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

NCT04353661 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: GE42063
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (2)

• Change in 129Xenon (129Xe) Magnetic Resonance Imaging (MRI) Ventilation Defect Percentage (VDP) From Baseline 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.

  Baseline up to Week 24

• Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over 48 Weeks

  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.

  Baseline up to Week 48

Secondary Outcomes (3)

• Number of Participants With Adverse Events (AE) With Severity Determined According To The World Health Organization (WHO) Toxicity Scale

  Baseline up to Week 52

• Change in 129Xe MRI VDP From Baseline to Week 48

  Baseline to Week 48

• 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

Study Arms (3)

Arm A Open-label: azithromycin + SOC therapy

EXPERIMENTAL

Participants will receive azithromycin and SOC theraphy for 52 weeks.

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

Arm A Open-label: SOC therapy

ACTIVE COMPARATOR

Participants will receive SOC theraphy for 52 weeks.

Other: HP xenon (¹²⁹XE)

Arm B Observational: SOC therapy

ACTIVE COMPARATOR

Participants will receive SOC theraphy for 52 weeks.

Other: HP xenon (¹²⁹XE)

Interventions

Azithromycin DRUG

Azithromycin will be administered orally.

Arm A Open-label: azithromycin + SOC therapy

HP xenon (¹²⁹XE) OTHER

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

Arm A Open-label: SOC therapy; Arm A Open-label: azithromycin + SOC therapy; Arm B Observational: SOC therapy

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (2)

Duke Asthma Allergy and Airway Center

Durham, North Carolina, 27705-2671, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Genetech

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multicenter, open-label, parallel group, randomized controlled trial (RCT).

Study Record Dates

• First Submitted: April 14, 2020
• First Posted: April 20, 2020
• Study Start: November 16, 2021
• Primary Completion: June 29, 2023
• Study Completion: June 29, 2023
• Last Updated: December 24, 2024
• Results First Posted: December 24, 2024

Record last verified: 2024-11

Locations

US (2)