Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies

Phase 3

Completed

Conditions: Dyslipidemias
High Cholesterol
Hypercholesterolemia
Familial Hypercholesterolemia
Atherosclerotic Cardiovascular Disease

Interventions: Drug: Placebo
Drug: Obicetrapib

Registration Number: NCT05142722

Lead Sponsor: NewAmsterdam Pharma

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2530

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	one placebo tablet once daily
obicetrapib 10mg	Obicetrapib	one 10mg obicetrapib tablet once daily

Primary Outcome Measures

Name	Time	Method
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 84 [PUC]	84 Days	LS mean percent change from baseline to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) in the obicetrapib group compared to the placebo group \[PUC\]. LDL-C level was measured by preparative ultracentrifugation (PUC).

Secondary Outcome Measures

Name	Time	Method
Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 180 [Martin/Hopkins]	180 Days	LS mean percent change from baseline to Day 180 in Low-Density Lipoprotein Cholesterol (LDL-C) in the obicetrapib group compared to the placebo group \[Martin/Hopkins\]. LDL-C value was calculated using the Martin/Hopkins equation unless TG \>= 400 mg/dL or LDL-C \<= 50 mg/dL; where, LDL-C value was measured directly by preparative ultracentrifugation (PUC).
Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 365 [PUC]	365 Days	LS mean percent change from baseline to Day 365 in Low-Density Lipoprotein Cholesterol (LDL-C) in the obicetrapib group compared to the placebo group \[PUC\]. LDL-C level was measured by preparative ultracentrifugation (PUC).
Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 84	84 Days	LS mean percent change from baseline to Day 84 in apolipoprotein B (ApoB) in obicetrapib group compared to the placebo group.
Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 180	180 Days	LS mean percent change from baseline to Day 180 in apolipoprotein B (ApoB) in obicetrapib group compared to the placebo group.
Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 365	365 Days	LS mean percent change from baseline to Day 365 in apolipoprotein B (ApoB) in obicetrapib group compared to the placebo group.
Percent Change in Non-HDL-C From Baseline to Day 84	84 Days	LS mean percent change from baseline to Day 84 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) in obicetrapib group compared to the placebo group.
Percent Change in Non-HDL-C From Baseline to Day 180	180 Days	LS mean percent change from baseline to Day 180 in Non-high-density Lipoprotein Cholesterol (non-HDL-C) in obicetrapib group compared to the placebo group.
Percent Change in Non-HDL-C From Baseline to Day 365	365 Days	LS mean percent change from baseline to Day 365 in Non-high-density Lipoprotein Cholesterol (non-HDL-C) in obicetrapib group compared to the placebo group.
Percent Change in HDL-C From Baseline to Day 84	84 Days	LS mean percent change from baseline to Day 84 in High-density Lipoprotein Cholesterol (HDL-C) in obicetrapib group compared to the placebo group.
Percent Change in HDL-C From Baseline to Day 180	180 Days	LS mean percent change from baseline to Day 180 in High-density Lipoprotein Cholesterol (HDL-C) in obicetrapib group compared to the placebo group.
Percent Change in HDL-C From Baseline to Day 365	365 Days	LS mean percent change from baseline to Day 365 in High-density Lipoprotein Cholesterol (HDL-C) in obicetrapib group compared to the placebo group.
Percent Change in Lp(a) From Baseline to Day 84	84 Days	LS mean percent change from baseline to Day 84 in Lipoprotein (a) \[Lp(a)\] in obicetrapib group compared to the placebo group.
Percent Change in Apolipoprotein A1 (ApoA1) From Baseline to Day 84	84 Days	LS mean percent change from baseline to Day 84 in Apolipoprotein A1 (ApoA1) in obicetrapib group compared to the placebo group.
Percent Change in Total Cholesterol From Baseline to Day 84	84 Days	LS mean percent change from baseline to Day 84 in Total Cholesterol (TC) in obicetrapib group compared to the placebo group.
Percent Change in Total Cholesterol From Baseline to Day 180	180 Days	LS mean percent change from baseline to Day 180 in Total Cholesterol in obicetrapib group compared to the placebo group.
Percent Change in Total Cholesterol From Baseline to Day 365	365 Days	LS mean percent change from baseline to Day 365 in Total Cholesterol in obicetrapib group compared to the placebo group.
Percent Change in Triglycerides From Baseline to Day 84	84 Days	LS mean percent change from baseline to Day 84 in Triglycerides in obicetrapib group compared to the placebo group.
Percent Change in Triglycerides From Baseline to Day 180	180 Days	LS mean percent change from baseline to Day 180 in Triglycerides in obicetrapib group compared to the placebo group.
Percent Change in Triglycerides From Baseline to Day 365	365 days	LS mean percent change from baseline to Day 365 in Triglycerides in obicetrapib group compared to the placebo group.

Trial Locations

Locations (174): Pinnacle Research Group
🇺🇸
Anniston, Alabama, United States
Central Alabama Research
🇺🇸
Birmingham, Alabama, United States
Synexus Clinical Research US, Inc. / Simon Williamson Clinic, PC
🇺🇸
Birmingham, Alabama, United States
The Center for Clinical Trials, Inc
🇺🇸
Saraland, Alabama, United States
Syed Research Consultants, LLC
🇺🇸
Sheffield, Alabama, United States
Clinical Research Institute of Arizona, LLC
🇺🇸
Sun City West, Arizona, United States
Synexus Clinical Research US, Inc. / Orange Grove Family Practice
🇺🇸
Tucson, Arizona, United States
Eclipse Clinical Research
🇺🇸
Tucson, Arizona, United States
American Institute of Research
🇺🇸
Beverly Hills, California, United States
Orange County Research Center
🇺🇸
Tustin, California, United States
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Pinnacle Research Group
🇺🇸Anniston, Alabama, United States