Study Evaluating the Effects of ARO-RAGE in Healthy Subjects and Patients with Inflammatory Lung Disease

Phase 1

Conditions: Inflammatory Lung Disease
MedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 20.0Level: PTClassification code 10011762Term: Cystic fibrosisSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2022-003466-20-PL

Lead Sponsor: Arrowhead Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 142

Inclusion Criteria

Asthma Cohorts C1 to C3: Male and nonpregnant, nonlactating volunteers aged 18 to 60 years (19 to 60 years of age, where applicable according to local regulation). Subjects must have a clinical diagnosis of asthma. Asthma severity must be mild-to-moderate, with severity measured by the type/quantity of medication required to keep the subject’s asthma under control (as detailed in the protocol). Asthma subjects must have a Screening prebronchodilator ppFEV1 =70% and blood eosinophil count =200 cells/µL. Asthma subjects must be able to produce an acceptable induced sputum sample at Screening. Asthma subjects with a recent asthma exacerbation, or ALT or AST >2×ULN, will be excluded.

High FeNO” Asthma Cohorts D1 and D2: Male and nonpregnant, nonlactating volunteers aged 18 to 65 years (19 to 65 years of age, where applicable according to local regulation) having a clinical diagnosis of asthma. Asthma must be treated with a stable daily maintenance controller regimen that includes inhaled corticosteroids (ICS). Asthma may not be treated with biologic therapies. Subjects must have a Screening prebronchodilator ppFEV1 =40%. In addition, subjects must have FeNO =35 ppb at all Screening visits. Asthma subjects with a recent asthma exacerbation, or ALT or AST >2×ULN, will be excluded.

CF Cohort E1: Male and nonpregnant, nonlactating volunteers aged 18 to 60 years (19 to 60 years of age, where applicable according to local regulation) having clinical diagnosis of CF. Subjects must be on a stable CF therapeutic regimen (including cystic fibrosis transmembrane conductance regulator [CFTR] modulator, if applicable) for 6 weeks prior to Screening. Subjects must have ppFEV1 =40% and =80% at Screening. CF subjects with a recent CF exacerbation, or ALT or AST >2.5×ULN, will be excluded.

Please refer to the study Protocol to see all the inclusion criteria
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 69
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion Criteria for asthma Cohorts C1 to C3
1. Acute lower respiratory infection or asthma exacerbation within 30 days prior to first dose
2. Acute upper respiratory infection within 7 days prior to first dose
3. Positive COVID-19 test during Screening window. Any record of a positive test during the Screening window, whether protocol-mandated antigen test or any NAAT or antigen test obtained outside of this study, serves as a potential exclusion criterion (see below).
a. In the event of a positive COVID-19 test during Screening, and if the PI deems the subject clinically appropriate to proceed to study drug dosing and no other exclusion criteria are met (eg, #1 or #4), the PI may elect to proceed to randomize the subject. In such a case, the first dose may not be given until >7 days after both clinical resolution of infection and conversion of antigen test from positive to negative (if such results are available), whichever is later. If necessary, the Screening period may be extended to >28 days, but in no case will the Screening period be extended to >45 days.
4. Chronic or acute infection that is clinically significant or requires treatment with systemic antibiotics, antivirals, antifungals, or antiparasitics within 30 days prior to first dose.
a. Please note that a positive sputum bacterial culture from Study Day 1 does not meet this exclusion criterion
5. Use of systemic corticosteroid therapy within 90 days prior to first dose
6. Use of immunosuppressive medication (eg, methotrexate, cyclosporine, azathioprine, etc.) within 90 days prior to first dose. See Section 8.2.5.4 for more details.
7. Use of biologic therapies for asthma (ie, anti-IgE, anti-IL5/IL5R, anti-IL4R, anti-TSLP) within 16 weeks prior to first dose
8. Prior history of bronchial thermoplasty treatment
9. Diagnosis of vocal cord dysfunction, reactive airways dysfunction syndrome, panic attacks with hyperventilation, or other mimics of asthma
10. 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 ofpatient safety or study results (including, but not limited to: COPD, interstitial lung disease, cystic fibrosis, allergic bronchopulmonary aspergillosis, bronchiectasis, tuberculosis, etc). Any concomitant pulmonary disease must be discussed with the Medical Monitor during Screening.
11. Any history of organ transplant
12. Human immunodeficiency virus infection, as shown by presence of anti-HIV antibodies (seropositive)
13. Seropositive for HBV or HCV (positive result for anti-HCV antibodies must be confirmed with positive HCV RNA test for exclusion)
14. Uncontrolled hypertension (SBP >150 mmHg or DBP >100 mmHg) at Screening
15. 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.
16. A family history of congenital long QT syndrome or unexplained sudden cardiac death
17. Use of medications known to prolong the QTc interval within 30 days prior to first dose (eg, azithromycin)
18. Use of theophylline within 30 days prior to first dose
19. Symptomatic heart failure (per NYHA guidelines

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-RAGE in patients with Inflammatory Lung Disease;Secondary Objective: Secondary<br>•To assess the pulmonary safety of ARO-RAGE in patients using spirometry and diffusion capacity measurements<br>• To assess the PK of ARO-RAGE in patients <br><br>Exploratory<br>To assess the PD effects of ARO-RAGE in patients <br>To assess the efficacy of ARO-RAGE in patients;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
Secondary end point(s): • Change from baseline over time through EOS in FEV1 as a safety assessment<br>• Change from baseline over time through EOS in FVC as a safety assessment<br>• Change from baseline over time through EOS in DLCO as a safety assessment<br>• Plasma PK parameters of ARO-RAGE after each dose of study drug;Timepoint(s) of evaluation of this end point: Cohorts C<br>• Change in FEV1: at all visits<br>• Change in FVC: at all visits<br>• Change in DLCO: at visits 2, 6, 11 and 15<br>• Plasma PK parameters of ARO-RAGE: at visits 2, 3, 7 and 8<br>Cohorts D<br>• Change in FEV1: at all visits<br>• Change in FVC: at all visits<br>• Change in DLCO: at visits 3,4,5 and 9<br>Cohort E<br>• Change in FEV1: at all visits<br>• Change in FVC: at all visits<br>• Change in DLCO: at visits 2, 4, 5 and 8<br>• Plasma PK parameters of ARO-RAGE: at visits 2 and 4

Related Trials