Clinical trial NCT04375514: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Cystic Fibrosis, Pulmonary
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-05-05
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment
timeFrame: single dose phase: Up to 29 (+/- 2) days; multiple dose phase: Up to 113 (+/- 5 days) post-dose for patients with CF
Secondary outcomes:
measure: Change from Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride (all in mmol/L)
timeFrame: Baseline, single dose phase: Up to 29 (+/- 2) days; multiple dose phase: Up to 113 (+/- 5 days) post-dose for patients with CF
measure: Change from Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers
timeFrame: Baseline, Up through Day 29 after a single dose
measure: PK of ARO-ENaC: Maximum observed Plasma Concentration (Cmax)
timeFrame: single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
measure: PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax)
timeFrame: single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
measure: PK of ARO-ENaC: Terminal Elilmination Half-Life (t1/2)
timeFrame: single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
measure: PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)
timeFrame: single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
measure: PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)
timeFrame: single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
measure: PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast)
timeFrame: single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
Other outcomes:
Locations:
city: Chermside
country: Australia
facility: Research Site
state: Queensland
city: South Brisbane
country: Australia
facility: Research Site
state: Queensland
city: Nedlands
country: Australia
facility: Research Site
state: Western Australia
city: Hamilton
country: Australia
facility: Research Site
city: Grafton
country: New Zealand
facility: Research Site
state: Auckland
city: Christchurch
country: New Zealand
facility: Research Site
city: Dunedin
country: New Zealand
facility: Research Site
Study officials:
References: