Back to resultsStudy of ARO-ENaC in Healthy Volunteers and in Patients With Cystic Fibrosis
Primary Purpose
Cystic Fibrosis, Pulmonary
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ARO-ENaC
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis, Pulmonary
Eligibility Criteria
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
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ARO-ENaC
Placebo
Arm Description
ARO-ENaC Inhalation
Sterile normal saline (0.9% NaCl)
Outcomes
Primary Outcome Measures
Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment
Secondary Outcome Measures
Change from Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride (all in mmol/L)
Change from Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers
PK of ARO-ENaC: Maximum observed Plasma Concentration (Cmax)
PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax)
PK of ARO-ENaC: Terminal Elilmination Half-Life (t1/2)
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast)
Full Information
NCT ID
NCT04375514
First Posted
April 30, 2020
Last Updated
October 20, 2022
Sponsor
Arrowhead Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04375514
Brief Title
Study of ARO-ENaC in Healthy Volunteers and in Patients With Cystic Fibrosis
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Terminated
Why Stopped
Business decision
Study Start Date
August 10, 2020 (Actual)
Primary Completion Date
September 3, 2021 (Actual)
Study Completion Date
September 3, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arrowhead Pharmaceuticals
4. Oversight
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
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis, Pulmonary
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ARO-ENaC
Arm Type
Experimental
Arm Description
ARO-ENaC Inhalation
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Sterile normal saline (0.9% NaCl)
Intervention Type
Drug
Intervention Name(s)
ARO-ENaC
Intervention Description
single or multiple doses of ARO-ENaC by inhalation of nebulized solution
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
calculated volume to match active treatment by inhalation of nebulized solution
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment
Time Frame
single dose phase: Up to 29 (+/- 2) days; multiple dose phase: Up to 113 (+/- 5 days) post-dose for patients with CF
Secondary Outcome Measure Information:
Title
Change from Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride (all in mmol/L)
Time Frame
Baseline, single dose phase: Up to 29 (+/- 2) days; multiple dose phase: Up to 113 (+/- 5 days) post-dose for patients with CF
Title
Change from Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers
Time Frame
Baseline, Up through Day 29 after a single dose
Title
PK of ARO-ENaC: Maximum observed Plasma Concentration (Cmax)
Time Frame
single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
Title
PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax)
Time Frame
single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
Title
PK of ARO-ENaC: Terminal Elilmination Half-Life (t1/2)
Time Frame
single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
Title
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)
Time Frame
single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
Title
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)
Time Frame
single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
Title
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast)
Time Frame
single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Facility Information:
Facility Name
Research Site
City
Chermside
State/Province
Queensland
ZIP/Postal Code
4032
Country
Australia
Facility Name
Research Site
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Research Site
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Research Site
City
Hamilton
ZIP/Postal Code
3204
Country
Australia
Facility Name
Research Site
City
Grafton
State/Province
Auckland
ZIP/Postal Code
1010
Country
New Zealand
Facility Name
Research Site
City
Christchurch
ZIP/Postal Code
8140
Country
New Zealand
Facility Name
Research Site
City
Dunedin
ZIP/Postal Code
9054
Country
New Zealand
12. IPD Sharing Statement
Plan to Share IPD
No
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Study of ARO-ENaC in Healthy Volunteers and in Patients With Cystic Fibrosis
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