E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary hyperlipidaemia and mixed dyslipidaemia |
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E.1.1.1 | Medical condition in easily understood language |
High concentrations 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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10058108 |
E.1.2 | Term | Dyslipidaemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 | 10016205 |
E.1.2 | Term | Familial hyperlipidaemia |
E.1.2 | System Organ Class | 100000004850 |
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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 characterize the safety and tolerability of long-term administration of AMG 145
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E.2.2 | Secondary objectives of the trial |
To characterize the long-term administration of AMG 145 as assessed by low density lipoprotein cholesterol (LDL-C) in subjects with primary hyperlipidaemia and subjects with mixed dyslipidaemia |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects will be eligible for the study if they complete a qualifying AMG 145 parent study protocol while still on assigned study medication. |
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E.4 | Principal exclusion criteria |
Subjects will be ineligible for the study if they fulfill any of the following criteria:
- Discontinued assigned study drug during the qualifying study for any reason including an adverse event or serious adverse event
- Female subject is not willing to use an acceptable method(s) of effective birth control during treatment with investigational product (IP) and for an additional 15 weeks after the end of treatment with IP. Female subjects, who have had a hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or who are postmenopausal, are not required to use contraception
o Menopause 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 (e.g., 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
o Acceptable methods of effective birth control include: 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 (pills, shots, implants or patches), intrauterine devices (IUDs), or two (2) barrier methods (each partner must use one barrier
method) with spermicide – males must use a condom with spermicide; females must choose either a diaphragm with spermicide, OR cervical cap with spermicide, OR contraceptive sponge with spermicide. Note: Additional medications given during treatment with evolocumab may alter the contraceptive requirements. These additional medications may require an increase in the number of contraceptive methods and/or length of time that contraception is to be utilized after the last dose of protocol-required therapies. The investigator is to discuss these contraceptive changes with the study subject.
- Female subject is pregnant or breast feeding, planning to become pregnant or planning to breastfeed during treatment with IP and/ or within 15 weeks after the end of treatment with IP.
- Unreliability as a study participant based on the investigator's (or designee’s) knowledge of the subject (eg, inability or unwillingness to adhere to the protocol)
- Disorder that would interfere with understanding and giving informed consent or compliance with protocol requirements
- Have an unstable medical condition, in the judgment of the investigator.
- Subject’s medical condition requires lipid measurement and/or adjustment of background lipid-regulating therapy during the first 12 weeks of study participation
- Known sensitivity to any of the products to be administered during dosing
- Currently enrolled in another investigational device or drug study (excluding AMG 145 parent study), or less than 30 days since ending another investigational device or drug study(s),or receiving other investigational agent(s) |
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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 |
The timepoints vary depending on whether the subject is on the QM or Q2W regimen and has prior experience of self-injection. The following are all the potential timepoints but please refer to the protocol for further details: Day 1, weeks 2, 4, 8, 12, 24, 36, 44, 46, 48, 50, 52, 56, at every quarterly visit, weeks 100, 102, 104, 116, 128, 140, 152, EoS or early termination. |
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E.5.2 | Secondary end point(s) |
• Percent change from baseline in LDL-C at week 48 and week 104
• Change from baseline in LDL-C at week 48 and week 104
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline (day 1) and weeks 48 and 104 |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Background lipid lowering therapy |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 24 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 286 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Czech Republic |
Denmark |
France |
Germany |
Hong Kong |
Hungary |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
New Zealand |
Norway |
Poland |
Russian Federation |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
Turkey |
United Kingdom |
United States |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 4 |