An Evaluation of the AeriSeal System for CONVERTing Collateral Ventilation Status in Patients With Severe Emphysema

Emphysema or COPD Clinical Trial

— CONVERT_II  

Official title:

An Evaluation of the AeriSeal System for CONVERTing Collateral Ventilation Status in Patients With Severe Emphysema: The CONVERT II Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06035120
• Other study ID #: 630-2000-01
• Status: Recruiting
• Phase: N/A
• Start date: February 22, 2024
• Est. completion date: March 31, 2028

Study information

• Verified date: April 2024
• Source: Pulmonx Corporation
• Contact: Christina Kutzavitch, PhD
• Phone: +1 650-216-0134
• Email: ckutzavitch[@]pulmonx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 30 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: March 31, 2028
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Subject is willing and able to provide informed consent and to participate in the study.

2. Subject is aged = 22 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 6 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 an HRCT from the screening institution 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 = 250 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 (7.3 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), or serum creatinine > 2.0 mg/dL (177 µmol/L).

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 ßHCG 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.

Related Conditions & MeSH terms

• Emphysema
• Emphysema or COPD
• Pulmonary Emphysema

Intervention

Device:
• AeriSeal System
The AeriSeal System comprises AeriSeal Foam and the AeriSeal Balloon Catheter Preparation Kit that is used for bronchoscopic delivery of AeriSeal Foam to the targeted regions of the lung.

Locations

Country	Name	City	State
Australia	Macquarie University	Macquarie Park
Germany	Ruhrlandklinik - West German Lung Center	Essen
Germany	Universitätsklinikum Halle	Halle
Germany	Asklepios Klinik Barmbek	Hamburg
Germany	Thoraxklinik am Universitats klinikum Heidelberg	Heidelberg
Italy	ASST Spedali Civili, University Hospital	Brescia
Spain	Hospital Universitario y Politecnico La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Pulmonx Corporation

Countries where clinical trial is conducted

Australia,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Post-bronchodilator forced expiratory volume in 1 second (FEV1) change	Absolute, percent and percent predicted change	Month 3, Month 6, Month 12, Month 24
Other	Post-bronchodilator forced expiratory volume in 1 second (FEV1), responder rate	Percentage of subjects achieving a =12% increase	Month 3, Month 12, Month 24
Other	Residual volume (RV), responder rate	The percentage of subjects achieving a = 310 mL decrease in RV	Month 3, Month 12, Month 24
Other	Residual volume (RV), change	Absolute and percent predicted change in RV	Day 45, Month 6, Month 12
Other	Treated lobe volume reduction (TLVR) by high-resolution computed tomography (HRCT), change	Absolute change in TLVR	Day 45, Month 6, Month 12
Other	Treated lobe volume reduction (TLVR) by high-resolution computed tomography (HRCT), responder rate	The percentage of subjects achieving a = 350 mL decrease in TLVR	Day 45, Month 12
Other	Residual volume to total lung capacity (RV/TLC) ratio	Absolute change in RV/TLC ratio	Month 3, Month 6, Month 12, Month 24
Other	Forced vital capacity (FVC), change	Absolute and percent change in FVC	Month 3, Month 6, Month 12, Month 24
Other	Diffusion capacity of carbon monoxide (DLCO), change	Absolute and percent predicted change in DLCO	Month 6, Month 12
Other	Chronic Obstructive Pulmonary Disease assessment test (CAT), change	Absolute change. Minimum score: 0, maximum score: 40. Lower scores indicate a better outcome.	Month 3, Month 6, Month 12
Other	Chronic Obstructive Pulmonary Disease assessment test (CAT), responder rate	The percentage of subjects achieving a = 2-point decrease	Month 3, Month 6, Month 12
Other	St. George's Respiratory Questionnaire (SGRQ), total score change	Absolute change in SGRQ total score. Minimum score: 0, maximum score: 100. Lower scores indicate a better outcome.	Month 3, Month 6, Month 12
Other	St. George's Respiratory Questionnaire (SGRQ), responder rate	The percentage of converters achieving a = 4-point decrease in SGRQ total score	Month 3, Month 12
Other	Six Minute Walking Test (6MWT), responder rate	Percentage of subjects achieving a = 26 meter increase	Month 6, Month 12
Other	Modified Medical Research Council (mMRC) Dyspnea Scale, total score change	Absolute change in total mMRC Dyspnea Scale score. Minimum score: 0, maximum score: 4. Lower scores indicate a better outcome.	Month 3, Month 6, Month 12
Other	Modified Medical Research Council (mMRC) Dyspnea Scale, responder rate	The percentage of subjects achieving a = 1-point decrease	Month 3, Month 6, Month 12
Primary	Converters, responder rate	The percentage of study subjects that successfully convert from a positive collateral ventilation status (CV+) in the treated lobe to having little to no collateral ventilation (CV-) by Chartis.	45 days post-AeriSeal treatment (index or repeat)
Secondary	Post-bronchodilator forced expiratory volume in 1 second (FEV1), responder rate	The percentage of converters achieving a = 12% increase in FEV1	Month 6 post-Zephyr Valve
Secondary	Residual volume (RV), responder rate	The percentage of converters achieving a = 310 mL decrease in RV	Month 6 post-Zephyr Valve
Secondary	Treated lobe volume reduction (TLVR) by high-resolution computed tomography (HRCT), responder rate	The percentage of converters achieving a = 350 mL decrease in TLVR	Month 6 post-Zephyr Valve
Secondary	St. George's Respiratory Questionnaire (SGRQ), responder rate	The percentage of converters achieving a = 4-point decrease in SGRQ total score	Month 6 post-Zephyr Valve