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 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051614 |
E.1.2 | Term | Arteriosclerotic cardiovascular disease |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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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 |
The primary objective of the trial is to evaluate the effect of AMG 890 administered subcutaneous (SC) every 12 weeks (Q12W) compared with placebo, on percent change from baseline in Lp(a) after 36 weeks of treatment |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of AMG 890 administered SC Q12W compared with placebo, on percent change from baseline in: - Lp(a) after 48 weeks of treatment - Low-density lipoprotein cholesterol (LDL-C) after 36 and 48 weeks of treatment - Apolipoprotein(B) (ApoB) after 36 and 48 weeks of treatment
To characterize the pharmacokinetic (PK) properties of AMG 890 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects are eligible to be included in the study only if all of the following criteria apply:
101 Subject has provided informed consent prior to initiation of any study specific activities/procedures. 102 Age 18 to 80 years 103 Fasting Lp(a) > 150 nmol/L during screening (approximately corresponds to > 60 mg/dL) 104 Atherosclerotic cardiovascular disease based on 1 of the following: • History of coronary revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) • Diagnosis of coronary artery disease with or without prior myocardial infarction • Diagnosis of atherosclerotic cerebrovascular disease • Diagnosis of peripheral arterial disease 105 For subjects receiving lipid-lowering therapy (not required to participate in this study), lipid-lowering therapy, including statin dose, must remain stable per local guidelines for ≥ 4 weeks prior to and during screening |
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E.4 | Principal exclusion criteria |
Subjects are excluded from the study if any of the following criteria apply:
Disease Related 201 Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 during screening 202 History or clinical evidence of active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN), or total bilirubin (TBL) > 2 × ULN during screening 203 Inherited or other bleeding disorders 204 Recent cardiovascular event (myocardial infarction, unstable angina, PCI, CABG, or stroke) within 6 months prior to day 1 205 Planned cardiac surgery, PCI or carotid stenting, or planned major non-cardiac surgery during the study period
Other Medical Conditions 206 Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 5 years prior to day 1 207 Moderate to severe heart failure (New York Heart Association (NYHA) Functional Classification III or IV at day 1) or last known left ventricular ejection fraction < 30% 208 Uncontrolled cardiac arrhythmia defined as recurrent and highly symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular response, or supraventricular tachycardia that are not controlled by medications, in the past 3 months prior to day 1 209 Uncontrolled hypertension at day 1, defined as an average systolic blood pressure of ≥ 160 mmHg or an average diastolic blood pressure of ≥ 100 mmHg at rest after a minimum of 3 measurements 210 Fasting triglycerides ≥ 400 mg/dL (4.5 mmol/L) during screening 211 Type 1 diabetes or poorly controlled (HbA1c ≥ 8.5%) type 2 diabetes mellitus as determined by central laboratory at screening 212 Known active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction in the judgment of the investigator at day 1
Prior/Concomitant Therapy 213 Previously received treatment with antisense oligonucleotides (ASO), siRNA therapies (eg, inclisiran), or any experimental therapy targeting Lp(a) 214 Currently receiving Niacin or < 3 months since last Niacin treatment at day 1 215 Currently undergoing lipid apheresis or < 3 months since last apheresis treatment at day 1 216 Subject has taken a cholesterol ester transfer protein inhibitor (eg, anacetrapib, dalcetrapib, evacetrapib) or lomitapide in the last 12 months prior to day 1
Prior/Concurrent Clinical Study Experience 217 Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. 218 Use of any herbal medicines, vitamins or supplements known to affect lipid metabolism (eg, fish oils > 1000 mg/day, red yeast rice extract), within 30 days prior to day 1
Other Exclusions 219 Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 90 days after the last dose of investigation product. 220 Female subjects of childbearing potential unwilling to use a highly effective method of contraception during treatment and for an additional 90 days after the last dose of investigation product. Refer to Section 11.5 for additional contraceptive information. 221 Female subjects of childbearing potential with a positive serum pregnancy test assessed at Screening or positive urine pregnancy test on day 1. 222 Subject has known sensitivity to any of the products to be administered during dosing. 223 Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the subject and investigator’s knowledge. 224 History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change in Lp(a) from baseline at week 36 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Percentage change from baseline in: - Lp(a) at week 48 - LDL-C at week 36 and week 48 - ApoB at week 36 and week 48
2. PK parameters for AMG 890 including, but not limited to, maximum observed concentration (Cmax), and the area under the concentration time curve (AUC) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Lp(a) at week 48 LDL-C at week 36 and week 48 ApoB at week 36 and week 48 |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Australia |
Canada |
Japan |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |