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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Non-alcoholic Steatohepatitis

Intervention / Treatment
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* Drug: ARO-HSD Injection
* Drug: sterile normal saline (0.9% NaCl)


Participation Criteria
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Eligibility Criteria
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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 - -

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARO-HSD<br> | Drug: ARO-HSD Injection<br>* single or multiple doses of ARO-HSD by subcutaneous (sc) injections<br>|
| Placebo Comparator: Placebo<br> | Drug: sterile normal saline (0.9% NaCl)<br>* calculated volume to match active treatment, by sc injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment |  | single dose phase: Up to 113 (+/-2 days) post-dose; multiple dose phase: (Up to 196 (+/- 14 days) post-dose for patients with NASH | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK of ARO-HSD: Maximum observed Plasma Concentration (Cmax) |  | Up through Day 29 after a single dose | 
| PK of ARO-HSD: Time to Maximum Plasma Concentration (Tmax) |  | Up through Day 29 after a single dose | 
| PK of ARO-HSD: Terminal Elimination Half-Life (t1/2) |  | Up through Day 29 after a single dose | 
| PK of ARO-HSD: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) |  | Up through Day 29 after a single dose | 
| PK of ARO-HSD: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) |  | Up through Day 29 after a single dose |