Clinical trial NCT06035120: An Evaluation of the AeriSeal System for CONVERTing Collateral Ventilation Status in Patients With Severe Emphysema
Official title: An Evaluation of the AeriSeal System for CONVERTing Collateral Ventilation Status in Patients With Severe Emphysema: The CONVERT II Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Emphysema, Pulmonary
Emphysema or COPD
Keywords: Collateral Ventilation
Bronchoscopic Lung Volume Reduction
Hyperinflation
Lead sponsor: Pulmonx Corporation
Sponsor class: INDUSTRY
First posted: 2023-09-13
Enrollment: 200
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study is designed as a single-arm clinical trial in which eligible subjects with an identified fissure gap in the target lobe will be treated with the AeriSeal System to determine the rate of conversion from having collateral ventilation (CV+) to having little to no collateral ventilation (CV-). Subjects who convert to CV- status with AeriSeal will then undergo BLVR using Zephyr Valve per standard of care.
Primary purpose: TREATMENT

Brief summary: This is a prospective, open-label, multi-center, single-arm study planned to enroll 200 subjects with heterogeneous emphysema and collateral ventilation (CV) in the target lobe. Subjects will undergo instillation of AeriSeal Foam in the target lobe and subsequent assessment of CV status using Chartis Pulmonary Assessment System. Subjects with CV- status will then undergo placement of Zephyr Valve in the target lobe for bronchoscopic lung volume reduction (BLVR) and be followed for 24 months.

Detailed description: This is a multicenter, prospective, single-arm, pivotal trial with a 24-month follow-up to evaluate the safety and effectiveness of the AeriSeal System to block CV. The study plans to enroll up to 200 subjects at up to 35 clinical centers in US and OUS. Study subjects will be patients with severe, heterogeneous emphysema and collateral ventilation in the lobe targeted who are candidates for BLVR. Subjects meeting initial eligibility will undergo a bronchoscopy procedure under general anesthesia during which the presence of CV will be confirmed using Chartis. All enrolled subjects meeting final eligibility will undergo the AeriSeal procedure. Conversion of collateral ventilation status from CV+ to CV- in the target lobe will be evaluated by Chartis at Day 45 post-AeriSeal treatment (primary effectiveness endpoint). All subjects not converted from CV+ to CV- status will undergo a repeat of the AeriSeal procedure, provided that the total volume from both the initial and the repeat treatments does not exceed 40 mL in up to 3 segments. All subjects converted from CV+ to CV- status after either the index or repeat AeriSeal procedure will undergo BLVR with Zephyr Valve per standard of care in accordance with the approved instructions for use and will be followed through Month 24 (end of study). All CV+ subjects who remain CV+ after the repeat procedure or do not undergo the repeat AeriSeal procedure will be followed through Month 24 (end of study).

Eligibility criteria: Inclusion Criteria:

1. Subject is willing and able to provide informed consent and to participate in the study.
2. Subject is aged ≥ 40 and ≤ 80 years at the time of the ICF signature date.
3. Subject has completed a documented pulmonary rehabilitation (in clinic or home-based) program within 12 months prior to Baseline.
4. Subject has stopped smoking for at least 8 weeks prior to the ICF signature date as confirmed by carboxyhemoglobin or cotinine levels.
5. Subject has a recent HRCT meeting the scan parameter requirements and performed within 3 months of the ICF signature date with the following findings at -910 Hounsfield Units:

   1. At least one (1) lobe with segmental emphysema destruction score ≥ 50%.
   2. Subject has heterogenous emphysema, defined as difference in emphysema destruction score of ≥ 15 between the density scores of the target lobe and the ipsilateral non-target lobe(s) per QCT report with % voxel density of \< -910 HU. For non-target lobes that include the RML, calculate the combination of non-target lobes as a single density score using volume-weighted percent.
   3. LUL, LLL, RUL, RLL, or RUL+RML are targets for valve intervention.
   4. Subject has a gap in the interlobar fissure that corresponds to one or more segments and the fissure(s) contacting the target lobe is ≥ 80% complete per QCT report.
   5. Subject has 98% of the fissure gap confined to a maximum of 3 segments within the target lobe per Fissure Targeting Report (FTR).
6. Subject has 6MWD ≥ 150 m and ≤ 450 m.
7. Subject has clinically significant dyspnea with an mMRC score of ≥ 2.
8. Subject has post-bronchodilation FEV1 ≥ 15% predicted and ≤ 45% predicted.
9. Subject has an FEV1/FVC ratio of \< 0.7.
10. Subject has post-bronchodilation TLC, measured by body plethysmography, ≥ 100% predicted.
11. Subject has post-bronchodilation RV ≥ 175% predicted, measured by body plethysmography.
12. Subject has post-bronchodilation DLCO ≥ 20% predicted.
13. Subject has received preventative vaccinations against potential respiratory infections, including COVID-19, consistent with local recommendation or policy.
14. Subject is on optimal medical management for more than one month prior to the ICF signature date.
15. Subject has collateral ventilation (CV+) as confirmed per the Chartis assessment prior to the AeriSeal Index Procedure.

Exclusion Criteria:

1. Subject has prior lung volume reduction surgery, lobectomy or pneumonectomy, lung transplantation, airway stent placement, pleurodesis, or BLVR of any type, except BLVR using Zephyr Valve with \< 50% TLVR at 6 months, followed by valve removal \> 6 months prior to ICF signature date.
2. Subject has visible radiological abnormality on HRCT scan such as pulmonary nodule greater than 0.8 cm in diameter (does not apply, if present for 2 years or more without increase in size or if deemed benign by biopsy) or active pulmonary infection (e.g., unexplained parenchymal infiltrate, significant interstitial lung disease or significant pleural disease).
3. Post-COVID-19 pathology on CT, including ground glass opacities with or without consolidation, adjacent pleura thickening, interlobular septal thickening, or air bronchograms.
4. Large bullae encompassing greater than 1/3 of the total lung.
5. Subject had 3 or more COPD exacerbations requiring hospitalization within 12 months preceding the ICF signature date or a COPD exacerbation requiring hospitalization within 8 weeks of the ICF signature date. Subjects may be re-considered for future enrollment.
6. Subject has asthma as their primary diagnosis.
7. Subject has chronic bronchitis (defined as greater than 4 tablespoons of sputum production per day) as their primary diagnosis.
8. Subject has clinically significant bronchiectasis.
9. Subjects with evidence of active respiratory infection should be considered for enrollment only after satisfactory resolution.
10. Subject requires invasive ventilatory support. Note: The use of Continuous Positive Airway Pressure (CPAP) or BiPAP devices for sleep apnea is permitted.
11. Subject has severe gas exchange abnormalities as defined by any one of the following tests, conducted at rest, on room air, as tolerated.

    * PaCO2 ≥ 50 mm Hg (6.7 kPa)
    * PaO2 \< 45 mm Hg (6.0 kPa)
12. Subject has pulmonary hypertension, defined as mean pulmonary systolic pressure \> 45 mm Hg.
13. Subject has known documented alpha-1 antitrypsin deficiency.
14. Subject has clinically significant hematological disorder.
15. Subject has recent significant unplanned or unexplained weight loss or other relevant comorbidities considered by the investigator to be potentially confounding or limiting to the subject's participation in the study.
16. Subject has non-atrial arrhythmias or conduction abnormalities on EKG.
17. Subject has high cardiac risk after undergoing cardiac risk assessment in accordance with published guidelines (Fleisher 2007) or has ischemic heart disease, congestive heart failure, cerebrovascular disease (stroke or TIA within 6 months of the ICF signature date), serum creatinine \> 2.0 mg/dL (177 μmol/L), or left ventricular ejection fraction (LVEF) \< 45% on echocardiogram.
18. Subject has uncontrolled exercise induced syncope.
19. Subject has evidence of severe disease which in the judgment of the investigator may compromise the anticipated treatment effect or the subject's survival for the duration of at least 12 months.
20. Subject has any other condition that the investigator believes would interfere with the intent of the study or would make participation not in the best interest of the subject including but not limited to alcoholism, high risk for drug abuse, or noncompliance in returning for follow-up visits.
21. Subject cannot tolerate corticosteroids or relevant antibiotics.
22. Subject use of systemic corticosteroids \> 20 mg/day prednisolone or equivalent within four (4) weeks of the ICF signature date. Subjects may be re-considered for future enrollment.
23. Subject use of immunosuppressive agents within four (4) weeks of the ICF signature date. Subjects may be re-considered for future enrollment.
24. Subject is unable to temporarily discontinue heparins and oral anticoagulants (e.g., warfarin, dicumarol) according to local pre-procedural protocols. Note: Antiplatelet drugs including aspirin, thienopyridines and ticagrelor are permitted.
25. Subject has allergy or sensitivity to medications required to safely perform bronchoscopy under conscious sedation or general anesthesia.
26. Subject has known allergy to the following device components: Polyether block amide (PEBAX), Polyvinyl Alcohol or Glutaraldehyde, Nitinol (nickel-titanium) or its constituent metals (nickel or titanium) or Silicone.
27. Subject is a female who is pregnant (positive βHCG Pregnancy test), breast-feeding, or planning to be pregnant in the next 12 months.
28. Subject has Body Mass Index \< 18 kg/m2 or \> 35 kg/m2.
29. Subject participated in an investigational study of a drug, biologic, or device not currently approved for marketing within 30 days prior to the ICF signature date. Note: Subjects being followed as part of a long-term surveillance of a non-pulmonary study that has reached its primary endpoint are eligible for participation in this study.

Primary outcomes:
measure: Converters, responder rate
timeFrame: 45 days post-AeriSeal treatment (index or repeat)
Secondary outcomes:
measure: Post-bronchodilator forced expiratory volume in 1 second (FEV1), responder rate
timeFrame: Month 6 post-Zephyr Valve
measure: Residual volume (RV), responder rate
timeFrame: Month 6 post-Zephyr Valve
measure: Treated lobe volume reduction (TLVR) by high-resolution computed tomography (HRCT), responder rate
timeFrame: Month 6 post-Zephyr Valve
measure: St. George's Respiratory Questionnaire (SGRQ), responder rate
timeFrame: Month 6 post-Zephyr Valve
Other outcomes:
measure: Post-bronchodilator forced expiratory volume in 1 second (FEV1) change
timeFrame: Month 3, Month 6, Month 12, Month 24
measure: Post-bronchodilator forced expiratory volume in 1 second (FEV1), responder rate
timeFrame: Month 3, Month 12, Month 24
measure: Residual volume (RV), responder rate
timeFrame: Month 3, Month 12, Month 24
measure: Residual volume (RV), change
timeFrame: Day 45, Month 6, Month 12
measure: Treated lobe volume reduction (TLVR) by high-resolution computed tomography (HRCT), change
timeFrame: Day 45, Month 6, Month 12
measure: Treated lobe volume reduction (TLVR) by high-resolution computed tomography (HRCT), responder rate
timeFrame: Day 45, Month 12
measure: Residual volume to total lung capacity (RV/TLC) ratio
timeFrame: Month 3, Month 6, Month 12, Month 24
measure: Forced vital capacity (FVC), change
timeFrame: Month 3, Month 6, Month 12, Month 24
measure: Diffusion capacity of carbon monoxide (DLCO), change
timeFrame: Month 6, Month 12
measure: Chronic Obstructive Pulmonary Disease assessment test (CAT), change
timeFrame: Month 3, Month 6, Month 12
measure: Chronic Obstructive Pulmonary Disease assessment test (CAT), responder rate
timeFrame: Month 3, Month 6, Month 12
measure: St. George's Respiratory Questionnaire (SGRQ), total score change
timeFrame: Month 3, Month 6, Month 12
measure: St. George's Respiratory Questionnaire (SGRQ), responder rate
timeFrame: Month 3, Month 12
measure: Six Minute Walking Test (6MWT), responder rate
timeFrame: Month 6, Month 12
measure: Modified Medical Research Council (mMRC) Dyspnea Scale, total score change
timeFrame: Month 3, Month 6, Month 12
measure: Modified Medical Research Council (mMRC) Dyspnea Scale, responder rate
timeFrame: Month 3, Month 6, Month 12
Locations:
city: Phoenix
country: United States
facility: Banner University Medical Center
state: Arizona
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham Lung Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Cleveland
country: United States
facility: Cleveland VA Northeast
state: Ohio
city: Philadelphia
country: United States
facility: Penn Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin (MCW)
state: Wisconsin
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Brisbane
country: Australia
facility: Wesley Hospital
city: Macquarie Park
country: Australia
facility: Macquarie University
city: Vienna
country: Austria
facility: Klinik Floridsdorf
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Limoges
country: France
facility: CHU Limoges
city: Paris
country: France
facility: Hopital Bichat-APHP
city: Strasbourg
country: France
facility: CHRU Strasbourg
city: Toulouse
country: France
facility: CHU Toulouse
city: Essen
country: Germany
facility: Ruhrlandklink, Uni Essen
city: Halle
country: Germany
facility: Universitätsklinikum Halle
city: Hamburg
country: Germany
facility: Asklepios Klinik Barmbek
city: Heidelberg
country: Germany
facility: Thoraxklinik am Universitats klinikum Heidelberg
city: Hemer
country: Germany
facility: Lungenklinik Hemer
city: Brescia
country: Italy
facility: ASST Spedali Civili, University Hospital
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: London
country: United Kingdom
facility: Royal Brompton Hospital
state: England
Study officials:
affiliation: Pulmonx Corporation
name: Ryan Melloy, MBA
role: STUDY_DIRECTOR
References: