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: 10 September 2018
• Main ID: EUCTR2011-000032-28-GB
• Date of registration: 17/01/2011
• Prospective Registration: Yes
• Primary sponsor: Synageva Biopharma Corp.
• 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 Deficiency
• Date of first enrolment: 18/04/2011
• 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: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Ireland, Italy, Taiwan, United Kingdom, United States

Contacts

• Name: Amy Simonds
• Affiliation: Synageva BioPharma Corp.

• Name: Amy Simonds
• Affiliation: Synageva BioPharma Corp.

Key inclusion & exclusion criteria

Inclusion criteria:
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 in the protocol
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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 SBC-102 within 14 days prior to the first dose of SBC-102 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: 14.1 Level: SOC Classification code 10027433 Term: Metabolism and nutrition disorders System Organ Class: 10027433 - Metabolism and nutrition disorders
MedDRA version: 14.1 Level: HLGT Classification code 10021605 Term: Inborn errors of metabolism System Organ Class: 10027433 - Metabolism and nutrition disorders
MedDRA version: 14.1 Level: HLT Classification code 10024579 Term: Lysosomal storage disorders System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: recombinant human lysosomal acid lipase (rhLAL)
Product Code: SBC-102
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: not available
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)

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 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.

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

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)

NCT01371825

LAL-CL03

Source(s) of Monetary Support

Synageva BioPharma Corp.