A Study Of ¹²⁹XE MRI To Assess Disease Progression In Patients With COPD Treated With Or Without Azithromycin And Standard-of-Care Medications

Study Overview
=================
Brief Summary
-----------------
This study will test whether daily use of azithromycin will reduce the rate of exacerbations and improve lung ventilation and perfusion assessed by XE-MRI. The sensitivity of XE-MRI to detect COPD progression will be compared with standard clinical assessment measures including standard lung function tests, 6 minute walk test, and patient reported quality of life.

Official Title
-----------------
¹²⁹XE MRI Assessment Of Disease Progression In Patients With Chronic Obstructive Pulmonary Disease Treated With Standard-of-Care Medications With Or Without Daily Open-Label Azithromycin Treatment To Prevent Acute Exacerbation

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Drug: Azithromycin
* Other: HP xenon (¹²⁹XE)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Current or former smokers with years ≥ 10 pack years mMRC dyspnea score > 1 Post-bronchodilator FEV-1/forced vital capacity (FVC) <0.70 at Visit 1 or Visit 2 Cohort A: GOLD Stage 2-4 COPD with a history of ≥ 2 moderate/severe exacerbations within a 12-month period in the 24 months prior to screening Cohort B: GOLD Stage 1 COPD with a history of ≥1 moderate/severe exacerbations within a 12-month period in the 24 months prior to screening Receiving SOC background drug therapy as per GOLD or British Thoracic Society (BTS) guidance for COPD for 12 weeks prior to screening Visit 1 On an eligible bronchodilator medication (LABA ± LAMA) ± ICS therapy for ≥12 weeks prior to Visit 1 Chest X-ray or CT scan within 6 months prior to Visit 1, or during the screening period (prior to Visit 2), that confirms the absence of clinically significant lung disease besides COPD Use of contraceptive measures Exclusion Criteria: Diagnosis of significant respiratory disease other than COPD Comorbid conditions that may interfere with the evaluation of an investigational medical product Known sensitivity or allergy to azithromycin A COPD exacerbation and or pneumonia within 4 weeks prior to Visit 1 Use of systemic corticosteroids within 4 weeks (oral or intravenous) or within 12 weeks (intramuscular IM) prior to screening Visit 1 MRI is contraindicated Any known arrhythmia, bradycardia or severe cardiac insufficiency Participant can not hold breath for 15 seconds Participant does not fit in the ¹²⁹XE vest coil used for MRI Pregnant, lactating, or intending to become pregnant during the study or within 4 weeks after the last dose of the investigational medical product History or evidence of substance abuse that would pose a risk to participants safety, interfere with the conduct of the study, or have an impact on the study results For participants in Cohort A: Known significant hearing impairment as indicated by a score of ≥ 26 on the Hearing Handicap Inventory in the Elderly-Screening Questionnaire or as determined by the investigator History of Clostridium difficile (C. difficile) diarrhea Clinically significant ECG changes, which in the opinion of investigator warrants further investigation or with a QTc interval > 450 ms

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a multicenter, open-label, parallel group, randomized controlled trial (RCT).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A Open-label: azithromycin + SOC therapy<br>Participants will receive azithromycin and SOC theraphy for 52 weeks. | Drug: Azithromycin<br>* Azithromycin will be administered orally.<br>Other: HP xenon (¹²⁹XE)<br>* HP xenon (¹²⁹XE) will be administered at specified timepoints and the total dose bag volume should target 20% of the patient's forced vital capacity followed by a breath hold of up to 15 seconds<br>|
| Active Comparator: Arm A Open-label: SOC therapy<br>Participants will receive SOC theraphy for 52 weeks. | Other: HP xenon (¹²⁹XE)<br>* HP xenon (¹²⁹XE) will be administered at specified timepoints and the total dose bag volume should target 20% of the patient's forced vital capacity followed by a breath hold of up to 15 seconds<br>|
| Active Comparator: Arm B Observational: SOC therapy<br>Participants will receive SOC theraphy for 52 weeks. | Other: HP xenon (¹²⁹XE)<br>* HP xenon (¹²⁹XE) will be administered at specified timepoints and the total dose bag volume should target 20% of the patient's forced vital capacity followed by a breath hold of up to 15 seconds<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ¹²⁹XE MRI VDP from Baseline to 24 weeks |  | Baseline up to Week 24 | 
| Rate of Moderate/Severe AEs |  | Baseline up to Week 48 | 
| Rate of Moderate/Severe Exacerbation | A moderate COPD exacerbation is defined as new or increased COPD symptoms (e.g., dyspnea, sputum volume, and sputum purulence) for at least 2 consecutive days that lead to treatment with systemic corticosteroids and/or antibiotics. A severe COPD exacerbation is defined as new or increased COPD symptoms (e.g., dyspnea, sputum volume, and sputum purulence) for at least 2 consecutive days that lead to hospitalization or death. | Baseline up to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Pre-bronchodilator FEV-1 (Liters) |  | Baseline up to Week 24 | 
| Absolute Change in Pre-bronchodilator FEV-1 (Liters) |  | Baseline up to Week 48 | 
| Number of Participant with Adverse Events With Severity Determined According To The World Health Organization (WHO) Toxicity Scale |  | Baseline up to 24 months |