Study of ARO-ANG3 in Adults With Mixed Dyslipidemia (ARCHES-2)

A Double-blind, Placebo-controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-ANG3 in Adults With Mixed Dyslipidemia

The purpose of AROANG3-2001 is to evaluate the efficacy and safety of ARO-ANG3 in participants with mixed dyslipidemia. Participants will initially receive 2 subcutaneous injections of ARO-ANG3 or placebo. Participants who complete the double-blind treatment period may opt to continue in an open-label extension during which they will receive up to 8 doses of ARO-ANG3.

Study Overview

• Status: Completed
• Conditions: Mixed Dyslipidemia
• Intervention / Treatment: Drug: ARO-ANG3; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Nedlands, Australia, 6009
    • Research Site 18
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Research Site 6
  • Queensland
    • Sippy Downs, Queensland, Australia, 4556
      • Research Site 21
• Canada
  • Québec, Canada, G1G 3Z4
    • Research Site 12
  • Québec, Canada, H7T2P5
    • Research Site 9
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Research Site 25
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Research Site 16
• New Zealand
  • Birkenhead, New Zealand, 0626
    • Research Site 19
  • Christchurch, New Zealand, 8011
    • Research Site 13
  • Hamilton, New Zealand, 3200
    • Research Site 20
  • Rotorua, New Zealand, 3010
    • Research Site 14
• United States
  • California
    • Huntington Park, California, United States, 90255
      • Research Site 5
  • Florida
    • Hialeah, Florida, United States, 33012
      • Research Site 7
    • Miami, Florida, United States, 33144
      • Research Site 17
    • Port Orange, Florida, United States, 32127
      • Research Site 8
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Research Site 24
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Research Site 10
  • Nevada
    • Las Vegas, Nevada, United States, 89121
      • Research Site 23
  • New York
    • New York, New York, United States, 10029
      • Research Site 22
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Research Site 15
    • Morehead City, North Carolina, United States, 28557
      • Research Site 2
  • Ohio
    • Marion, Ohio, United States, 43302
      • Research Site 1
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Research Site 4
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site 11

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 triglycerides (TG) ≥ 150 mg/dL but ≤ 499 mg/dL
• Fasting levels at Screening of LDL-C ≥ 70 mg/dL OR non-HDL-C ≥ 100 mg/dL after at least 4 weeks of stable diet and stable optimal statin therapy
• Mean fasting TG ≥ 150 mg/dL and ≤ 499 mg/dL during Screening collected at two separate and consecutive visits and at least 7 days apart and not more than 17 days apart
• Willing to follow diet counseling and maintain a stable diet per Investigator judgment based on local standard of care
• Participants of childbearing potential must agree to use highly-effective contraception during the study and for at least 24 weeks from last dose of study medication
• Women of childbearing potential must have a negative pregnancy test and cannot be breastfeeding
• Women of childbearing potential on hormonal contraceptives must be stable on the medication for ≥ 2 menstrual cycles prior to Day 1
• Men must not donate sperm during the study and for at least 24 weeks following the last dose of study medication
• Able and willing to provide written informed consent and to comply with study requirements

Exclusion Criteria:

• Current use or use within 365 days from Day 1 of any hepatocyte targeted siRNA or antisense oligonucleotide molecule
• Active pancreatitis within 12 weeks prior to Day 1
• 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 Day 1
• Major surgery within 12 weeks of Day 1 or planned surgery during the study
• Planned coronary intervention (e.g., stent placement or heart bypass) during 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 Day 1
• History of bleeding diathesis or coagulopathy
• Current diagnosis of nephrotic syndrome
• Systemic use of corticosteroids or anabolic steroids within 4 weeks prior to Day 1 or planned use during the study
• 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
Placebo Comparator: Placebo; Calculated volume to match active treatment by sc injection at Day 1 and Week 12 during the double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.	Drug: ARO-ANG3; ARO-ANG3 Injection; Drug: Placebo; Sterile Normal Saline (0.9% NaCl)
Experimental: ARO-ANG3 50 mg; Two doses of ARO-ANG3 by subcutaneous (sc) injection at Day 1 and Week 12 during double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.	Drug: ARO-ANG3; ARO-ANG3 Injection
Experimental: ARO-ANG3 100 mg; Two doses of ARO-ANG3 bysc injection at Day 1 and Week 12 during double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.	Drug: ARO-ANG3; ARO-ANG3 Injection
Experimental: ARO-ANG3 200 mg; Two doses of ARO-ANG3 by sc injection at Day 1 and Week 12 during double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.	Drug: ARO-ANG3; ARO-ANG3 Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in Fasting TG at Week 24	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	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 Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24		Baseline, Week 24
Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24		Baseline, Week 24
Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24		Baseline, Week 24
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24	TEAEs are adverse events (AEs) that occur following IP administration or a pre-existing condition exacerbated following IP administration. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A serious adverse event (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.	From first dose of IP up to Week 24
Percent Change From Baseline in Fasting TG Over Time		Baseline, up to Week 36 (double-blind treatment period)
Percent Change From Baseline in Fasting Non-HDL-C Over Time		Baseline, up to Week 36 (double-blind treatment period)
Percent Change From Baseline in Fasting Total ApoB Over Time		Baseline, up to Week 36 (double-blind treatment period)
Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time		Baseline, up to Week 36 (double-blind treatment period)
Percent Change From Baseline in ANGPTL3 Over Time		Baseline, up to Week 36 (double-blind treatment period)
Percent Change From Baseline in Fasting HDL-C Over Time		Baseline, up to Week 36 (double-blind treatment period)
Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period		Baseline, Day 1: pre-dose, 15 minutes, 1, 3, 6 hours post-dose; Day 2: 24 hours post-dose; Week 12: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose (double-blind treatment period)
Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period	Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. TEAEs=AEs with onset after administration of the study drug, or when a pre-existing medical condition increases in severity or frequency after study drug administration. Serious adverse event (SAE)= 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; is a medically important event or reaction.	up to Week 36 (double-blind treatment period)
Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period	Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. TEAEs=AEs with onset after administration of the study drug, or when a pre-existing medical condition increases in severity or frequency after study drug administration. Serious adverse event (SAE)= 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; is a medically important event or reaction.	From first dose of study drug in the OLE up to Month 24 (open-label extension)
Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period		Baseline, OLE Baseline, Months 1-24 (open-label extension)
Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period		Baseline, OLE Baseline, Months 1-24 (open-label extension)
Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period		Baseline, OLE Baseline, Months 1-24 (open-label extension)
Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period		Baseline, OLE Baseline, Months 1-24 (open-label extension)
Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period		Baseline, OLE Baseline, Months 1-24 (open-label extension)
Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period		Baseline, OLE Baseline, Months 1-24 (open-label extension)

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Publications and helpful links

General Publications

• Dimitriadis K, Theofilis P, Iliakis P, Pyrpyris N, Dri E, Sakalidis A, Soulaidopoulos S, Tsioufis P, Fragkoulis C, Chrysohoou C, Tsiachris D, Tsioufis K. Management of dyslipidemia in coronary artery disease: the present and the future. Coron Artery Dis. 2024 Sep 1;35(6):516-524. doi: 10.1097/MCA.0000000000001375. Epub 2024 Apr 29.
• Rosenson RS, Gaudet D, Hegele RA, Ballantyne CM, Nicholls SJ, Lucas KJ, San Martin J, Zhou R, Muhsin M, Chang T, Hellawell J, Watts GF; ARCHES-2 Trial Team. Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia. N Engl J Med. 2024 Sep 12;391(10):913-925. doi: 10.1056/NEJMoa2404147. Epub 2024 May 29.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2021
• Primary Completion (Actual): August 30, 2022
• Study Completion (Actual): September 25, 2024

Study Registration Dates

• First Submitted: April 2, 2021
• First Submitted That Met QC Criteria: April 2, 2021
• First Posted (Actual): April 6, 2021

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias
• Other Study ID Numbers: AROANG3-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: No