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

Phase 1

Completed

Conditions: Non-alcoholic Steatohepatitis

Interventions: Drug: ARO-HSD Injection
Drug: sterile normal saline (0.9% NaCl)

Registration Number: NCT04202354

Lead Sponsor: Arrowhead Pharmaceuticals

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 50

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1: ARO-HSD 25 mg	ARO-HSD Injection	Normal healthy volunteers randomized to double blind ARO-HSD 25 mg on Day 1 only.
Cohort 1: Placebo	sterile normal saline (0.9% NaCl)	Normal healthy volunteers randomized to double blind placebo on Day 1 only.
Cohort 2: ARO-HSD 50 mg	ARO-HSD Injection	Normal healthy volunteers randomized to double blind ARO-HSD 50 mg on Day 1 only.
Cohort 2: Placebo	sterile normal saline (0.9% NaCl)	Normal healthy volunteers randomized to double blind placebo on Day 1 only.
Cohort 3: ARO-HSD 100 mg	ARO-HSD Injection	Normal healthy volunteers randomized to double blind ARO-HSD 100 mg on Day 1 only.
Cohort 3: Placebo	sterile normal saline (0.9% NaCl)	Normal healthy volunteers randomized to double blind placebo on Day 1 only.
Cohort 4: ARO-HSD 200 mg	ARO-HSD Injection	Normal healthy volunteers randomized to double blind ARO-HSD 200 mg on Day 1 only.
Cohort 4: Placebo	sterile normal saline (0.9% NaCl)	Normal healthy volunteers randomized to double blind placebo on Day 1 only.
Cohort 1b: ARO-HSD 25 mg	ARO-HSD Injection	Participants with suspected non-alcoholic steatohepatitis (NASH) receive open-label ARO-HSD 25 mg on Days 1 and 29.
Cohort 3b: ARO-HSD 100 mg	ARO-HSD Injection	Participants with suspected NASH receive open-label ARO-HSD 100 mg on Days 1 and 29.
Cohort 4b: ARO-HSD 200 mg	ARO-HSD Injection	Participants with suspected NASH receive open-label ARO-HSD 200 mg on Days 1 and 29.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Possibly or Probably Related to Treatment	From first dose of study drug through Day 113 (±5 days)	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.

Secondary Outcome Measures

Name	Time	Method
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: 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: Terminal Elimination Half-Life (t1/2)	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: 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
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