First in Human Study to Assess an Implant to Treat Severe Emphysema (BREATHE-1)

Bronchoscopic RElease of Air Trapped in Hyperinflated Emphysematous Lung

The goal of this clinical trial is to test the feasibility of an implant for severe emphysema in up to 30 participants. The main questions it aims to answer are:

Is it safe? Does it work?

Participants who meet eligibility criteria will have up to two procedures 30 days apart, in which up to 3 implants will be placed in each lung during the procedure(s). Participants will be asked to return for follow-up visits at 30 days, and 3, 6, and 12 months after the procedure(s).

Study Overview

• Status: Recruiting
• Conditions: Emphysema or COPD
• Intervention / Treatment: Device: Apreo Implant Group

Detailed Description

This is a first-in-human, prospective, multi-center, single-arm study assessing the safety, feasibility and preliminary efficacy of the Apreo Implant for severe emphysema in up to 30 participants. Initially all participants will undergo an Apreo Procedure involving placement of up to three implants in a native bronchial tree of one lung followed by a second Apreo Procedure 30 days later to place up to three implants in the contralateral native lung bronchial tree if indicated.

Once the fifth participant has undergone his or her first implantation procedure, implantations in currently enrolled or new participants will be paused to allow for a Safety Review Committee (SRC) to convene and review safety data once the 5th participant has completed the 7-day phone follow-up after their second Apreo Procedure (or first if only one procedure). This would be at a minimum acute procedural safety for up to 10 implantation procedures conducted in these first 5 participants, 30-day safety assessments for all 5 participants after their first lung implantations, bronchoscopic inspection 30 days after implantation of all implants in the first lung, and 7-day safety data after their first and second lung implantations. The SRC will provide comments and recommendations, including the restart of implantation for new participants, if deemed appropriate.

After the first 10 participants have completed the 7-day phone follow-up after the second Apreo Procedure (or first if only one procedure), their safety data will be reviewed by the SRC. This would include at a minimum acute procedural safety for up to 20 implantation procedures conducted in these first 10 participants, 30-day safety assessments for all 10 participants after their first lung implantations, bronchoscopic inspection 30 days after implantation of all implants in the first lung, and 7-day safety data after their first and second lung implantations. Following the review of the first 10 participants' safety data, the SRC may allow any subsequently enrolled participants to undergo one Apreo Procedure (rather than two separate procedures if appropriate for a participant) to deploy Apreo Implants in both the left and right lung airways as indicated or to continue to have all participants undergo two separate Apreo Procedures if indicated. A total of up to 30 participants will be enrolled overall.

All participants will be followed at 30 days, three, six and twelve months post the first Apreo Procedure.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shirin Hasan; Phone Number: +1 408-250-5881; Email: shasan@thefoundry.com
• Study Contact Backup: Name: Karun Naga; Phone Number: +1 310-709-1818; Email: karun@thefoundry.com

Study Locations

• Australia
  • New South Wales
    • Macquarie, New South Wales, Australia, 2109
      • Recruiting
      • Macquarie University Hospital
      • Contact: Callum Rutherford; Phone Number: +61 434 949 605; Email: callum.rutherford@mq.edu.au
      • Principal Investigator: Alvin Ing, Prof
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Recruiting
      • Royal Melbourne Hospital
      • Contact: Jemma Christie; Phone Number: +61 417 005 117; Email: Jemma.Christie@mh.org.au
      • Principal Investigator: Daniel Steinfort, A/Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 35 and ≤ 80 years old
2. Computed tomography (CT) scan evidence of homogeneous or heterogeneous emphysema
3. At least one target lobe with > 35% destruction (percent of voxels with < -950 Hounsfield units on CT)
4. Post-bronchodilator ratio of FEV1/FVC < 0.7 at screening
5. Post-bronchodilator FEV1 percent predicted ≥20% and ≤50% of predicted at screening
6. Post-bronchodilator RV > 180% predicted
7. Post-bronchodilator RV/TLC ≥ 0.55 at screening
8. Marked dyspnea, scoring ≥ 2 on the modified Medical Research Council scale of 0-4
9. Cotinine testing at screening indicates nonsmoker and stopped smoking at least 8 weeks before entering the trial and agrees to refrain from smoking for duration of study participation
10. Participation in a pulmonary rehabilitation program and/or confirmed to have been engaged or attempted regular physical activity in the 12 months prior to the first Apreo Procedure and agrees to continue or restart regular physical activity for the duration of the study
11. Fully vaccinated for Covid-19 (up to date per Australian Government Guidelines) and has current pneumococcus and influenza vaccination (or documented clinical intolerance)
12. Cognitively and physically able to provide written informed consent and complete participant questionnaires

Exclusion Criteria:

1. Arterial blood PaCO2 > 60 mmHg (8 kPa) or PaO2 ≤ 45 mmHg (6 kPa)
2. DLCO <20% at screening
3. Steroid therapy of 10 mg prednisolone (prednisone) or more per day
4. Three or more acute exacerbations of COPD in the past year before enrollment
5. Two or more hospitalizations for acute exacerbations of COPD or respiratory infections in the past year before enrollment
6. Any acute exacerbation of COPD or respiratory infection less than 4 weeks before the first Apreo Procedure
7. Previous lung volume reduction surgery or lobectomy, segmentectomy or bullectomy, vapor, glue, or other pulmonary device implant
8. Known history of pulmonary arterial hypertension
9. Presence of a giant bulla (≥ 30% of hemithorax)
10. History of excessive dynamic airway collapse of the trachea or main bronchi
11. History of adult asthma or chronic bronchitis
12. Presence of suspicious pulmonary nodule/infiltrate that requires additional follow-up, diagnostics or treatment
13. Unequivocal and symptomatic bronchiectasis
14. Unequivocal lung cancer or other current cancer diagnosis except non-metastasized basal cell skin cancer
15. Uncontrolled hypertension (blood pressure that is inadequately treated or resistant to treatment) with a systolic > 200 mmHg or diastolic > 110 mmHg at screening or prior to first Apreo Procedure
16. Uncorrectable coagulopathy or other condition likely to increase risk of peri- or post- Apreo Procedure bleeding
17. On anticoagulant or antiplatelet therapy and unable or unwilling to hold for Apreo Procedure
18. Coronary artery disease with angina
19. History of myocardial infarction within 6 months
20. History of a stroke less than 1 year before the first Apreo Procedure
21. Clinical history of heart failure with documented LVEF ≤ 40%
22. Clinical history of diabetes with a HbA1c > 9.0%
23. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 (CKD-EPI) OR participant with kidney failure (Stage 5 kidney disease)
24. Mechanical ventilator dependence except participants using nocturnal bi-level positive airway pressure (biPAP) or continuous positive airway pressure (CPAP) are allowed if it would not preclude safe implantation of the study device
25. Pregnant, lactating, or women of childbearing potential who plan to become pregnant within the study duration
26. Known hypersensitivity to nitinol
27. Significantly immunocompromised, such as organ transplant recipients, those with congenital immune deficiencies, AIDS, or severe rheumatoid arthritis
28. Any disease or condition likely to limit survival to less than one year
29. Concomitant illnesses or medications that may pose a significant increased risk for complications following an Apreo Procedure
30. Currently enrolled in another trial and actively receiving experimental treatment
31. Any condition in the opinion of the investigator that would interfere with safe and complete collection of study data including the safe conduction of bronchoscopy procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apreo Implant Group; This group will undergo up to 2 procedures and will receive up to 3 implants during in each lung.	Device: Apreo Implant Group; One or two procedures involving placement of up to three Apreo implants in the bronchial tree of each lung.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Serious Adverse Events (SAE) at 6 Months	Rate of occurrence of serious adverse events related to the study device and/or study procedure through 6 months post-study procedure	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device Evaluation: Device Deployment Assessment	Evaluation of the ability to deploy the Apreo Implant in target airways (There is no scale - questions are assessed individually)	During Procedure
Device Evaluation: Device Usability Survey	Evaluate operator device use challenges (There is no scale - questions are assessed individually)	During Procedure
Device Evaluation: Instructions for Use (IFU) Survey	Evaluate operator understanding of instructions for use (There is no scale - questions are assessed individually)	During Procedure
Efficacy Evaluation: Airway Patency at 30 Days	Assess implant obstruction bronchoscopically using semi-quantitative scale (0 =no narrowing of the airway to 5= >75% to 100% narrowing)	30 Days
Efficacy Evaluation: Airway Patency at 3 Months	Assess implant obstruction bronchoscopically using semi-quantitative scale (0 =no narrowing of the airway to 5= >75% to 100% narrowing)	3 Months
Efficacy Evaluation: Airway Patency at 6 Months	Assess implant obstruction bronchoscopically using semi-quantitative scale (0 =no narrowing of the airway to 5= >75% to 100% narrowing)	6 Months
Efficacy Evaluation: Airway Patency at 12 Months	Assess implant obstruction bronchoscopically using semi-quantitative scale (0 =no narrowing of the airway to 5= >75% to 100% narrowing)	12 Months
Efficacy Evaluation: Mucus Assessment at 30 Days	Assess mucus within the Apreo Implant bronchoscopically using a semi-quantitative scale (0=No mucus to 5=copious mucus)	30 Days
Efficacy Evaluation: Mucus Assessment at 3 Months	Assess mucus within the Apreo Implant bronchoscopically using a semi-quantitative scale (0=No mucus to 5=copious mucus)	3 Months
Efficacy Evaluation: Mucus Assessment at 6 Months	Assess mucus within the Apreo Implant bronchoscopically using a semi-quantitative scale (0=No mucus to 5=copious mucus)	6 Months
Efficacy Evaluation: Mucus Assessment at 12 Months	Assess mucus within the Apreo Implant bronchoscopically using a semi-quantitative scale (0=No mucus to 5=copious mucus)	12 Months
Efficacy Evaluation: Computed Tomography (CT) Scan at 6 Months	CT evaluation of Apreo Implant diameter	6 Months
Efficacy Evaluation: CT Scan at 12 Months	CT evaluation of Apreo Implant diameter	12 Months
Efficacy Evaluation: Forced Expiratory Volume in 1 Second (FEV1) at 1-3 Days	Change in FEV1 between Baseline and 1-3 days post-procedure	1-3 Days
Efficacy Evaluation: FEV1 at 30 Days	Change in FEV1 between Baseline and 30 days post-procedure	30 Days
Efficacy Evaluation: FEV1 at 3 Months	Change in FEV1 between Baseline and 3 months post-procedure	3 Months
Efficacy Evaluation: FEV1 at 6 Months	Change in FEV1 between Baseline and 6 months post-procedure	6 Months
Efficacy Evaluation: FEV1 at 12 Months	Change in FEV1 between Baseline and 12 months post-procedure	12 Months
Efficacy Evaluation: Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) at 6 Months	Change in DLCO between baseline and 6 months post-procedure	6 Months
Efficacy Evaluation: Residual Volume (RV) at 6 Months	Change in RV between baseline and 6 months as assessed by quantitative CT	6 Months
Efficacy Evaluation: Residual Volume (RV) at 12 Months	Change in RV between baseline and 12 months as assessed by quantitative CT	12 Months
Efficacy Evaluation: Arterial Blood Gas (ABG): PaO2 at 6 Months	Change in PaO2 between baseline and 6 months	6 Months
Efficacy Evaluation: Arterial Blood Gas (ABG): PaCO2 at 6 Months	Change in PaCO2 between baseline and 6 months	6 Months
Safety: Procedural Complications	Percentage of participants with acute procedural complications within 24 hours of study procedure	Through 24 hours post-procedure
Safety: Rate of SAEs	Rate of occurrence of serious adverse events related to the device and/or Apreo procedure through 12 months	Through 12 Months
Safety: Rate of Adverse Device Effects	Rate of adverse device effects through 12 months post-procedure	Through 12 Months
Efficacy Evaluation: Forced Expiratory Volume at 1 Second/ Forced Vital Capacity (FEV1/FVC) at 1-3 Days	Change in FEV1/FVC between Baseline and 1-3 days post-procedure	1-3 Days
Efficacy Evaluation: FEV1/FVC at 30 Days	Change in FEV1/FVC between Baseline and 30 days post-procedure	30 Days
