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

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Azithromycin; Other: HP xenon (¹²⁹XE)

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • North Carolina
    • Durham, North Carolina, United States, 27705-2671
      • Duke Asthma Allergy and Airway Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A Open-label: azithromycin + SOC therapy; Participants will receive azithromycin and SOC theraphy for 52 weeks.	Drug: Azithromycin; Azithromycin will be administered orally.; Other: HP xenon (¹²⁹XE); 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
Active Comparator: Arm A Open-label: SOC therapy; Participants will receive SOC theraphy for 52 weeks.	Other: HP xenon (¹²⁹XE); 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
Active Comparator: Arm B Observational: SOC therapy; Participants will receive SOC theraphy for 52 weeks.	Other: HP xenon (¹²⁹XE); 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

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	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

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Genetech

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2021
• Primary Completion (Actual): June 29, 2023
• Study Completion (Actual): June 29, 2023

Study Registration Dates

• First Submitted: April 14, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 20, 2020

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Chronic Disease; Disease Progression; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: GE42063

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No