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 |
Abnormal amounts of lipids in the blood |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020604 |
E.1.2 | Term | Hypercholesterolemia |
E.1.2 | System Organ Class | 100000004861 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058110 |
E.1.2 | Term | Dyslipidemia |
E.1.2 | System Organ Class | 100000004861 |
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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 describe the safety and tolerability of long-term administration of evolocumab. |
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E.2.2 | Secondary objectives of the trial |
- To describe the effects of long-term administration of evolocumab on low density lipoprotein cholesterol (LDL-C) levels.
- To describe the effects of long-term administration of evolocumab in subjects achieving LDLC level of < 40 mg/dL (1.03 mmol/L).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject has provided informed consent prior to initiation of any study specific activities/procedures
-Subject has completed FOURIER while still receiving assigned Investigational Product. |
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E.4 | Principal exclusion criteria |
- Permanent discontinuation of Investigational Product during FOURIER for any reason including an adverse event or serious adverse event
- Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded
- Subject not likely to be available to complete protocol required study visits or procedures, and/or to comply with required study to the best of the subject and investigator's knowledge
- History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
-Known sensitivity to any of the active substances or excipients (eg. sodium acetate) to be administered during dosing.
- Female subject is pregnant or breast feeding, planning to become pregnant or planning to breastfeed during treatment with evolocumab and within 15 weeks after the end of treatment with evolocumab.
- Female subject of childbearing potential not willing to use an acceptable method(s) of effective birth control during treatment with evolocumab and for an additional 15 weeks after the end of treatment with IP. Female subjects of nonchildbearing potential are not required to use contraception during the study and include those who have had a hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or who are postmenopausal. Postmenopausal is defined as 12 months of spontaneous and continuous amenorrhea in a female ≥ 55 years old; or age < 55 years but no spontaneous menses for at least 2 years; or age < 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (eg, spontaneous or secondary to hysterectomy), and with postmenopausal gonadotropin levels (luteinizing hormone and follicle stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (<5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved. Acceptable methods of effective birth control include: true sexual abstinence (when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (eg.,calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception]), surgical contraceptive methods (vasectomy or bilateral tubal ligation), use of hormonal birth control methods (oral, intravaginal, transdermal, injectable, or implantable), intrauterine devices (IUDs), intrauterine hormonal releasing system (IUS) or two (2) barrier methods (each partner must use one barrier method) and at least one of barrier methods must incude spermicide – males must use a condom; females must choose either aDiaphragm, OR Cervical cap, OR Contraceptive sponge (a female condom is not an option because of the risk of tearing when both partners use a condom). If spermicide is not available in the country or region, the two barrier method without spermicide is acceptable. Note: Additional medications given during treatment with evolocumab may alter the contraceptive requirements. These additional medications may require the use of highly effective methods of contraception and/or an increase in the length of time that contraception is to be utilized or length of time that breastfeeding is to be avoided after the last dose of protocol-required therapies. The investigator is to discuss these contraceptive changes with the study subject. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Subject incidence of adverse events |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
260 weeks (approximately 5 years) |
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E.5.2 | Secondary end point(s) |
- Percent change of LDL-C from baseline at each scheduled scheduled visits - Achievment of an LDL-C < 40 mg/dL(1.03 mmol/L) at each scheduled visits.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline and each scheduled visit |
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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 | 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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 61 |
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 |
Czech Republic |
Hungary |
Poland |
Russian Federation |
Slovakia |
Ukraine |
United States |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |