E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
dyslipidemia heterozygous familial hypercholesterolemia (HeFH) atherosclerotic cardiovascular disease (ASCVD) |
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E.1.1.1 | Medical condition in easily understood language |
treatment of high cholesterol and atherosclerotic heart and blood vessel disease (the narrowing of arteries from a buildup of plaque)
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020049 |
E.1.2 | Term | High cholesterol |
E.1.2 | System Organ Class | 10022891 - Investigations |
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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 | 10057079 |
E.1.2 | Term | Heterozygous familial hypercholesterolemia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 26.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051615 |
E.1.2 | Term | Atherosclerotic cardiovascular disease |
E.1.2 | System Organ Class | 10047065 - Vascular 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 | 10076622 |
E.1.2 | Term | Atherosclerotic plaque |
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 |
To evaluate the effect of obicetrapib on LDL-C levels at Day 84. |
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E.2.2 | Secondary objectives of the trial |
-to evaluate the effect of obicetrapib on LDL-C levels at Days 180 and 365 -to evaluate the effect of obicetrapib on ApoB, non-high-density lipoprotein cholesterol (non-HDL-C), HDL-C, total cholesterol (TC), and triglycerides (TG) at Days 84, 180, and 365 -to evaluate the effect of obicetrapib on lipoprotein (a) (Lp[a]) and apolipoprotein A1 (ApoA1) at Day 84 -to evaluate the safety and tolerability profile of obicetrapib in a broadly representative population of adult males and females of all ages, including elderly and very elderly participants, assessed by AEs, events of special interest (ESIs), vital signs (including blood pressure), ECG measurements, and clinical laboratory values
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ABPM substudy This substudy is designed for a non-inferiority assessment in systolic blood pressure from Screening (Visit 1) to Day 270 (Visit 6) between obicetrapib and placebo. |
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E.3 | Principal inclusion criteria |
1. Are willing and able to give written informed consent before initiation of any study-related procedures and willing to comply with all required study procedures; 2. Are male or female ≥18 years of age at Screening (Visit 1); o Females may be enrolled if all 3 of the following criteria are met: -They are not pregnant; -They are not breastfeeding; and -They do not plan on becoming pregnant during the study; o Females of childbearing potential must have a negative urine pregnancy test at Screening (Visit 1); 3. Have underlying HeFH and/or a history of ASCVD 4. Are on maximally tolerated lipid-modifying therapy as an adjunct to a lipid-lowering diet and other lifestyle modifications defined as follows: -A statin at a maximally tolerated stable dose; -Ezetimibe for at least 8 weeks with or without maximally tolerated statin prior to Screening (Visit 1); -Bempedoic acid for at least 8 weeks in combination with a maximally tolerated statin prior to Screening (Visit 1); and/or -A proprotein convertase subtilisin/kexin type 9 (PCSK9)-targeted therapy alone or in combination with other lipid-modifying therapy for at least 4 stable doses prior to Screening (Visit 1)
Note: At least 70% of the participants enrolled into this study must be taking HISs. HISs include the following: - Atorvastatin 40 and 80 mg; and -Rosuvastatin 20 and 40 mg 5. Have a fasting serum LDL-C as follows: o Have a fasting serum LDL-C ≥55 mg/dL (≥1.4 mmol/L) to <100 mg/dL (<2.6 mmol/L) OR non-HDL-C ≥85mg/dL (≥2.2 mmol/L) to <130 mg/dL (<3.4 mmol/L) with at least 1 of the following risk enhancers: -Recent MI (>3 and <12 months prior to Randomization); -Type 2 diabetes mellitus; - Current daily cigarette smoking; - Age of >60 years; - High sensitivity C-reactive protein (hsCRP) >=2.0 mg/L (>=19.0 nmol/L) at Screening (Visit 1) or within 6 months prior to Screening (Visit 1) -Fasting TG >150 mg/dL (>1.7 mmol/L); -Fasting Lp(a) >30 mg/dL (>70 nmol/L); and/or -Fasting HDL-C <40 mg/dL (<1.0 mmol/L); OR -Have a fasting serum LDL-C ≥100 mg/dL (≥2.6 mmol/L) OR non-HDL-C ≥130 mg/dL (≥3.4 mmol/L).; 6. Have fasting TG <500 mg/dL (<5.7 mmol/L) at Screening; and 7. Have an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration equation at Screening (Visit 1).
Other protocol-defined criteria apply. |
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E.4 | Principal exclusion criteria |
1.Have current or any previous history of New York Heart Association class III or IV HF or left ventricular ejection fraction <30%; 2.Have been hospitalized for HF within 5 years prior to Screening (Visit ); 3.Have had any of the following clinical events within 3 months prior to Screening (Visit 1): o Non-fatal MI; o Non-fatal stroke; o Non-elective coronary revascularization; and/or o Hospitalization for unstable angina and/or chest pain; 4.Have uncontrolled severe hypertension, defined as either systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg prior to Randomization (Visit 2) taken as the average of triplicate measurements. One triplicate retest will be allowed during the same visit, at which point if the retest result is no longer exclusionary, the participant may be randomized; 5.Have a formal diagnosis of homozygous familial hypercholesterolemia; 6.Have active liver disease, defined as any known current infectious, neoplastic, or metabolic pathology of the liver; unexplained elevations inalanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 x upper limit of normal (ULN); or total bilirubin >2 x ULN at Screening; 7.Have HbA1c ≥10% (≥0.100 hemoglobin fraction) or a fasting glucose ≥270 mg/dL (≥15.0 mmol/L) at Screening (Visit 1); 8.Have thyroid-stimulating hormone >1.5 x ULN at Screening (Visit 1); 9.Have creatine kinase >3 x ULN at Screening (Visit 1); 10.Have a history of a malignancy that required surgery (excluding local and wide local excision), radiation therapy, and/or systemic therapy during the 3 years prior to Randomization (Visit 2); 11.Have a known history of alcohol and/or drug abuse within 5 years prior to Randomization (Visit 2); 12.Have received treatment with other investigational products or devices within 30 days of Screening (Visit 1) or 5 half lives of the previous investigational product, whichever is longer; 13.Are taking gemfibrozil or have taken gemfibrozil within 30 days of Screening (Visit 1); 14.Have planned use of other investigational products or devices during the course of the study; 15.Have participated in any clinical study evaluating obicetrapib; 16.Have a known allergy or hypersensitivity to the study drug, placebo, or any of the excipients in the study drug or placebo; or 17.Have any participant condition that, according to the Investigator, could interfere with the conduct of the study, such as, but not limited to, the following: o Are unable to communicate or to cooperate with the Investigator; o Are unable to understand the protocol requirements, instructions and study-related restrictions, and the nature, scope, and possible consequences of the study (including participants whose cooperation is doubtful due to drug abuse or alcohol dependency); o Are unlikely to comply with the protocol requirements, instructions,and study-related restrictions (eg, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study); o Have any medical or surgical condition which, in the opinion of the Investigator, would put the participant at increased risk from participating in the study; or o Are directly involved in the conduct of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
the percent change from Baseline to Day 84 in fasting LDL-C in the obicetrapib group compared to the placebo group |
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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. Percent change from Baseline to Days 180 and 365 in LDL-C in the obicetrapib group compared to the placebo group 2.Percent change from Baseline to Days 84, 180 and 365 in ApoB in the obicetrapib group compared to the placebo group; 3.Percent change from Baseline to Day 84, 180 and 365 in non-HDL-C in the obicetrapib group compared to the placebo group; 4.Percent change from Baseline to Days 84, 180, and 365 in HDL-C in the obicetrapib group compared to the placebo group; 5.Percent change from Baseline to Day 84 in Lp(a) and ApoA1 in the obicetrapib group compared to the placebo group; 6.Percent change from Baseline to Days 84, 180, and 365 in fasting TC in the obicetrapib group compared to the placebo group; and 7.Percent change from Baseline to Days 84, 180, and 365 in fasting TG in the obicetrapib group compared to the placebo group. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Baseline, 180, 365 2,3,4,6,7) Baseline, Day 84, 180, 365 5) Baseline, Day 84
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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 | 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 | 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 | 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 | Yes |
E.8.2.3 | Other | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 |
China |
Georgia |
Japan |
United States |
Czechia |
Denmark |
Netherlands |
Poland |
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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 | 4 |
E.8.9.1 | In the Member State concerned days | 9 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 31 |