A research study to look at the safety, effectiveness and the effects on the body of a new drug, SBC-102, in children with growth problems caused by a deficiency in the enzyme that breaks down fats

• Register: EUCTR
• Last refreshed on: 12 March 2018
• Main ID: EUCTR2011-000032-28-IE
• Date of registration: 16/05/2013
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals Inc.
• Public title: A research study to look at the safety, effectiveness and the effects on the body of a new drug, SBC-102, in children with growth problems caused by a deficiency in the enzyme that breaks down fats
• Scientific title: An Open Label, Multicenter, Dose Escalation Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of SBC-102 in Children with Growth Failure Due to Lysosomal Acid Lipase Deficiency - SBC-102 in Children with Growth Failure Due to Lysosomal Acid Lipase D
• Date of first enrolment: 12/07/2013
• Target sample size: 10
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000032-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Egypt, France, Germany, Ireland, Italy, Saudi Arabia, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Raquel Cerezo, Assoc Dir Clin Ops
• Affiliation: Alexion Pharmaceuticals Inc

• Name: Raquel Cerezo, Assoc Dir Clin Ops
• Affiliation: Alexion Pharmaceuticals Inc

Key inclusion & exclusion 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 understands the full nature and
purpose of the study, including possible risks and side effects, and
provides written informed consent/permission prior to any study
procedures being performed.

2. Male or female child with a documented decreased LAL activity
relative to the normal range of the lab performing the assay or
documented result of molecular genetic testing (2 mutations) confirming
a diagnosis of LAL Deficiency.
3. Growth failure* with onset before 6 months of age, as defined by:
weight decreasing across at least 2 of the 11 major centiles on a
standard World Health Organization (WHO) weight-for-age (WFA)
chart (1st, 3rd, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97th, 99th);
OR
body weight in kg below the 10th centile on a standard WHO WFA
chart AND no weight gain for the 2 weeks prior to screening;
OR
loss of >5% of birth weight in a child who is older than 2 weeks of
age.
*NOTE regarding Inclusion Criterion # 3: In the unusual circumstance
where a child has a rapidly progressive course of LAL Deficiency but
does not meet growth failure criteria as defined above, the child may be
included in the study if the Investigator has substantial clinical concerns
based on evidence of the rapid disease progression requiring urgent
medical intervention. Inclusion under these exceptional circumstances
requires submission of a written summary of the infant’s medical status
for review by the Sponsor and must be approved by a written
confirmation from the Sponsor after consultation with the Safety
Committee (SC). The subject must meet all other entry criteria as stated.
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
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, congestive heart failure, ongoing circulatory collapse requiring inotropic support, acute or chronic renal failure, additional severe congenital abnormality, or other extenuating circumstances such as life-threatening under nutrition or rapidly progressive liver disease.
2. Subject is >24 months of age. (Note: Subjects >8 months of age on the date of first infusion will not be eligible for the primary efficacy analysis.)
3. 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Growth failure in children due to lysosomal acid lipase deficiency (Wolman disease).
MedDRA version: 19.0 Level: HLT Classification code 10024579 Term: Lysosomal storage disorders System Organ Class: 100000004850
MedDRA version: 19.0 Level: HLGT Classification code 10021605 Term: Inborn errors of metabolism System Organ Class: 10027433 - Metabolism and nutrition disorders
MedDRA version: 19.0 Level: SOC Classification code 10027433 Term: Metabolism and nutrition disorders System Organ Class: 10027433 - Metabolism and nutrition disorders

Intervention(s)

Product Name: sebelipase alfa
Product Code: SBC-102, recombinant human lysosomal acid lipase
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: sebelipase alfa
CAS Number: 1276027-63-4
Current Sponsor code: SBC-102
Other descriptive name: recombinant human lysosomal acid lipase (rhLAL)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: continuously, see protocol

Secondary Objective: (1) to evaluate the safety and tolerability of SBC-102 in children with growth failure due to LAL Deficiency;
(2) to evaluate the effect of SBC-102 therapy on survival beyond 12 months of age in children with growth failure due to LAL Deficiency;
(3) to evaluate the effects of SBC-102 on growth parameters in children with growth failure due to LAL Deficiency;
(4) to evaluate the effects of SBC-102 on hepatomegaly, splenomegaly, and liver function in children with growth failure due to LAL Deficiency;
(5) to determine the effects of SBC 102 on hematological parameters in children with growth failure due to LAL Deficiency; and
(6) to characterize the PK of SBC 102 delivered by intravenous (IV) infusion.

Main Objective: The primary objective of the study is to evaluate the effect of SBC-102 therapy on survival at 12 months of age in children with growth failure due to LAL Deficiency.

Primary end point(s): Efficacy: proportion of subjects surviving to 12 months of age

Secondary Outcome(s)

Secondary end point(s): Efficacy: (1) 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);
(2) changes from baseline in aspartate aminotransferase (AST) and ALT;
(3) normalization of hemoglobin levels without requirement for blood transfusion; and
(4) change from baseline in serum ferritin.

Safety: incidence of AEs, SAEs, and IRRs; changes from baseline clinical laboratory tests; changes in vital signs during and post-infusion relative to pre-infusion values; physical examination findings; use of concomitant medications/therapies; and characterization of ADAs

Pharmacokinetics: maximum observed serum concentration (Cmax) and apparent serum clearance (CL), as data permit. The impact of ADAs on SBC-102 PK will also be explored.

Timepoint(s) of evaluation of this end point: continuously, see protocol

Secondary ID(s)

2011-000032-28-GB

NCT01371825

LAL-CL03

Source(s) of Monetary Support

Alexion Pharmaceuticals Inc.