Clinical trial NCT04353661: A Study Of ¹²⁹XE MRI To Assess Disease Progression In Patients With COPD Treated With Or Without Azithromycin And Standard-of-Care Medications
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2020-04-20
Enrollment: 12
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multicenter, open-label, parallel group, randomized controlled trial (RCT).
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in 129Xenon (129Xe) Magnetic Resonance Imaging (MRI) Ventilation Defect Percentage (VDP) From Baseline to Week 24
timeFrame: Baseline up to Week 24
measure: Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over 48 Weeks
timeFrame: Baseline up to Week 48
Secondary outcomes:
measure: Number of Participants With Adverse Events (AE) With Severity Determined According To The World Health Organization (WHO) Toxicity Scale
timeFrame: Baseline up to Week 52
measure: Change in 129Xe MRI VDP From Baseline to Week 48
timeFrame: Baseline to Week 48
measure: Change in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1, Liters) From Baseline to Week 24 and Week 48
timeFrame: Baseline to Week 24 and Week 48
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Asthma Allergy and Airway Center
state: North Carolina
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
affiliation: Genetech
name: Clinical Trials
role: STUDY_DIRECTOR
References: