Randomized Study to Evaluate the Effect of Obicetrapib 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 in participants with underlying heterozygous familial hypercholesterolemia (HeFH) and/or ASCVD to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to diet and maximally tolerated lipid-lowering therapy

Detailed Description
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This study will be a placebo-controlled, double-blind, randomized, phase 3 study in participants with underlying HeFH and/or ASCVD 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 28 days. Afterwards patients will be randomized to placebo or 10 mg obicetrapib for a 365 day treatment period. After the treatment period, patients 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 10mg Obicetrapib in Participants With HeFH and/or ASCVD Who Are Not Adequately Controlled by Their Lipid Modifying Therapies

Conditions
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Hypercholesterolemia, Familial Hypercholesterolemia, Atherosclerotic Cardiovascular Disease, Dyslipidemias, High Cholesterol

Intervention / Treatment
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* Drug: Placebo
* Drug: Obicetrapib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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; Have underlying heterozygous familial hypercholesterolemia (HeFH) and/or a history of established ASCVD 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 for at least 8 weeks prior to Screening Atorvastatin 40 and 80 mg; and Rosuvastatin 20 and 40 mg; Ezetimibe with or without maximally tolerated statin for at least 8 weeks prior to Screening Bempedoic acid with a maximally tolerated statin for at least 8 weeks prior to Screening A PCSK-9 targeted therapy alone or in combination with other lipid-modifying therapy for at least 4 stable doses prior to Screening Have a fasting serum LDL-C at Screening as follows: Fasting serum LDL-C ≥ 55 to < 100 mg/dL (≥1.4 to <2.6 mmol/L) OR non-HDL-C ≥85 mg/dL (≥2.2 mmol/L) to < 130 mg/dL (<3.4 mmol/L) with at least 1 of the following risk enhancers at Screening; 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 or within 6 months prior to Screening Fasting triglycerides (TG) > 150 mg/dL (>1.7 mmol/L); Fasting lipoprotein (a) > 30 mg/dL (>70 nmol/L); and/or Fasting HDL-C < 40 mg/dL (<1.0 mmol/L); OR Fasting serum LDL-C ≥ 100 mg/dL (≥2.6 mmol/L) or non-HDL-C ≥130 mg/dL (≥3.4 mmol/L) Fasting triglyceride (TG) < 500 mg/dL (<5.7 mmol/L) at Screening; and Have an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 at Screening Exclusion Criteria: New York Heart Association class III or IV heart failure or 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; Uncontrolled severe hypertension, defined as either systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥100 mmHg prior to Randomization; Formal diagnosis of homozygous familial hypercholesterolemia (HoFH); Active liver disease; HbA1c ≥10% or a fasting glucose ≥270 mg/dL (≥15.0 mmol/L) at Screening; Thyroid-stimulating hormone >1.5 X upper limit of normal (ULN) at Screening; Creatine kinase > 3 X upper limit of normal (ULN) at Screening; History of malignancy that required surgery (excluding local and wide local excision), radiation therapy, and/or systemic therapy during the 3 years prior to Randomization; Known history of alcohol and/or drug abuse within 5 years prior to Randomization Received treatment with other investigational products or devices within 30 days of Screening or 5 half-lives of the previous investigational product, whichever is longer; Are taking gemfibrozil or have taken gemfibrozil within 30 days of Screening Planned use of other investigational products or devices during the course of the study; Participated in any clinical trial evaluating obicetrapib; or Known allergy or hypersensitivity to obicetrapib, placebo, or any of the excipients in obicetrapib or placebo Any condition that, according to the Investigator, could interfere with the conduct of the study

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 10mg<br>one 10mg obicetrapib tablet once daily | Drug: Obicetrapib<br>* 10mg obicetrapib tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-C | obicetrapib compared to placebo on LDL-C | Percent change from baseline to Day 84 in LDL-C | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-C | obicetrapib compared to placebo on LDL-C | Percent change from baseline to Days 180 and 365 in LDL-C | 
| apolipoprotein B (ApoB) | obicetrapib compared to placebo on ApoB | Percent change from baseline to Day 84, Day 180, and Day 365 in ApoB | 
| non-HDL-C | obicetrapib compared to placebo on non-HDL-C | Percent change from baseline to Day 84, Day 180, and Day 365 in non-HDL-C | 
| HDL-C | obicetrapib compared to placebo on HDL-C | Percent change from baseline to Day 84, Day 180, and Day 365 in HDL-C | 
| Total Cholesterol | obicetrapib compared to placebo on TC | Percent change from baseline to Day 84, Day 180, and Day 365 in TC | 
| Triglycerides | obicetrapib compared to placebo on TG | Percent change from baseline to Day 84, Day 180, and Day 365 in TG | 
| Lipoprotein A [Lp(a)] | obicetrapib compared to placebo on Lp(a) | Percent change from baseline to Day 84 in Lp(a) | 
| Apolipoprotein A1 (ApoA1) | obicetrapib compared to placebo on ApoA1 | Percent change from baseline to Day 84 in ApoA1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obicetrapib, BROADWAY, Cholesteryl ester transfer protein (CETP) inhibitor, Heterozygous Familial Hypercholesterolemia (HeFH), Atherosclerotic Cardiovascular Disease (ASCVD)