Trial Outcomes & Findings for A Study Of ¹²⁹XE MRI To Assess Disease Progression In Patients With COPD Treated With Or Without Azithromycin And Standard-of-Care Medications (NCT NCT04353661)

Last Updated: 2024-12-24

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Baseline up to Week 24

Results posted on

2024-12-24

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A Open-label: Azithromycin + SOC Therapy Participants received azithromycin and SOC therapy for 52 weeks.	Arm A Open-label: SOC Therapy Participants received SOC therapy for 52 weeks.	Arm B Observational: SOC Therapy Participants received SOC therapy for 52 weeks.
Overall Study STARTED	3	5	4
Overall Study COMPLETED	2	4	2
Overall Study NOT COMPLETED	1	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A Open-label: Azithromycin + SOC Therapy Participants received azithromycin and SOC therapy for 52 weeks.	Arm A Open-label: SOC Therapy Participants received SOC therapy for 52 weeks.	Arm B Observational: SOC Therapy Participants received SOC therapy for 52 weeks.
Overall Study Protocol Violation	0	0	1
Overall Study Study termination by the Sponsor	1	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline up to Week 24

Population: ITT population. Overall number of participants analyzed is the number of participants with data available for analyses.

Outcome measures

Outcome measures
Measure	Arm A Open-label: Azithromycin + SOC Therapy n=3 Participants Participants received azithromycin and SOC therapy for 52 weeks.	Arm A Open-label: SOC Therapy n=4 Participants Participants received SOC therapy for 52 weeks.	Arm B Observational : SOC Therapy n=2 Participants Participants received SOC therapy for 52 weeks.
Change in 129Xenon (129Xe) Magnetic Resonance Imaging (MRI) Ventilation Defect Percentage (VDP) From Baseline to Week 24	6.33 ventilation defect percentage Standard Deviation 12.70	-1.75 ventilation defect percentage Standard Deviation 5.12	-1.00 ventilation defect percentage Standard Deviation 7.07

PRIMARY outcome

Timeframe: Baseline up to Week 48

Population: ITT population

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.

Outcome measures

Outcome measures
Measure	Arm A Open-label: Azithromycin + SOC Therapy n=3 Participants Participants received azithromycin and SOC therapy for 52 weeks.	Arm A Open-label: SOC Therapy n=5 Participants Participants received SOC therapy for 52 weeks.	Arm B Observational : SOC Therapy n=4 Participants Participants received SOC therapy for 52 weeks.
Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over 48 Weeks	1.41 exacerbations per year Standard Deviation 1.70	1.06 exacerbations per year Standard Deviation 1.11	0.23 exacerbations per year Standard Deviation 0.47

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Safety population

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.

Outcome measures

Outcome measures
Measure	Arm A Open-label: Azithromycin + SOC Therapy n=3 Participants Participants received azithromycin and SOC therapy for 52 weeks.	Arm A Open-label: SOC Therapy n=5 Participants Participants received SOC therapy for 52 weeks.	Arm B Observational : SOC Therapy n=4 Participants Participants received SOC therapy for 52 weeks.
Number of Participants With Adverse Events (AE) With Severity Determined According To The World Health Organization (WHO) Toxicity Scale Grade 1	0 Number of Participants	1 Number of Participants	0 Number of Participants
Number of Participants With Adverse Events (AE) With Severity Determined According To The World Health Organization (WHO) Toxicity Scale Grade 2	1 Number of Participants	1 Number of Participants	1 Number of Participants
Number of Participants With Adverse Events (AE) With Severity Determined According To The World Health Organization (WHO) Toxicity Scale Grade 3	1 Number of Participants	1 Number of Participants	1 Number of Participants
Number of Participants With Adverse Events (AE) With Severity Determined According To The World Health Organization (WHO) Toxicity Scale Grade 4	1 Number of Participants	2 Number of Participants	1 Number of Participants

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population. Overall number analyzed is the number of participants with data available for analyses.

Outcome measures

Outcome measures
Measure	Arm A Open-label: Azithromycin + SOC Therapy n=2 Participants Participants received azithromycin and SOC therapy for 52 weeks.	Arm A Open-label: SOC Therapy n=3 Participants Participants received SOC therapy for 52 weeks.	Arm B Observational : SOC Therapy n=3 Participants Participants received SOC therapy for 52 weeks.
Change in 129Xe MRI VDP From Baseline to Week 48	0.50 ventilation defect percentage Standard Deviation 6.36	-6.00 ventilation defect percentage Standard Deviation 9.85	-4.67 ventilation defect percentage Standard Deviation 7.77

SECONDARY outcome

Timeframe: Baseline to Week 24 and Week 48

Population: ITT Population. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.

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.

