E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
A rare genetic disorder caused by mutations in the gene ALMS1 |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068814 |
E.1.2 | Term | Alstrom syndrome |
E.1.2 | System Organ Class | 100000004850 |
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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 this study is to evaluate the long-term safety and tolerability of PBI-4050, administered orally once daily, in subjects with Alström syndrome (ALMS) who have completed treatment in a preceding Prometic-sponsored ALMS study with PBI-4050. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: - To evaluate the effect of PBI-4050 on metabolic syndrome parameters (fasting plasma glucose, fasting insulin, and HbA1c) - To assess the effect of PBI-4050 on liver stiffness using transient elastography (FibroScan®) - To assess the effect of PBI-4050 on the fat content and fibrosis burden in the liver using magnetic resonance imaging (MRI) - To assess the effect of PBI-4050 on cardiac fibrosis using MRI
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject completed the End of Treatment visit of the preceding Prometic-sponsored ALMS study with PBI-4050. 2. Subject has signed informed consent. 3. Subject has a documented diagnosis of ALMS. 4. Subject must be willing to forego other forms of experimental drug treatment during the study. 5. Female subjects of child-bearing potential who are sexually active with a nonsterile male partner must agree to use adequate birth control throughout the study and for 30 days after the last dose of PBI-4050. Male subjects who have not been vasectomized and partner with a woman of childbearing potential must be willing to use an acceptable contraceptive method throughout the study and for 30 days after the last dose of PBI-4050.
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E.4 | Principal exclusion criteria |
1. Subject discontinued PBI-4050 for safety reasons from any preceding Prometic-sponsored ALMS study with PBI-4050. 2. Subject has had a documented episode of severe hypoglycaemia within 12 months before the Week 1, Day 1 visit and investigator judges that the subject is unable to adequately monitor his/her glucose levels in accordance with local standard practice. Severe hypoglycaemia is defined as an episode of confirmed hypoglycaemia (glucose < 3.0 mmol/L) that required parenteral treatment with intramuscular injection of glucagon or intravenous injection of dextrose, an episode of confirmed hypoglycaemia that did not require parenteral treatment but involved severe neuroglycopenic symptoms, or an episode of unconfirmed hypoglycaemia that resulted in seizure or coma. 3. Subject has uncontrolled hypertension with 170/100 mm Hg at the Week 1, Day 1 visit that, in the judgment of the investigator, makes the subject inappropriate for entry into the study. 4. Woman who is pregnant, breast-feeding, or planning a pregnancy during the course of the study as determined at the Week 1, Day 1 visit. 5. Subject has any condition that, in the investigator’s opinion, is likely to interfere with study conduct and compliance. 6. Subject has a history of an allergic reaction to PBI-4050 or any of its excipients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is safety of PBI‑4050. The following safety variables will be analysed descriptively. • Adverse Events (AEs): All AEs will be coded to a Preferred Term and associated Lower Level Term, and System Organ Class according to the Medical Dictionary for Regulation Activities (MedDRA version 18.0) before the database lock. |
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E.5.2 | Secondary end point(s) |
The following secondary endpoints will be analysed for efficacy and summarized descriptively at each time point as applicable. • Changes from baseline in metabolic syndrome parameters: o FPG o HbA1c o Fasting insulin o C-peptide o HOMA-B and HOMA-S • Change from baseline in the liver stiffness (measured in kPa correlated to fibrosis) by using a transient elastography (FibroScan) • Change from baseline in the fat content and fibrosis burden in liver MRI • Change from baseline in cardiac fibrosis on cardiac MRI.
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | 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 | 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.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 15 |