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: ARO-ENaC; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Hamilton, Australia, 3204
    • Research Site 2
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • Research Site 3
    • South Brisbane, Queensland, Australia, 4101
      • Research Site 4
  • Washington
    • Nedlands, Washington, Australia, 6009
      • Research Site 1
• New Zealand
  • Christchurch, New Zealand, 8140
    • Research Site 8
  • Dunedin, New Zealand, 9054
    • Research Site 7
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Research Site 6

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: Yes

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

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3; Normal healthy volunteers receive double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Drug: ARO-ENaC; single or multiple doses of ARO-ENaC by inhalation of nebulized solution
Placebo Comparator: Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 20 mg, Days 1-3; Normal healthy volunteers receive double-blind placebo for ARO-ENaC 20 mg on Days 1, 2, 3	Drug: Placebo; calculated volume of normal saline to match active treatment by inhalation of nebulized solution
Experimental: Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3; Normal healthy volunteers receive double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Drug: ARO-ENaC; single or multiple doses of ARO-ENaC by inhalation of nebulized solution
Placebo Comparator: Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 40 mg, Days 1-3; Normal healthy volunteers receive double-blind placebo for ARO-ENaC 40 mg on Days 1, 2, 3	Drug: Placebo; calculated volume of normal saline to match active treatment by inhalation of nebulized solution
Experimental: Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3; Normal healthy volunteers receive double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Drug: ARO-ENaC; single or multiple doses of ARO-ENaC by inhalation of nebulized solution
Placebo Comparator: Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 65 mg, Days 1-3; Normal healthy volunteers receive double-blind placebo for ARO-ENaC 65 mg on Days 1, 2, 3	Drug: Placebo; calculated volume of normal saline to match active treatment by inhalation of nebulized solution
Experimental: Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3; Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Drug: ARO-ENaC; single or multiple doses of ARO-ENaC by inhalation of nebulized solution
Placebo Comparator: Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 180 mg, Days 1-3; Normal healthy volunteers receive double-blind placebo for ARO-ENaC 180 mg on Days 1, 2, 3	Drug: Placebo; calculated volume of normal saline to match active treatment by inhalation of nebulized solution
Experimental: Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy; Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 with the purpose of collecting bronchoscopic samples	Drug: ARO-ENaC; single or multiple doses of ARO-ENaC by inhalation of nebulized solution
Placebo Comparator: Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy; Normal healthy volunteers receive double-blind placebo for ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples	Drug: Placebo; calculated volume of normal saline to match active treatment by inhalation of nebulized solution
Experimental: Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24; Participants with cystic fibrosis receive double-blind ARO-ENaC 40 mg dosed on Days 1, 2, and 3, and 40 mg dosed on Days 22, 23, and 24	Drug: ARO-ENaC; single or multiple doses of ARO-ENaC by inhalation of nebulized solution
Placebo Comparator: Cystic Fibrosis Cohort: Placebo; Participants with cystic fibrosis receive double-blind placebo for ARO-ENaC 40 mg dosed on Days 1, 2, and 3, and Days 22, 23, and 24.	Drug: Placebo; calculated volume of normal saline to match active treatment by inhalation of nebulized solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. Treatment-emergent AEs (TEAEs)=AEs with onset on or after administration of study drug through end of study. 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.	Normal Healthy Volunteers: Up to 29 (+/- 2) days post-dose; Participants with cystic fibrosis (CF): Up to 113 (+/- 5) days post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride	Normal Healthy Volunteers: Baseline, Days 2, 3, 4, 8, 15, 18, 29 ; Participants with CF: Baseline, Days 2, 3, 4, 15, 22, 23. 24, 29, 37, 57, 71, 85, 91, 113
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers	Baseline, Up through Day 29 after a single dose
Pharmacokinetics (PK) of ARO-ENaC: Maximum Observed Plasma Concentration (Cmax) in Normal Healthy Volunteers	Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Cmax in Participants With CF	Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax) in Normal Healthy Volunteers	Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Tmax in Participants With CF	Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
PK of ARO-ENaC: Elimination Half-Life (t1/2) in Normal Healthy Volunteers	Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast) in Normal Healthy Volunteers	Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: AUClast in Participants With CF	Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) in Normal Healthy Volunteers	Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Plasma Clearance (CL/F) in Normal Healthy Volunteers	Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: CL/F in Participants With CF	Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
PK of ARO-ENaC: Amount Recovered in Urine Over 0 to 24 Hours Postdose (Ae0-24h) in Normal Healthy Volunteers	Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Fraction Excreted in Urine as Unchanged Drug Over 0 to 24 Hours Postdose (fe0-24h) in Normal Healthy Volunteers	Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Renal Clearance (CLR) in Normal Healthy Volunteers	Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2020
• Primary Completion (Actual): May 9, 2021
• Study Completion (Actual): May 13, 2022

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 (Estimated): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; 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