Outcome measures

Outcome measures
Measure	Arm A Open-label: Azithromycin + SOC Therapy n=1 Participants Participants received azithromycin and SOC therapy for 52 weeks.	Arm A Open-label: SOC Therapy n=2 Participants Participants received SOC therapy for 52 weeks.	Arm B Observational : SOC Therapy n=2 Participants Participants received SOC therapy for 52 weeks.
Change in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1, Liters) From Baseline to Week 24 and Week 48 Change from Baseline at Week 24	0.15 liters Standard Deviation NA The standard deviation was not estimable for a single participant.	-0.01 liters Standard Deviation 0.21	-0.12 liters Standard Deviation 0.04
Change in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1, Liters) From Baseline to Week 24 and Week 48 Change from Baseline at Week 48	0.19 liters Standard Deviation NA The standard deviation was not estimable for a single participant.	-0.03 liters Standard Deviation 0.17	-0.26 liters Standard Deviation 0.14

Adverse Events

Cohort A - SOC + Azithromycin

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort A - SOC

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Cohort B - SOC

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort A - SOC + Azithromycin n=3 participants at risk Participants received azithromycin and SOC theraphy for 52 weeks.	Cohort A - SOC n=5 participants at risk Participants received SOC theraphy for 52 weeks	Cohort B - SOC n=4 participants at risk Participants received SOC theraphy for 52 weeks.
Infections and infestations Respiratory syncytial virus infection	0.00% 0/3 • Baseline up to Week 48	0.00% 0/5 • Baseline up to Week 48	25.0% 1/4 • Number of events 1 • Baseline up to Week 48
Injury, poisoning and procedural complications Accident	0.00% 0/3 • Baseline up to Week 48	0.00% 0/5 • Baseline up to Week 48	25.0% 1/4 • Number of events 1 • Baseline up to Week 48
Injury, poisoning and procedural complications Limb injury	0.00% 0/3 • Baseline up to Week 48	0.00% 0/5 • Baseline up to Week 48	25.0% 1/4 • Number of events 1 • Baseline up to Week 48
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	33.3% 1/3 • Number of events 2 • Baseline up to Week 48	20.0% 1/5 • Number of events 1 • Baseline up to Week 48	0.00% 0/4 • Baseline up to Week 48
Skin and subcutaneous tissue disorders Subcutaneous emphysema	0.00% 0/3 • Baseline up to Week 48	20.0% 1/5 • Number of events 1 • Baseline up to Week 48	0.00% 0/4 • Baseline up to Week 48

Other adverse events

Other adverse events
Measure	Cohort A - SOC + Azithromycin n=3 participants at risk Participants received azithromycin and SOC theraphy for 52 weeks.	Cohort A - SOC n=5 participants at risk Participants received SOC theraphy for 52 weeks	Cohort B - SOC n=4 participants at risk Participants received SOC theraphy for 52 weeks.
Ear and labyrinth disorders Hypoacusis	33.3% 1/3 • Number of events 1 • Baseline up to Week 48	0.00% 0/5 • Baseline up to Week 48	0.00% 0/4 • Baseline up to Week 48
Endocrine disorders Thyroid mass	0.00% 0/3 • Baseline up to Week 48	20.0% 1/5 • Number of events 1 • Baseline up to Week 48	0.00% 0/4 • Baseline up to Week 48
Infections and infestations COVID-19	66.7% 2/3 • Number of events 2 • Baseline up to Week 48	20.0% 1/5 • Number of events 1 • Baseline up to Week 48	0.00% 0/4 • Baseline up to Week 48
Infections and infestations Influenza	0.00% 0/3 • Baseline up to Week 48	0.00% 0/5 • Baseline up to Week 48	25.0% 1/4 • Number of events 1 • Baseline up to Week 48
Infections and infestations Pneumonia	0.00% 0/3 • Baseline up to Week 48	20.0% 1/5 • Number of events 1 • Baseline up to Week 48	0.00% 0/4 • Baseline up to Week 48
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/3 • Baseline up to Week 48	0.00% 0/5 • Baseline up to Week 48	25.0% 1/4 • Number of events 1 • Baseline up to Week 48
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign lung neoplasm	0.00% 0/3 • Baseline up to Week 48	20.0% 1/5 • Number of events 1 • Baseline up to Week 48	0.00% 0/4 • Baseline up to Week 48
Nervous system disorders Headache	0.00% 0/3 • Baseline up to Week 48	20.0% 1/5 • Number of events 1 • Baseline up to Week 48	0.00% 0/4 • Baseline up to Week 48
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	33.3% 1/3 • Number of events 1 • Baseline up to Week 48	40.0% 2/5 • Number of events 3 • Baseline up to Week 48	25.0% 1/4 • Number of events 1 • Baseline up to Week 48
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • Baseline up to Week 48	20.0% 1/5 • Number of events 1 • Baseline up to Week 48	0.00% 0/4 • Baseline up to Week 48
Respiratory, thoracic and mediastinal disorders Dysphonia	33.3% 1/3 • Number of events 1 • Baseline up to Week 48	0.00% 0/5 • Baseline up to Week 48	0.00% 0/4 • Baseline up to Week 48
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • Baseline up to Week 48	0.00% 0/5 • Baseline up to Week 48	25.0% 1/4 • Number of events 1 • Baseline up to Week 48
Skin and subcutaneous tissue disorders Psoriasis	33.3% 1/3 • Number of events 1 • Baseline up to Week 48	0.00% 0/5 • Baseline up to Week 48	0.00% 0/4 • Baseline up to Week 48

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Arm A Open-label: Azithromycin + SOC Therapy n=3 Participants Participants received azithromycin and SOC therapy for 52 weeks.	Arm A Open-label: SOC Therapy n=5 Participants Participants received SOC therapy for 52 weeks.	Arm B Observational: SOC Therapy n=4 Participants Participants received SOC therapy for 52 weeks.	Total n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	10 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants