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

March 3, 2026 updated by: Arrowhead Pharmaceuticals

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

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

229

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Nedlands
      • Perth, Nedlands, Australia, 6009
        • Research Site 43
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Research Site 42
    • Queensland
      • Brisbane, Queensland, Australia, 4064
        • Research Site 44
      • Sippy Downs, Queensland, Australia, 4556
        • Research Site 45
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Research Site 46
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Research Site 47
  • Canada
    • Ontario
      • Concord, Ontario, Canada, L4K 4M2
        • Research Site 49
      • London, Ontario, Canada, N6A 5A5
        • Research Site 50
      • Toronto, Ontario, Canada, M4G 3E8
        • Research Site 51
    • Quebec
      • Chicoutimi, Quebec, Canada, G7H5H6
        • Research Site 52
      • Greenfield, Quebec, Canada, J4V2G8
        • Research Site 53
      • Montreal, Quebec, Canada, H2W2T2
        • Research Site 54
  • Germany
      • Aachen, Germany, 52074
        • Research Site 55
      • Leipzig, Germany, 0 4103
        • Research Site 56
  • Hungary
      • Baja, Hungary, 6500
        • Research Site 57
      • Baja, Hungary, 6500
        • Research Site 58
      • Balatonföldvár, Hungary, H-8230
        • Research Site 59
      • Békéscsaba, Hungary, 5600
        • Research Site 60
      • Debrecen, Hungary, 4032
        • Research Site 61
      • Gyöngyös, Hungary, 3200
        • Research Site 62
      • Komárom, Hungary, 2921
        • Research Site 63
      • Nyíregyháza, Hungary, 4400
        • Research Site 65
      • Nyíregyháza, Hungary, 4405
        • Research Site 64
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Research Site 66
      • Dordrecht, Netherlands, 3318 AT
        • Research Site 67
      • Sneek, Netherlands, 08601
        • Research Site 68
  • New Zealand
      • Christchurch, New Zealand, 8011
        • Research Site 69
      • Hamilton, New Zealand, 3200
        • Research Site 70
      • Papatoetoe, New Zealand, 2025
        • Research Site 71
      • Rotorua, New Zealand, 3010
        • Research Site 72
    • Auckland
      • Grafton, Auckland, New Zealand, 1010
        • Research Site 73
  • Poland
      • Bydgoszcz, Poland, 85-605
        • Research Site 74
      • Elblag, Poland, 82-300
        • Research Site 75
      • Gdynia, Poland, 81-157
        • Research Site 76
      • Lodz, Poland, 94-048
        • Research Site 83
      • Oświęcim, Poland, 32-600
        • Research Site 78
      • Poznan, Poland, 61-655
        • Research Site 79
      • Puławy, Poland, 24-100
        • Research Site 80
      • Rzeszów, Poland, 35-055
        • Research Site 81
      • Wołomin, Poland, 05-200
        • Research Site 82
      • Łęczyca, Poland, 99-100
        • Research Site 77
  • United States
    • California
      • Beverly Hills, California, United States, 90211
        • Research Site 2
      • Palm Springs, California, United States, 92292
        • Research Site 4
    • Florida
      • Boca Raton, Florida, United States, 33434
        • Research Site 5
      • Fort Lauderdale, Florida, United States, 33308
        • Research Site 6
      • Miami, Florida, United States, 33144
        • Research Site 10
      • Miami, Florida, United States, 33144
        • Research Site 9
      • Miami, Florida, United States, 33155
        • Research Site 11
      • Miami, Florida, United States, 33173
        • Research Site 8
      • Miami Springs, Florida, United States, 33166
        • Research Site 12
      • Port Orange, Florida, United States, 32127
        • Research Site 14
    • Georgia
      • Dunwoody, Georgia, United States, 30338
        • Research Site 16
    • Illinois
      • Arlington Heights, Illinois, United States, 60005
        • Research Site 17
    • Kentucky
      • Lexington, Kentucky, United States, 40503
        • Research Site 18
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Research Site 20
    • Mississippi
      • Tupelo, Mississippi, United States, 38801
        • Research Site 21
    • Montana
      • Kalispell, Montana, United States, 59901
        • Research Site 22
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Research Site 23
    • Nevada
      • Las Vegas, Nevada, United States, 89121
        • Research Site 24
    • New York
      • Long Island City, New York, United States, 11106
        • Research Site 25
      • New Windsor, New York, United States, 12553
        • Research Site 26
      • New York, New York, United States, 10029
        • Research Site 27
    • North Carolina
      • Morehead City, North Carolina, United States, 28557
        • Research Site 29
    • North Dakota
      • Fargo, North Dakota, United States, 58104
        • Research Site 30
    • Ohio
      • Dayton, Ohio, United States, 45419
        • Research Site 31
      • Franklin, Ohio, United States, 45005
        • Research Site 32
      • Maumee, Ohio, United States, 43537
        • Research Site 33
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73135
        • Research Site 34
    • South Carolina
      • Greenville, South Carolina, United States, 29607
        • Research Site 35
    • Tennessee
      • Chattanooga, Tennessee, United States, 37421
        • Research Site 36
    • Texas
      • Houston, Texas, United States, 77030
        • Research Site 38
      • Houston, Texas, United States, 77099
        • Research Site 39
      • San Antonio, Texas, United States, 78249
        • Research Site 40
    • Virginia
      • Manassas, Virginia, United States, 20110
        • Research Site 41

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 triglycerides (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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Placebo, Day 1 and Week 12
Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Drug: Placebo
calculated volume to match active treatment by sc injection
Experimental: ARO-APOC3 10 mg
Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.
Drug: ARO-APOC3
2 doses of ARO-APOC3 by subcutaneous (sc) injection
Experimental: ARO-APOC3 25 mg
Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.
Drug: ARO-APOC3
2 doses of ARO-APOC3 by subcutaneous (sc) injection
Experimental: ARO-APOC3 50 mg
Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.
Drug: ARO-APOC3
2 doses of ARO-APOC3 by subcutaneous (sc) injection

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline Over Time Through Week 48 in Fasting TG
Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
Percent Change From Baseline at Week 24 in Apolipoprotein (Apo)C-III
Time Frame: Baseline, Week 24
Baseline, Week 24
Percent Change From Baseline Over Time Through Week 48 in ApoC-III
Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
Percent Change From Baseline at Week 24 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C)
Time Frame: Baseline, Week 24
Baseline, Week 24
Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C)
Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
Percent Change From Baseline at Week 24 in Fasting High-Density Lipoprotein Cholesterol (HDL-C)
Time Frame: Baseline, Week 24
Baseline, Week 24
Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C
Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
Percent Change From Baseline at Week 24 in Fasting Total Apolipoprotein B (ApoB)
Time Frame: Baseline, Week 24
Baseline, Week 24
Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB
Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
Percent Change From Baseline at Week 24 in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C)
Time Frame: Baseline, Week 24
LDL-C analyses used both Martin-Hopkins methodology and ultracentrifugation. The Martin-Hopkins formula is a method for calculating LDL-C that improves accuracy by using an adjustable factor for estimating very-low-density lipoprotein (VLDL) cholesterol cholesterol based on triglyceride and non-HDL cholesterol levels.
Baseline, Week 24
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C
Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
LDL-C analyses used both Martin-Hopkins methodology (MHM) and ultracentrifugation (UC). The Martin-Hopkins formula is a method for calculating LDL-C that improves accuracy by using an adjustable factor for estimating very-low-density lipoprotein (VLDL) cholesterol cholesterol based on triglyceride and non-HDL cholesterol levels.
Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12
Time Frame: Day 1: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose; Week 12: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose
Day 1: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose; Week 12: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From first dose of study drug up to Week 48
An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with this treatment. A serious AE (SAE) is an AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is a medically important event or reaction. TEAEs are AEs that occur following investigational product (IP) administration or a pre-existing condition exacerbated following IP administration.
From first dose of study drug up to Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Arrowhead Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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)

March 24, 2026

Last Update Submitted That Met QC Criteria

March 3, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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