Clinical Investigation of a Modified Staged Treatment Algorithm Using the AeriSeal System

A Multicenter, Prospective, Single-Arm Clinical Investigation of a Modified Staged Treatment Algorithm Using the AeriSeal System - the AeriSeal-STAGE Trial

A multicenter, prospective, single-arm clinical investigation to evaluate the short term and long term safety of a modified staged treatment algorithm using the AeriSeal System.

The AeriSeal-STAGE trial will be a prospective, multicenter study that intends to evaluate the safety of a modified staged treatment algorithm with an escalation of dose using the AeriSeal System in the treatment of subjects with severe emphysema in a controlled trial design setting as compared to published data from prior studies. The trial is anticipated to enroll fifteen (15) study subjects with homogeneous, or upper lobe predominant heterogeneous emphysema, in three (3) centers in Europe.

Inclusion Criteria:

1. Subject is willing and able to provide informed consent and to participate in the study
2. Subject is ≥ 40 years of age
3. Subject has a diagnosis of homogenous or heterogeneous upper lobe predominant emphysema confirmed by computerized tomography (CT) scan.
4. Subject has at least two (2) non-adjacent subsegments appropriate for treatment based upon CT scan in 2 different upper lobe segments in each lung (total 4 available subsegments)
5. Subject has clinically significant dyspnea scoring >1 on the mMRC scale of 0 - 4
6. Subject has a Six-Minute Walk Test (6MWT) distance ≥ 250 meters
7. Subject has post-bronchodilator FEV1 ≤ 45% predicted
8. Subject has Total Lung Capacity >100% predicted
9. Subject has Residual Volume >175% predicted
10. Subject has stopped smoking for at least 8 weeks prior to entering the study as confirmed by carboxyhemoglobin or cotinine levels
11. Subject has received preventive vaccinations against potential respiratory infections consistent with local recommendations or policy

Exclusion Criteria:

1. Subject has severe bullous emphysema as judged by Investigator.

2. Subject has prior lung volume reduction surgery, prior lobectomy or pneumonectomy, prior lung transplantation, prior airway stent placement, prior pleurodesis, or prior endobronchial lung volume reduction therapy of any type

3. Subject has evidence of active respiratory infection

4. Subject has an ongoing chronic obstructive pulmonary disease (COPD) exacerbation or bronchospasm

5. Subject has a known allergy to the device components:

   1. Polyether block amide - PEBAX®
   2. Polyvinyl Alcohol
   3. Glutaraldehyde

6. Subject requires ventilatory support (invasive or non-invasive)

7. Subject has diffusing capacity of the lungs for carbon monoxide (DLco) < 20% predicted

8. Subject has a post-bronchodilator FEV1 < 20% predicted

9. Subject cannot tolerate corticosteroids or relevant antibiotics

10. Subject has relevant comorbidities as judged by the Investigator, or is deconditioned and cannot tolerate the stress of post-treatment inflammatory response

11. Subject has a history of recurrent clinically significant respiratory infections, defined as three (3) or more COPD exacerbations requiring hospitalization during the year prior to enrollment

12. Subject has severe gas exchange abnormalities as defined by any one of the following:

    1. Partial pressure of arterial carbon dioxide (PaCO2) >55 mm Hg
    2. Partial pressure arterial oxygen (PaO2) <45 mm Hg on room air
    3. Peripheral capillary oxygen saturation (SpO2) < 90% on ≥ 4 L/min supplemental O2, at rest

13. Subject has Pulmonary hypertension, defined as peak systolic pressure > 45 mm Hg on echocardiogram or right heart catheterization

14. Subject use of systemic steroids >20 mg/day or equivalent and/or immunosuppressive agents in the 4 weeks prior to procedure

15. Subject unable to temporarily interrupt use of heparins or oral anticoagulants (e.g., warfarin, dicumarol) per Institutional recommendations. Note: antiplatelet drugs including aspirin and clopidogrel are permitted

16. Subject has alpha1 -antitrypsin serum level of <80 mg/kg (i.e. < 11 µmol/L) at Screening

17. Subject's CT scan indicates the presence of any the following radiologic abnormalities:

    1. Pulmonary nodule on CT scan greater than 0.8 cm in diameter [Does not apply if present for 2 years or more without increase in size or if proven benign by biopsy/positron emission tomography (PET)]
    2. Radiologic picture consistent with active pulmonary infection, e.g., unexplained parenchymal infiltrate
    3. Significant interstitial lung disease
    4. Significant pleural disease

18. Subject's baseline electrocardiogram (EKG) indicates arrhythmias or conduction abnormalities

19. Subject has high cardiac risk after undergoing cardiac risk assessment in accordance with published guidelines or ischemic heart disease, congestive heart failure, renal failure or cerebrovascular disease

20. Clinically significant asthma (reversible airway obstruction), chronic bronchitis, or bronchiectasis

21. Allergy or sensitivity to medications required to safely perform bronchoscopy and the AeriSeal System treatment under general anesthesia or conscious sedation

22. Participation in an investigational study of a drug, biologic, or device within 30 days prior to entering the study or planned during the course of the study.

23. Body mass index (BMI) < 15 kg/m2 or > 35 kg/m2

24. Female subject pregnant or breast-feeding

25. Abnormal screening laboratory test results as compared to reference lab normals at individual sites as follows:

    1. Blood urea nitrogen > 1.5 x upper limit of normal
    2. Creatinine > 1.5 x upper limit of normal
    3. Aspartate aminotransferase > 1.5 x upper limit of normal
    4. Alanine aminotransferase > 1.5 x upper limit of normal
    5. Alkaline phosphatase > 1.5 x upper limit of normal
    6. White blood cells (total) absolute < 3 x 109/L or > 1.25 x upper limit of normal
    7. Hematocrit < 34 or > 1.25 x upper limit of normal
    8. Platelets < 100 or > 450 K/µL
    9. Prothrombin time or International Normalized Ratio (INR) > 1.5 x upper limit of normal
    10. Partial thromboplastin time > 1.5x upper limit of normal
    11. Positive Beta human chorionic gonadotropin (β-HCG) Pregnancy test (if female)

26. Subject has evidence of severe disease which in the judgment of the investigator may compromise survival for the duration of the study (24 months) e.g.:

    1. Human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS)
    2. Active malignancy
    3. Stroke or Transient ischemic attack (TIA) within 12 months of Screening visit
    4. Myocardial infarction within 6 months of Screening visit
    5. Congestive heart failure within 6 months of Screening visit defined as clinical evidence of right or left heart failure or left ventricular ejection fraction < 45% on echocardiogram

27. Subject has been diagnosed with diabetes mellitus

28. Any 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 i.e., alcoholism, high risk for drug abuse or noncompliance in returning for follow-up visits