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

Phase 2

Terminated

Conditions: Chronic Obstructive Pulmonary Disease

Interventions: Drug: Azithromycin
Other: HP xenon (¹²⁹XE)

Registration Number: NCT04353661

Lead Sponsor: Genentech, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 12

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A Open-label: azithromycin + SOC therapy	HP xenon (¹²⁹XE)	Participants will receive azithromycin and SOC theraphy for 52 weeks.
Arm A Open-label: SOC therapy	HP xenon (¹²⁹XE)	Participants will receive SOC theraphy for 52 weeks.
Arm B Observational: SOC therapy	HP xenon (¹²⁹XE)	Participants will receive SOC theraphy for 52 weeks.
Arm A Open-label: azithromycin + SOC therapy	Azithromycin	Participants will receive azithromycin and SOC theraphy for 52 weeks.

Primary Outcome Measures

Name	Time	Method
Change in 129Xenon (129Xe) Magnetic Resonance Imaging (MRI) Ventilation Defect Percentage (VDP) From Baseline to Week 24	Baseline up to Week 24	Hyperpolarized 129Xe gas was administered to the participants at specified timepoints. MRI using hyperpolarized 129Xe was used for 3D mapping of ventilation and gas distribution in the alveolar space and its uptake in interstitial barrier tissues as well as its transfer to red blood cells. Positive change from baseline indicated worse outcomes.
Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over 48 Weeks	Baseline up to Week 48	A moderate COPD exacerbation was defined as new or increased COPD symptoms (e.g., dyspnea, sputum volume, and sputum purulence) for at least 2 consecutive days that led to treatment with systemic corticosteroids and/or antibiotics. A severe COPD exacerbation was defined as new or increased COPD symptoms (e.g., dyspnea, sputum volume, and sputum purulence) for at least 2 consecutive days that led to hospitalization or death.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AE) With Severity Determined According To The World Health Organization (WHO) Toxicity Scale	Baseline up to Week 52	An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptoms, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. The WHO toxicity grading scale was used for assessing adverse event severity. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening; Grade 5: death. There were no participants with grade 5 AEs. Participants were counted once at their highest AE reported.
Change in 129Xe MRI VDP From Baseline to Week 48	Baseline to Week 48	Hyperpolarized 129Xe gas was administered to the participants at specified timepoints. MRI using hyperpolarized 129Xe was used for 3D mapping of ventilation and gas distribution in the alveolar space and its uptake in interstitial barrier tissues as well as its transfer to red blood cells. Positive change from baseline indicated worse outcomes.
Change in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1, Liters) From Baseline to Week 24 and Week 48	Baseline to Week 24 and Week 48	FEV1 is the volume of air (in liters) exhaled in the first second during forced exhalation after maximal inspiration. Positive change from baseline indicated better outcomes.

Trial Locations

Locations (2): Duke Asthma Allergy and Airway Center
🇺🇸
Durham, North Carolina, United States
University of Virginia Health System
🇺🇸
Charlottesville, Virginia, United States