Study of ARO-DIMERPA in Adult Participants With Mixed Hyperlipidemia

Phase 1/2a, Double-blind, Placebo-controlled, Single and Multiple Dose-escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of ARO-DIMERPA in Adult Subjects With Mixed Hyperlipidemia

Study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD), and effects on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TGs) of single-dose ARO-DIMERPA and multiple doses of ARO-DIMERPA in adult participants with mixed hyperlipidemia.

Study Overview

• Status: Recruiting
• Conditions: Hyperlipidemia; Mixed
• Intervention / Treatment: Drug: ARO-DIMERPA; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Medical Monitor; Phone Number: 626-304-3400; Email: ARODIMERPA-1001@arrowheadpharma.com

Study Locations

• New Zealand
  • Christchurch, New Zealand, 8011
    • Recruiting
    • Research Site 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Willing to follow diet counseling as per Investigator judgment based on local standard of care
• Specific fasting TG, LDL-C, and non-high density lipoprotein cholesterol levels at Screening
• Participants of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of the study or last dose of study drug, whichever is later; participants must not donate sperm or eggs during the study and for at least 90 days following the end of the study or last dose of study drug whichever is later

Exclusion Criteria:

• Current use or use within last 365 days or within 5-half-lives before Day 1 based on plasma PK, whichever is longer, of any hepatocyte-targeted siRNA
• Current use or use within last 90 days or within 5-half-lives before Day 1 based on plasma PK, whichever is longer, of any antisense oligonucleotide therapy
• Current use or use within last 60 days from Day 1 of any PCSK9 inhibitor monoclonal antibodies (eg, evolocumab or alirocumab)
• Uncontrolled hypertension
• History of bleeding diathesis or coagulopathy
• Current diagnosis of nephrotic syndrome

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: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARO-DIMERPA; ARO-DIMERPA in single or multiple ascending doses	Drug: ARO-DIMERPA; Subcutaneous (SC) injection
Placebo Comparator: Placebo; Placebo (normal saline, 0.9%) in single or multiple matching doses	Drug: Placebo; Calculated volume to match active treatment by SC injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)	Up to Week 36

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change from Baseline in Fasting LDL-C	Baseline to Week 36
Percent Change from Baseline in Fasting TGs	Baseline to Week 36
Percent Change from Baseline in Serum apoC-III	Baseline to Week 36
Percent Change from Baseline in Serum PCSK9	Baseline to Week 36
PK of ARO-DIMERPA: Maximum Observed Plasma Concentration (Cmax)	Through 24 hours postdose
PK of ARO-DIMERPA: Time to Maximum Plasma Concentration (Tmax)	Through 24 hours postdose
PK of ARO-DIMERPA: Area Under the Plasma Concentration (AUC) Versus Time Curve From Time Zero to 24 Hours (AUC0-24)	Through 24 hours postdose
PK of ARO-DIMERPA: AUC Versus Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUC0-t)	Through 24 hours postdose
PK of ARO-DIMERPA: AUC Versus Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf)	Through 24 hours postdose
PK of ARO-DIMERPA: Apparent Terminal Elimination Half-life (t1/2)	Through 24 hours postdose
PK of ARO-DIMERPA: Apparent Systemic Clearance (CL/F)	Through 24 hours postdose
PK of ARO-DIMERPA: Apparent Terminal-phase Volume of Distribution (Vz/F)	Through 24 hours postdose
PK of ARODIMERPA: Recovery of Unchanged Drug (Ae) in Urine From Time Zero to 24 Hours Postdose	Through 24 hours postdose
PK of ARO-DIMERPA: Percentage of Administered Drug Recovered (Fe) in Urine From Time Zero to 24 Hours Postdose	Through 24 hours postdose
PK of ARO-DIMERPA: Renal Clearance (CLR)	Through 24 hours postdose

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: October 30, 2025
• First Submitted That Met QC Criteria: October 30, 2025
• First Posted (Estimated): November 3, 2025

Study Record Updates

• Last Update Posted (Actual): January 9, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hyperlipoproteinemia Type II
• Other Study ID Numbers: ARODIMERPA-1001

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.: Yes