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

NewAmsterdam Pharma354 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

354

Conditions

Dyslipidemias High Cholesterol Hypercholesterolemia Familial Hypercholesterolemia

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (96)

Site 01022

Jonesboro, Arkansas, United States

Site 01015

Toluca Lake, California, United States

Site 01009

Sarasota, Florida, United States

Site 01023

Boise, Idaho, United States

Site 01018

Chicago, Illinois, United States

Site 01012

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 Lp(a) From Baseline to Day 365

LS mean percent change from baseline to Day 365 in Lipoprotein (a) \[Lp(a)\] in obicetrapib group compared to the placebo group

Time frame: 365 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

Precent 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

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

Overview

Conditions

Interventions

Eligibility

Locations (96)

Outcomes

Primary Outcomes

Secondary Outcomes