E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Growth failure in children due to lysosomal acid lipase deficiency (Wolman disease). |
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E.1.1.1 | Medical condition in easily understood language |
Lysosomal Acid Lipase (LAL) Deficiency |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10027433 |
E.1.2 | Term | Metabolism and nutrition disorders |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10021605 |
E.1.2 | Term | Inborn errors of metabolism |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10024579 |
E.1.2 | Term | Lysosomal storage disorders |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of SBC-102 therapy on overall survival at 12 months of age in children with growth failure due to LAL Deficiency. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term safety of SBC-102 To determine the effect of SBC-102 on growth To characterize the repeat-dose pharmacokinetics of SBC 102 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject’s parent or legal guardian understands the full nature and purpose of the study, including possible risks and side effects of study treatment and procedures, and provides written informed consent/permission prior to any study procedures being performed. 2. Subject completed treatment in study LAL-CL03. OR Subject received treatment with SBC-102 for at least 4 months under an expanded access treatment regimen, 3. Subject had no life-threatening or unmanageable study drug toxicity during treatment with SBC-102 under study LAL-CL03 or an expanded access treatment regimen. 4. Subjects must be <12 months of age unless previously enrolled in study LAL-CL03. |
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E.4 | Principal exclusion criteria |
1. Clinically important concurrent disease including, but not restricted to, congestive heart failure, acute or chronic renal failure, additional severe congenital abnormality, or other extenuating circumstances, including life threatening undernutrition or rapidly progressing liver disease, that in the opinion of the investigator would interfere with study participation. 2. Myeloablative preparation, or other systemic pre-transplant conditioning, for haematopoietic stem cell or liver transplantation. 3. Previous haematopoietic stem cell transplant. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint, the proportion of subjects surviving to 12 months of age, will be derived from the survivor function estimated by the product-limit method. The Kaplan-Meier survival curve will be presented and assumptions for the analysis method will be checked. An exact, two-sided CI will be calculated around the survival rate estimated by the product-limit method. All subjects enrolled in LAL-CL03 who received at least one complete infusion of IMP, regardless of whether they enter the extension study or not, will be considered in the analysis. Subjects who are alive at the time they prematurely end their participation in study LAL-CL03 or LAL-CL05, or who are alive at the end of study LAL-CL03 but do not enroll in study LAL-CL05 will be censored in the survival analysis; age of the subject on the date of the last study visit will be used in the analysis. Any deaths occurring while a subject is treated under study LAL-CL03 or LAL-CL05 will be counted. The survival estimate derived from this study will be compared to the near 0% survival rate reported in the literature for untreated subjects by 12 months of age. The product-limit analysis will be conducted in the Full Analysis Set for all subjects and, as subject numbers permit, for each dose level and other subgroups of interest. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Survival rates at 18 months, 24 months, and other timepoints, as data permit, and median survival time. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Germany |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Subjects may continue treatment under this protocol until SBC-102 receives marketing approval in the region where the subject is being treated (or the Sponsor discontinues pursuit of marketing approval). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 28 |