Clinical trial NCT05142722: Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies
Official title: A Placebo-Controlled, Double-Blind, Randomized Phase 3 Study to Evaluate the Effect of 10mg Obicetrapib in Participants with HeFH And/or ASCVD Who Are Not Adequately Controlled by Their Lipid Modifying Therapies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dyslipidemias
High Cholesterol
Hypercholesterolemia
Familial Hypercholesterolemia
Atherosclerotic Cardiovascular Disease
Keywords: obicetrapib
BROADWAY
Cholesteryl ester transfer protein (CETP) inhibitor
Heterozygous Familial Hypercholesterolemia (HeFH)
Atherosclerotic Cardiovascular Disease (ASCVD)
Lead sponsor: NewAmsterdam Pharma
Sponsor class: INDUSTRY
First posted: 2021-12-03
Enrollment: 2530
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo-controlled, double-blind, randomized
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: LDL-C
timeFrame: Percent change from baseline to Day 84 in LDL-C
Secondary outcomes:
measure: LDL-C
timeFrame: Percent change from baseline to Days 180 and 365 in LDL-C
measure: apolipoprotein B (ApoB)
timeFrame: Percent change from baseline to Day 84, Day 180, and Day 365 in ApoB
measure: non-HDL-C
timeFrame: Percent change from baseline to Day 84, Day 180, and Day 365 in non-HDL-C
measure: HDL-C
timeFrame: Percent change from baseline to Day 84, Day 180, and Day 365 in HDL-C
measure: Total Cholesterol
timeFrame: Percent change from baseline to Day 84, Day 180, and Day 365 in TC
measure: Triglycerides
timeFrame: Percent change from baseline to Day 84, Day 180, and Day 365 in TG
measure: Lipoprotein A [Lp(a)]
timeFrame: Percent change from baseline to Day 84 in Lp(a)
measure: Apolipoprotein A1 (ApoA1)
timeFrame: Percent change from baseline to Day 84 in ApoA1
Other outcomes:
measure: Major adverse cardiac event (MACE)
timeFrame: Baseline to Day 400
measure: Cardiovascular hospitalizations
timeFrame: Baseline to Day 400
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group
state: Alabama
city: Birmingham
country: United States
facility: Central Alabama Research
state: Alabama
city: Birmingham
country: United States
facility: Synexus Clinical Research US, Inc. / Simon Williamson Clinic, PC
state: Alabama
city: Saraland
country: United States
facility: The Center for Clinical Trials, Inc
state: Alabama
city: Sheffield
country: United States
facility: Syed Research Consultants, LLC
state: Alabama
city: Sun City West
country: United States
facility: Clinical Research Institute of Arizona, LLC
state: Arizona
city: Tucson
country: United States
facility: Synexus Clinical Research US, Inc. / Orange Grove Family Practice
state: Arizona
city: Tucson
country: United States
facility: Eclipse Clinical Research
state: Arizona
city: Beverly Hills
country: United States
facility: American Institute of Research
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Vista
country: United States
facility: Synexus Clinical Research US, Inc.
state: California
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials
state: Florida
city: Fort Pierce
country: United States
facility: Pioneer Clinical Studies
state: Florida
city: Hialeah
country: United States
facility: New Generation of Medical Research
state: Florida
city: Jacksonville
country: United States
facility: East Coast Institute for Research, LLC
state: Florida
city: Jacksonville
country: United States
facility: East Coast Institute for Research, LLC - Jacksonville University Blvd
state: Florida
city: Lake City
country: United States
facility: East Coast Institute for Research- Lake City
state: Florida
city: Maitland
country: United States
facility: ClinCloud LLC
state: Florida
city: Miami
country: United States
facility: Columbus Clinical Services, LLC
state: Florida
city: Miami
country: United States
facility: Kendall South Medical Center, Inc.
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute Inc
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: St. Augustine
country: United States
facility: East Coast Institute for Research
state: Florida
city: The Villages
country: United States
facility: Synexus Clinical Research US, Inc.
state: Florida
city: Atlanta
country: United States
facility: Synexus Clinical Research US, Inc.
state: Georgia
city: Canton
country: United States
facility: East Coast Institute for Research - Canton
state: Georgia
city: Columbus
country: United States
facility: Centricity Research
state: Georgia
city: Macon
country: United States
facility: East Coast Institute for Research, LLC
state: Georgia
city: Peachtree Corners
country: United States
facility: Alta Pharmaceutical Research Center
state: Georgia
city: Savannah
country: United States
facility: SouthCoast Health
state: Georgia
city: Addison
country: United States
facility: Biofortis, Inc
state: Illinois
city: Skokie
country: United States
facility: Evanston Premier Healthcare Research LLC
state: Illinois
city: Evansville
country: United States
facility: Synexus Clinical Research US, Inc.
state: Indiana
city: Indianapolis
country: United States
facility: Midwest Institute for Clinical Research
state: Indiana
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center
state: Kansas
city: Louisville
country: United States
facility: Louisville Metabolic and Atherosclerosis Research Center (L-MARC)
state: Kentucky
city: Owensboro
country: United States
facility: Research Integrity, LLC
state: Kentucky
city: Alexandria
country: United States
facility: Cambridge Medical Trials
state: Louisiana
city: Bossier City
country: United States
facility: Grace Research, LLC
state: Louisiana
city: Marrero
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: Metairie
country: United States
facility: Tandem Clinical Research GI - Metairie
state: Louisiana
city: Shreveport
country: United States
facility: Grace Research, LLC
state: Louisiana
city: Zachary
country: United States
facility: Southern Clinical Research, LLC
state: Louisiana
city: Bangor
country: United States
facility: Northern Light Cardiology
state: Maine
city: Silver Spring
country: United States
facility: Privia Medical Group, LLC
state: Maryland
city: Troy
country: United States
facility: Oakland Medical Research
state: Michigan
city: Troy
country: United States
facility: Arcturus Healthcare, Troy Internal Medicine Research Division
state: Michigan
city: Las Vegas
country: United States
facility: AB Clinical Trials
state: Nevada
city: Bridgeton
country: United States
facility: Inspira Medical Centers dba Internal Medicine Associates, P.A.
state: New Jersey
city: Bronx
country: United States
facility: Chear Center LLC
state: New York
city: New Windsor
country: United States
facility: Mid Hudson Medical Research
state: New York
city: New York
country: United States
facility: Synexus Clinical Research US, Inc.
state: New York
city: New York
country: United States
facility: Tandem Clinical Research GI, LLC
state: New York
city: Morehead City
country: United States
facility: Diabetes and Endocrinology Consultants, P.C.
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research, LLC
state: North Dakota
city: Stow
country: United States
facility: Summit Research Group, LLC
state: Ohio
city: Rapid City
country: United States
facility: Monument Health Clinical Research
state: South Dakota
city: Powell
country: United States
facility: Cardiovascular Research of Knoxville, LLC
state: Tennessee
city: Amarillo
country: United States
facility: Amarillo Heart Clinical Research Institute, Inc
state: Texas
city: Baytown
country: United States
facility: Inquest Clinical Research
state: Texas
city: Bellaire
country: United States
facility: Apex Mobile Clinical Research
state: Texas
city: Conroe
country: United States
facility: Javara Inc.
state: Texas
city: Coppell
country: United States
facility: Prime Revival Research Institute, LLC
state: Texas
city: Dallas
country: United States
facility: Thyroid, Endocrinology & Diabetes, PA
state: Texas
city: Tomball
country: United States
facility: Northwest Houston Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: Synexus Clinical Research US, Inc.
state: Utah
city: Manassas
country: United States
facility: Manassas Clinical Research Center
state: Virginia
city: Suffolk
country: United States
facility: Hampton Roads Center for Clinical Research
state: Virginia
city: Tacoma
country: United States
facility: Universal Research Group, LLC
state: Washington
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Beijing
country: China
facility: Peking University First Hospital
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
city: Changchun
country: China
facility: China-Japan Union Hospital Of Jilin University
city: Changde
country: China
facility: The First People's Hospital of Changde City
city: Changzhou
country: China
facility: The Second People's Hospital of Changzhou
city: Chifeng
country: China
facility: Affiliated Hospital of Chifeng University
city: Chifeng
country: China
facility: Chifeng Municipal Hospital
city: Daqing
country: China
facility: Daqing People's Hospital
city: Foshan
country: China
facility: Foshan First People's Hospital
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Guangzhou Medical university
city: Harbin
country: China
facility: Heilongjiang Provincial Hospital
city: Hunan
country: China
facility: The First Affiliated Hospital Of University Of South China
city: Jinan
country: China
facility: Jinan Central Hospital
city: Langfang
country: China
facility: Hebei Petro China Central Hospital
city: Lishui
country: China
facility: Lishui Central Hospital
city: Luoyang
country: China
facility: Luoyang Third People's Hospital
city: Nanyang
country: China
facility: The First affiliated Hospital of Nanyang Medical College
city: Panjin
country: China
facility: Panjin Liaoyou Gem Flower Hospital
city: Renqiu
country: China
facility: Huabei Petroleum Administration Bureau General Hospital
city: Tianjin
country: China
facility: Tianjin People's Hospital
city: Tianjin
country: China
facility: Tianjin Fourth Central Hospital
city: Wenzhou
country: China
facility: Wenzhou People's Hospital
city: Xi'an
country: China
facility: Xi'an Gaoxin Hospital
city: Xianyang
country: China
facility: Xianyang Hospital of Yan 'an University
city: Xinxiang
country: China
facility: The Third Affiliatied Hospital of Xinxiang Medical University
city: Zaozhuang
country: China
facility: Zaozhuang Municipal Hospital
city: Brandýs Nad Labem
country: Czechia
facility: Medicus Services SRO
city: Brno
country: Czechia
facility: Centrum pro zdravi - kardiologie s.r.o.
city: Brno
country: Czechia
facility: Kardiologicka ambulance Brno s.r.o.
city: Bílina
country: Czechia
facility: Hornicka nemocnice s poliklinikou Bilina s.r.o.
city: Hodonín
country: Czechia
facility: Cevni ambulance - MATMED s.r.o.
city: Krnov
country: Czechia
facility: MUDr. Tomas Edelsberger - diabetologicka ambulance
city: Liberec
country: Czechia
facility: KARDIOLOGIE - LIBEREC s.r.o.
city: Olomouc
country: Czechia
facility: PreventaMed s.r.o.
city: Ostrava
country: Czechia
facility: CCR Ostrava s.r.o.
city: Pardubice
country: Czechia
facility: CCR Czech a.s.
city: Prague
country: Czechia
facility: Kardiologie COR s.r.o.
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen S
country: Denmark
facility: Amager Hospital
city: Esbjerg
country: Denmark
facility: Sydvestjysk Hospital
city: Herning
country: Denmark
facility: Godstrup Regional Hospital (Gødstrup)
city: Viborg
country: Denmark
facility: Viborg Regional Hospital
city: Batumi
country: Georgia
facility: Health LTD
city: Tbilisi
country: Georgia
facility: JSC Curatio
city: Tbilisi
country: Georgia
facility: Acad. G. Chapidze Emergency Cardiology Center LTD
city: Tbilisi
country: Georgia
facility: Bokhua Memorial Cardiovascular Center LTD
city: Tbilisi
country: Georgia
facility: Vitamedi LTD
city: Tbilisi
country: Georgia
facility: Medi Club Georgia LLC
city: Tbilisi
country: Georgia
facility: Georgian-Ducht Hospital LTD
city: Tbilisi
country: Georgia
facility: The First Medical Center LTD
city: Tbilisi
country: Georgia
facility: Adapti LTD
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Chiba
country: Japan
facility: New Tokyo Heart Clinic
city: Fukuoka
country: Japan
facility: Japan Community Health Care Organization Kyushu Hospital
city: Hiroshima
country: Japan
facility: Hiroshima Prefectural Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Hyōgo
country: Japan
facility: Hyogo Prefectural Harima-Himeji General Medical Center
city: Ishikawa
country: Japan
facility: Ishikawa Prefectural Central Hospital
city: Ishikawa
country: Japan
facility: Komatsu Municipal Hospital
city: Ishikawa
country: Japan
facility: Public Central Hospital of Matto lshikawa
city: Kanagawa
country: Japan
facility: Showa University Northern Yokohama Hospital
city: Kitakyushu
country: Japan
facility: Kokura Memorial Hospital
city: Niigata
country: Japan
facility: Niigata University Medical & Dental Hospital
city: Okayama
country: Japan
facility: The Sakakibara Heart Institute of Okayama
city: Osaka
country: Japan
facility: Sakurabashi Watanabe Hospital
city: Osaka
country: Japan
facility: National Cerebral and Cardiovascular Center Research Institute
city: Osaka
country: Japan
facility: Osaka Medical and Pharmaceutical University Hospital
city: Tokyo
country: Japan
facility: Tokyo Saiseikai Central Hospital
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Amsterdam
country: Netherlands
facility: Academic Medical Center - Department of Vascular Medicine
city: Arnhem
country: Netherlands
facility: Ziekenhuis Rijnstate
city: Blaricum
country: Netherlands
facility: Tergooiziekenhuizen Blaricum
city: Capelle Aan Den IJssel
country: Netherlands
facility: IJsselland ziekenhuis
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Deventer
country: Netherlands
facility: Ziekenhuis Deventer
city: Doetinchem
country: Netherlands
facility: Slingeland Ziekenhuis
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Harderwijk
country: Netherlands
facility: St. Jansdal Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina Ziekenhuis (CWZ)
city: Roermond
country: Netherlands
facility: Laurentius Hospital Roermond
city: Roosendaal
country: Netherlands
facility: Bravis ziekenhuis - Locatie Roosendaal
city: Rotterdam
country: Netherlands
facility: Ikazia Ziekenhuis
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Venlo
country: Netherlands
facility: VieCuri Medisch Centrum
city: Zutphen
country: Netherlands
facility: Gelre Ziekenhuizen - Locatie Zutphen
city: Zwijndrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis - Location Dordrecht
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Kermed - Renata Bijata-Bronisz I Ewa Kowalinska Spólka Jawna
city: Bydgoszcz
country: Poland
facility: CENTRUM MEDYCZNE INTERCOR Sp. z o.o.
city: Elblag
country: Poland
facility: NZOZ Twoje Zdrowie EL Sp. z o.o.
city: Gdynia
country: Poland
facility: Indywidualna Specjalistyczna Praktyka Lekarska w Dziedzinie Kardiologii, lek. med. Krzysztof Cymerman
city: Katowice
country: Poland
facility: Silmedic Sp. z o.o.
city: Kraków
country: Poland
facility: Krakowskie Centrum Medyczne Sp. z o.o.
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Lodz
country: Poland
facility: Indywidualna Specjalistyczna Praktyka Lekarska Wlodzimierz Kus
city: Lublin
country: Poland
facility: Clinical Best Solutions - Lublin
city: Lublin
country: Poland
facility: KO - MED Centra Kliniczne Lublin II
city: Olsztyn
country: Poland
facility: Futuremeds Olsztyn
city: Ostrowiec Świętokrzyski
country: Poland
facility: Ostrowieckie Centrum Medyczne spólka cywilna Anna Olech-Cudzik
city: Ruda Slaska
country: Poland
facility: Aka-Med Centrum Spólka Z Ograniczona Odpowiedzialnoscia
city: Staszów
country: Poland
facility: Nowe Zdrowie-Ck Kieltucki i Wspolnicy Spolka Jawna
city: Torun
country: Poland
facility: Prywatny Gabinet Lekarski Jacek Gessek
city: Warszawa
country: Poland
facility: FutureMeds Warszawa Centrum
city: Warszawa
country: Poland
facility: Clinical Best Solutions Sp. z.o.o Spolka Komandytowa
city: Warszawa
country: Poland
facility: FutureMeds Targowek
city: Wrocław
country: Poland
facility: FutureMeds Sp. z o.o
city: Wrocław
country: Poland
facility: 4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny ZOZ we Wroclawiu
city: Łódź
country: Poland
facility: FutureMeds Lodz
Study officials:
affiliation: NewAmsterdam Pharma
name: Marc Ditmarsch
role: STUDY_DIRECTOR
References: