Fissure Closure With the AeriSeal System for CONVERTing Collateral Ventilation Status (CONVERT)

NCT04559464 | Completed DMC

• 1 other identifier: 630-0030-01
• Study Type: interventional
• Target: 102
• Locations: 7 countries
• Sites: 14

Brief Summary

This is a prospective, open-label, multi-center, single-arm study to be conducted at up to 20 investigational sites. The Study plans to enroll up to 140 subjects with severe emphysema and collateral ventilation in the target lobe. This protocol is designed to evaluate the utility of the AeriSeal System to occlude collateral air channels in a target lung lobe with collateral ventilation (CV) and convert the target lung lobe to having little to no collateral ventilation. Subjects can then receive Zephyr Valves to achieve atelectasis in the targeted lobe, once AeriSeal has converted the CV+ lobe to a CV- one. Therefore, the study will have two Stages:

• Stage 1 will address the closure of the lobar fissure gaps (or collateral air channels) to block collateral ventilation (CV) with the AeriSeal System; conversion of the CV+ target lobe to CV-. Conversion of collateral ventilation will be evaluated by Chartis after 45 days. In the case of unsuccessful conversion, a second treatment of AeriSeal may be attempted, provided that the total application volume from both the initial and the repeat treatments does not exceed 40 mL in up to three (3) segments. Clinical Assessments post-AeriSeal will be conducted at 28 and 45 days after first treatment and repeated after the second treatment, if applicable. For the purpose of protocol follow-up, the Day 45 post-AeriSeal final treatment will equal Day 0 for Stage 2.
• Stage 2 will include successfully converted subjects; CV+ to CV- conversion in Stage 1. Converted CV- target lobes will follow standard of care and receive CE marked Zephyr Endobronchial valves per the Zephyr IFU to perform bronchoscopic lung volume reduction (BLVR). Clinical assessments will be conducted at 45 Days, 3-months, 6-months, and 12-months post-Zephyr Valve procedure.

Conditions

Emphysema; COPD; Severe Emphysema

Keywords

Bronchoscopic lung volume reduction; Zephyr Valves; AeriSeal

Outcome Measures

Primary Outcomes (2)

• Percentage of subjects converted from a positive collateral ventilation status (CV+) to having little to no collateral ventilation (CV-) in the treated lobe.

  The primary AeriSeal endpoint will be the percentage of study subjects that are successfully converted from a positive collateral ventilation status (CV+) in the treated lobe to having little to no collateral ventilation (CV-) in the treated lobe six (6) weeks after delivery of AeriSeal.

  6-weeks post-AeriSeal treatment

• Treated Lobe Volume Reduction (TLVR) responders

  The primary Zephyr Valve endpoint is the percentage of subjects achieving TLVR ≥ 350 mL (TLVR Responders) at 45-days post-valve treatment. That is, the percentage of CV+ to CV- converted subjects from Stage 1 who subsequently receive valves and have Treated Lobe Volume Reduction (TLVR) of ≥ 350 mL, via High-resolution computed tomography (HRCT) at 45-days post-valve treatment.

  45-days post-Zephyr Valve treatment

Secondary Outcomes (2)

• Forced Expiratory Volume in 1 second (FEV1)

  3-months

• Residual volume (RV)

  3-months

Other Outcomes (10)

• Forced Expiratory Volume in 1 second (FEV1)

  6-months and 12-months

• Residual volume (RV)

  6-months and 12-months

• Six-Minute Walk Distance (6MWD)

  3-months, 6-months, and 12-months

Study Arms (1)

AeriSeal and Zephyr Valve Treatment

OTHER

Stage 1 will address the closure of the lobar fissure gaps (or collateral air channels) to block collateral ventilation (CV) with the AeriSeal System (conversion of the CV+ target lobe to CV-). Stage 2 will include successfully converted subjects in Stage 1. Converted CV- target lobes will follow standard of care and receive the Zephyr Endobronchial valves per the Zephyr Instructions for Use (IFU) to perform bronchoscopic lung volume reduction (BLVR).

Device: AeriSeal; Device: Zephyr Valves

Interventions

AeriSeal DEVICE

The AeriSeal Foam functions by blocking both small airways and collateral channels causing absorption atelectasis in the treated region of the lung. Occlusion with the foam also yields a targeted fibrotic response which durably reduces lung hyperinflation. The reduction in hyperinflation allows the healthier parts of the lung to re-inflate and improve breathing mechanics and gas exchange. In this study, the AeriSeal delivery will be limited to three segments that contain the collateral channel(s) between lung lobes. A minimum 10 mL volume of AeriSeal will be delivered per segment, with a total delivered volume limit of 40 mL per subject (including re-treatment, if needed) in a total of three segments.

AeriSeal and Zephyr Valve Treatment

Zephyr Valves DEVICE

The Zephyr Valves are implantable bronchial valves intended to control airflow in order to improve lung function in patients with hyperinflation associated with severe emphysema and/or to reduce air leaks.

Also known as: Bronchoscopic Lung Volume Reduction (BLVR), Zephyr System

AeriSeal and Zephyr Valve Treatment

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is willing and able to provide Informed Consent and to participate in the study.
• Subject is ≥ 40 and ≤ 75 years of age at the time Informed Consent signature.
• Subject has at least one lobe with ≥ 50% emphysema destruction (at -910 HU) as determined by QCT.
• Subject has a diagnosis of homogenous or heterogeneous emphysema, confirmed by HRCT scan. Heterogeneous emphysema defined as ≥ 15% difference (at -910 HU) in emphysema destruction score of adjacent lobes by HRCT.
• Subject has a gap in the interlobar fissure that corresponds to one or more segments as determined by QCT.
• Subject has clinically significant dyspnea with a mMRC Dyspnea score ≥ 2.
• Subject has a Six-Minute Walk Distance ≥ 250 meters.
• Subject has post-bronchodilator FEV1 ≥ 15% predicted and ≤ 50% predicted.
• Subject has post-bronchodilator Total Lung Capacity ≥ 100% predicted.
• Subject has post-bronchodilator Residual Volume ≥ 150% predicted if heterogeneous emphysema and ≥ 200% predicted if homogeneous emphysema.
• Subject has stopped smoking for at least eight (8) weeks prior to Screening visit as confirmed by carboxyhemoglobin or cotinine levels.
• Subject has received preventive vaccinations against potential respiratory infections consistent with local recommendations or policy.

You may not qualify if:

• Subject has severe bullous emphysema where bulla is ≥ 1/3 of the total lung volume.
• Subject has had prior lung volume reduction surgery, prior lobectomy or pneumonectomy, prior lung transplantation, prior airway stent placement, prior ipsilateral pleurodesis, or prior endobronchial lung volume reduction therapy of any type.
• Subject has evidence of active respiratory infection.
• Subject has an ongoing COPD exacerbation or bronchospasm.
• Subject has a known allergy to the device components:
• Polyether block amide - PEBAX®
• Polyvinyl Alcohol
• Glutaraldehyde
• Nitinol (nickel-titanium) or its constituent metals (nickel or titanium)
• Silicone
• Subject requires invasive ventilatory support (NOTE: The use of continuous Positive Airway Pressure (CPAP) and BiPAP devices for Sleep Apnea is permitted).
• Subject has post-bronchodilator Diffusion Capacity (DLCO) \< 20% predicted.
• Subject cannot tolerate corticosteroids or relevant antibiotics.
• Subject has other relevant comorbidities as judged by the Investigator or is deconditioned and cannot tolerate the stress of post-treatment inflammatory response.
• Subject has had three (3) or more COPD exacerbations requiring hospitalization during the year prior to Informed Consent signature.

Sponsors & Collaborators

• Pulmonx Corporation: lead

Study Sites (14)

The Wesley Hospital

Brisbane, Australia

Location

Macquarie University Hospital

Sydney, Australia

Location

CHU Limoges

Limoges, 87042, France

Location

CHU Toulouse

Toulouse, 31059, France

Location

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Ruhrlandklinik Essen

Essen, 45239, Germany

Location

ThoraxKlinik

Heidelberg, 69126, Germany

Location

ASST Spedali Civili, University Hospital

Brescia, 25123, Italy

Location

University Medical Center Groningen

Groningen, 9700 RB, Netherlands

Location

University Hospital of Zurich

Zurich, Rämistrasse 100, 8006, Switzerland

Location

Golden Jublilee National Hospital

Clydebank, Scotland, G81 4DY, United Kingdom

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

Nottingham University Hospitals

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Emphysema; Pulmonary Disease, Chronic Obstructive

Interventions

Pneumonectomy

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures

Study Officials

• Joshua Percy

  Pulmonx Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Stage 1 will address the closure of the lobar fissure gaps (or collateral air channels) to block collateral ventilation (CV) with the AeriSeal System (conversion of the CV+ target lobe to CV-). Stage 2 will include successfully converted subjects in Stage 1. Converted CV- target lobes will follow standard of care and receive the Zephyr Endobronchial valves per the Zephyr Instructions for Use (IFU) to perform bronchoscopic lung volume reduction (BLVR).

Study Record Dates

• First Submitted: September 16, 2020
• First Posted: September 22, 2020
• Study Start: December 15, 2020
• Primary Completion: October 24, 2023
• Study Completion: October 21, 2024
• Last Updated: November 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); GB (4); DE (3); AU (2); FR (2); NL (1); CH (1)