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

Arrowhead Pharmaceuticals

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Cystic Fibrosis, Pulmonary

Treatments: Drug: ARO-ENaC; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04375514

AROENaC1001

Details and patient eligibility

About

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.

Enrollment: 43 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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43 participants in 12 patient groups, including a placebo group

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

Experimental group

Description:

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

Treatment:

Drug: ARO-ENaC

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

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

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

Experimental group

Description:

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

Treatment:

Drug: ARO-ENaC

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

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

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

Experimental group

Description:

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

Treatment:

Drug: ARO-ENaC

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

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

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

Experimental group

Description:

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

Treatment:

Drug: ARO-ENaC

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

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

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

Experimental group

Description:

Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 with the purpose of collecting bronchoscopic samples

Treatment:

Drug: ARO-ENaC

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

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

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

Experimental group

Description:

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

Treatment:

Drug: ARO-ENaC

Cystic Fibrosis Cohort: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo