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

Cystic Fibrosis, Pulmonary Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04375514
• Other study ID #: AROENaC1001
• Status: Terminated
• Phase: Phase 1
• Start date: August 10, 2020
• Est. completion date: September 3, 2021

Study information

• Verified date: October 2022
• Source: Arrowhead Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 43
• Est. completion date: September 3, 2021
• Est. primary completion date: September 3, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Cystic Fibrosis, Pulmonary
• Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• ARO-ENaC
single or multiple doses of ARO-ENaC by inhalation of nebulized solution
• Placebo
calculated volume to match active treatment by inhalation of nebulized solution

Locations

Country	Name	City	State
Australia	Research Site	Chermside	Queensland
Australia	Research Site	Hamilton
Australia	Research Site	Nedlands	Western Australia
Australia	Research Site	South Brisbane	Queensland
New Zealand	Research Site	Christchurch
New Zealand	Research Site	Dunedin
New Zealand	Research Site	Grafton	Auckland

Sponsors (1)

Lead Sponsor	Collaborator
Arrowhead Pharmaceuticals

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Change from Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers		Baseline, Up through Day 29 after a single dose
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)