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

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

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).

Study Overview

• Status: Completed
• Conditions: Dyslipidemias; Hypercholesterolemia; Hyperlipoproteinemias; Lipid Metabolism, Inborn Errors; Familial Hypercholesterolemia; Metabolic Disease; High Cholesterol; Genetic Disease, Inborn; Lipid Metabolism Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Obicetrapib

Detailed Description

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
• Enrollment (Actual): 354
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Brampton, Canada, L6Z 4N5
    • Site 06007
  • Chicoutimi, Canada, G7H 7K9
    • Site 06008
  • Halifax, Canada, B3H 3A7
    • Site 06005
  • Montreal, Canada, H3A 1A1
    • Site 06009
  • Montréal, Canada, H2W 1R7
    • Site 06003
  • Québec, Canada, G1V 4W2
    • Site 06004
  • Sherbrooke, Canada, J1H 5N4
    • Site 06006
  • Vancouver, Canada, V6Z 2C7
    • Site 06001
  • Victoria, Canada, V8T 5G4
    • Site 06002
• Czechia
  • Brno, Czechia, 65691
    • Site 02006
  • Hradec Králové, Czechia, 500 05
    • Site 02002
  • Praha, Czechia, 128 08
    • Site 02003
  • Praha, Czechia, 140 21
    • Site 02005
  • Praha, Czechia, 15006
    • Site 02004
  • Uherské Hradiště, Czechia, 686 01
    • Site 02001
• Georgia
  • Batumi, Georgia, 6000
    • Site 022001
  • Tbilisi, Georgia, 112
    • Site 022003
  • Tbilisi, Georgia, 131
    • Site 022004
  • Tbilisi, Georgia, 144
    • Site 022010
  • Tbilisi, Georgia, 159
    • Site 022006
  • Tbilisi, Georgia, 159
    • Site 022007
  • Tbilisi, Georgia, 159
    • Site 022008
  • Tbilisi, Georgia, 186
    • Site 022002
  • Tbilisi, Georgia, 186
    • Site 022005
  • Tbilisi, Georgia, 579
    • Site 022009
• Netherlands
  • Amsterdam, Netherlands, 1105AZ
    • Site 04001
  • Arnhem, Netherlands, 6815 AD
    • Site 04003
  • Deventer, Netherlands, 7416 SE
    • Site 04002
  • Eindhoven, Netherlands, 5631 BM
    • Site 04004
  • Roosendaal, Netherlands, 4708 AE
    • Site 04005
  • Rotterdam, Netherlands, 3015 GD
    • Site 04006
• Norway
  • Bodø, Norway, 8008
    • Site 023003
  • Oslo, Norway, 587
    • Site 023002
• Poland
  • Białystok, Poland, 15-276
    • Site 05002
  • Zabrze, Poland, 41-800
    • Site 05005
  • Zamosc, Poland, 22-400
    • Site 05001
  • Łódź, Poland, 92-213
    • Site 05003
  • Łódź, Poland, 93-338
    • Site 05004
• South Africa
  • Bloemfontein, South Africa, 9301
    • Site 018001
  • Cape Town, South Africa, 7530
    • Site 018002
  • Centurion, South Africa, 154
    • Site 018009
  • Centurion, South Africa, 157
    • Site 018006
  • Parow, South Africa, 7500
    • Site 018004
  • Somerset West, South Africa, 7130
    • Site 018003
  • Somerset West, South Africa, 7130
    • Site 018005
  • Tongaat, South Africa, 4400
    • Site 018007
  • Umhlanga, South Africa, 4321
    • Site 018008
• Spain
  • Barcelona, Spain, 8036
    • Site 017001
  • Barcelona, Spain, 8907
    • Site 17002
  • Córdoba, Spain, 14004
    • Site 17003
  • Figueras, Spain, 17600
    • Site 17018
  • Granada, Spain, 18014
    • Site 17011
  • Huelva, Spain, 21007
    • Site 17017
  • Huesca, Spain, 22002
    • Site 17012
  • La Coruña, Spain, 15001
    • Site 17004
  • Las Palmas De Gran Canaria, Spain, 35016
    • Site 17008
  • Madrid, Spain, 28034
    • Site 17010
  • Madrid, Spain, 28041
    • Site 17016
  • Málaga, Spain, 29010
    • Site 17007
  • Sabadell, Spain, 8208
    • Site 17013
  • Santiago De Compostela, Spain, 15706
    • Site 17015
  • Sevilla, Spain, 41009
    • Site 17009
  • Sevilla, Spain, 41013
    • Site 17006
  • Valencia, Spain, 46014
    • Site 17014
  • Zaragoza, Spain, 50009
    • Site 17005
• United Kingdom
  • Birmingham, United Kingdom, B21 9RY
    • Site 014006
  • Bristol, United Kingdom, BS2 8HW
    • Site 014012
  • Cardiff, United Kingdom, CF14 4XW
    • Site 014009
  • Chichester, United Kingdom, PO19 6SE
    • Site 014010
  • Dundee, United Kingdom, DD1 9SY
    • Site 014001
  • London, United Kingdom, NW3 2QG
    • Site 014002
  • Manchester, United Kingdom, M23 9LT
    • Site 014003
  • Penzance, United Kingdom, TR19 7HU
    • Site 014011
  • Stevenage, United Kingdom, SG14AB
    • Site 014005
  • West Bromwich, United Kingdom, B71 4HJ
    • Site 014004
  • Wirral, United Kingdom, CH62 6EE
    • Site 014008
• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Site 01022
  • California
    • Toluca Lake, California, United States, 91602
      • Site 01015
  • Florida
    • Sarasota, Florida, United States, 34230
      • Site 01009
  • Idaho
    • Boise, Idaho, United States, 83702
      • Site 01023
  • Illinois
    • Chicago, Illinois, United States, 60602
      • Site 01018
  • Iowa
    • Iowa City, Iowa, United States, 52240
      • Site 01012
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Site 01007
  • Mississippi
    • Port Gibson, Mississippi, United States, 39105
      • Site 01005
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Site 01006
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Site 01011
    • Norfolk, Nebraska, United States, 68701
      • Site 01004
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Site 01002
    • New Providence, New Jersey, United States, 07901
      • Site 01010
  • New York
    • North Massapequa, New York, United States, 11758
      • Site 01001
  • North Carolina
    • Morganton, North Carolina, United States, 28655
      • Site 01020
    • Winston-Salem, North Carolina, United States, 27157
      • Site 01019
  • Tennessee
    • Chattanooga, Tennessee, United States, 37405
      • Site 01008
  • Texas
    • El Paso, Texas, United States, 79905
      • Site 01016
    • Houston, Texas, United States, 76706
      • Site 01013
  • Virginia
    • Suffolk, Virginia, United States, 23434
      • Site 01014

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	84 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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).	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.	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	365 days

Collaborators and Investigators

• Sponsor: NewAmsterdam Pharma
• Investigators: Study Director: Marc Ditmarsch, NewAmsterdam Pharma

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2022
• Primary Completion (Actual): May 28, 2024
• Study Completion (Actual): May 28, 2024

Study Registration Dates

• First Submitted: June 15, 2022
• First Submitted That Met QC Criteria: June 15, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 10, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: LDL-C; Cholesteryl ester transfer protein (CETP) inhibitor; Heterozygous Familial Hypercholesterolemia (HeFH); Obicetrapib; BROOKLYN
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hypercholesterolemia; Dyslipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias
• Other Study ID Numbers: TA-8995-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No