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

• Sponsor: Arrowhead Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04375514
• Collaborator: (none)
• Enrollment: 43
• Locations: 7
• Arms: 2
• Actual Duration (Months): 12.8
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis, Pulmonary	Drug: ARO-ENaC; Drug: Placebo	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Aug 10, 2020
• Actual Primary Completion Date: Sep 3, 2021
• Actual Study Completion Date: Sep 3, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ARO-ENaC ARO-ENaC Inhalation	Drug: ARO-ENaC; single or multiple doses of ARO-ENaC by inhalation of nebulized solution
Placebo Comparator: Placebo Sterile normal saline (0.9% NaCl)	Drug: Placebo; calculated volume to match active treatment by inhalation of nebulized solution

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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]

2. Change from Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers [Baseline, Up through Day 29 after a single dose]

3. 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)]

4. 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)]

5. 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)]

6. 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)]

7. 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)]

8. 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)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Chermside	Queensland	Australia	4032
2	Research Site	South Brisbane	Queensland	Australia	4101
3	Research Site	Nedlands	Western Australia	Australia	6009
4	Research Site	Hamilton		Australia	3204
5	Research Site	Grafton	Auckland	New Zealand	1010
6	Research Site	Christchurch		New Zealand	8140
7	Research Site	Dunedin		New Zealand	9054

Sponsors and Collaborators

• Arrowhead Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Arrowhead Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04375514
• Other Study ID Numbers: AROENaC1001
• First Posted: May 5, 2020
• Last Update Posted: Feb 24, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Cystic Fibrosis; Pulmonary Fibrosis; Fibrosis

Study Results

No Results Posted as of Feb 24, 2022