Clinical trial NCT05854550: First in Human Study to Assess an Implant to Treat Severe Emphysema
Official title: Bronchoscopic RElease of Air Trapped in Hyperinflated Emphysematous Lung
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Emphysema or COPD
Keywords: hyperinflation
air-trapping
emphysema
COPD
Lead sponsor: Apreo Health, Inc.
Sponsor class: INDUSTRY
First posted: 2023-05-11
Enrollment: 48
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Eligibility 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

Primary outcomes:
measure: Rate of Serious Adverse Events (SAE) at 6 Months
timeFrame: 6 Months
Secondary outcomes:
measure: Device Evaluation: Device Deployment Assessment
timeFrame: During Procedure
measure: Device Evaluation: Device Usability Survey
timeFrame: During Procedure
measure: Device Evaluation: Instructions for Use (IFU) Survey
timeFrame: During Procedure
measure: Efficacy Evaluation: Airway Patency at 30 Days
timeFrame: 30 Days
measure: Efficacy Evaluation: Airway Patency at 3 Months
timeFrame: 3 Months
measure: Efficacy Evaluation: Airway Patency at 6 Months
timeFrame: 6 Months
measure: Efficacy Evaluation: Airway Patency at 12 Months
timeFrame: 12 Months
measure: Efficacy Evaluation: Mucus Assessment at 30 Days
timeFrame: 30 Days
measure: Efficacy Evaluation: Mucus Assessment at 3 Months
timeFrame: 3 Months
measure: Efficacy Evaluation: Mucus Assessment at 6 Months
timeFrame: 6 Months
measure: Efficacy Evaluation: Mucus Assessment at 12 Months
timeFrame: 12 Months
measure: Efficacy Evaluation: Computed Tomography (CT) Scan at 6 Months
timeFrame: 6 Months
measure: Efficacy Evaluation: CT Scan at 12 Months
timeFrame: 12 Months
measure: Efficacy Evaluation: Forced Expiratory Volume in 1 Second (FEV1) at 1-3 Days
timeFrame: 1-3 Days
measure: Efficacy Evaluation: FEV1 at 30 Days
timeFrame: 30 Days
measure: Efficacy Evaluation: FEV1 at 3 Months
timeFrame: 3 Months
measure: Efficacy Evaluation: FEV1 at 6 Months
timeFrame: 6 Months
measure: Efficacy Evaluation: FEV1 at 12 Months
timeFrame: 12 Months
measure: Efficacy Evaluation: Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) at 6 Months
timeFrame: 6 Months
measure: Efficacy Evaluation: Residual Volume (RV) at 6 Months
timeFrame: 6 Months
measure: Efficacy Evaluation: Residual Volume (RV) at 12 Months
timeFrame: 12 Months
measure: Efficacy Evaluation: Arterial Blood Gas (ABG): PaO2 at 6 Months
timeFrame: 6 Months
measure: Efficacy Evaluation: Arterial Blood Gas (ABG): PaCO2 at 6 Months
timeFrame: 6 Months
measure: Safety: Procedural Complications
timeFrame: Through 24 hours post-procedure
measure: Safety: Rate of SAEs
timeFrame: Through 12 Months
measure: Safety: Rate of Adverse Device Effects
timeFrame: Through 12 Months
measure: Efficacy Evaluation: Forced Expiratory Volume at 1 Second/ Forced Vital Capacity (FEV1/FVC) at 1-3 Days
timeFrame: 1-3 Days
measure: Efficacy Evaluation: FEV1/FVC at 30 Days
timeFrame: 30 Days
measure: Efficacy Evaluation: FEV1/FVC at 3 Months
timeFrame: 3 Months
measure: Efficacy Evaluation: FEV1/FVC at 6 Months
timeFrame: 6 Months
measure: Efficacy Evaluation: FEV1/FVC at 12 Months
timeFrame: 12 Months
measure: Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 1-3 Days
timeFrame: 1-3 Days
measure: Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 30 Days
timeFrame: 30 Days
measure: Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 3 Months
timeFrame: 3 Months
measure: Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 6 Months
timeFrame: 6 Months
measure: Efficacy Evaluation: RV Assessed by Pulmonary Function Testing at 12 Months
timeFrame: 12 Months
measure: Efficacy Evaluation: Residual Volume/Total Lung Capacity (RV/TLC) at 1-3 Days
timeFrame: 1-3 Days
measure: Efficacy Evaluation: RV/TLC at 30 Days
timeFrame: 30 Days
measure: Efficacy Evaluation: RV/TLC at 3 Months
timeFrame: 3 Months
measure: Efficacy Evaluation: RV/TLC at 6 Months
timeFrame: 6 Months
measure: Efficacy Evaluation: RV/TLC at 12 Months
timeFrame: 12 Months
measure: Efficacy Evaluation: Forced Vital Capacity (FVC) at 1-3 Days
timeFrame: 1-3 Days
measure: Efficacy Evaluation: FVC at 30 Days
timeFrame: 30 Days
measure: Efficacy Evaluation: FVC at 3 Months
timeFrame: 3 Months
measure: Efficacy Evaluation: FVC at 6 Months
timeFrame: 6 Months
measure: Efficacy Evaluation: FVC at 12 Months
timeFrame: 12 Months
measure: Efficacy Evaluation: Six Minute Walk Test (6MWT) at 1-3 Days
timeFrame: 1-3 Days
measure: Efficacy Evaluation: Six Minute Walk Test (6MWT) at 30 Days
timeFrame: 30 Days
measure: Efficacy Evaluation: Six Minute Walk Test (6MWT) at 3 Months
timeFrame: 3 Months
measure: Efficacy Evaluation: Six Minute Walk Test (6MWT) at 6 Months
timeFrame: 6 Months
measure: Efficacy Evaluation: Six Minute Walk Test (6MWT) at 12 Months
timeFrame: 12 Months
measure: Efficacy Evaluation: Modified Borg Dyspnoea Scale at 1-3 Days
timeFrame: 1-3 Days
measure: Efficacy Evaluation: Modified Borg Dyspnoea Scale at 30 Days
timeFrame: 30 Days
measure: Efficacy Evaluation: Modified Borg Dyspnoea Scale at 3 Months
timeFrame: 3 Months
measure: Efficacy Evaluation: Modified Borg Dyspnoea Scale at 6 Months
timeFrame: 6 Months
measure: Efficacy Evaluation: Modified Borg Dyspnoea Scale at 12 Months
timeFrame: 12 Months
measure: 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)
timeFrame: 1-3 Days
measure: 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)
timeFrame: 30 Days
measure: 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)
timeFrame: 3 Months
measure: 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)
timeFrame: 6 Months
measure: 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)
timeFrame: 12 Months
measure: 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)
timeFrame: 1-3 Days
measure: 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)
timeFrame: 30 Days
measure: 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)
timeFrame: 3 Months
measure: 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)
timeFrame: 6 Months
measure: 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)
timeFrame: 12 Months
measure: 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
timeFrame: 1-3 Days
measure: 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
timeFrame: 30 Days
measure: 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
timeFrame: 3 Months
measure: 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
timeFrame: 6 Months
measure: 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
timeFrame: 12 Months
Other outcomes:
Locations:
city: Macquarie
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
Study officials:
References: