E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lysosomal Acid Lipase (LAL) Deficiency is a rare autosomal recessive lipid storage disorder that is caused by deficient activity or absence, of the lysosomal enzyme, LAL. It is an extremely rare disorder, with an estimated prevalence of less than 0.2 lives per 100,000. Although a single disease, LAL Deficiency has two phenotypes, Cholesteryl Ester Storage Disease (CESD) and Wolman Disease (WD). Both forms of the disease lead to the accumulation of fats, in various tissues and cell types. |
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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 |
The primary objective of the study is to evaluate the safety and tolerability of SBC-102 in patients with liver dysfunction due to LAL deficiency (vital signs, physical examination, clinical laboratory tests, immunogenicity tests, adverse event assessment, concomitant medications). |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to characterise the pharmacokinetics of SBC-102 delivered by intravenous infusion after single and multiple doses [pre and post infusion Day 0 and 21].
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient understands the full nature and purpose of the study, including possible risks and side effects, and is willing and able to comply with all study procedures and provide informed consent
2. Male or female patients ≥ 18 years ≤ 65 years of age
3. Documented decreased LAL activity relative to the normal range of the lab performing the assay or documented result of molecular genetic testing confirming diagnosis of LAL deficiency
4. Evidence of liver involvement based on clinical presentation and/or laboratory test results (ALT or AST ≥ 1.5xULN)
5. If on a statin or ezetimibe, must be on a stable dose for at least 4 weeks prior to screening
6. All women must have negative serum pregnancy test at screening and cannot be breast feeding
7. Female subjects of childbearing potential must agree to use a highly effective and approved contraceptive method(s) for the duration of the study and continue to use for 30 days after last dose of study drug. A highly effective method of contraception is defined as:
a. strict abstinence;
b. bilateral tubal ligation;
c. combined oral contraceptives (estrogens and progesterone), implanted or injectable contraceptives on a stable dose for at least 1 month prior to the Screening visit;
d. hormonal intra uterine device (IUD) inserted at least 1 month prior to the Screening visit;
e. vasectomized partner for at least 3 months prior to the Screening visit.
Male subjects, and their partners must be using, and continue to use for 30 days after last dose of study drug, an acceptable method of birth control. Women considered not of childbearing potential must be surgically sterile (total hysterectomy, bilateral salpingo-oophorectomy) or post-menopausal, which is defined as a complete cessation of menstruation for at least one year after the age of 45 years.
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E.4 | Principal exclusion criteria |
1. Clinically significant concurrent disease, serious inter-current illness, concomitant medications or other extenuating circumstances that, in the opinion of the Investigator, would either interfere with study participation or the interpretation of the effects of SBC-102.
2. Clinically significant abnormal values on laboratory screening tests, other than liver function or lipid panel tests. Subjects with an abnormal laboratory value that is of borderline significance may be allowed to undergo repeat testing once within a 30 day period.
3. Patient has participated in a study employing an investigational drug within 30 days of the screening
4. Child-Pugh Class C or AST and/or ALT persistently elevated > 3xULN at screening (2 or more occasions)
5. Previous hematopoietic bone marrow or liver transplant
6. Patient has received prior treatment with enzyme replacement therapy
7. Subject has a total score of 8 or more on a screening Alcohol Use Disorders Identification Test (AUDIT)
8. Patients with known hypersensitivity to eggs
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective is to evaluate the safety and tolerability of SBC-102 in patients with liver dysfunction due to LAL deficiency.
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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) |
To characterize the pharmacokinetics of SBC-102 delivered by IV infusion after single and multiple doses |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visit 2 and Visit 6:
- Immediately pre-dose
- At 10(±1), 15(±1), 20(±1), 40(±2), 60(±2) and 90(±2 minutes during the infusion and at the end of infusion
• At 5(±1), 10(±1), 20(±1), 30(±1), 40(±2), 60(±2) and 120(±2) minutes of the infusion |
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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 | No |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | No |
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 | Yes |
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 | 4 |
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 |
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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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Last visit of last subject. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |