E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Familial HDL-c Deficiency |
|
E.1.1.1 | Medical condition in easily understood language |
genetic defect for lack of HDL cholesterol |
|
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020604 |
E.1.2 | Term | Hypercholesterolemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
A pilot study to investigate the safety and efficacy of CER-001 infusions in patients with familial HDL-c deficiency due to defects in genes coding for ApoA-I, ABCA1 or LCAT. |
|
E.2.2 | Secondary objectives of the trial |
• markers of vascular endpoints
o vessel wall inflammation (assessed by PET-CT) and
o atherosclerosis (assessed by 3T-carotid MRI)
• ApoA-I levels (pharmacokinetic parameters)
• lipids and lipoproteins (pharmacodynamics parameters)
• cholesterol flux
• dermatologic and ocular features of HDL deficiency
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female subjects with genetically confirmed homozygous familial HDL-c deficiency.
• Females of childbearing potential that agree and commit to use an acceptable form of birth control for the entire study. Acceptable forms of birth control for this study are defined as a barrier method plus hormonal therapy (implants, injections, oral contraceptives and IUDs) or abstinence. |
|
E.4 | Principal exclusion criteria |
• Use of an investigational agent within 30 days of the first dose of CER-001.
• Females who are pregnant, breastfeeding, or plan to become pregnant during the study.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Percent change in carotid total vessel area (TVA) and normalized wall index (NWI) assessed by MRI from baseline to Week 26
• Percent change in carotid target to background ratio (TBR) assessed by PET-CT from baseline to Week 4
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline day 1, week 4, week 26. |
|
E.5.2 | Secondary end point(s) |
Secondary Efficacy Measurements:
• Percent change in carotid TVA and NWI assessed by MRI from baseline to Week 4
• Changes in pharmacodynamic parameters over time;
• Change in cholesterol flux (TICE and TCE) from baseline to Week 26; and
• Changes in dermatologic and ocular features from baseline to Week 4
Pharmacokinetic Measurements:
• Single dose pharmacokinetic parameters following the first and final doses
Safety and Tolerance:
• Adverse event profile
• Changes in clinical laboratory measurements
• Development of antibodies to ApoA-I and their neutralizing potential |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline day 1, week 4, week 26. |
|
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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 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
|
Last visit of the last subject undergoing the trial |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |