Study to Evaluate ARO-APOC3 in Adults With Severe Hypertriglyceridemia (SHASTA-2)

A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults With Severe Hypertriglyceridemia

The purpose of AROAPOC3-2001 is to evaluate the efficacy and safety of ARO-APOC3 in participants with severe hypertriglyceridemia. Participants will receive 2 subcutaneous injections of ARO-APOC3.

Study Overview

• Status: Completed
• Conditions: Severe Hypertriglyceridemia
• Intervention / Treatment: Drug: ARO-APOC3; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 229
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Nedlands
    • Perth, Nedlands, Australia, 6009
      • Linear Clinical Research
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4064
      • Core Research Group
    • Sippy Downs, Queensland, Australia, 4556
      • University of the Sunshine Coast
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
• Canada
  • Ontario
    • Concord, Ontario, Canada, L4K 4M2
      • LMC Diabetes & Endocrinology
    • London, Ontario, Canada, N6A 5A5
      • Lawson Health Research Institute
    • Toronto, Ontario, Canada, M4G 3E8
      • LMC Manna Research - Bayview
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H5H6
      • Centre d'Etudes Cliniques ECOGENE-21
    • Greenfield, Quebec, Canada, J4V2G8
      • ViaCar Recherches Cliniques Inc.
    • Montréal, Quebec, Canada, H2W2T2
      • Institut de Recherches Cliniques de Montreal
• Germany
  • Aachen, Germany, 52074
    • Uniklinik RWTH
  • Leipzig, Germany, 0 4103
    • Universitätsklinikum Leipzig
• Hungary
  • Baja, Hungary, 6500
    • Principal SMO Kft
  • Baja, Hungary, 6500
    • Lausmed Kft.
  • Balatonföldvár, Hungary, H-8230
    • DRC Gyogyszervizsgalo Kozpont Balatonfured
  • Bekescsaba, Hungary, 5600
    • Belgyogyaszati - Kardiologiai Maganrendelo
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem
  • Gyöngyös, Hungary, 3200
    • Pharma4trial Ltd
  • Komárom, Hungary, 2921
    • Selye János Kórház
  • Nyiregyhaza, Hungary, 4405
    • Borbanya Praxis Kft.
  • Nyíregyháza, Hungary, 4400
    • Medifarma-98 Kft.
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Uni Van Amsterdam Academisch Medisch Centrum
  • Dordrecht, Netherlands, 3318 AT
    • Albert Schweitzer Ziekenhuis
  • Sneek, Netherlands, 08601
    • D&A Research
• New Zealand
  • Christchurch, New Zealand, 8011
    • Lipid and Diabetes Research Group
  • Hamilton, New Zealand, 3200
    • Lakeland Clinical Trials - Waikato
  • Papatoetoe, New Zealand, 2025
    • Middlemore Clinical Trials
  • Rotorua, New Zealand, 3010
    • Lakeland Clinical Trials - Rotorua
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Auckland Clinical Studies
• Poland
  • Bydgoszcz, Poland, 85-605
    • Spolka Lekarzy Intercor Sp.z.o.o.
  • Elbląg, Poland, 82-300
    • NZOZ TWOJE ZDROWIE EL Sp.z.o.o.
  • Gdynia, Poland, 81-157
    • Indywidualna Specjalistyczna Praktyka Lekarska w Dziedzinie Kardiologii lek.
  • Leczyca, Poland, 99-100
    • Zaklad Opieki Zdrowotnej Leczyca
  • Oświęcim, Poland, 32-600
    • Medicome Sp. z.o.o.
  • Poznań, Poland, 61-655
    • Praktyka Lekarska Ewa Krzyzagorska
  • Puławy, Poland, 24-100
    • KO-MED M Konieczny Cent. Wielosp. Opieki
  • Rzeszów, Poland, 35-055
    • Centrum Medyczne Medyk
  • Wołomin, Poland, 05-200
    • Centrum Medyczne K2J2
  • Łódź, Poland, 94-048
    • All-MED Centrum Medyczne
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Westside Medical Associates of Los Angeles
    • Palm Springs, California, United States, 92292
      • Desert Oasis Healthcare (Desert Medical Group, Inc.)
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Preventive Cardiology Inc.
    • Fort Lauderdale, Florida, United States, 33308
      • Invesclinic U.S., LLC
    • Miami, Florida, United States, 33155
      • AppleMed Research Group
    • Miami, Florida, United States, 33173
      • HeartWell LLP
    • Miami, Florida, United States, 33144
      • A Positive Research, Inc.
    • Miami, Florida, United States, 33144
      • Y&L Advance Health care, Inc. D/B/A Elite Clinical Research
    • Miami Springs, Florida, United States, 33166
      • Ocean Blue Medical Research Center Inc.
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
  • Georgia
    • Dunwoody, Georgia, United States, 30338
      • Alta Pharmaceutical Research Center
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Northwest Heart Clinical Research
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • The Research Group of Lexington, LLC
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Cardiology Associates Research, LLC
  • Montana
    • Kalispell, Montana, United States, 59901
      • Glacier View Research Institute
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Physicians Clinic Heart Consultants
  • Nevada
    • Las Vegas, Nevada, United States, 89121
      • Clinical Research of South Nevada
  • New York
    • Long Island City, New York, United States, 11106
      • NYC Research, Inc.
    • New Windsor, New York, United States, 12553
      • Mid Hudson Medical Research, PLLC
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai (ISMMS)
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research, Inc
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research LLC
  • Ohio
    • Dayton, Ohio, United States, 45419
      • PriMed Clinical Research
    • Franklin, Ohio, United States, 45005
      • Prestige Clinical Research
    • Maumee, Ohio, United States, 43537
      • Advanced Medical Research, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73135
      • South Oklahoma Heart Research, LLC
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Tribe Clinical Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-CllinSearch, LLC
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions, Inc.
    • San Antonio, Texas, United States, 78249
      • BFHC Research
  • Virginia
    • Manassas, Virginia, United States, 20110
      • Manassas Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Based on medical history, evidence of TG ≥ 500 mg/dL and ≤ 4000 mg/dL at Screening
• Fasting TG ≥ 500 mg/dL at Screening
• Willing to follow diet counseling per Investigator judgment based on local standard of care
• Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception
• Willing to provide written informed consent and to comply with study requirements

Exclusion Criteria:

• Active pancreatitis within 12 weeks prior to first dose
• Any planned bariatric surgery or similar procedures to induce weight loss from consent to end of study
• Acute coronary syndrome event within 24 weeks of first dose
• Major surgery within 12 weeks of first dose
• Planned coronary intervention (e.g., stent placement or heart bypass) or any non-cardiac major surgical procedure throughout the study
• Uncontrolled hypertension
• Human immunodeficiency virus (HIV) infection, seropositive for Hepatitis B (HBV), seropositive for Hepatitis C (HCV)
• Uncontrolled hypothyroidism or hyperthyroidism
• Hemorrhagic stroke within 24 weeks of first dose
• Malignancy within the last 2 years prior to date of consent requiring systemic treatment (some exceptions apply)

Note: additional inclusion/exclusion criteria may apply per protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARO-APOC3 10 mg, Day 1 and Week 12; 2 doses of ARO-APOC3 by subcutaneous (sc) injection	Drug: ARO-APOC3; 2 doses of ARO-APOC3 by subcutaneous (sc) injection
Experimental: ARO-APOC3 25 mg, Day 1 and Week 12; 2 doses of ARO-APOC3 by sc injection	Drug: ARO-APOC3; 2 doses of ARO-APOC3 by subcutaneous (sc) injection
Experimental: ARO-APOC3 50 mg, Day 1 and Week 12; 2 doses of ARO-APOC3 by sc injection	Drug: ARO-APOC3; 2 doses of ARO-APOC3 by subcutaneous (sc) injection
Placebo Comparator: Placebo, Day 1 and Week 12; calculated volume to match active treatment by sc injection	Drug: Placebo; calculated volume to match active treatment by sc injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change from Baseline in Fasting Triglycerides (TG) at Week 24	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24	Baseline, Week 24
Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24	Baseline, Week 24
Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24	Baseline, Week 24
Percent Change from Baseline in Fasting TG Over Time Through Week 48	Baseline, up to Week 48
Percent Change from Baseline in Apolipoprotein (Apo)C-III at Week 24	Baseline, Week 24
Percent Change from Baseline in ApoC-III Over Time Through Week 48	Baseline, up to Week 48
Percent Change from Baseline in Fasting Non-HDL-C Over Time Through Week 48	Baseline, up to Week 48
Percent Change from Baseline in Fasting HDL-C Over Time Through Week 48	Baseline, up to Week 48
Percent Change from Baseline in Fasting Total ApoB Over Time Through Week 48	Baseline, up to Week 48
Percent Change from Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation	Baseline, Week 24
Percent Change from Baseline in Fasting LDL-C Using Ultracentrifugation Over Time Through Week 48	Baseline, up to Week 48
Change from Baseline in Plasma Concentration of ARO-APOC3 Over Time Through Week 48	Baseline, up to Week 48
Number of Participants with Adverse Events (AEs) and/or Serious Adverse Events (SAEs) Possibly or Probably Related to Treatment	up to Week 48

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2021
• Primary Completion (Actual): March 9, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: January 19, 2021
• First Submitted That Met QC Criteria: January 19, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypertriglyceridemia
• Other Study ID Numbers: AROAPOC3-2001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes