Clinical trial NCT06347016: Study of Plozasiran in Adults With Severe Hypertriglyceridemia
Official title: Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Plozsiran 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: 300
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 (≥5.65 mmol/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%
* 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 (except inclisiran, which is permitted)
* 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
* 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 Subjects Who Achieve Fasting TG Levels of < 500 mg/dL (<5.65 mmol/L) at Month 10 and Month 12
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 Subjects Who Achieve Fasting TG Levels of <150mg/dL (<1.69 mmol/L) at Month 10 and Month 12 Compared to Placebo
timeFrame: Month 10, Month 12
measure: Number of Subjects 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) and Other Glycemic Control Parameters 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: Change from Baseline in 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 Subjects 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 Subjects Receiving Plozasiran Over Time Through Month 12
timeFrame: From first dose of study drug through Month 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Ascension St. Vincents Birmingham
state: Alabama
city: Mobile
country: United States
facility: IMC-Diagnostic and Medical Clinic LLC
state: Alabama
city: Beverly Hills
country: United States
facility: National Heart Institute
state: California
city: Canoga Park
country: United States
facility: Hope Clinical Research
state: California
city: Huntington Beach
country: United States
facility: National Institute of Clinical Research, Inc.
state: California
city: Lincoln
country: United States
facility: Clinical Trials Research
state: California
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System
state: California
city: Oxnard
country: United States
facility: FOMAT Medical Research
state: California
city: Clearwater
country: United States
facility: Innovative Research of West Florida, Inc.
state: Florida
city: North Miami
country: United States
facility: Harmony Clinical Research
state: Florida
city: Sarasota
country: United States
facility: Cardiovascular Center of Sarasota Foundation for Research and Education
state: Florida
city: Lawrenceville
country: United States
facility: Georgia Clinical Research, LLC
state: Georgia
city: Sugar Hill
country: United States
facility: RNA America Health Sciences
state: Georgia
city: Elkhart
country: United States
facility: Midwest Cardiovascular Research and Education Foundation
state: Indiana
city: Indianapolis
country: United States
facility: Ascension St. Vincent Heart Center
state: Indiana
city: South Bend
country: United States
facility: The South Bend Clinic LLC
state: Indiana
city: Overland Park
country: United States
facility: Midwest Heart and Vascular Specialists
state: Kansas
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center, Stormont-Vail West
state: Kansas
city: Metairie
country: United States
facility: Southern Clinical Research Associates
state: Louisiana
city: Annapolis
country: United States
facility: Annapolis Internal Medicine
state: Maryland
city: Jackson
country: United States
facility: Elite Clinical Research
state: Mississippi
city: Fremont
country: United States
facility: Methodist Physicians Clinic
state: Nebraska
city: Norfolk
country: United States
facility: Velocity Clinical Research
state: Nebraska
city: Morristown
country: United States
facility: Overlook Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Jack D. Weiler Hospital
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Riverhead
country: United States
facility: Northwell Health Physician Partners at Peconic
state: New York
city: Asheboro
country: United States
facility: Triad Internal Medicine
state: North Carolina
city: Wilmington
country: United States
facility: Wilmington Health
state: North Carolina
city: Beavercreek
country: United States
facility: Internal Medicine Care Beavercreek
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Riverside Methodist Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Horsham
country: United States
facility: AMS Cardiology
state: Pennsylvania
city: Newport
country: United States
facility: Capital Area Research, LLC
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Fort Mill
country: United States
facility: Piedmont Research Partners
state: South Carolina
city: Greenville
country: United States
facility: Tribe Clinical Research
state: South Carolina
city: Chattanooga
country: United States
facility: University Diabetes & Endocrine Consultants
state: Tennessee
city: Fort Worth
country: United States
facility: Diabetes and Thyroid Center of Fort Worth
state: Texas
city: Houston
country: United States
facility: Juno Research LLC
state: Texas
city: Houston
country: United States
facility: Care and Cure Clinic
state: Texas
city: Houston
country: United States
facility: Spring Clinical Research
state: Texas
city: Sugar Land
country: United States
facility: Sugar Lakes Family Practice
state: Texas
city: Tomball
country: United States
facility: Northwest Houston Clinical Research, PLLC
state: Texas
city: Victoria
country: United States
facility: Crossroads Clinical Research
state: Texas
city: Bountiful
country: United States
facility: Cope Family Medicine
state: Utah
city: Saint George
country: United States
facility: Chrysalis Clinical Research
state: Utah
city: Manassas
country: United States
facility: Manassas Clinical Research Center
state: Virginia
city: Roanoke
country: United States
facility: Roanoke Heart Institute
state: Virginia
city: Caba
country: Argentina
facility: Expertia S.A- Mautalen Salud e Investigación
state: Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: CINME - Centro De Investigaciones Metabolicas
state: Buenos Aires
city: Córdoba
country: Argentina
facility: Centro Medico Colon
state: Cordoba
city: Godoy Cruz
country: Argentina
facility: CIPADI Centro Integral de Prevención y Atención en Diabetes
state: Mendoza
city: Rosario
country: Argentina
facility: Instituto Medico Fundación Grupo Colaborativo Rosario Investigación y Prevención Medica
state: Santa FE
city: Salvador
country: Brazil
facility: Hospital Cardio Pulmonar
state: Bahia
city: Brasília
country: Brazil
facility: CECAP - Centro de Cardiologia Clínica
state: Distrito Federal
city: Belo Horizonte
country: Brazil
facility: CARDRESEARCH - Cardiologia Assistencial
state: Minas Gerais
city: Campinas
country: Brazil
facility: IPECC - Instituto de Pesquisa Clínica de Campinas
state: Sao Paulo
city: Santo André
country: Brazil
facility: Pesquisare Saúde
state: Sao Paulo
city: São José Do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
state: Sao Paulo
city: Aracaju
country: Brazil
facility: Centro de Pesquisa Clinica do Coracao
state: Sergipe
city: Recife
country: Brazil
facility: Hospital Agamenon Magalhães
city: Byala
country: Bulgaria
facility: MHAT Yuliya Vrevska - Byala, EOOD
city: Dimitrovgrad
country: Bulgaria
facility: Medical Center Diamedical - 2013 OOD
city: Haskovo
country: Bulgaria
facility: MHAT-Haskovo AD
city: Kyustendil
country: Bulgaria
facility: Medical Center Hera - Kyustendil EOOD
city: Ruse
country: Bulgaria
facility: Medical Center Rusemed EOOD
city: Sevlievo
country: Bulgaria
facility: Medical Center Unimed EOOD
city: Sofia
country: Bulgaria
facility: Second medical center - Sofia ЕOOD
city: Sofia
country: Bulgaria
facility: Medical Center Acad. I. Penchev, EOOD
city: Sofia
country: Bulgaria
facility: UMHAT Alexandrovska EAD
city: Sofia
country: Bulgaria
facility: Medical Center Hera EOOD
city: Sofia
country: Bulgaria
facility: Medical Center Sv. Dimitar
city: Sofia
country: Bulgaria
facility: Kalimat"-M.C.
city: Sofia
country: Bulgaria
facility: UMHAT SofiaMed, OOD
city: Stara Zagora
country: Bulgaria
facility: Medical Center ZARA-MED EOOD
city: North Vancouver
country: Canada
facility: Medical Arts Health Research Group
state: British Columbia
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Laval
country: Canada
facility: Centre de Recherche Clinique de Laval
state: Quebec
city: Québec
country: Canada
facility: Recherche Clinique Sigma Inc
state: Quebec
city: Terrebonne
country: Canada
facility: Centre de Medecine Metabolique de Lanaudiere
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice u svate Anny v Brne
city: Náchod
country: Czechia
facility: EDUMED s.r.o.
city: Olomouc
country: Czechia
facility: PreventaMed s.r.o.
city: Praha
country: Czechia
facility: MUDr. Jan KVASNIČKA,CSc. Angiologie kardiologie a interna
city: Slaný
country: Czechia
facility: Nemocnice Slany
city: Teplice
country: Czechia
facility: Unilabs Diagnostics, k.s
city: Trutnov
country: Czechia
facility: Kardiologicka ambulance MUDr. Ferkl s.r.o.
city: Marseille
country: France
facility: Assistance Publique Hopitaux de Marseille AP HM Hopital de La Conception
state: Bouches-du-Rhône
city: Pessac
country: France
facility: Groupe Hospitalier Sud Hôpital Haut-Lévêque
state: Gironde
city: Bayonne
country: France
facility: Centre Hospitalier de la côte Basque
state: Pyrenees Atlantiques
city: Lyon
country: France
facility: Hopital Saint Joseph Saint Luc
state: Rhone
city: Paris
country: France
facility: APHP Hôpital Universitaire Pitié Salpêtrière
city: Deggingen
country: Germany
facility: MVZ Jung GbR
state: Baden Wuerttemberg
city: Wallerfing
country: Germany
facility: Gemeinschaftspraxis Dr. Josef Grosskopf und Dr. Wilma Grosskopf
state: Bayern
city: Magdeburg
country: Germany
facility: SMO.MD GmbH
state: Sachsen Anhalt
city: Berlin
country: Germany
facility: Charité - Campus Charité Mitte
city: Békéscsaba
country: Hungary
facility: Belgyogyaszati es Kardiologiai Maganrendelo
city: Kaposvár
country: Hungary
facility: Obudai Egeszsegugyi Centrum Kft.
city: Miskolc
country: Hungary
facility: IPR Hungary Kft.
city: Pécs
country: Hungary
facility: COROMed-SMO Kft.
city: Pécs
country: Hungary
facility: Da Vinci Maganklinika
city: Zalaegerszeg
country: Hungary
facility: Belvarosi Egeszseghaz Kft.
city: Daugavpils
country: Latvia
facility: Medical Centre OLVI
city: Daugavpils
country: Latvia
facility: Daugavpils Regional Hospital
city: Daugavpils
country: Latvia
facility: Department of Internal Medicine, Daugavpils Regional Hospital
city: Kuldīga
country: Latvia
facility: Dr. R. Eglites Private practice
city: Riga
country: Latvia
facility: Pauls Stradins Clinical University Hospital SLLC
city: Riga
country: Latvia
facility: Riga East Clinical University Hospital
city: Riga
country: Latvia
facility: Medical Centre DAP
city: Tukums
country: Latvia
facility: Inese Petrova General Practitioner Practice
city: Kaunas
country: Lithuania
facility: Kaunas City Polyclinic, Silainiai Subdivision
city: Kaunas
country: Lithuania
facility: Klinikiniai sprendimai, JSC
city: Kaunas
country: Lithuania
facility: Inmedica, JSC
city: Vilnius
country: Lithuania
facility: Centre of Cardiology and Angiology, Vilnius University Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos, Public Institution
city: Šiauliai
country: Lithuania
facility: Pirmoji Viltis, JSC
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research (NZCR)
city: New Plymouth
country: New Zealand
facility: Te Whatu Ora Taranaki
city: Newtown
country: New Zealand
facility: Wellington Regional Hospital
city: Bydgoszcz
country: Poland
facility: MICS Centrum Medyczne Bydgoszcz
city: Gdynia
country: Poland
facility: Centrum Medyczne Pratia Gdynia
city: Katowice
country: Poland
facility: Clinical Medical Research Sp. z o.o.
city: Malbork
country: Poland
facility: Centrum Badawcze Panaceum Agnieszka Brzezicka, Magdalena Lenkiewicz Sp z o.o.
city: Szczecin
country: Poland
facility: Twoja Przychodnia-Szczecinskie Centrum Medyczne Sp. z o. o.
city: Toruń
country: Poland
facility: Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu
city: Wrocław
country: Poland
facility: NZOZ Zdrowie s.c. Agnieszka i Donald Drożdż
city: Zamość
country: Poland
facility: Velocity Zamosc
city: Łódź
country: Poland
facility: Indywidualna Specjalistyczna Praktyka Lekarska
city: Bratislava
country: Slovakia
facility: Kardiovaskularne centrum, s.r.o.
city: Nové Zámky
country: Slovakia
facility: Kardiologická ambulancia Cardioamb s.r.o
city: Prešov
country: Slovakia
facility: Medispol s.r.o.
city: Rožňava
country: Slovakia
facility: Tatratrial s.r.o.
city: Centurion
country: South Africa
facility: Dr IO Ebrahim Inc
state: Gauteng
city: Krugersdorp
country: South Africa
facility: DJW Navorsing
state: Gauteng
city: Pretoria
country: South Africa
facility: RYEXO Clinical Research
state: Gauteng
city: Durban
country: South Africa
facility: Dr. Jeevren Reddy's surgery
state: KwaZulu-Natal
city: Cape Town
country: South Africa
facility: Canal Walk Medical and Wellness Centre
state: Western Cape
city: Cape Town
country: South Africa
facility: Corbod Research
state: Western Cape
city: Cape Town
country: South Africa
facility: Langeberg Clinical Trials
state: Western Cape
city: Cape Town
country: South Africa
facility: Tiervlei Trial Centre
state: Western Cape
city: Cape Town
country: South Africa
facility: UCT Lipid Laboratory
state: Western Cape
city: Mossel Bay
country: South Africa
facility: Eden Heart
state: Western Cape
city: Plettenberg Bay
country: South Africa
facility: Tsitsikamma Clinical Research Initiative
state: Western Cape
city: Somerset West
country: South Africa
facility: Dr JM Engelbrecht Trial Site
state: Western Cape
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
state: La Coruña
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
References: