Non-alcoholic SteatohepatitisPhase 1/2NCT04202354
Study of ARO-HSD in Healthy Volunteers and Patients With Non-Alcoholic Steatohepatitis (NASH) or Suspected NASH
A Phase 1/2 study testing ARO-HSD Injection and sterile normal saline (0.9% NaCl) in people with Non-alcoholic Steatohepatitis, run by Arrowhead Pharmaceuticals at 1 site in New Zealand.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-alcoholic Steatohepatitis
- What is being tested?
- ARO-HSD Injection and sterile normal saline (0.9% NaCl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteNew Zealand
- Study dates
- 3 Mar 2020to 3 Sep 2021
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- NOTE: additional inclusion/exclusion criteria may apply, per protocol
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Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Non-alcoholic Steatohepatitis
- Being tested
- ARO-HSD Injection, sterile normal saline (0.9% NaCl)
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARO-HSD InjectionDrug
single or multiple doses of ARO-HSD by subcutaneous (sc) injections
sterile normal saline (0.9% NaCl)Drug
calculated volume to match active treatment, by sc injection
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: ARO-HSD 25 mg | Experimental | Normal healthy volunteers randomized to double blind ARO-HSD 25 mg on Day 1 only. Receives: Drug: ARO-HSD Injection |
| Cohort 1: Placebo | Placebo comparator | Normal healthy volunteers randomized to double blind placebo on Day 1 only. Receives: 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. Receives: Drug: ARO-HSD Injection |
| Cohort 2: Placebo | Placebo comparator | Normal healthy volunteers randomized to double blind placebo on Day 1 only. Receives: 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. Receives: Drug: ARO-HSD Injection |
| Cohort 3: Placebo | Placebo comparator | Normal healthy volunteers randomized to double blind placebo on Day 1 only. Receives: 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. Receives: Drug: ARO-HSD Injection |
| Cohort 4: Placebo | Placebo comparator | Normal healthy volunteers randomized to double blind placebo on Day 1 only. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: ARO-HSD Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From first dose of study drug through Day 113 (±5 days)
Secondary outcomes (11)
Pharmacokinetics (PK) of ARO-HSD: Plasma Concentrations
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24 hours postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2019
- Study start3 Mar 2020
- Primary completion3 Sep 2021
- Study completion3 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-alcoholic SteatohepatitisStudies of the same condition, open and under way.
- More trials run by Arrowhead PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arrowhead Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04202354
- Sponsor's protocol ID
- AROHSD1001
- Status last verified
- Sep 2025
- First submitted
- 16 Dec 2019
- Last updated
- 3 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 36513186