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

Hypercholesterolemia Clinical Trial

— BROADWAY  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05142722
• Other study ID #: TA-8995-302
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 15, 2021
• Est. completion date: September 2024

Study information

• Verified date: September 2023
• Source: NewAmsterdam Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2532
• Est. completion date: September 2024
• Est. primary completion date: November 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Atherosclerotic Cardiovascular Disease
• Cardiovascular Diseases
• Dyslipidemias
• Familial Hypercholesterolemia
• High Cholesterol
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• Placebo
placebo tablet made to resemble active
• Obicetrapib
10mg obicetrapib tablet

Locations

Country	Name	City	State
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	West China Hospital, Sichuan University	Chengdu	Sichuan
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 Fourth Central Hospital	Tianjin
China	Tianjin People's 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
Czechia	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
Denmark	Aarhus University Hospital	Aarhus
Denmark	Amager Hospital	Copenhagen S
Denmark	Sydvestjysk Hospital	Esbjerg
Denmark	Godstrup Regional Hospital (Gødstrup)	Herning
Denmark	Viborg Regional Hospital	Viborg
Georgia	Health LTD	Batumi
Georgia	Acad. G. Chapidze Emergency Cardiology Center LTD	Tbilisi
Georgia	Adapti LTD	Tbilisi
Georgia	Bokhua Memorial Cardiovascular Center LTD	Tbilisi
Georgia	Georgian-Ducht Hospital LTD	Tbilisi
Georgia	JSC Curatio	Tbilisi
Georgia	Medi Club Georgia LLC	Tbilisi
Georgia	The First Medical Center LTD	Tbilisi
Georgia	Vitamedi LTD	Tbilisi
Japan	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	Hyogo
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	National Cerebral and Cardiovascular Center Research Institute	Osaka
Japan	Osaka Medical and Pharmaceutical University Hospital	Osaka
Japan	Sakurabashi Watanabe Hospital	Osaka
Japan	Tokyo Saiseikai Central Hospital	Tokyo
Netherlands	Jeroen Bosch Ziekenhuis	's-Hertogenbosch
Netherlands	Noordwest Ziekenhuisgroep	Alkmaar
Netherlands	Academic Medical Center - Department of Vascular Medicine	Amsterdam
Netherlands	Onze Lieve Vrouwe Gasthuis	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
Poland	CENTRUM MEDYCZNE INTERCOR Sp. z o.o.	Bydgoszcz
Poland	Centrum Medyczne Kermed - Renata Bijata-Bronisz I Ewa Kowalinska Spólka Jawna	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.	Kraków
Poland	Indywidualna Specjalistyczna Praktyka Lekarska Wlodzimierz Kus	Lodz
Poland	Instytut Centrum Zdrowia Matki Polki	Lodz
Poland	FutureMeds Lodz	Lódz
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 Swietokrzyski
Poland	Aka-Med Centrum Spólka Z Ograniczona Odpowiedzialnoscia	Ruda Slaska
Poland	Nowe Zdrowie-Ck Kieltucki i Wspolnicy Spolka Jawna	Staszów
Poland	Prywatny Gabinet Lekarski Jacek Gessek	Torun
Poland	Clinical Best Solutions Sp. z.o.o Spolka Komandytowa	Warszawa
Poland	FutureMeds Targowek	Warszawa
Poland	FutureMeds Warszawa Centrum	Warszawa
Poland	4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny ZOZ we Wroclawiu	Wroclaw
Poland	FutureMeds Sp. z o.o	Wroclaw
United States	Biofortis, Inc	Addison	Illinois
United States	Cambridge Medical Trials	Alexandria	Louisiana
United States	Amarillo Heart Clinical Research Institute, Inc	Amarillo	Texas
United States	Pinnacle Research Group	Anniston	Alabama
United States	Synexus Clinical Research US, Inc.	Atlanta	Georgia
United States	Northern Light Cardiology	Bangor	Maine
United States	Inquest Clinical Research	Baytown	Texas
United States	Apex Mobile Clinical Research	Bellaire	Texas
United States	American Institute of Research	Beverly Hills	California
United States	Central Alabama Research	Birmingham	Alabama
United States	Synexus Clinical Research US, Inc. / Simon Williamson Clinic, PC	Birmingham	Alabama
United States	Excel Medical Clinical Trials	Boca Raton	Florida
United States	Grace Research, LLC	Bossier City	Louisiana
United States	Inspira Medical Centers dba Internal Medicine Associates, P.A.	Bridgeton	New Jersey
United States	Chear Center LLC	Bronx	New York
United States	East Coast Institute for Research - Canton	Canton	Georgia
United States	Centricity Research	Columbus	Georgia
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	Synexus Clinical Research US, Inc.	Evansville	Indiana
United States	Lillestol Research, LLC	Fargo	North Dakota
United States	Pioneer Clinical Studies	Fort Pierce	Florida
United States	New Generation of Medical Research	Hialeah	Florida
United States	Midwest Institute for Clinical Research	Indianapolis	Indiana
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	AB Clinical Trials	Las Vegas	Nevada
United States	Louisville Metabolic and Atherosclerosis Research Center (L-MARC)	Louisville	Kentucky
United States	East Coast Institute for Research, LLC	Macon	Georgia
United States	ClinCloud LLC	Maitland	Florida
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	Tandem Clinical Research	Marrero	Louisiana
United States	Tandem Clinical Research GI - Metairie	Metairie	Louisiana
United States	Columbus Clinical Services, LLC	Miami	Florida
United States	Kendall South Medical Center, Inc.	Miami	Florida
United States	Diabetes and Endocrinology Consultants, P.C.	Morehead City	North Carolina
United States	Advanced Research Institute Inc	New Port Richey	Florida
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	Research Integrity, LLC	Owensboro	Kentucky
United States	Alta Pharmaceutical Research Center	Peachtree Corners	Georgia
United States	Progressive Medical Research	Port Orange	Florida
United States	Cardiovascular Research of Knoxville, LLC	Powell	Tennessee
United States	Monument Health Clinical Research	Rapid City	South Dakota
United States	East Coast Institute for Research	Saint Augustine	Florida
United States	Synexus Clinical Research US, Inc.	Salt Lake City	Utah
United States	The Center for Clinical Trials, Inc	Saraland	Alabama
United States	SouthCoast Health	Savannah	Georgia
United States	Syed Research Consultants, LLC	Sheffield	Alabama
United States	Grace Research, LLC	Shreveport	Louisiana
United States	Privia Medical Group, LLC	Silver Spring	Maryland
United States	Evanston Premier Healthcare Research LLC	Skokie	Illinois
United States	Summit Research Group, LLC	Stow	Ohio
United States	Hampton Roads Center for Clinical Research	Suffolk	Virginia
United States	Clinical Research Institute of Arizona, LLC	Sun City West	Arizona
United States	Universal Research Group, LLC	Tacoma	Washington
United States	Synexus Clinical Research US, Inc.	The Villages	Florida
United States	Northwest Houston Clinical Research	Tomball	Texas
United States	Cotton-O'Neil Clinical Research Center	Topeka	Kansas
United States	Arcturus Healthcare, Troy Internal Medicine Research Division	Troy	Michigan
United States	Oakland Medical Research	Troy	Michigan
United States	Eclipse Clinical Research	Tucson	Arizona
United States	Synexus Clinical Research US, Inc. / Orange Grove Family Practice	Tucson	Arizona
United States	Orange County Research Center	Tustin	California
United States	Synexus Clinical Research US, Inc.	Vista	California
United States	Southern Clinical Research, LLC	Zachary	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
NewAmsterdam Pharma

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Major adverse cardiac event (MACE)	evaluate the effect of obicetrapib on major adverse cardiac events	Baseline to Day 400
Other	Cardiovascular hospitalizations	evaluate the effect of obicetrapib on cardiovascular hospitalizations	Baseline to Day 400
Primary	LDL-C	obicetrapib compared to placebo on LDL-C	Percent change from baseline to Day 84 in LDL-C
Secondary	LDL-C	obicetrapib compared to placebo on LDL-C	Percent change from baseline to Days 180 and 365 in LDL-C
Secondary	apolipoprotein B (ApoB)	obicetrapib compared to placebo on ApoB	Percent change from baseline to Day 84, Day 180, and Day 365 in ApoB
Secondary	non-HDL-C	obicetrapib compared to placebo on non-HDL-C	Percent change from baseline to Day 84, Day 180, and Day 365 in non-HDL-C
Secondary	HDL-C	obicetrapib compared to placebo on HDL-C	Percent change from baseline to Day 84, Day 180, and Day 365 in HDL-C
Secondary	Total Cholesterol	obicetrapib compared to placebo on TC	Percent change from baseline to Day 84, Day 180, and Day 365 in TC
Secondary	Triglycerides	obicetrapib compared to placebo on TG	Percent change from baseline to Day 84, Day 180, and Day 365 in TG
Secondary	Lipoprotein A [Lp(a)]	obicetrapib compared to placebo on Lp(a)	Percent change from baseline to Day 84 in Lp(a)
Secondary	Apolipoprotein A1 (ApoA1)	obicetrapib compared to placebo on ApoA1	Percent change from baseline to Day 84 in ApoA1