Study of ARO-HSD in Healthy Volunteers and Patients With Non-Alcoholic Steatohepatitis (NASH) or Suspected NASH

A Phase 1/2a Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of ARO-HSD in Normal Healthy Volunteers as Well as in Patients With NASH or Suspected NASH

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of single and multiple doses of ARO-HSD in healthy adult volunteers and in patients with NASH or suspected NASH.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Steatohepatitis
• Intervention / Treatment: Drug: ARO-HSD Injection; Drug: sterile normal saline (0.9% NaCl)

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Auckland Clinical Studies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Women of child bearing 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
• On a stable diet for at least 4 weeks with no plans to significantly alter diet or weight over course of study
• Normal electrocardiogram (ECG) at Screening
• No abnormal finding of clinical relevance (other than NASH, suspected NASH in patients) at Screening that could adversely impact subject safety during the study or adversely impact study results.

Exclusion Criteria:

• Clinically significant health concerns (other than NASH, suspected NASH in patients)
• Human immunodeficiency virus (HIV) infection, seropositive for Hepatitis B Virus (HBV), seropositive for Hepatitis C Virus (HCV)
• Uncontrolled hypertension
• Excessive use of alcohol within three months prior to Screening
• Use of illicit drugs within 1 year prior to Screening, or positive urine drug screen at Screening
• Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study

NOTE: additional inclusion/exclusion criteria may apply, per protocol

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Study Plan

How is the study designed?

Design Details

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

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: ARO-HSD 25 mg; Normal healthy volunteers randomized to double blind ARO-HSD 25 mg on Day 1 only.	Drug: ARO-HSD Injection; single or multiple doses of ARO-HSD by subcutaneous (sc) injections
Placebo Comparator: Cohort 1: Placebo; Normal healthy volunteers randomized to double blind placebo on Day 1 only.	Drug: sterile normal saline (0.9% NaCl); calculated volume to match active treatment, by sc injection
Experimental: Cohort 2: ARO-HSD 50 mg; Normal healthy volunteers randomized to double blind ARO-HSD 50 mg on Day 1 only.	Drug: ARO-HSD Injection; single or multiple doses of ARO-HSD by subcutaneous (sc) injections
Placebo Comparator: Cohort 2: Placebo; Normal healthy volunteers randomized to double blind placebo on Day 1 only.	Drug: sterile normal saline (0.9% NaCl); calculated volume to match active treatment, by sc injection
Experimental: Cohort 3: ARO-HSD 100 mg; Normal healthy volunteers randomized to double blind ARO-HSD 100 mg on Day 1 only.	Drug: ARO-HSD Injection; single or multiple doses of ARO-HSD by subcutaneous (sc) injections
Placebo Comparator: Cohort 3: Placebo; Normal healthy volunteers randomized to double blind placebo on Day 1 only.	Drug: sterile normal saline (0.9% NaCl); calculated volume to match active treatment, by sc injection
Experimental: Cohort 4: ARO-HSD 200 mg; Normal healthy volunteers randomized to double blind ARO-HSD 200 mg on Day 1 only.	Drug: ARO-HSD Injection; single or multiple doses of ARO-HSD by subcutaneous (sc) injections
Placebo Comparator: Cohort 4: Placebo; Normal healthy volunteers randomized to double blind placebo on Day 1 only.	Drug: sterile normal saline (0.9% NaCl); calculated volume to match active treatment, by sc injection
Experimental: Cohort 1b: ARO-HSD 25 mg; Participants with suspected non-alcoholic steatohepatitis (NASH) receive open-label ARO-HSD 25 mg on Days 1 and 29.	Drug: ARO-HSD Injection; single or multiple doses of ARO-HSD by subcutaneous (sc) injections
Experimental: Cohort 3b: ARO-HSD 100 mg; Participants with suspected NASH receive open-label ARO-HSD 100 mg on Days 1 and 29.	Drug: ARO-HSD Injection; single or multiple doses of ARO-HSD by subcutaneous (sc) injections
Experimental: Cohort 4b: ARO-HSD 200 mg; Participants with suspected NASH receive open-label ARO-HSD 200 mg on Days 1 and 29.	Drug: ARO-HSD Injection; single or multiple doses of ARO-HSD by subcutaneous (sc) injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Possibly or Probably Related to Treatment	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 through Day 113 (±5 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (PK) of ARO-HSD: Plasma Concentrations	Normal Healthy Volunteers: Day 1: 2 hours pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 8, 12, 18, 24; Day 2: 48 hours post-dose, Days 8, 15, 29. NASH Participants: Day 1: 2 hours pre-dose, 30 minutes, 1, 2, 24, hours post-dose, Days 8, 15, 29
PK of ARO-HSD in Normal Healthy Volunteers: Maximum Observed Plasma Concentration (Cmax)	Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24, 48 hours postdose
PK of ARO-HSD in Normal Healthy Volunteers: Time to Reach Cmax (Tmax)	Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24, 48 hours postdose
PK of ARO-HSD in Normal Healthy Volunteers: Terminal Elimination Half-Life (t1/2)	Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24, 48 hours postdose
PK of ARO-HSD in Normal Healthy Volunteers: Area Under the Concentration-Time Curve From Dosing (Time 0) to the Time of the Last Measured Concentration (AUClast)	Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24, 48 hours postdose
PK of ARO-HSD in Normal Healthy Volunteers: Area Under the Curve From Time 0 to Infinity (AUCinf)	Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24, 48 hours postdose
Secondary: PK of ARO-HSD in Normal Healthy Volunteers: Oral Clearance (CL/F)	Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24, 48 hours postdose
PK of ARO-HSD in Normal Healthy Volunteers: Apparent Volume of Distribution During the Terminal-Phase (Vz/F)	Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24, 48 hours postdose
Urine PK of ARO-HSD in Normal Healthy Volunteers: Amount of Unchanged Drug Recovered in Urine Over 0-24 Hours Postdose (Ae0-24h)	Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24 hours postdose
Urine PK of ARO-HSD in Normal Healthy Volunteers: Percentage of the Administrated Drug Recovered in Urine Over 0-24 Hours (Fe0-24h)	Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24 hours postdose
Urine PK of ARO-HSD in Normal Healthy Volunteers: Renal Clearance (CLr)	Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24 hours postdose

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Publications and helpful links

General Publications

• Mak LY, Gane E, Schwabe C, Yoon KT, Heo J, Scott R, Lee JH, Lee JI, Kweon YO, Weltman M, Harrison SA, Neuschwander-Tetri BA, Cusi K, Loomba R, Given BD, Christianson DR, Garcia-Medel E, Yi M, Hamilton J, Yuen MF. A phase I/II study of ARO-HSD, an RNA interference therapeutic, for the treatment of non-alcoholic steatohepatitis. J Hepatol. 2023 Apr;78(4):684-692. doi: 10.1016/j.jhep.2022.11.025. Epub 2022 Dec 10.

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2020
• Primary Completion (Actual): September 3, 2021
• Study Completion (Actual): September 3, 2021

Study Registration Dates

• First Submitted: December 16, 2019
• First Submitted That Met QC Criteria: December 16, 2019
• First Posted (Actual): December 17, 2019

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: AROHSD1001

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