Subjects With Lysosomal Acid Lipase Deficiency

Alexion Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Cholesterol Ester Storage Disease (CESD); Lysosomal Acid Lipase Deficiency; LAL-Deficiency

Treatments: Drug: sebelipase alfa

Study type: Interventional

Funder types: Industry

Identifiers

NCT01488097

LAL-CL04

Details and patient eligibility

About

This was an extension study to Study LAL-CL01 (NCT01307098). The primary objective of the study was to evaluate the long-term safety and tolerability of sebelipase alfa in participants with liver dysfunction due to lysosomal acid lipase (LAL) deficiency.

Full description

Participants who successfully received all 4 doses of sebelipase alfa in Study LAL-CL01 and opted to continue treatment in the extension study underwent screening assessments to determine study eligibility. Eligible participants initiated treatment in the extension study at least 4 weeks after their last dose of sebelipase alfa in Study LAL-CL01. This extension study consisted of a treatment period of up to 5 years, and a follow-up period of approximately 30 days after the last dose of sebelipase alfa.

Cholesteryl ester storage disease (CESD) is the late onset phenotype for LAL deficiency, a lysosomal storage disorder, which also has an early onset phenotype that primarily affects infants. CESD can present in childhood but often goes unrecognized until adulthood when the underlying pathology is advanced. Many of the signs and symptoms are common to patients with other liver conditions.

CESD is an autosomal recessive genetic condition and is characterized by hepatomegaly, persistently abnormal liver function tests (LFTs) and type II hyperlipidemia. Splenomegaly and evidence of mild hypersplenism may affect some patients. Untreated, CESD may lead to fibrosis, cirrhosis, liver failure and death.

Enrollment: 8 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant received all 4 scheduled doses of sebelipase alfa in Study LAL-CL01 with no life-threatening or unmanageable study drug toxicity.

Exclusion criteria

• Clinically significant concurrent disease, serious inter-current illness, concomitant medications or other extenuating circumstances
• Clinically significant abnormal values on laboratory screening tests, other than LFTs or lipid panel tests

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 1 patient group

Open-Label Sebelipase Alfa

Experimental group

Description:

Participants were administered sebelipase alfa once weekly (qw) as an intravenous (IV) infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 milligrams per kilogram \[mg/kg\]) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing every other week (qow) at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.

Treatment:

Drug: sebelipase alfa