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

NCT04202354 | Completed Phase 1 Results FDA Drug

• 1 other identifier: AROHSD1001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-alcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• 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

Study Arms (11)

Cohort 1: ARO-HSD 25 mg

EXPERIMENTAL

Normal healthy volunteers randomized to double blind ARO-HSD 25 mg on Day 1 only.

Drug: ARO-HSD Injection

Cohort 1: Placebo

PLACEBO COMPARATOR

Normal healthy volunteers randomized to double blind placebo on Day 1 only.

Drug: sterile normal saline (0.9% NaCl)

Cohort 2: ARO-HSD 50 mg

EXPERIMENTAL

Normal healthy volunteers randomized to double blind ARO-HSD 50 mg on Day 1 only.

Drug: ARO-HSD Injection

Cohort 2: Placebo

PLACEBO COMPARATOR

Normal healthy volunteers randomized to double blind placebo on Day 1 only.

Drug: sterile normal saline (0.9% NaCl)

Cohort 3: ARO-HSD 100 mg

EXPERIMENTAL

Normal healthy volunteers randomized to double blind ARO-HSD 100 mg on Day 1 only.

Drug: ARO-HSD Injection

Cohort 3: Placebo

PLACEBO COMPARATOR

Normal healthy volunteers randomized to double blind placebo on Day 1 only.

Drug: sterile normal saline (0.9% NaCl)

Cohort 4: ARO-HSD 200 mg

EXPERIMENTAL

Normal healthy volunteers randomized to double blind ARO-HSD 200 mg on Day 1 only.

Drug: ARO-HSD Injection

Cohort 4: Placebo

PLACEBO COMPARATOR

Normal healthy volunteers randomized to double blind placebo on Day 1 only.

Drug: sterile normal saline (0.9% NaCl)

Cohort 1b: ARO-HSD 25 mg

EXPERIMENTAL

Participants with suspected non-alcoholic steatohepatitis (NASH) receive open-label ARO-HSD 25 mg on Days 1 and 29.

Drug: ARO-HSD Injection

Cohort 3b: ARO-HSD 100 mg

EXPERIMENTAL

Participants with suspected NASH receive open-label ARO-HSD 100 mg on Days 1 and 29.

Drug: ARO-HSD Injection

Cohort 4b: ARO-HSD 200 mg

EXPERIMENTAL

Participants with suspected NASH receive open-label ARO-HSD 200 mg on Days 1 and 29.

Drug: ARO-HSD Injection

Interventions

ARO-HSD Injection DRUG

single or multiple doses of ARO-HSD by subcutaneous (sc) injections

Cohort 1: ARO-HSD 25 mg; Cohort 1b: ARO-HSD 25 mg; Cohort 2: ARO-HSD 50 mg; Cohort 3: ARO-HSD 100 mg; Cohort 3b: ARO-HSD 100 mg; Cohort 4: ARO-HSD 200 mg; Cohort 4b: ARO-HSD 200 mg

sterile normal saline (0.9% NaCl) DRUG

calculated volume to match active treatment, by sc injection

Cohort 1: Placebo; Cohort 2: Placebo; Cohort 3: Placebo; Cohort 4: Placebo

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Arrowhead Pharmaceuticals: lead

Study Sites (1)

Auckland Clinical Studies

Grafton, Auckland, 1010, New Zealand

Location

Related Publications (1)

• 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.

  PMID: 36513186 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Chief Operating Officer
• Organization: Arrowhead Pharmaceuticals, Inc.

info@arrowheadpharma.com

1 (626) 304-3400

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2019
• First Posted: December 17, 2019
• Study Start: March 3, 2020
• Primary Completion: September 3, 2021
• Study Completion: September 3, 2021
• Last Updated: October 3, 2025
• Results First Posted: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1)