Efficacy Evaluation: FEV1/FVC at 3 Months	Change in FEV1/FVC between Baseline and 3 Months post-procedure	3 Months
Efficacy Evaluation: FEV1/FVC at 6 Months	Change in FEV1/FVC between Baseline and 6 Months post-procedure	6 Months
Efficacy Evaluation: FEV1/FVC at 12 Months	Change in FEV1/FVC between Baseline and 12 Months post-procedure	12 Months
Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 1-3 Days	Change in RV between Baseline and 1-3 Days	1-3 Days
Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 30 Days	Change in RV between Baseline and 30 Days	30 Days
Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 3 Months	Change in RV between Baseline and 3 Months	3 Months
Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 6 Months	Change in RV between Baseline and 6 Months	6 Months
Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 12 Months	Change in RV between Baseline and 12 Months	12 Months
Efficacy Evaluation: Residual Volume/Total Lung Capacity (RV/TLC) at 1-3 Days	Change in RV/TLC between Baseline and 1-3 Days	1-3 Days
Efficacy Evaluation: RV/TLC at 30 Days	Change in RV/TLC between Baseline and 30 Days	30 Days
Efficacy Evaluation: RV/TLC at 3 Months	Change in RV/TLC between Baseline and 3 Months	3 Months
Efficacy Evaluation: RV/TLC at 6 Months	Change in RV/TLC between Baseline and 6 Months	6 Months
Efficacy Evaluation: RV/TLC at 12 Months	Change in RV/TLC between Baseline and 12 Months	12 Months
Efficacy Evaluation: Forced Vital Capacity (FVC) at 1-3 Days	Change in FVC between Baseline and 1-3 Days	1-3 Days
Efficacy Evaluation: FVC at 30 Days	Change in FVC between Baseline and 30 Days	30 Days
Efficacy Evaluation: FVC at 3 Months	Change in FVC between Baseline and 3 Months	3 Months
Efficacy Evaluation: FVC at 6 Months	Change in FVC between Baseline and 6 Months	6 Months
Efficacy Evaluation: FVC at 12 Months	Change in FVC between Baseline and 12 Months	12 Months
Efficacy Evaluation: Six Minute Walk Test (6MWT) at 1-3 Days	Change in 6MWT between Baseline and 1-3 Days	1-3 Days
Efficacy Evaluation: Six Minute Walk Test (6MWT) at 30 Days	Change in 6MWT between Baseline and 30 Days	30 Days
Efficacy Evaluation: Six Minute Walk Test (6MWT) at 3 Months	Change in 6MWT between Baseline and 3 Months	3 Months
Efficacy Evaluation: Six Minute Walk Test (6MWT) at 6 Months	Change in 6MWT between Baseline and 6 Months	6 Months
Efficacy Evaluation: Six Minute Walk Test (6MWT) at 12 Months	Change in 6MWT between Baseline and 12 Months	12 Months
Efficacy Evaluation: Modified Borg Dyspnoea Scale at 1-3 Days	Change in Modified BORG Dyspnea Scale between Baseline and 1-3 Days (scale is 0= no difficulty breathing to 10=maximal difficulty)	1-3 Days
Efficacy Evaluation: Modified Borg Dyspnoea Scale at 30 Days	Change in Modified BORG Dyspnea Scale between Baseline and 30 Days (scale is 0= no difficulty breathing to 10=maximal difficulty)	30 Days
Efficacy Evaluation: Modified Borg Dyspnoea Scale at 3 Months	Change in Modified BORG Dyspnea Scale between Baseline and 3 Months (scale is 0= no difficulty breathing to 10=maximal difficulty)	3 Months
Efficacy Evaluation: Modified Borg Dyspnoea Scale at 6 Months	Change in Modified BORG Dyspnea Scale between Baseline and 6 Months (scale is 0= no difficulty breathing to 10=maximal difficulty)	6 Months
Efficacy Evaluation: Modified Borg Dyspnoea Scale at 12 Months	Change in Modified BORG Dyspnea Scale between Baseline and 12 Months (scale is 0= no difficulty breathing to 10=maximal difficulty)	12 Months
Efficacy Evaluation: COPD Assessment Test (CAT) at 1-3 Days (CAT scores range from 0 to 40, with higher score denoting higher impact of COPD on a participant's life)	Change in CAT between Baseline and 1-3 Days	1-3 Days
Efficacy Evaluation: COPD Assessment Test (CAT) at 30 Days (CAT scores range from 0 to 40, with higher score denoting higher impact of COPD on a participant's life)	Change in CAT between Baseline and 30 Days	30 Days
Efficacy Evaluation: Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) at 3 Months (CAT scores range from 0 to 40, with higher score denoting higher impact of COPD on a participant's life)	Change in CAT between Baseline and 3 Months	3 Months
Efficacy Evaluation: COPD Assessment Test (CAT) at 6 Months (CAT scores range from 0 to 40, with higher score denoting higher impact of COPD on a participant's life)	Change in CAT between Baseline and 6 Months	6 Months
Efficacy Evaluation: COPD Assessment Test (CAT) at 12 Months (CAT scores range from 0 to 40, with higher score denoting higher impact of COPD on a participant's life)	Change in CAT between Baseline and 12 Months	12 Months
Efficacy Evaluation: St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) at 1-3 Days (scores range from 0 to 100, with higher scores indicating more limitations to daily living)	Change in SGRQ-C between Baseline and 1-3 Days	1-3 Days
Efficacy Evaluation: St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) at 30 Days (scores range from 0 to 100, with higher scores indicating more limitations to daily living)	Change in SGRQ-C between Baseline and 30 Days	30 Days
Efficacy Evaluation: St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) at 3 Months (scores range from 0 to 100, with higher scores indicating more limitations to daily living)	Change in SGRQ-C between Baseline and 3 Months	3 Months
Efficacy Evaluation: St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) at 6 Months (scores range from 0 to 100, with higher scores indicating more limitations to daily living)	Change in SGRQ-C between Baseline and 6 Months	6 Months
Efficacy Evaluation: St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) at 12 Months (scores range from 0 to 100, with higher scores indicating more limitations to daily living)	Change in SGRQ-C between Baseline and 12 Months	12 Months
Efficacy Evaluation: Modified Medical Research Council (mMRC) Dyspnea Scale (0=no breathlessness except with strenuous exercise to 4=too breathless to leave the house or breathless when dressing or undressing) at 1-3 Days	Change in mMRC between Baseline and 1-3 Days	1-3 Days
Efficacy Evaluation: Modified Medical Research Council (mMRC) Dyspnea Scale (0=no breathlessness except with strenuous exercise to 4=too breathless to leave the house or breathless when dressing or undressing) at 30 Days	Change in mMRC between Baseline and 30 Days	30 Days
Efficacy Evaluation: Modified Medical Research Council (mMRC) Dyspnea Scale (0=no breathlessness except with strenuous exercise to 4=too breathless to leave the house or breathless when dressing or undressing) at 3 Months	Change in mMRC between Baseline and 3 Months	3 Months
Efficacy Evaluation: Modified Medical Research Council (mMRC) Dyspnea Scale (0=no breathlessness except with strenuous exercise to 4=too breathless to leave the house or breathless when dressing or undressing) at 6 Months	Change in mMRC between Baseline and 6 Months	6 Months
Efficacy Evaluation: Modified Medical Research Council (mMRC) Dyspnea Scale (0=no breathlessness except with strenuous exercise to 4=too breathless to leave the house or breathless when dressing or undressing) at 12 Months	Change in mMRC between Baseline and 12 Months	12 Months

Collaborators and Investigators

• Sponsor: Apreo Health, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: April 20, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Actual): May 11, 2023

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: COPD; emphysema; hyperinflation; air-trapping
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Chronic Disease; Pulmonary Emphysema; Emphysema
• Other Study ID Numbers: CIP-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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