Clinical trial NCT06347003: Study of Plozasiran (ARO-APOC3) in Adults With Severe Hypertriglyceridemia
Official title: Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Plozasiran in Adults With Severe Hypertriglyceridemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Severe Hypertriglyceridemia
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-04-04
Enrollment: 405
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This Phase 3 study will evaluate the safety and efficacy of plozasiran injection (ARO-APOC3) in adult participants with severe hypertriglyceridemia (SHTG). After providing informed consent eligible participants will be randomized to receive 4 doses (once every 3 months) of plozasiran or placebo, and be evaluated for efficacy and safety. After month 12, eligible participants will be offered an opportunity to continue in an optional open-label extension under a separate protocol.


Eligibility criteria: Inclusion Criteria:

* Established diagnosis of severe hypertriglyceridemia (SHTG) and prior documented evidence (medical history) of fasting TG levels of ≥ 500 mg/dL (≥5.65mmol/L)
* Mean fasting TG level ≥500 mg/dL (≥5.65 mmol/L) collected at 2 separate and consecutive visits at least 7 days apart and no more than 17 days apart during the screening period
* Fasting low density lipoprotein-cholesterol (LDL-C) ≤130 mg/dL (≤3.37 mmol/L) at screening
* Screening HbA1C ≤8.5%
* Willing to follow diet counseling and maintain a stable low-fat diet
* Must be on standard of care lipid-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator)

Exclusion Criteria:

* Use of any hepatocyte-targeted small interfering ribonucleic acid (siRNA) that targets lipids and/or triglycerides within 365 days before Day 1 (except inclisiran, which is permitted). Administration of investigational drug and inclisiran must be separated by at least 4 weeks
* Use of any other hepatocyte-targeted siRNA or antisense oligonucleotide molecule within 60 days or within 5-half-lives before Day 1 based on plasma pharmacokinetics (PK), whichever is longer
* Known diagnosis of familial chylomicronemia syndrome (FCS) (type 1 Hyperlipoproteinemia) by documentation of confirmed homozygote or double heterozygote for loss-of-function mutations in type 1-causing genes
* Acute pancreatitis within 4 weeks prior to screening
* Body mass index \>45kg/m\^2

Note: Additional Inclusion/Exclusion criteria may apply per protocol

Primary outcomes:
measure: Percent Change in Fasting Serum Triglyceride (TG) Levels from Baseline to Month 12 Compared to Placebo
timeFrame: Baseline, Month 12
Secondary outcomes:
measure: Percent Change in Fasting Serum TG Levels from Baseline to Month 10 Compared to Placebo
timeFrame: Baseline, Month 10
measure: Proportion of Participants Who Achieve Fasting TG Levels of <500 mg/dL (<5.65 mmol/L) at Month 10 and Month 12 Compared to Placebo
timeFrame: Month 10, Month 12
measure: Adjudicated Abdominal Clinical Event Rate (Including Emergency Room Visits or Hospitalizations for Abdominal Pain Attributed to Hypertriglyceridemia and Events of Documented Pancreatitis) During the Treatment Period Compared to Placebo at Month 12
timeFrame: Month 12
measure: Proportion of Participants Who Achieve Fasting TG Levels of <150 mg/dL (<1.69 mmol/L) at Month 10 and Month 12 Compared to Placebo
timeFrame: Month 10, Month 12
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) Over Time through Month 12 as Compared to Placebo
timeFrame: From first dose of study drug through Month 12
measure: Incidence Rates of New-Onset Diabetes Mellitus (NODM) Throughout the Course of Treatment
timeFrame: From first dose of study drug through Month 12
measure: Incidence Rates of Impaired Glucose Tolerance Throughout the Course of Treatment
timeFrame: From first dose of study drug through Month 12
measure: Incidence Rates of Worsening of Existing Diabetes Throughout the Course of Treatment
timeFrame: From first dose of study drug through Month 12
measure: Change from Baseline in Hemoglobin A1c (HbA1c) During the Treatment Period Compared to Placebo
timeFrame: From first dose of study drug through Month 12
measure: Change from Baseline in Fasting Blood Glucose During the Treatment Period Compared to Placebo
timeFrame: From first dose of study drug through Month 12
measure: Change from Baseline in C-peptide During the Treatment Period Compared to Placebo
timeFrame: From first dose of study drug through Month 12
measure: Change from Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) During the Treatment Period Compared to Placebo
timeFrame: From first dose of study drug through Month 12
measure: Incidence Rates of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) Associated with Worsening Glycemic Control During the Treatment Period Compared to Placebo
timeFrame: From first dose of study drug through Month 12
measure: Initiation of New Medication for Hyperglycemia Among Study Participants Not Known to Have Pre-existing Diabetes Mellitus During the Treatment Period Compared to Placebo
timeFrame: From first dose of study drug through Month 12
measure: Adjudicated Major Adverse Cardiovascular Events (MACE) Rates During the Treatment Period Compared to Placebo
timeFrame: From first dose of study drug through Month 12
measure: Incidence of Anti-drug Antibodies (ADA) to Plozasiran in Participants Receiving Plozasiran Over Time Through Month 12
timeFrame: From first dose of study drug through Month 12
measure: Titers of Anti-drug Antibodies (ADA) to Plozasiran in Participants Receiving Plozasiran Over Time Through Month 12
timeFrame: From first dose of study drug through Month 12
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: National Institute of Clinical Research
state: California
city: Lake Forest
country: United States
facility: Orange County Research Center
state: California
city: Montclair
country: United States
facility: Catalina Research Institute
state: California
city: Panorama City
country: United States
facility: Velocity Clinical Research, Panorama City
state: California
city: Redding
country: United States
facility: The Cardiovascular Center
state: California
city: Colorado Springs
country: United States
facility: Legacy Clinical Trials
state: Colorado
city: Hialeah
country: United States
facility: Neoclinical Research
state: Florida
city: Lake City
country: United States
facility: East Coast Institute for Research, LLC
state: Florida
city: Miami Lakes
country: United States
facility: Panax Clinical Research
state: Florida
city: Mount Dora
country: United States
facility: Adult Medicine of Lake County
state: Florida
city: Orlando
country: United States
facility: Florida Institute for Clinical Research
state: Florida
city: Pensacola
country: United States
facility: Baptist Hospital Cardiology
state: Florida
city: Tamarac
country: United States
facility: TBC Research
state: Florida
city: Tampa
country: United States
facility: R & B Medical Center
state: Florida
city: Macon
country: United States
facility: East Coast - Institute for Research
state: Georgia
city: Savannah
country: United States
facility: Meridian Clinical Research
state: Georgia
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Eunice
country: United States
facility: Horizon Research Group of Opelousas, LLC
state: Louisiana
city: Baltimore
country: United States
facility: Ascension Saint Agnes Heart care
state: Maryland
city: Flint
country: United States
facility: Elite Clinical Research Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota, Lillehei Clinical Research Unit
state: Minnesota
city: Olive Branch
country: United States
facility: Olive Branch Family Medical Centre
state: Mississippi
city: Jefferson City
country: United States
facility: Jefferson City Medical Group
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Heart and Vascular
state: Missouri
city: Omaha
country: United States
facility: Methodist Physicians Clinic Heart Consultants
state: Nebraska
city: Omaha
country: United States
facility: Midwest Regional Health Services LLC
state: Nebraska
city: Las Vegas
country: United States
facility: Santa Rosa Medical Centers of Nevada
state: Nevada
city: Bronx
country: United States
facility: CHEAR Center LLC
state: New York
city: Long Island City
country: United States
facility: Endocrine Associates of West Village
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Vestal
country: United States
facility: Vestal Velocity Clinical Research
state: New York
city: Morehead City
country: United States
facility: Carteret Medical Group
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati-COM
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Norman
country: United States
facility: Lynn Institute of Norman
state: Oklahoma
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Powell
country: United States
facility: Cardiovascular Research Center of Knoxville
state: Tennessee
city: El Paso
country: United States
facility: Dr. David Turbay MD PLLC
state: Texas
city: Houston
country: United States
facility: Gonzalez Research Institute
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine-Center for Cardiometabolic Disease Prevention
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital Department of Medicine Research
state: Texas
city: Houston
country: United States
facility: Synergy Groups Medical LLC
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network LLC
state: Texas
city: Houston
country: United States
facility: PlanIt Research PLLC
state: Texas
city: Houston
country: United States
facility: Endocrine and Psychiatry Center
state: Texas
city: Laredo
country: United States
facility: Andres Garcia Zuniga MD PA
state: Texas
city: Missouri City
country: United States
facility: Synergy Groups Medical
state: Texas
city: Plano
country: United States
facility: Stryde Research
state: Texas
city: San Antonio
country: United States
facility: VIP Trials
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Ramos Mejía
country: Argentina
facility: DIM Clinica Privada
state: Buenos Aires
city: San Isidro
country: Argentina
facility: Centro Medico Santa Maria De La Salud
state: Buenos Aires
city: Temperley
country: Argentina
facility: CIMeT - Centro de Investigaciones Médicas Temperley
state: Buenos Aires
city: Córdoba
country: Argentina
facility: Sanatorio Privado Duarte Quiroz De Clinica Colombo SA
state: Cordoba
city: Córdoba
country: Argentina
facility: CEMAIC - Centro Medico Privado
state: Cordoba
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Centro Privado de Medicina Familiar - Mind Out Research
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Centro Medico Dra Laura Maffei Investigacion Clinica Aplicada
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Glenny Corp. S.A.
city: Cordoba
country: Argentina
facility: Instituto Privado de Investigaciones Clinicas de Cordoba
city: Cordoba
country: Argentina
facility: Centro Medico Luquez
city: Blacktown
country: Australia
facility: Paratus Clinical Research Western Sydney
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Merewether
country: Australia
facility: Hunter Diabetes Centre and Aim Centre
state: New South Wales
city: Box Hill
country: Australia
facility: Eastern Clinical Research Unit - Endocrinology
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Crawley
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Gozée
country: Belgium
facility: De Meulemeester, Marc
city: Hasselt
country: Belgium
facility: Jesse Ziekenhuis
city: Mechelen
country: Belgium
facility: AZ Sint-Maarten
city: Namur
country: Belgium
facility: Respisom
city: Roeselare
country: Belgium
facility: AZ Delta VZW
city: Wetteren
country: Belgium
facility: BVBA Dr. Luc Capiau
city: Salvador
country: Brazil
facility: Hospital Santa Izabel - Santa Casa de Misericordia da Bahia
state: Bahia
city: Salvador
country: Brazil
facility: Hospital Ana Nery
state: Bahia
city: Salvador
country: Brazil
facility: Fundação Bahiana de Cardiologia
state: Bahia
city: Vitória
country: Brazil
facility: CEDOES - Diagnóstico e Pesquisa
state: Espírito Santo
city: Belo Horizonte
country: Brazil
facility: Hospital Vera Cruz - NUPEC - Nucleo de Pesquisa Clinica
state: Minas Gerais
city: Campina Grande do Sul
country: Brazil
facility: Sociedade Hospitalar Angelina Caron
state: Parana
city: Curitiba
country: Brazil
facility: Núcleo de Pesquisa Clínica SS
state: Paraná
city: Belém
country: Brazil
facility: HUJBB-UFPA - Hospital Universitário João de Barros Barreto - Universidade Federal do Pará
state: Para
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Nucleo de Pesquisa Clínica do Rio Grande do Sul-NPCRS
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: Centro Médico de Campinas
state: Sao Paulo
city: São Paulo
country: Brazil
facility: CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Incor - Instituto do Coração - HCFMUSP
state: Sao Paulo
city: Votuporanga
country: Brazil
facility: Integral Pesquisa e Ensino
state: Sao Paulo
city: Blagoevgrad
country: Bulgaria
facility: MHAT 'Puls' AD
city: Burgas
country: Bulgaria
facility: Medical Center 4LIFE EOOD
city: Kardzhali
country: Bulgaria
facility: Medical Center Rodopimed EOOD
city: Pleven
country: Bulgaria
facility: Medical Center Medconsult Pleven OOD
city: Pleven
country: Bulgaria
facility: MHAT Heart and Brain
city: Plovdiv
country: Bulgaria
facility: UMHAT Kaspela, EOOD
city: Plovdiv
country: Bulgaria
facility: UMHAT "Pulmed" OOD
city: Plovdiv
country: Bulgaria
facility: MHAT Sv. Karidad, EAD
city: Ruse
country: Bulgaria
facility: Medical Center- Prolet Ltd
city: Sofia
country: Bulgaria
facility: MHAT Lyulin EAD
city: Sofia
country: Bulgaria
facility: MHAT Sv. Sofia, OOD
city: Sofia
country: Bulgaria
facility: UMHAT Sveta Ekaterina
city: Sofia
country: Bulgaria
facility: UMHAT 'Tsaritsa Yoanna - ISUL', EAD
city: Sofia
country: Bulgaria
facility: UMHAT Tsaritsa Yoanna - ISUL EAD
city: Sofia
country: Bulgaria
facility: Diagnostic Consultation Center Convex EOOD
city: Victoria
country: Canada
facility: Discovery Clinical Services
state: British Columbia
city: Brampton
country: Canada
facility: Centricity Research Brampton Endocrinology
state: Ontario
city: London
country: Canada
facility: John P. Robarts Research Institute
state: Ontario
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group Inc.
state: Ontario
city: Waterloo
country: Canada
facility: Clinical Research Solutions Inc.
state: Ontario
city: Montréal
country: Canada
facility: Institut de Recherches Cliniques de Montréal
state: Quebec
city: Québec
country: Canada
facility: Clinique des Maladies Lipidiques de Québec
state: Quebec
city: Halifax
country: Canada
facility: Nova Scotia Health Authority
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical University
state: Anhui
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Guanzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou People s Hospital
state: Guangxi
city: Xingtai
country: China
facility: Xingtai Central Hospital
state: Hebei
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: The Third Hospital of Changsha
state: Hunan
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology
state: Inner Mongolia
city: Suzhou
country: China
facility: Suzhou Municipal Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tongren Hospital
state: Shanghai
city: Yuncheng
country: China
facility: Yuncheng Central Hospital
state: Shanxi
city: Chendu
country: China
facility: Sichuan Provincial People s Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Union Medical Center
state: Tianjin
city: Beijing
country: China
facility: Peking University First Hospital
state: Xicheng
city: Wenzhou
country: China
facility: Wenzhou People s Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: The First People's Hospital of Hangzhou Linping District
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of NanChang University
city: Krapinske Toplice
country: Croatia
facility: Special Hospital for Medical Rehabilitation
city: Zagreb
country: Croatia
facility: Clinical Hospital Dubrava
city: Zagreb
country: Croatia
facility: Polyclinic Solmed
city: Zagreb
country: Croatia
facility: University Hospital Center Zagreb
city: Praha 4
country: Czechia
facility: Institut klinicke a experimentalni mediciny
state: Prague
city: Praha
country: Czechia
facility: Fakultni Thomayerova nemocnice
state: Prague
city: Hodonín
country: Czechia
facility: CTC Hodonin s.r.o.
city: Hradec Králové
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Ostrava
country: Czechia
facility: CCR Ostrava s.r.o.
city: Praha 1-Nove Mesto
country: Czechia
facility: Kardiologie Vinohrady s.r.o.
city: Praha 4-Krc
country: Czechia
facility: Pharmacy - Fakultni Thomayerova nemocnice
city: Uherské Hradiště
country: Czechia
facility: MEDICAL PLUS, s.r.o.
city: Ústí Nad Labem
country: Czechia
facility: Krajska zdravotni a.s. - Masarykova nemocnice v Usti nad Labem o.z.
city: Budapest
country: Hungary
facility: Clinexpert Kft
city: Budapest
country: Hungary
facility: Belvaros-Lipotvaros Egeszsegugyi Szolgalat
city: Budapest
country: Hungary
facility: Privát Doktor Zrt.
city: Budapest
country: Hungary
facility: UNO Medical Trials Kft.
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpontzh
city: Veszprém
country: Hungary
facility: Minoseg Orvoscsoport Kft
city: Rozzano
country: Italy
facility: IRCCS Istituto Clinico Humanitas
state: Milano
city: Palermo
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
state: Sicily
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Żarów
country: Poland
facility: Centrum Medyczne Serafin med
state: Swidnica
city: Bydgoszcz
country: Poland
facility: NZOZ Centrum Medyczne KERmed
city: Elbląg
country: Poland
facility: Centrum Kliniczno - Badawcze J. Brzezicki, B. Gornikiewicz-Brzezicka Lekarze Społka Partnerska
city: Katowice
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej TERAPIA-OPTIMA
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalistyczny im. Jana Pawla II
city: Kraków
country: Poland
facility: Pratia MCM Krakow
city: Kraków
country: Poland
facility: Krakowskie Centrum Medyczne
city: Warsaw
country: Poland
facility: FutureMeds Targowek
city: Warszawa
country: Poland
facility: FutureMeds Warszawa Centrum
city: Wrocław
country: Poland
facility: CM Sedimed Wroclaw
city: Wrocław
country: Poland
facility: FutureMeds Wroclaw
city: Łódź
country: Poland
facility: FutureMeds Lodz
city: Braşov
country: Romania
facility: S.C Centrul Medical Unirea S.R.L
state: Brasov
city: Cluj-Napoca
country: Romania
facility: Spitalul Angiocare SRL
state: Cluj
city: Alba Iulia
country: Romania
facility: S.C Diana Barbonta S.R.L
state: Jud. Alba
city: Ploieşti
country: Romania
facility: CMI Dr Busegeanu Mihaela Magdalena
state: Jud. Prahova
city: Timişoara
country: Romania
facility: S.C Medicali s S.R.L
state: Timis
city: Bucuresti
country: Romania
facility: S.C Clinica Medicala Data Plus S.R.L
city: Deva
country: Romania
facility: Spitalul Judetean de Urgenta Deva
city: Galaţi
country: Romania
facility: S.C Diamed Obesity S.R.L
city: Târgu-Mureş
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Targu Mures
city: Kosice
country: Slovakia
facility: Kardiologicka a Interna Ambulancia
state: Košice Region
city: Moldava Nad Bodvou
country: Slovakia
facility: Kardiologicka Ambulancia MEDI M&M s.r.o.
state: Košice Region
city: Banska Bystrica
country: Slovakia
facility: Kardiointerna s r o
city: Bardejov
country: Slovakia
facility: Alian s.r.o.
city: Bratislava
country: Slovakia
facility: Cliniq s.r.o.
city: Žilina
country: Slovakia
facility: Medivasa s.r.o.
city: Barcelona
country: Spain
facility: Hospital Quironsalud Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Valencia
country: Spain
facility: INCLIVA
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Torpoint
country: United Kingdom
facility: Rame Medical limited
state: Cornwall
city: Torquay
country: United Kingdom
facility: Torbay Hospital
state: Devon
city: Plymouth
country: United Kingdom
facility: Knowle House Surgery
state: Devpn
city: London
country: United Kingdom
facility: Barts Health
city: London
country: United Kingdom
facility: Velocity North London
Study officials:
References: