Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies.

Study Overview
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Brief Summary
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This study will be a placebo-controlled, double-blind, randomized, phase 3 study to Evaluate the Efficacy, Safety, and Tolerability of Obicetrapib in Participants with a History of Heterozygous Familial Hypercholesterolemia (HeFH).

Detailed Description
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This study will be a placebo-controlled, double-blind, randomized, phase 3 study in participants with HeFH to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to diet and maximally tolerated lipid-lowering therapy. The screening period for this study will take up to 14 days. Afterwards, patients will be randomized to placebo or 10 mg obicetrapib for an 365-day treatment period. After the treatment period, participants will have an end-of-study follow-up visit.

Official Title
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A Placebo-Controlled, Double-Blind, Randomized, Phase 3 Study to Evaluate the Effect of 10 mg Obicetrapib in Participants With a History of HeFH Who Are Not Adequately Controlled by Their Lipid Modifying Therapies

Conditions
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Metabolic Disease, Dyslipidemias, High Cholesterol, Hypercholesterolemia, Familial Hypercholesterolemia, Lipid Metabolism Disorder, Lipid Metabolism, Inborn Errors, Genetic Disease, Inborn, Hyperlipoproteinemias

Intervention / Treatment
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* Drug: Obicetrapib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a history of heterozygous familial hypercholesterolemia (HeFH) by 1) Genotyping (not a screening assessment), WHO Criteria/Dutch Lipid Clinical Network Criteria with a score of > 8 points; and/or Simon Broome Register Diagnostic Criteria for definite or possible Familial Hypercholesterolemia (FH) Maximally tolerated lipid Modifying therapy for at least 8 weeks prior to screening such as: ATV (40 or 80), or (ROS 20 or 40 mg), Ezetimide, Bempedoic Acid, PCSK9 targeted therapy for at least 4 doses Fasting serum LDL-C ≥70 mg/dL (≥1.80 mmol/L) Exclusion Criteria: New York Heart Association class II or IV heart failure or last known left ventricular ejection fraction < 30%; Hospitalized for heart failure within 5 years prior to Screening Major adverse cardiac event (MACE) within 3 months prior to Screening; HbA1c ≥10%, or fasting glucose Formal diagnosis of homozygous familial hypercholesterolemia (HoFH) Uncontrolled severe hypertension, defined as either systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥100 mmHg prior to Randomization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo-Controlled, double-blind, randomized
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>one placebo tablet once daily | Drug: Placebo<br>* placebo tablet made to resemble active<br>|
| Experimental: Obicetrapib 10 mg<br>one 10 mg Obicetrapib tablet once daily | Drug: Obicetrapib<br>* 10 mg Obicetrapib tablet<br>* Other names: CETP-inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Low Density Lipoprotein-Cholesterol (LDL-C) | Obicetrapib compared to placebo on Low Density Lipoprotein-Cholesterol (LDL-C) | Percent change from baseline to Day 84 in Low Density Lipoprotein-Cholesterol (LDL-C) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apolipoprotein B (ApoB) | obicetrapib compared to placebo on ApoB | Percent change from baseline to Day 84, 180, and 365 in ApoB | 
| non-HDL-C | obicetrapib compared to placebo on non-HDL-C | Percent change from baseline to Day 84, 180, and 364 in non-HDL-C | 
| HDL-C | obicetrapib compared to placebo on HDL-C | Percent change from baseline to Day 84, 180, and 365 in HDL-C | 
| Lp(a) | obicetrapib compared to placebo on Lp(a) | Percent change from baseline to Day 84 and 365 in Lp(a) | 
| Total Cholesterol | obicetrapib compared to placebo on Total Cholesterol | Percent change from baseline to Day 84, 180, and 365 in Total Cholesterol | 
| Triglycerides | obicetrapib compared to placebo on Triglycerides | Percent change from baseline to Day 84, 180, and 365 in Triglycerides | 
| Low Density Lipoprotein-Cholesterol (LDL-C) | obicetrapib compared to placebo on Low Density Lipoprotein-Cholesterol (LDL-C) | Percent change from baseline to Day 180, and 365 in Low Density Lipoprotein-Cholesterol (LDL-C) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obicetrapib, BROOKLYN, Cholesteryl ester transfer protein (CETP) inhibitor, Heterozygous Familial Hypercholesterolemia (HeFH), LDL-C