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

NCT04375514 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: AROENaC1001
• Study Type: interventional
• Target: 43
• Locations: 2 countries
• Sites: 7

Brief Summary

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.

Conditions

Cystic Fibrosis, Pulmonary

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• 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)

Study Arms (12)

Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3

EXPERIMENTAL

Normal healthy volunteers receive double-blind ARO-ENaC 20 mg on Days 1, 2, 3

Drug: ARO-ENaC

Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 20 mg, Days 1-3

PLACEBO COMPARATOR

Normal healthy volunteers receive double-blind placebo for ARO-ENaC 20 mg on Days 1, 2, 3

Drug: Placebo

Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3

EXPERIMENTAL

Normal healthy volunteers receive double-blind ARO-ENaC 40 mg on Days 1, 2, 3

Drug: ARO-ENaC

Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 40 mg, Days 1-3

PLACEBO COMPARATOR

Normal healthy volunteers receive double-blind placebo for ARO-ENaC 40 mg on Days 1, 2, 3

Drug: Placebo

Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3

EXPERIMENTAL

Normal healthy volunteers receive double-blind ARO-ENaC 65 mg on Days 1, 2, 3

Drug: ARO-ENaC

Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 65 mg, Days 1-3

PLACEBO COMPARATOR

Normal healthy volunteers receive double-blind placebo for ARO-ENaC 65 mg on Days 1, 2, 3

Drug: Placebo

Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3

EXPERIMENTAL

Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3

Drug: ARO-ENaC

Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 180 mg, Days 1-3

PLACEBO COMPARATOR

Normal healthy volunteers receive double-blind placebo for ARO-ENaC 180 mg on Days 1, 2, 3

Drug: Placebo

Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy

EXPERIMENTAL

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

Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy

PLACEBO COMPARATOR

Normal healthy volunteers receive double-blind placebo for ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples

Drug: Placebo

Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24

EXPERIMENTAL

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

Cystic Fibrosis Cohort: Placebo

PLACEBO COMPARATOR

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

Interventions

ARO-ENaC DRUG

single or multiple doses of ARO-ENaC by inhalation of nebulized solution

Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24; Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3; Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy; Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3; Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3; Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3

Placebo DRUG

calculated volume of normal saline to match active treatment by inhalation of nebulized solution

Cystic Fibrosis Cohort: Placebo; Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 180 mg, Days 1-3; Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy; Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 20 mg, Days 1-3; Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 40 mg, Days 1-3; Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 65 mg, Days 1-3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Arrowhead Pharmaceuticals: lead

Study Sites (7)

Research Site 3

Chermside, Queensland, 4032, Australia

Location

Research Site 4

South Brisbane, Queensland, 4101, Australia

Location

Research Site 1

Nedlands, Washington, 6009, Australia

Location

Research Site 2

Hamilton, 3204, Australia

Location

Research Site 6

Grafton, Auckland, 1010, New Zealand

Location

Research Site 8

Christchurch, 8140, New Zealand

Location

Research Site 7

Dunedin, 9054, New Zealand

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Limitations and Caveats

On 01 July 2021 a voluntary suspension of dosing by the Sponsor was initiated. All subjects who had completed all planned doses continued safety follow-up according to the scheduled activities. This suspension of dosing was due to preliminary findings in the 6-month chronic rat good laboratory practice (GLP) toxicology study. The voluntary suspension was unrelated to any safety findings in the AROENaC1001 study. Subsequent to this, the Sponsor decided to terminate the AROENaC1001 study.

Results Point of Contact

• Title: Chief Operating Officer
• Organization: Arrowhead Pharmaceuticals, Inc.

info@arrowheadpharma.com

1 (626) 304-3400

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: May 5, 2020
• Study Start: July 30, 2020
• Primary Completion: May 9, 2021
• Study Completion: May 13, 2022
• Last Updated: December 17, 2025
• Results First Posted: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); NZ (3)