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

Phase 2TerminatedNCT04375514

Arrowhead Pharmaceuticals43 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Cystic Fibrosis, Pulmonary

Interventions

ARO-ENaCDRUG

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

PlaceboDRUG

calculated volume of normal saline to match active treatment by inhalation of nebulized solution

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (7)

Research Site 3

Chermside, Queensland, Australia

Research Site 4

South Brisbane, Queensland, Australia

Research Site 1

Nedlands, Washington, Australia

Research Site 2

Hamilton, Australia

Outcomes

Primary Outcomes

Number of Participants With Adverse Events (AEs)

Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. Treatment-emergent AEs (TEAEs)=AEs with onset on or after administration of study drug through end of study. Serious adverse event (SAE)= an AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction.

Time frame: Normal Healthy Volunteers: Up to 29 (+/- 2) days post-dose; Participants with cystic fibrosis (CF): Up to 113 (+/- 5) days post-dose

Secondary Outcomes

Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride

Time frame: Normal Healthy Volunteers: Baseline, Days 2, 3, 4, 8, 15, 18, 29 ; Participants with CF: Baseline, Days 2, 3, 4, 15, 22, 23. 24, 29, 37, 57, 71, 85, 91, 113

Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers

Time frame: Baseline, Up through Day 29 after a single dose

Pharmacokinetics (PK) of ARO-ENaC: Maximum Observed Plasma Concentration (Cmax) in Normal Healthy Volunteers

Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)

PK of ARO-ENaC: Cmax in Participants With CF

Time frame: Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD

PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax) in Normal Healthy Volunteers

Data from ClinicalTrials.gov

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