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

NewAmsterdam Pharma2,530 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

2,530

Conditions

Dyslipidemias High Cholesterol Hypercholesterolemia

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (181)

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

Outcomes

Primary Outcomes

Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 84 [PUC]

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).

Time frame: 84 Days

Secondary Outcomes

Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 180 [Martin/Hopkins]

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).

Time frame: 180 Days

Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 365 [PUC]

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).

Time frame: 365 Days

Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 84

LS mean percent change from baseline to Day 84 in apolipoprotein B (ApoB) in obicetrapib group compared to the placebo group.

Time frame: 84 Days

Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 180

LS mean percent change from baseline to Day 180 in apolipoprotein B (ApoB) in obicetrapib group compared to the placebo group.

Time frame: 180 Days

Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 365

LS mean percent change from baseline to Day 365 in apolipoprotein B (ApoB) in obicetrapib group compared to the placebo group.

Time frame: 365 Days

Percent Change in Non-HDL-C From Baseline to Day 84

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.

Time frame: 84 Days

Percent Change in Non-HDL-C From Baseline to Day 180

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.

Time frame: 180 Days

Percent Change in Non-HDL-C From Baseline to Day 365

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.

Time frame: 365 Days

Percent Change in HDL-C From Baseline to Day 84

LS mean percent change from baseline to Day 84 in High-density Lipoprotein Cholesterol (HDL-C) in obicetrapib group compared to the placebo group.

Time frame: 84 Days

Percent Change in HDL-C From Baseline to Day 180

LS mean percent change from baseline to Day 180 in High-density Lipoprotein Cholesterol (HDL-C) in obicetrapib group compared to the placebo group.

Time frame: 180 Days

Percent Change in HDL-C From Baseline to Day 365

LS mean percent change from baseline to Day 365 in High-density Lipoprotein Cholesterol (HDL-C) in obicetrapib group compared to the placebo group.

Time frame: 365 Days

Percent Change in Lp(a) From Baseline to Day 84

LS mean percent change from baseline to Day 84 in Lipoprotein (a) \[Lp(a)\] in obicetrapib group compared to the placebo group.

Time frame: 84 Days

Percent Change in Apolipoprotein A1 (ApoA1) From Baseline to Day 84

LS mean percent change from baseline to Day 84 in Apolipoprotein A1 (ApoA1) in obicetrapib group compared to the placebo group.

Time frame: 84 Days

Percent Change in Total Cholesterol From Baseline to Day 84

LS mean percent change from baseline to Day 84 in Total Cholesterol (TC) in obicetrapib group compared to the placebo group.

Time frame: 84 Days

Percent Change in Total Cholesterol From Baseline to Day 180

LS mean percent change from baseline to Day 180 in Total Cholesterol in obicetrapib group compared to the placebo group.

Time frame: 180 Days

Percent Change in Total Cholesterol From Baseline to Day 365

LS mean percent change from baseline to Day 365 in Total Cholesterol in obicetrapib group compared to the placebo group.

Time frame: 365 Days

Percent Change in Triglycerides From Baseline to Day 84

LS mean percent change from baseline to Day 84 in Triglycerides in obicetrapib group compared to the placebo group.

Time frame: 84 Days

Percent Change in Triglycerides From Baseline to Day 180

LS mean percent change from baseline to Day 180 in Triglycerides in obicetrapib group compared to the placebo group.

Time frame: 180 Days

Percent Change in Triglycerides From Baseline to Day 365

LS mean percent change from baseline to Day 365 in Triglycerides in obicetrapib group compared to the placebo group.

Time frame: 365 days

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

Overview

Conditions

Interventions

Eligibility

Locations (181)

Outcomes

Primary Outcomes

Secondary Outcomes