A Trial to Evaluate the Efficacy and Safety of ARO-INHBE in Adults With Metabolic Dysfunction-Associated Steatohepatitis

A Phase 2, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of ARO-INHBE in Adults With Metabolic Dysfunction-Associated Steatohepatitis With or Without Type 2 Diabetes Mellitus

This study is designed to evaluate the safety and efficacy of ARO-INHBE in adults with suspected metabolic dysfunction-associated steatohepatitis (MASH).

Study Overview

• Status: Not yet recruiting
• Conditions: Metabolic Dysfunction-Associated Steatohepatitis
• Intervention / Treatment: Drug: Placebo; Drug: ARO-INHBE

• Study Type: Interventional
• Enrollment (Estimated): 252
• Phase: Phase 2

Contacts and Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• BMI between 30.0 to 50.0 kilograms (kg)/square meter (m^2) (inclusive) with body weight ≤159 kg at Screening
• Stable body weight
• Participants on background glucagon-like peptide-1 (GLP-1) (or GLP-1/glucose-dependent insulinotropic polypeptide [GIP]) therapy must be on a stable dose for ≥6 months
• Participants not on GLP-1 (or GLP-1/GIP) therapy must be treatment naïve or off therapy for ≥6 months.

Key Exclusion Criteria:

• Clinical or laboratory signs of decompensated liver disease, history of esophageal varices, ascites, or hepatic encephalopathy, or history of cirrhosis on biopsy performed prior to Screening.
• History or evidence of hepatic disease of non-metabolic dysfunction-associated steatotic liver disease (MASLD) etiology (viral hepatitis, alcoholic liver disease, primary biliary cholangitis [PBC], primary sclerosing cholangitis [PSC], Wilson's disease, alpha-1 antitrypsin [A1AT] deficiency, hemochromatosis, or autoimmune hepatitis).
• Type 1 diabetes mellitus (T1DM) or uncontrolled Type 2 diabetes mellitus (T2DM).
• Use of non-GLP-1 receptor medications known to cause weight loss within 3 months prior to Screening.
• Use of medications associated with weight gain (for example, tricyclic antidepressants, mirtazapine, paroxetine, atypical antipsychotics) unless on a stable dose ≥3 months prior to Screening with anticipated continuation on this dose throughout the trial.
• Clinically significant end-organ disease.
• Major surgery within 90 days of Screening.
• Use of hepatocyte-targeted ribonucleic acid interference (RNAi) therapies within 6 months of Screening.
• Insulin use within 6 months of Screening (except short-term peri-procedural/inpatient use).

Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARO-INHBE Low Dose; Participants will receive ARO-INHBE at a low dose on Days 1, 85, 169, and 253.	Drug: ARO-INHBE; Subcutaneous (SC) injection
Placebo Comparator: Placebo for ARO-INHBE Low Dose; Participants will receive placebo on Days 1, 85, 169, and 253.	Drug: Placebo; SC injection
Experimental: ARO-INHBE High Dose (Schedule 1); Participants will receive ARO-INHBE at a high dose on Days 1, 85, 169, and 253.	Drug: ARO-INHBE; Subcutaneous (SC) injection
Placebo Comparator: Placebo for ARO-INHBE High Dose (Schedule 1); Participants will receive placebo on Days 1, 85, 169, and 253.	Drug: Placebo; SC injection
Experimental: ARO-INHBE High Dose (Schedule 2); Participants will receive ARO-INHBE at a high dose on Days 1, 85, and 169.	Drug: ARO-INHBE; Subcutaneous (SC) injection
Experimental: Placebo for ARO-INHBE High Dose (Schedule 2); Participants will receive placebo on Days 1, 85, and 169.	Drug: Placebo; SC injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in Liver Fat Content (LFC) by Magnetic Resonance Imaging-proton Density Fat Fraction (MRI-PDFF) at Week 48	Baseline, Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Resolution of Steatohepatitis and No Worsening of Liver Fibrosis (Histology)	Week 48
Percentage of Participants With Improvement in Liver Fibrosis by ≥1 Stage and No Worsening of Steatohepatitis (Histology)	Week 48
Change From Baseline in Non-alcoholic Fatty Liver Disease Activity Score (NAS) Total Score and Individual Subscores (Steatosis, Hepatocyte Ballooning, and Lobular Inflammation) at Week 48	Baseline, Week 48
Change From Baseline in Fibrosis Stage (Histology) at Week 48	Baseline, Week 48
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Baseline up to Week 48
Change From Baseline in LFC by MRI-PDFF at Week 24	Baseline, Week 24
Percentage of Participants With >30%, >50%, and >70% Reduction in LFC From Baseline by MRI-PDFF at Week 24 and Week 48	Week 24 and Week 48
Change From Baseline Through Week 48 in Body Weight	Baseline through Week 48
Change From Baseline Through Week 48 in Body Composition (Total Adipose Tissue [TAT], Visceral Adipose Tissue [VAT] Volume, and Total Lean Tissue [TLT]), by Whole-body Magnetic Resonance Imaging (WB-MRI)	Baseline through Week 48
Change From Baseline Through Week 48 in Serum Activin E Protein	Baseline through Week 48
Change From Baseline in Markers of Hepatic Steatosis at Week 48	Baseline through Week 48
Change From Baseline in Markers of Inflammation at Week 48	Baseline through Week 48
Change From Baseline in Markers of Fibrosis at Week 48	Baseline through Week 48

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: July 10, 2026
• First Submitted That Met QC Criteria: September 30, 2026
• First Posted (Actual): October 6, 2026

Study Record Updates

• Last Update Posted (Actual): October 6, 2026
• Last Update Submitted That Met QC Criteria: September 30, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: MASH
• Other Study ID Numbers: AROINHBE-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.: Yes