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

NCT ID: NCT05142722

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 2530 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-15
• Study Completion Date: 2024-09-26

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.

Conditions

Dyslipidemias; High Cholesterol; Hypercholesterolemia; Familial Hypercholesterolemia; Atherosclerotic Cardiovascular Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

one placebo tablet once daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo tablet made to resemble active

obicetrapib 10mg

one 10mg obicetrapib tablet once daily

Group Type: EXPERIMENTAL

Obicetrapib

Intervention Type: DRUG

10mg obicetrapib tablet

Interventions

Placebo

placebo tablet made to resemble active

Intervention Type: DRUG

Obicetrapib

10mg obicetrapib tablet

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NewAmsterdam Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Ditmarsch

Role: STUDY_DIRECTOR

NewAmsterdam Pharma

Locations

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

Synexus Clinical Research US, Inc.

Vista, California, United States

Excel Medical Clinical Trials

Boca Raton, Florida, United States

Pioneer Clinical Studies

Ft. Pierce, Florida, United States

New Generation of Medical Research

Hialeah, Florida, United States

East Coast Institute for Research, LLC

Jacksonville, Florida, United States

East Coast Institute for Research, LLC - Jacksonville University Blvd

Jacksonville, Florida, United States

East Coast Institute for Research- Lake City

Lake City, Florida, United States

ClinCloud LLC

Maitland, Florida, United States

Columbus Clinical Services, LLC

Miami, Florida, United States

Kendall South Medical Center, Inc.

Miami, Florida, United States

Advanced Research Institute Inc

New Port Richey, Florida, United States

Progressive Medical Research

Port Orange, Florida, United States

East Coast Institute for Research

Saint Augustine, Florida, United States

Synexus Clinical Research US, Inc.

The Villages, Florida, United States

Synexus Clinical Research US, Inc.

Atlanta, Georgia, United States

East Coast Institute for Research - Canton

Canton, Georgia, United States

Centricity Research

Columbus, Georgia, United States

East Coast Institute for Research, LLC

Macon, Georgia, United States

Alta Pharmaceutical Research Center

Peachtree Corners, Georgia, United States

SouthCoast Health

Savannah, Georgia, United States

Biofortis, Inc

Addison, Illinois, United States

Evanston Premier Healthcare Research LLC

Skokie, Illinois, United States

Synexus Clinical Research US, Inc.

Evansville, Indiana, United States

Midwest Institute for Clinical Research

Indianapolis, Indiana, United States

Cotton-O'Neil Clinical Research Center

Topeka, Kansas, United States

Louisville Metabolic and Atherosclerosis Research Center (L-MARC)

Louisville, Kentucky, United States

Research Integrity, LLC

Owensboro, Kentucky, United States

Cambridge Medical Trials

Alexandria, Louisiana, United States

Grace Research, LLC

Bossier City, Louisiana, United States

Tandem Clinical Research

Marrero, Louisiana, United States

Tandem Clinical Research GI - Metairie

Metairie, Louisiana, United States

Grace Research, LLC

Shreveport, Louisiana, United States

Southern Clinical Research, LLC

Zachary, Louisiana, United States

Northern Light Cardiology

Bangor, Maine, United States

Privia Medical Group, LLC

Silver Spring, Maryland, United States

Oakland Medical Research

Troy, Michigan, United States

Arcturus Healthcare, Troy Internal Medicine Research Division

Troy, Michigan, United States

AB Clinical Trials

Las Vegas, Nevada, United States

Inspira Medical Centers dba Internal Medicine Associates, P.A.

Bridgeton, New Jersey, United States

Mid Hudson Medical Research

New Windsor, New York, United States

Synexus Clinical Research US, Inc.

New York, New York, United States

Tandem Clinical Research GI, LLC

New York, New York, United States

Chear Center LLC

The Bronx, New York, United States

Diabetes and Endocrinology Consultants, P.C.

Morehead City, North Carolina, United States

Lillestol Research, LLC

Fargo, North Dakota, United States

Summit Research Group, LLC

Stow, Ohio, United States

Monument Health Clinical Research

Rapid City, South Dakota, United States

Cardiovascular Research of Knoxville, LLC

Powell, Tennessee, United States

Amarillo Heart Clinical Research Institute, Inc

Amarillo, Texas, United States

Inquest Clinical Research

Baytown, Texas, United States

Apex Mobile Clinical Research

Bellaire, Texas, United States

Javara Inc.

Conroe, Texas, United States

Prime Revival Research Institute, LLC

Coppell, Texas, United States

Thyroid, Endocrinology & Diabetes, PA

Dallas, Texas, United States

Northwest Houston Clinical Research

Tomball, Texas, United States

Synexus Clinical Research US, Inc.

Salt Lake City, Utah, United States

Manassas Clinical Research Center

Manassas, Virginia, United States

Hampton Roads Center for Clinical Research

Suffolk, Virginia, United States

Universal Research Group, LLC

Tacoma, Washington, United States

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Peking University First Hospital

Beijing, , China

The First Affiliated Hospital of Bengbu Medical College

Bengbu, , China

Cangzhou Central Hospital

Cangzhou, , China

China-Japan Union Hospital Of Jilin University

Changchun, , China

The First People's Hospital of Changde City

Changde, , China

The Second People's Hospital of Changzhou

Changzhou, , China

Affiliated Hospital of Chifeng University

Chifeng, , China

Chifeng Municipal Hospital

Chifeng, , China

Daqing People's Hospital

Daqing, , China

Foshan First People's Hospital

Foshan, , China

Guangdong Provincial People's Hospital

Guangzhou, , China

The Third Affiliated Hospital of Guangzhou Medical university

Guangzhou, , China

Heilongjiang Provincial Hospital

Harbin, , China

The First Affiliated Hospital Of University Of South China

Hunan, , China

Jinan Central Hospital

Jinan, , China

Hebei Petro China Central Hospital

Langfang, , China

Lishui Central Hospital

Lishui, , China

Luoyang Third People's Hospital

Luoyang, , China

The First affiliated Hospital of Nanyang Medical College

Nanyang, , China

Panjin Liaoyou Gem Flower Hospital

Panjin, , China

Huabei Petroleum Administration Bureau General Hospital

Renqiu, , China

Tianjin People's Hospital

Tianjin, , China

Tianjin Fourth Central Hospital

Tianjin, , China

Wenzhou People's Hospital

Wenzhou, , China

Xi'an Gaoxin Hospital

Xi'an, , China

Xianyang Hospital of Yan 'an University

Xianyang, , China

The Third Affiliatied Hospital of Xinxiang Medical University

Xinxiang, , China

Zaozhuang Municipal Hospital

Zaozhuang, , China

Hornicka nemocnice s poliklinikou Bilina s.r.o.

Bílina, , Czechia

Medicus Services SRO

Brandýs nad Labem, , Czechia

Centrum pro zdravi - kardiologie s.r.o.

Brno, , Czechia

Kardiologicka ambulance Brno s.r.o.

Brno, , Czechia

Cevni ambulance - MATMED s.r.o.

Hodonín, , Czechia

MUDr. Tomas Edelsberger - diabetologicka ambulance

Krnov, , Czechia

KARDIOLOGIE - LIBEREC s.r.o.

Liberec, , Czechia

PreventaMed s.r.o.

Olomouc, , Czechia

CCR Ostrava s.r.o.

Ostrava, , Czechia

CCR Czech a.s.

Pardubice, , Czechia

Kardiologie COR s.r.o.

Prague, , Czechia

Aarhus University Hospital

Aarhus, , Denmark

Amager Hospital

Copenhagen S, , Denmark

Sydvestjysk Hospital

Esbjerg, , Denmark

Godstrup Regional Hospital (Gødstrup)

Herning, , Denmark

Viborg Regional Hospital

Viborg, , Denmark

Health LTD

Batumi, , Georgia

JSC Curatio

Tbilisi, , Georgia

Acad. G. Chapidze Emergency Cardiology Center LTD

Tbilisi, , Georgia

Bokhua Memorial Cardiovascular Center LTD

Tbilisi, , Georgia

Vitamedi LTD

Tbilisi, , Georgia

Medi Club Georgia LLC

Tbilisi, , Georgia

Georgian-Ducht Hospital LTD

Tbilisi, , Georgia

The First Medical Center LTD

Tbilisi, , Georgia

Adapti LTD

Tbilisi, , Georgia

Chiba University Hospital

Chiba, , Japan

New Tokyo Heart Clinic

Chiba, , Japan

Japan Community Health Care Organization Kyushu Hospital

Fukuoka, , Japan

Hiroshima Prefectural Hospital

Hiroshima, , Japan

Hiroshima University Hospital

Hiroshima, , Japan

Hyogo Prefectural Harima-Himeji General Medical Center

Hyōgo, , Japan

Ishikawa Prefectural Central Hospital

Ishikawa, , Japan

Komatsu Municipal Hospital

Ishikawa, , Japan

Public Central Hospital of Matto lshikawa

Ishikawa, , Japan

Showa University Northern Yokohama Hospital

Kanagawa, , Japan

Kokura Memorial Hospital

Kitakyushu, , Japan

Niigata University Medical & Dental Hospital

Niigata, , Japan

The Sakakibara Heart Institute of Okayama

Okayama, , Japan

Sakurabashi Watanabe Hospital

Osaka, , Japan

National Cerebral and Cardiovascular Center Research Institute

Osaka, , Japan

Osaka Medical and Pharmaceutical University Hospital

Osaka, , Japan

Tokyo Saiseikai Central Hospital

Tokyo, , Japan

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Noordwest Ziekenhuisgroep

Alkmaar, , Netherlands

Onze Lieve Vrouwe Gasthuis

Amsterdam, , Netherlands

Academic Medical Center - Department of Vascular Medicine

Amsterdam, , Netherlands

Ziekenhuis Rijnstate

Arnhem, , Netherlands

Tergooiziekenhuizen Blaricum

Blaricum, , Netherlands

IJsselland ziekenhuis

Capelle aan den IJssel, , Netherlands

Reinier de Graaf Gasthuis

Delft, , Netherlands

Ziekenhuis Deventer

Deventer, , Netherlands

Slingeland Ziekenhuis

Doetinchem, , Netherlands

Martini Ziekenhuis

Groningen, , Netherlands

St. Jansdal Ziekenhuis

Harderwijk, , Netherlands

Canisius-Wilhelmina Ziekenhuis (CWZ)

Nijmegen, , Netherlands

Laurentius Hospital Roermond

Roermond, , Netherlands

Bravis ziekenhuis - Locatie Roosendaal

Roosendaal, , Netherlands

Ikazia Ziekenhuis

Rotterdam, , Netherlands

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

VieCuri Medisch Centrum

Venlo, , Netherlands

Gelre Ziekenhuizen - Locatie Zutphen

Zutphen, , Netherlands

Albert Schweitzer Ziekenhuis - Location Dordrecht

Zwijndrecht, , Netherlands

Centrum Medyczne Kermed - Renata Bijata-Bronisz I Ewa Kowalinska Spólka Jawna

Bydgoszcz, , Poland

CENTRUM MEDYCZNE INTERCOR Sp. z o.o.

Bydgoszcz, , Poland

NZOZ Twoje Zdrowie EL Sp. z o.o.

Elblag, , Poland

Indywidualna Specjalistyczna Praktyka Lekarska w Dziedzinie Kardiologii, lek. med. Krzysztof Cymerman

Gdynia, , Poland

Silmedic Sp. z o.o.

Katowice, , Poland

Krakowskie Centrum Medyczne Sp. z o.o.

Krakow, , Poland

FutureMeds Lodz

Lodz, , Poland

Instytut Centrum Zdrowia Matki Polki

Lodz, , Poland

Indywidualna Specjalistyczna Praktyka Lekarska Wlodzimierz Kus

Lodz, , Poland

Clinical Best Solutions - Lublin

Lublin, , Poland

KO - MED Centra Kliniczne Lublin II

Lublin, , Poland

Futuremeds Olsztyn

Olsztyn, , Poland

Ostrowieckie Centrum Medyczne spólka cywilna Anna Olech-Cudzik

Ostrowiec Świętokrzyski, , Poland

Aka-Med Centrum Spólka Z Ograniczona Odpowiedzialnoscia

Ruda Śląska, , Poland

Nowe Zdrowie-Ck Kieltucki i Wspolnicy Spolka Jawna

Staszów, , Poland

Prywatny Gabinet Lekarski Jacek Gessek

Torun, , Poland

FutureMeds Warszawa Centrum

Warsaw, , Poland

Clinical Best Solutions Sp. z.o.o Spolka Komandytowa

Warsaw, , Poland

FutureMeds Targowek

Warsaw, , Poland

FutureMeds Sp. z o.o

Wroclaw, , Poland

4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny ZOZ we Wroclawiu

Wroclaw, , Poland

Countries

United States; China; Czechia; Denmark; Georgia; Japan; Netherlands; Poland

References

Nicholls SJ, Nelson AJ, Ditmarsch M, Kastelein JJP, Ballantyne CM, Ray KK, Navar AM, Nissen SE, Goldberg AC, Brunham LR, Curcio D, Wuerdeman E, Neild A, Kling D, Hsieh A, Dicklin MR, Ference BA, Laufs U, Banach M, Mehran R, Catapano AL, Davidson MH. Obicetrapib on top of maximally tolerated lipid-modifying therapies in participants with or at high risk for atherosclerotic cardiovascular disease: rationale and designs of BROADWAY and BROOKLYN. Am Heart J. 2024 Aug;274:32-45. doi: 10.1016/j.ahj.2024.05.002. Epub 2024 May 4.

Reference Type: BACKGROUND

PMID: 38705341 (View on PubMed)

Nicholls SJ, Nelson AJ, Ditmarsch M, Kastelein JJP, Ballantyne CM, Ray KK, Navar AM, Nissen SE, Harada-Shiba M, Curcio DL, Neild A, Kling D, Hsieh A, Butters J, Ference BA, Laufs U, Banach M, Mehran R, Catapano AL, Huo Y, Szarek M, Balinskaite V, Davidson MH; BROADWAY Investigators. Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk. N Engl J Med. 2025 Jul 3;393(1):51-61. doi: 10.1056/NEJMoa2415820. Epub 2025 May 7.

Reference Type: RESULT

PMID: 40337982 (View on PubMed)

Davidson MH, Szarek M, Scheltens P, Vijverberg E, Hsieh A, Ditmarsch M, Kling D, Curcio D, Nicholls SJ, Ray KK, Cummings JL, Kastelein JJ. Effect of obicetrapib, a potent cholesteryl ester transfer protein inhibitor, on p-tau217 levels in patients with cardiovascular disease. J Prev Alzheimers Dis. 2025 Oct 17:100394. doi: 10.1016/j.tjpad.2025.100394. Online ahead of print.

Reference Type: DERIVED

PMID: 41109840 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://pubmed.ncbi.nlm.nih.gov/38705341/

Study design paper

https://pubmed.ncbi.nlm.nih.gov/40337982/

Study primary results paper

Other Identifiers

TA-8995-302

Identifier Type: -

Identifier Source: org_study_id