Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04375514




Registration number
NCT04375514
Ethics application status
Date submitted
30/04/2020
Date registered
5/05/2020
Date last updated
24/10/2022

Titles & IDs
Public title
Study of ARO-ENaC in Healthy Volunteers and in Patients With Cystic Fibrosis
Scientific 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
Secondary ID [1] 0 0
AROENaC1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis, Pulmonary 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ARO-ENaC
Treatment: Drugs - Placebo

Experimental: ARO-ENaC - ARO-ENaC Inhalation

Placebo Comparator: Placebo - Sterile normal saline (0.9% NaCl)


Treatment: Drugs: ARO-ENaC
single or multiple doses of ARO-ENaC by inhalation of nebulized solution

Treatment: Drugs: Placebo
calculated volume to match active treatment by inhalation of nebulized solution
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment
Timepoint [1] 0 0
single dose phase: Up to 29 (+/- 2) days; multiple dose phase: Up to 113 (+/- 5 days) post-dose for patients with CF
Secondary outcome [1] 0 0
Change from Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride (all in mmol/L)
Timepoint [1] 0 0
Baseline, single dose phase: Up to 29 (+/- 2) days; multiple dose phase: Up to 113 (+/- 5 days) post-dose for patients with CF
Secondary outcome [2] 0 0
Change from Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers
Timepoint [2] 0 0
Baseline, Up through Day 29 after a single dose
Secondary outcome [3] 0 0
PK of ARO-ENaC: Maximum observed Plasma Concentration (Cmax)
Timepoint [3] 0 0
single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
Secondary outcome [4] 0 0
PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax)
Timepoint [4] 0 0
single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
Secondary outcome [5] 0 0
PK of ARO-ENaC: Terminal Elilmination Half-Life (t1/2)
Timepoint [5] 0 0
single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
Secondary outcome [6] 0 0
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)
Timepoint [6] 0 0
single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
Secondary outcome [7] 0 0
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)
Timepoint [7] 0 0
single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
Secondary outcome [8] 0 0
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast)
Timepoint [8] 0 0
single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/08/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
3/09/2021
Sample size
Target
Accrual to date
Final
43
Recruitment in Australia
Recruitment state(s)
QLD,WA
Recruitment hospital [1] 0 0
Research Site - Chermside
Recruitment hospital [2] 0 0
Research Site - South Brisbane
Recruitment hospital [3] 0 0
Research Site - Nedlands
Recruitment hospital [4] 0 0
Research Site - Hamilton
Recruitment postcode(s) [1] 0 0
4032 - Chermside
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment postcode(s) [4] 0 0
3204 - Hamilton
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch
Country [3] 0 0
New Zealand
State/province [3] 0 0
Dunedin

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Arrowhead Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04375514
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04375514