Study of ARO-ENaC in Healthy Volunteers and in Patients With Cystic Fibrosis

A Phase 1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetic Effects of ARO-ENaC in Normal Healthy Volunteers and Safety, Tolerability and Efficacy in Patients With Cystic Fibrosis

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) of single doses of ARO-ENaC in healthy adult volunteers; and to evaluate the safety, tolerability, PK and efficacy of multiple doses of ARO-ENaC in patients with pulmonary cystic fibrosis.

Study Overview

• Status: Terminated
• Conditions: Cystic Fibrosis, Pulmonary
• Intervention / Treatment: Drug: Placebo; Drug: ARO-ENaC

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Hamilton, Australia, 3204
    • Research Site
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • Research Site
    • South Brisbane, Queensland, Australia, 4101
      • Research Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Research Site
• New Zealand
  • Christchurch, New Zealand, 8140
    • Research Site
  • Dunedin, New Zealand, 9054
    • Research Site
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Women of childbearing 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
• Normal electrocardiogram (ECG) at Screening
• Non-smoking
• Normal pulmonary function tests at Screening (NHVs only)
• No abnormal finding of clinical relevance at Screening other than CF for CF patients
• Confirmed diagnosis of CF based on source verifiable medical record (CF patients only)
• All other treatments for CF have been stable for at least 2 months and patient is willing to continue this treatment regimen without change for duration of study (CF patients only)

Exclusion Criteria:

• Acute lower respiratory infection within 30 days of Screening (NHVs only)
• History of asthma (specifically, those subjects at risk of bronchial hyperactivity), anaphylaxis or airway hyper-reactivity
• Clinically significant history of hyperkalemia or presence of hyperkalemia at Screening
• Clinically significant health concerns (other than CF in CF 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 one month prior to Screening
• Use of illicit drugs within 1 year prior to Screening
• Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study
• CF exacerbation within 30 days of Dosing (CF patients)
• History of solid organ transplant (CF patients)
• Diagnosis of hepatic cirrhosis (CF patients)

Note: additional inclusion/exclusion criteria may apply per protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARO-ENaC; ARO-ENaC Inhalation	Drug: ARO-ENaC; single or multiple doses of ARO-ENaC by inhalation of nebulized solution
Placebo Comparator: Placebo; Sterile normal saline (0.9% NaCl)	Drug: Placebo; calculated volume to match active treatment by inhalation of nebulized solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment	single dose phase: Up to 29 (+/- 2) days; multiple dose phase: Up to 113 (+/- 5 days) post-dose for patients with CF

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride (all in mmol/L)	Baseline, single dose phase: Up to 29 (+/- 2) days; multiple dose phase: Up to 113 (+/- 5 days) post-dose for patients with CF
Change from Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers	Baseline, Up through Day 29 after a single dose
PK of ARO-ENaC: Maximum observed Plasma Concentration (Cmax)	single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax)	single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
PK of ARO-ENaC: Terminal Elilmination Half-Life (t1/2)	single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)	single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)	single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast)	single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2020
• Primary Completion (Actual): September 3, 2021
• Study Completion (Actual): September 3, 2021

Study Registration Dates

• First Submitted: April 30, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 5, 2020

Study Record Updates

• Last Update Posted (Actual): October 24, 2022
• Last Update Submitted That Met QC Criteria: October 20, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Pulmonary Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: AROENaC1001

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