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

Phase 1

Conditions: Asthma and Chronic obstructive pulmonary disease (COPD)
MedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2022-003467-21-PL

Lead Sponsor: Arrowhead Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 104

Inclusion Criteria

Inclusion criteria for Patients with Asthma:
1. Male or nonpregnant, nonlactating female volunteers
2. Age 18 to 65 years at Screening
3. Diagnosis of asthma which must have been confirmed and documented (based on source verifiable medical record) for at least 12 months prior to Screening
4. Documented treatment with a total daily dose of inhaled corticosteroids =500 mcg
fluticasone propionate dry powder formulation (or equipotent inhaled corticosteroid) for at least 3 months prior to Screening
5. Documented treatment with at least 1 additional maintenance asthma controller medication (eg, a long-acting ß2-agonist [LABA], a leukotriene receptor antagonist [LTRA], or a long-acting muscarinic antagonist [LAMA]) for at least 3 months prior to Screening
6. Prebronchodilator ppFEV1 between 40% and 80% inclusive at Screening, prior to sputum induction
7. Stable dose of asthma controller medications for at least 28 days prior to Screening
8. If on allergen-specific immunotherapy, patients must be on a stable maintenance dose for at least 90 days prior to first dose
9. If on biologic therapy for asthma (eg, anti-IgE, anti-IL5/IL5R, anti-IL4R, or anti-thymic stromal lymphopoietin [TSLP]), patients must be on a stable maintenance dose for at least 16 weeks prior to first dose
10. Chest x-ray taken at Screening that, according to the Investigator, excludes significant alternative respiratory disease
11. Able and willing to provide written informed consent prior to the performance of any study-specific procedures
12. BMI between 18.0 and 35.0 kg/m2 at Screening
13. A 12-lead ECG at Screening with no abnormalities that may compromise participant’s safety in this study
14. Nonsmoker (defined as someone who has not smoked a cigarette for at least 6 months) with current nonsmoking status confirmed by urine cotinine at Screening AND previous smoking history prior to 6 months must be <10 pack-years. Subjects may be on nicotine replacement (patch or gum). Nicotine e-cigarettes (vapor) are not permitted. A positive urine cotinine result due to nicotine replacement is acceptable for enrollment at the
discretion of the PI
15. Participants of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 12 weeks following the end of the study or last dose of study drug, whichever is later. Subjects must not donate sperm or eggs during the study and for at least 12 weeks following the end of the study or last dose of study drug, whichever is later
16. Able and willing to comply with all study assessments and adhere to the protocol schedule
17. Able to produce an induced sputum sample at Screening that meets criteria of acceptable quality

Inclusion Criteria for patients with COPD:
1. Male or nonpregnant, nonlactating female
2. Age 40 to 70 years at Screening
3. Diagnosis of COPD for at least 12 months prior to Screening, based on source verifiable medical record, confirmed with a post-bronchodilator ratio of FEV1 to FVC < 0.7 at Screening
4. History of chronic bronchitis elicited on the SGRQ-C at Screening
5. Current smoker or ex-smoker (meaning >1 year of smoking cessation) with a smoking history of = 10 pack-years
6. Post-bronchodilator ppFEV1 between 30% and 80% inclusive at Screening, prior to sputum induction
7. Subjects treated with either single, double, or triple therapy for COPD, as described below:
a. Single therapy consisting of: long-acting beta agonist (LABA) or long-acti

Exclusion Criteria

1. Acute lower respiratory infection or asthma exacerbation within 30 days prior to 1st dose
2. Acute upper respiratory infection within 7 days prior to 1st dose
3. Positive COVID-19 test during Screening window
4. Prior history of bronchial thermoplasty treatment
5. Diagnosis of vocal cord dysfunction, reactive airways dysfunction syndrome, panic attacks with hyperventilation, or other mimics of asthma
6. Any concomitant pulmonary disease that, in the opinion of the Investigator and/or Medical Monitor, will interfere with the evaluation of the study drug or interpretation of patient safety or study results (including, but not limited to: interstitial lung disease, cystic fibrosis, lung cancer and tuberculosis). Any concomitant pulmonary disease must be discussed with the Medical
Monitor during Screening
7. Known unresolved parasitic infection or prior parasitic infection that has required antiparasitic therapy within 30 days prior to first dose
8. Any history of organ transplant
9. HIV infection, as shown by presence of anti-HIV antibodies (seropositive)
10. Seropositive for HBV or HCV (positive result for anti-HCV antibody must be confirmed with positive HCV RNA test for exclusion)
11. Uncontrolled hypertension (SBP >150 mmHg or DBP >100 mmHg) at Screening
12. A history of Torsades de Pointes, ventricular rhythm disturbances (eg, ventricular tachycardia or fibrillation), pathologic sinus bradycardia (<50 bpm with symptoms), heart block (excluding first-degree block, being PR prolongation only), congenital long QT syndrome, new ST segment elevation or depression, or new Q wave on ECG. Participants with a history of atrial arrhythmias should be discussed with the Medical Monitor
13. A family history of congenital long QT syndrome or unexplained sudden cardiac death
14. Use of medications known to prolong the QTc interval within 30 days prior to first dose (eg, azithromycin)
15. Use of theophylline within 30 days prior to first dose
16. Symptomatic heart failure (per NYHA guidelines), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction <20%), TIA, or CVA within 24 weeks prior to first dose
17. History of malignancy within the past 2 years except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. Participants with other curatively treated malignancies who have no evidence of metastatic disease and >2-year disease-free interval may be entered following approval by the Medical Monitor
18. History of major surgery within 12 weeks prior to first dose
19. Unwilling to limit alcohol consumption to within moderate limits for the duration of the study, as follows: not more than 14 units per week for women and 21 units per week for men (1 unit=150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol)
20. Use of illicit drugs (such as cocaine, PCP) within 1 year prior to Screening or positive urine drug screen at Screening (a urine drug screen deemed positive due to prescription medications or for benzodiazepines, opioids, or marijuana is acceptable and inclusion is at the discretion of the PI). Subjects who smoke or vape prescription THC/marijuana should be discussed with the Medical Monitor
21. Use of an investigational agent or device within 30 days or 5 half-lives (whichever is longer) prior to first dose or current participation in an investigational study
22. Blood donation (500 mL) within 7 days prior to first dose. Donat

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety and tolerability of ARO-MUC5AC in patients with asthma and COPD;Secondary Objective: Secondary<br>• To assess the pulmonary safety of ARO-MUC5AC in patients with asthma and COPD using spirometry<br>• To assess the pharmacokinetics (PK) of ARO-MUC5AC in patients with asthma and COPD<br><br>Exploratory<br>• To assess the pharmacodynamics (PD) of ARO-MUC5AC in patients with asthma and COPD<br>• To assess the efficacy of ARO-MUC5AC in patients with asthma and COPD;Primary end point(s): • The incidence and frequency of treatment-emergent adverse events (TEAEs) over time through end of study (EOS);Timepoint(s) of evaluation of this end point: All visits

Secondary Outcome Measures

Name	Time	Method

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