E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Homozygous Familial Hypercholesterolemia |
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E.1.1.1 | Medical condition in easily understood language |
High cholesterol due to genetic disorder |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 |
Primary:
To evaluate the effect of MBX-8025 on Low Density Lipoprotein Cholesterol (LDL-C).
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E.2.2 | Secondary objectives of the trial |
To evaluate the effects of MBX-8025 on other lipid parameters
To evaluate the safety and tolerability of MBX-8025 in patients with HoFH.
To evaluate steady-state trough plasma levels of MBX-8025 and its metabolites, M1, M2 and M3
Exploratory:
To evaluate the effects of MBX-8025 on proprotein convertase subtilisin/kexin type 9 (PCSK9) and high sensitivity C reactive protein (hs-CRP).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusions:
1. Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
2. Male or female with HoFH confirmed by genotype (two mutants alleles at the LDL-Receptor gene locus).
3. 18 years of age or older.
4. Existing lipid lowering therapies (statins, cholesterol absorption inhibitors, bile acid sequestrants, nicotinic acid and their combinations, LDL-C apheresis) on a stable regimen for at least four weeks before screening visit.
5. Stable lipid lowering diet compatible with a Step I diet of the AHA.
6. Fasting LDL-C ≥ 4.8 mmol/L (≥ 185.6 mg/dL) during screening.
7. For females of reproductive potential, use of at least one barrier contraceptive and a second effective birth control method during the study and for at least two weeks after the last dose. For male subjects, use of appropriate contraception (e.g., condoms) so their female partners of reproductive potential do not become pregnant during the study and for at least two weeks after the last dose.
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E.4 | Principal exclusion criteria |
Exclusions:
1. Treatment with lomitapide or mipomersen within two months of screening.
2. Heart Failure (HF) with New York Heart Association (NYHA) class III and class IV or a left ventricular ejection fraction (LVEF) of less than 30%.
3. Uncontrolled cardiac arrhythmia during the past three months of screening.
4. Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft or stroke during the past three months prior to Screening Visit.
5. Planned cardiac surgery, or planned revascularization, in the next four months.
6. Uncontrolled hypertension.
7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 times the upper limit of normal (ULN).
8. Unexplained creatine kinase (CK) ≥ 5 times the ULN.
9. For females, pregnancy or breast-feeding.
10. Any other condition(s) that would compromise the safety of the patient or compromise the quality of the clinical study as judged by the Investigator and/or Medical Monitor
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E.5 End points |
E.5.1 | Primary end point(s) |
The effect of MBX-8025 on Serum LDL-C. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
All visits after first drug administration: visit 4-10 |
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E.5.2 | Secondary end point(s) |
The effect of MBX-8025 on other lipid parameters, safety and tolerability and PK of MBX-8025 and it's metabolites. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All visits after first drug administration: visit 4-10 |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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.8.2.4 | 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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 |
Netherlands |
Norway |
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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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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |