E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with homozygous and heterozygous familial hypercholesterolemia or severe hypercholesterolemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020604 |
E.1.2 | Term | Hypercholesterolemia |
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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 |
To evaluate the safety and efficacy of extended dosing with ISIS 301012 (mipomersen) in patients with familial hypercholesterolemia or severe hypercholesterolemia on concomitant lipid-lowering therapy |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Satisfactory completion of dosing and Week 28 assessments in their initial study (ISIS 301012-CS5, ISIS 301012-CS7 or MIPO3500108) with an acceptable safety profile, per Investigator judgment 2. Able and willing to participate in a 130-week study 3. Satisfy one of the following: (a) Females: Non-pregnant and non-lactating; surgically sterile, post-menopausal, abstinent, or subject or partner compliant with an acceptable contraceptive regimen for 4 weeks prior to, during, and 24 weeks after the last dose of ISIS 301012 OR (b) Males: Surgically sterile, abstinent or subject or partner is utilizing an acceptable contraceptive method during and 24 weeks after the last dose of ISIS 301012 4. Given informed consent, or, in the case of minors, the subject’s parents/legal guardians must be capable and willing of giving informed consent, and, if appropriate for the subject’s age, the subject must be capable of giving consent/ assent for study participation.
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E.4 | Principal exclusion criteria |
1. Have any new condition or worsening of existing condition which in the opinion of the Investigator would make the subject unsuitable for enrollment, or could interfere with the subject participating in or completing the study. 2. Unwilling to limit alcohol consumption for the entire duration of the study, including follow-up: male subjects to a maximum of 2 drinks (20 g) per day, and 8 drinks (80 g) per week; female subjects to a maximum of 1 drink (10 g) per day, and 4 drinks (40 g) per week.
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety Endpoints All AEs and SAEs Platelets, liver transaminases, renal function tests Other laboratory results Vital signs and ECG Efficacy Endpoints Percent reduction in LDL-C, apo B, total cholesterol and non-HDL-C Pharmacokinetic Endpoints Mipomersen plasma concentrations at scheduled timepoints |
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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) | No |
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
| No |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |