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

• ClinicalTrials.gov Identifier: NCT05854550
• Recruitment Status: Recruiting
• First Posted: May 11, 2023
• Last Update Posted: October 4, 2023
• Sponsor: Apreo Health, Inc.
• Information provided by (Responsible Party): Apreo Health, Inc.

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Emphysema or COPD	Device: Apreo Implant Group	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Bronchoscopic RElease of Air Trapped in Hyperinflated Emphysematous Lung
• Actual Study Start Date: May 5, 2023
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: August 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Rate of Serious Adverse Events (SAE) at 6 Months [ Time Frame: 6 Months ]
   Rate of occurrence of serious adverse events related to the study device and/or study procedure through 6 months post-study procedure

Secondary Outcome Measures :

1. Device Evaluation: Device Deployment Assessment [ Time Frame: During Procedure ]
   Evaluation of the ability to deploy the Apreo Implant in target airways (There is no scale - questions are assessed individually)
2. Device Evaluation: Device Usability Survey [ Time Frame: During Procedure ]
   Evaluate operator device use challenges (There is no scale - questions are assessed individually)
3. Device Evaluation: Instructions for Use (IFU) Survey [ Time Frame: During Procedure ]
   Evaluate operator understanding of instructions for use (There is no scale - questions are assessed individually)
4. Efficacy Evaluation: Airway Patency at 30 Days [ Time Frame: 30 Days ]
   Assess implant obstruction bronchoscopically using semi-quantitative scale (0 =no narrowing of the airway to 5= >75% to 100% narrowing)
5. Efficacy Evaluation: Airway Patency at 3 Months [ Time Frame: 3 Months ]
   Assess implant obstruction bronchoscopically using semi-quantitative scale (0 =no narrowing of the airway to 5= >75% to 100% narrowing)
6. Efficacy Evaluation: Airway Patency at 6 Months [ Time Frame: 6 Months ]
   Assess implant obstruction bronchoscopically using semi-quantitative scale (0 =no narrowing of the airway to 5= >75% to 100% narrowing)
7. Efficacy Evaluation: Airway Patency at 12 Months [ Time Frame: 12 Months ]
   Assess implant obstruction bronchoscopically using semi-quantitative scale (0 =no narrowing of the airway to 5= >75% to 100% narrowing)
8. Efficacy Evaluation: Mucus Assessment at 30 Days [ Time Frame: 30 Days ]
   Assess mucus within the Apreo Implant bronchoscopically using a semi-quantitative scale (0=No mucus to 5=copious mucus)
9. Efficacy Evaluation: Mucus Assessment at 3 Months [ Time Frame: 3 Months ]
   Assess mucus within the Apreo Implant bronchoscopically using a semi-quantitative scale (0=No mucus to 5=copious mucus)
10. Efficacy Evaluation: Mucus Assessment at 6 Months [ Time Frame: 6 Months ]
    Assess mucus within the Apreo Implant bronchoscopically using a semi-quantitative scale (0=No mucus to 5=copious mucus)
11. Efficacy Evaluation: Mucus Assessment at 12 Months [ Time Frame: 12 Months ]
    Assess mucus within the Apreo Implant bronchoscopically using a semi-quantitative scale (0=No mucus to 5=copious mucus)
12. Efficacy Evaluation: Computed Tomography (CT) Scan at 6 Months [ Time Frame: 6 Months ]
    CT evaluation of Apreo Implant diameter
13. Efficacy Evaluation: CT Scan at 12 Months [ Time Frame: 12 Months ]
    CT evaluation of Apreo Implant diameter
14. Efficacy Evaluation: Forced Expiratory Volume in 1 Second (FEV1) at 1-3 Days [ Time Frame: 1-3 Days ]
    Change in FEV1 between Baseline and 1-3 days post-procedure
15. Efficacy Evaluation: FEV1 at 30 Days [ Time Frame: 30 Days ]
    Change in FEV1 between Baseline and 30 days post-procedure
16. Efficacy Evaluation: FEV1 at 3 Months [ Time Frame: 3 Months ]
    Change in FEV1 between Baseline and 3 months post-procedure
17. Efficacy Evaluation: FEV1 at 6 Months [ Time Frame: 6 Months ]
    Change in FEV1 between Baseline and 6 months post-procedure
18. Efficacy Evaluation: FEV1 at 12 Months [ Time Frame: 12 Months ]
    Change in FEV1 between Baseline and 12 months post-procedure
19. Efficacy Evaluation: Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) at 6 Months [ Time Frame: 6 Months ]
    Change in DLCO between baseline and 6 months post-procedure
20. Efficacy Evaluation: Residual Volume (RV) at 6 Months [ Time Frame: 6 Months ]
    Change in RV between baseline and 6 months as assessed by quantitative CT
21. Efficacy Evaluation: Residual Volume (RV) at 12 Months [ Time Frame: 12 Months ]
    Change in RV between baseline and 12 months as assessed by quantitative CT
22. Efficacy Evaluation: Arterial Blood Gas (ABG): PaO2 at 6 Months [ Time Frame: 6 Months ]
    Change in PaO2 between baseline and 6 months
23. Efficacy Evaluation: Arterial Blood Gas (ABG): PaCO2 at 6 Months [ Time Frame: 6 Months ]
    Change in PaCO2 between baseline and 6 months
24. Safety: Procedural Complications [ Time Frame: Through 24 hours post-procedure ]
    Percentage of participants with acute procedural complications within 24 hours of study procedure
25. Safety: Rate of SAEs [ Time Frame: Through 12 Months ]
    Rate of occurrence of serious adverse events related to the device and/or Apreo procedure through 12 months
26. Safety: Rate of Adverse Device Effects [ Time Frame: Through 12 Months ]
    Rate of adverse device effects through 12 months post-procedure
27. Efficacy Evaluation: Forced Expiratory Volume at 1 Second/ Forced Vital Capacity (FEV1/FVC) at 1-3 Days [ Time Frame: 1-3 Days ]
    Change in FEV1/FVC between Baseline and 1-3 days post-procedure
28. Efficacy Evaluation: FEV1/FVC at 30 Days [ Time Frame: 30 Days ]
    Change in FEV1/FVC between Baseline and 30 days post-procedure
29. Efficacy Evaluation: FEV1/FVC at 3 Months [ Time Frame: 3 Months ]
    Change in FEV1/FVC between Baseline and 3 Months post-procedure
30. Efficacy Evaluation: FEV1/FVC at 6 Months [ Time Frame: 6 Months ]
    Change in FEV1/FVC between Baseline and 6 Months post-procedure
31. Efficacy Evaluation: FEV1/FVC at 12 Months [ Time Frame: 12 Months ]
    Change in FEV1/FVC between Baseline and 12 Months post-procedure
32. Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 1-3 Days [ Time Frame: 1-3 Days ]
    Change in RV between Baseline and 1-3 Days
33. Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 30 Days [ Time Frame: 30 Days ]
    Change in RV between Baseline and 30 Days
34. Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 3 Months [ Time Frame: 3 Months ]
    Change in RV between Baseline and 3 Months
35. Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 6 Months [ Time Frame: 6 Months ]
    Change in RV between Baseline and 6 Months
36. Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 12 Months [ Time Frame: 12 Months ]
    Change in RV between Baseline and 12 Months
37. Efficacy Evaluation: Residual Volume/Total Lung Capacity (RV/TLC) at 1-3 Days [ Time Frame: 1-3 Days ]
    Change in RV/TLC between Baseline and 1-3 Days
38. Efficacy Evaluation: RV/TLC at 30 Days [ Time Frame: 30 Days ]
    Change in RV/TLC between Baseline and 30 Days
39. Efficacy Evaluation: RV/TLC at 3 Months [ Time Frame: 3 Months ]
    Change in RV/TLC between Baseline and 3 Months
40. Efficacy Evaluation: RV/TLC at 6 Months [ Time Frame: 6 Months ]
    Change in RV/TLC between Baseline and 6 Months
41. Efficacy Evaluation: RV/TLC at 12 Months [ Time Frame: 12 Months ]
    Change in RV/TLC between Baseline and 12 Months
42. Efficacy Evaluation: Forced Vital Capacity (FVC) at 1-3 Days [ Time Frame: 1-3 Days ]
    Change in FVC between Baseline and 1-3 Days
43. Efficacy Evaluation: FVC at 30 Days [ Time Frame: 30 Days ]
    Change in FVC between Baseline and 30 Days
44. Efficacy Evaluation: FVC at 3 Months [ Time Frame: 3 Months ]
    Change in FVC between Baseline and 3 Months
45. Efficacy Evaluation: FVC at 6 Months [ Time Frame: 6 Months ]
    Change in FVC between Baseline and 6 Months
46. Efficacy Evaluation: FVC at 12 Months [ Time Frame: 12 Months ]
    Change in FVC between Baseline and 12 Months
47. Efficacy Evaluation: Six Minute Walk Test (6MWT) at 1-3 Days [ Time Frame: 1-3 Days ]
    Change in 6MWT between Baseline and 1-3 Days
48. Efficacy Evaluation: Six Minute Walk Test (6MWT) at 30 Days [ Time Frame: 30 Days ]
    Change in 6MWT between Baseline and 30 Days
49. Efficacy Evaluation: Six Minute Walk Test (6MWT) at 3 Months [ Time Frame: 3 Months ]
    Change in 6MWT between Baseline and 3 Months
50. Efficacy Evaluation: Six Minute Walk Test (6MWT) at 6 Months [ Time Frame: 6 Months ]
    Change in 6MWT between Baseline and 6 Months
51. Efficacy Evaluation: Six Minute Walk Test (6MWT) at 12 Months [ Time Frame: 12 Months ]
    Change in 6MWT between Baseline and 12 Months
52. Efficacy Evaluation: Modified Borg Dyspnoea Scale at 1-3 Days [ Time Frame: 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)
53. Efficacy Evaluation: Modified Borg Dyspnoea Scale at 30 Days [ Time Frame: 30 Days ]
    Change in Modified BORG Dyspnea Scale between Baseline and 30 Days (scale is 0= no difficulty breathing to 10=maximal difficulty)
54. Efficacy Evaluation: Modified Borg Dyspnoea Scale at 3 Months [ Time Frame: 3 Months ]
    Change in Modified BORG Dyspnea Scale between Baseline and 3 Months (scale is 0= no difficulty breathing to 10=maximal difficulty)
55. Efficacy Evaluation: Modified Borg Dyspnoea Scale at 6 Months [ Time Frame: 6 Months ]
    Change in Modified BORG Dyspnea Scale between Baseline and 6 Months (scale is 0= no difficulty breathing to 10=maximal difficulty)
56. Efficacy Evaluation: Modified Borg Dyspnoea Scale at 12 Months [ Time Frame: 12 Months ]
    Change in Modified BORG Dyspnea Scale between Baseline and 12 Months (scale is 0= no difficulty breathing to 10=maximal difficulty)
57. 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) [ Time Frame: 1-3 Days ]
    Change in CAT between Baseline and 1-3 Days
58. 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) [ Time Frame: 30 Days ]
    Change in CAT between Baseline and 30 Days
59. 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) [ Time Frame: 3 Months ]
    Change in CAT between Baseline and 3 Months
60. 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) [ Time Frame: 6 Months ]
    Change in CAT between Baseline and 6 Months
61. 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) [ Time Frame: 12 Months ]
    Change in CAT between Baseline and 12 Months
62. 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) [ Time Frame: 1-3 Days ]
    Change in SGRQ-C between Baseline and 1-3 Days
63. 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) [ Time Frame: 30 Days ]
    Change in SGRQ-C between Baseline and 30 Days
64. 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) [ Time Frame: 3 Months ]
    Change in SGRQ-C between Baseline and 3 Months
65. 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) [ Time Frame: 6 Months ]
    Change in SGRQ-C between Baseline and 6 Months
66. 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) [ Time Frame: 12 Months ]
    Change in SGRQ-C between Baseline and 12 Months
67. 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 [ Time Frame: 1-3 Days ]
    Change in mMRC between Baseline and 1-3 Days
68. 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 [ Time Frame: 30 Days ]
    Change in mMRC between Baseline and 30 Days
69. 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 [ Time Frame: 3 Months ]
    Change in mMRC between Baseline and 3 Months
70. 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 [ Time Frame: 6 Months ]
    Change in mMRC between Baseline and 6 Months
71. 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 [ Time Frame: 12 Months ]
    Change in mMRC between Baseline and 12 Months

Eligibility Criteria

• Ages Eligible for Study: 35 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Shirin Hasan; +1 408-250-5881; shasan@thefoundry.com

Contact: Karun Naga; +1 310-709-1818; karun@thefoundry.com

Locations

Australia, New South Wales

Macquarie University Hospital; Recruiting

Macquarie, New South Wales, Australia, 2109

Contact: Callum Rutherford +61 434 949 605 callum.rutherford@mq.edu.au

Principal Investigator: Alvin Ing, Prof

Australia, Victoria

Royal Melbourne Hospital; Recruiting

Parkville, Victoria, Australia, 3050

Contact: Jemma Christie +61 417 005 117 Jemma.Christie@mh.org.au

Principal Investigator: Daniel Steinfort, A/Prof

Sponsors and Collaborators

Apreo Health, Inc.

More Information

• Responsible Party: Apreo Health, Inc.
• ClinicalTrials.gov Identifier: NCT05854550
• Other Study ID Numbers: CIP-0001
• First Posted: May 11, 2023
• Last Update Posted: October 4, 2023
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Apreo Health, Inc.:

hyperinflation; air-trapping; emphysema; COPD

Additional relevant MeSH terms:

Pulmonary Emphysema; Emphysema; Pathologic Processes; Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes