Lysosomal Acid Lipase Deficiency (LALD) MedDRA version: 18.1 Level: HLT Classification code 10024579 Term: Lysosomal storage disorders System Organ Class: 100000004850
Conditions
Interventions
Product Name: Sebelipase Alfa
Product Code: SBC-102
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: sebelipase
USAN: sebelipase alpha
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-
Sponsors
Alexion Pharmaceuticals Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject must meet all of the following criteria to be eligible to participate in this study: 1. Subject’s parent or legal guardian (if applicable) consents to participation in the study. 2. Confirmation of documented decreased LAL activty relative to the normal range of the lab performing the assay or a documented result of molecular genetic testing confirming a diagnosis of LAL deficiency. 3. Substantial clinical concerns, in the opinion of Investigator and Sponsor, of rapid disease progression requiring urgent medical intervention including, but not restricted to, the following: a) Marked abdominal distension and hepatomegaly b) Failure to thrive as evidenced by: i) Weight for height is 2 or more SD below the mean for gender and age ii) Weight curve has crossed downward by more than 2 major percentile lines on the WHO growth curves (1st, 3rd, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97th, 99th) after having previously achieved a stable pattern of growth c) Disturbance of coagulation (e.g., requirement for FFP; two values of PT >15 sec or PTT > 40 sec) d) Severe anemia (e.g., requirement for blood transfusion or hemoglobin =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A subject who meets any of the following criteria will be ineligible to participate in this study: 1. Clinically important concurrent disease or co-morbidities which, in the opinion of the Investigator and Sponsor, would interfere with study participation, including, but not restricted to: a) Additional severe congenital abnormality b) Presence of severe infection that requires treatment with parenteral anti-infective treatment within the past 14 days c) Previous history of circulatory collapse requiring inotropic support for more than 48 hours d) Congestive heart failure e) Acute or chronic renal failure f) Other extenuating circumstances such as life-threatening under nutrition or rapidly progressive liver disease 2. Subject will be > 8 months of age at the time of first dosing. 3. Subject has received an investigational medicinal product other than sebelipase alfa within 14 days prior to the first dose of sebelipase alfa in this study. 4. Myeloablative preparation, or other systemic pre-transplant conditioning, for hematopoietic stem cell or liver transplantation. 5. Previous hematopoietic stem cell or liver transplant. 6. Known hypersensitivity to eggs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the safety and tolerability of sebelipase alfa in infants with rapidly progressive LAL Deficiency.; Secondary Objective: The secondary objectives are to evaluate the effect of sebelipase alfa therapy on: (1) Survival at 12 months of age (2) Survival past 12 months of age; (3) Growth parameters; (4) Hepatomegaly, splenomegaly, and liver function; (5) Hematological parameters; and (6) to characterize the PK of sebelipase alfa delivered by intravenous (IV) infusion. ;Primary end point(s): Safety endpoints will include the incidence of adverse events (AEs), serious adverse events (SAEs), and IRRs; changes from baseline clinical laboratory tests; changes in vital signs (blood pressure, heart rate, respiratory rate, and temperature) during and post-infusion relative to pre-infusion values; physical examination findings; use of concomitant medications/therapies; and characterization of ADAs, including seroconversion rate, time to eroconversion, median and peak immunoglobulin G (IgG) ADA titer, time to peak IgG ADA titer, and tolerization. The impact of ADAs on safety endpoints will also be explored. Further characterization of ADAs, including inhibitory and/or neutralizing ADAs and measurement of specific ADA subtypes (e.g., IgE), may be performed, if appropriate.;Timepoint(s) of evaluation of this end point: Screening will occur within 21 days.Eligible patients will receive intravenous infusions of sebelipase alfa for up to 3 years. All patients will receive a starting dose of 1 mg·kg-1 qow. Dose increases (up to 3 mg·kg-1 qw) will be permitted during the treatment period. The follow-up period will be a minimum of 30 days following the last administration of sebelipase alfa. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Survival endpoints will include proportion of subjects surviving to 12, 18 and 24 months of age, and other timepoints, as data permit, and estimated median age at death. Survival rates and median age at death derived from this study will be compared to rates/times reported in the literature and previous studies. Other efficacy endpoints will include changes from baseline in percentiles and/or z-scores for WFA, WFL/WFH, and LFA/HFA and the corresponding growth status indicators of underweight, wasting, and stunting, as well as changes from baseline in z-scores for head circumference-for-age (HCFA) and mid-upper arm circumference-for-age (MUACFA); changes from baseline in aspartate aminotransferase (AST) and ALT; normalization of hemoglobin levels without requirement for blood transfusion; and change from baseline in serum ferritin. Exploratory efficacy endpoints will include changes and/or percent changes from baseline (or first available measurement if baseline data are unavailable) in alkaline phosphatase, gamma glutamyltransferase (GGT), albumin, and bilirubin (direct, indirect, and total); liver and spleen size/volume, as measured by ultrasound or magnetic resonance imaging (MRI); hepatomegaly and/or splenomegaly (abdominal girth, liver size, and spleen size) by physical examination; platelet levels; and serum lipid levels (total cholesterol, triglycerides, high density lipoprotein [HDL], low density lipoprotein [LDL]). Development will also be assessed using Denver II developmental screening test total score and four functional area scores (fine motor-adaptive, gross motor, personal-social, and language skills). The impact of anti-sebelipase alfa antibodies (ADAs) on efficacy endpoints will also be explored. The PK endpoint will include maximum observed serum concentration (Cmax), as data permit. The impact of ADAs on SBC-sebelipase alfa PK will also be explored. Explorat | — |
Countries
Finland, Italy, United Kingdom, United States
Contacts
Public ContactHarold Pestana, Assoc Dir Clin Ops
Alexion Pharmaceuticals Inc
Outcome results
None listed