Study of ARO-MUC5AC in Healthy Subjects and Patients With Muco-Obstructive Lung Disease

Asthma Clinical Trial

Official title:

A Phase 1/2a Study Evaluating the Effects of ARO-MUC5AC Inhalation Solution in Healthy Subjects and Patients With Muco-Obstructive Lung Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05292950
• Other study ID #: AROMUC5AC-1001
• Secondary ID: 2022-003467-21
• Status: Recruiting
• Phase: Phase 1
• Start date: June 27, 2022
• Est. completion date: November 2024

Study information

• Verified date: February 2024
• Source: Arrowhead Pharmaceuticals
• Contact: Medical Monitor
• Phone: 626-304-3400
• Email: AROMUC5AC[@]arrowheadpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of ARO-MUC5AC in normal healthy volunteers (NHVs), patients with moderate-to-severe asthma and patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). In part 1 NHVs will receive a single dose of ARO-MUC5AC or placebo. In part 2 of the study, NHVs, adult patients with asthma, and adult patients with COPD will receive 3 doses of ARO-MUC5AC or placebo.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 104
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Normal pulmonary function tests at Screening (NHVs only)

• Confirmed diagnosis of asthma or COPD based on source verifiable medical record (asthma and COPD patients only)

• No abnormal finding of clinical relevance at Screening (NHVs only)

• Stable dose of asthma controller medications for at least 28 days prior to Screening (asthma patients only)

• Documented treatment with an inhaled corticosteroid and at least 1 additional maintenance asthma controller medication for at least 3 months prior to Screening (asthma patients only)

• Non-smoking (NHVs and asthma patients)

• Current smoker or ex-smoker with smoking history of = 10 pack-years (COPD patients only)

• All COPD treatments have been stable for at least one month prior to Screening (COPD patients only)

• Able to produce an induced sputum sample at Screening

• Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception. Males must not donate sperm during the study and for at least 90 days following the last dose of study drug

• Willing to provide written informed consent and to comply with study requirements

Exclusion Criteria:

• Acute lower respiratory infection within 30 days prior to first dose and/or acute upper respiratory infection within 7 days prior to first dose

• Positive COVID-19 test during Screening window

• Any history of chronic pulmonary disease (NHVs only)

• Any concomitant pulmonary disease in asthma or COPD patients that could interfere with the evaluation of the study drug or interpretation of patient safety or study results

• Use of theophylline within 30 days prior to first dose

• History of lung volume reduction surgery or pneumonectomy (COPD patients)

• Need for chronic oxygen support at Screening

• Clinically significant health concerns (other than asthma in asthma patients)

• Human immunodeficiency virus (HIV) infection, seropositive for hepatitis B virus (HBV), seropositive for hepatitis C virus (HCV)

• Uncontrolled hypertension

• Unwilling to limit alcohol consumption to within moderate limits for the duration of the study

• Use of illicit drugs

• Use of an investigational agent or device within 30 days prior to first dose

Note: additional inclusion/exclusion criteria may apply per protocol

Related Conditions & MeSH terms

• Asthma
• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• ARO-MUC5AC
single or multiple doses of ARO- MUC5AC by inhalation of nebulized solution
• Placebo
calculated volume to match active treatment by inhalation of nebulized solution

Locations

Country	Name	City	State
Australia	Institute For Respiratory Health - Perth	Nedlands
Korea, Republic of	Jeonbuk National University Hospital	Jeonju
Korea, Republic of	Hanyang University Seoul Hospital	Seoul
New Zealand	New Zealand Clinical Research-Auckland	Auckland
New Zealand	New Zealand Research Sleep Institute	Auckland
Poland	Prywatny Gabinet Internistyczno-Alergologiczny	Bialystok
Poland	Krakmed.NZOZ	Kraków
Poland	Medicome SP.ZO.O	Oswiecim
Spain	Giromed Institute Barcelona	Barcelona
Thailand	Sriraj Hospital	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Arrowhead Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Korea, Republic of,  New Zealand,  Poland,  Spain,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Treatment-Emergent Adverse Events (TEAEs)		single dose phase: up to Day 29; multiple dose phase: up to Day 85
Secondary	Change Over Time from Baseline in Forced Expiratory Volume (FEV1)		single dose phase: up to Day 29; multiple dose phase: up to Day 85
Secondary	Change Over Time from Baseline in Forced Vital Capacity (FVC)		single dose phase: up to Day 29; multiple dose phase: up to Day 85
Secondary	PK of ARO-MUC5AC: Maximum Observed Plasma Concentration (Cmax)		single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD
Secondary	PK of ARO-MUC5AC: Area Under the Plasma Concentration versus Time Curve From Zero to 24 Hours (AUC0-24)		single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD
Secondary	PK of ARO-MUC5AC: Area Under the Plasma Concentration versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast)		single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD
Secondary	PK of ARO-MUC5AC: Area Under the Plasma Concentration versus Time Curve From Zero to Infinity (AUCinf)		single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD
Secondary	PK of ARO-MUC5AC: Terminal Elimination Half-Life (t1/2)		single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD
Secondary	PK of ARO-MUC5AC: Apparent Systemic Clearance (CL/F)		single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD
Secondary	PK of ARO-MUC5AC: Apparent Terminal-Phase Volume of Distribution (VZ/F)		single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD
Secondary	PK of ARO-MUC5AC: Recovery of Unchanged Drug in Urine Over 24 Hours (Amount Excreted; Ae)		through 24 hours post-dose
Secondary	PK of ARO-MUC5AC: Percentage of Administered Drug Recovered in Urine Over 0-24 Hours		through 24 hours post-dose
Secondary	PK of ARO-MUC5AC: Renal Clearance (CLr)		single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD