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.

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