Crossover From IDE Trial CLN0009, Lung Volume Reduction Coil Treatment in Patients With Emphysema (RENEW) Study, IDE G110066
Phase: NA
Conditions: Emphysema
Sponsor: Boston Scientific Corporation

CONFIDENTIAL 
CLN0016.p.D 
PneumRx, Inc. 
Page 1 of 46 
     
 
CLINICAL TRIAL PROTOCOL COVER SHEET 
 
 
Device: 
 
 
PneumRx® RePneu® Coil System 
 
 
Study Number & Rev.: 
CLN0016.p. Rev D 
 
 
Study Title: 
LVRC IDE Crossover Study  
(Crossover from IDE Trial CLN0009,  
Lung Volume Reduction Coil Treatment  
in Patients with Emphysema (RENEW)  
Study, IDE G110066) 
 
 
Study Design: 
Multicenter, single-arm, study of  the  
PneumRx, Inc. RePneu Coil System 
 
 
Sponsor Name: 
PneumRx, Inc. 
 
 
Sponsor Address: 
 
530 Logue Avenue 
Mountain View, California 94043 
USA 
 
 
Study Coordination  
PneumRx, Inc. 
and Data Analysis: 
 
 
Projected Initiation Date: 
December 2013 
 
 
Projected  
Completion Date: 
 
September 2019 
 
 
 
 
 
STATEMENT OF CONFIDENTIALITY 
The information contained herein is confidential information that is the sole and 
exclusive property of PneumRx, Inc. and may not be divulged to any person 
(except as required by law) without the prior written consent of PneumRx, Inc. 

CONFIDENTIAL 
CLN0016.p.D 
PneumRx, Inc. 
Page 2 of 46 
 
Revision History 
Revision 
DCO 
Effective Date 
Originator 
A 
2343 
23 Sep 13 
Kara Andersen Reiter 
B 
2373 
09 Oct 13 
Kara Andersen Reiter 
C 
3058 
23 Jun 15 
Stephanie Buech 
D 
3101 
24 Aug 15 
Stephanie Buech 
 
 

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CLN0016.p.D 
PneumRx, Inc. 
Page 4 of 46 
STATEMENT OF COMPLIANCE 
 
The Trial (entitled LVRC IDE Crossover Study) will be conducted in compliance with this 
Protocol, and with local, State, and Federal requirements, including FDA Good Clinical 
Practices, my overseeing IRB requirements, patient privacy requirements, and all 
applicable regulatory requirements. 
 
 
Protocol Title: LVRC IDE Crossover Study 
 
Version: CLN0016.p.D 
Revision Date: 24 August 2015 
 
 
 
 
 
 
 
Investigator's Name (please print) 
 
 
 
 
Investigator’s Title 
 
 
 
 
Investigator's Signature 
 
 
 
 
 
Date 

CONFIDENTIAL 
CLN0016.p.D 
PneumRx, Inc. 
Page 5 of 46 
Table of Contents 
 
1 
Protocol Synopsis ............................................................................................. 11 
2 
Introduction ....................................................................................................... 16 
2.1 
Background ............................................................................................. 16 
2.2 
Clinical Need ........................................................................................... 16 
2.3 
Description of the RePneu Coil System .................................................. 17 
2.4 
Historical Data ......................................................................................... 19 
3 
Study Objectives ............................................................................................... 22 
4 
Study Design ..................................................................................................... 22 
4.1 
Design Overview ..................................................................................... 22 
4.2 
Number of Subjects ................................................................................. 22 
4.2.1 
Pharmacological Treatment ......................................................... 22 
4.3 
Population ................................................................................................ 22 
4.4 
Demographic and Baseline Characteristics ............................................. 22 
4.5 
Safety Evaluation ..................................................................................... 23 
4.6 
Brief Description of Study ........................................................................ 23 
4.6.1 
Treatment .................................................................................... 24 
5 
Study Subject Recruitment .............................................................................. 26 
5.1 
Inclusion Criteria ...................................................................................... 26 
5.2 
Exclusion Criteria ..................................................................................... 26 
6 
Study Plan .......................................................................................................... 27 
6.1 
Investigator Training ................................................................................ 27 
6.1.1 
Informed Consent ........................................................................ 27 
6.1.2 
Study Identification Number ......................................................... 28 
6.1.3 
Pre-treatment/Screening Evaluations .......................................... 28 
6.2 
Treatment ................................................................................................ 28 
6.2.1 
Visit 2 - LVRC Placement ............................................................ 28 
6.2.2 
Visit 2, cont: Post Bronchoscopy Monitoring and Evaluations ..... 29 
6.2.3 
Visit 3 - 1 Week Post Visit 2 Follow Up Phone Call ..................... 29 
6.2.4 
Visit 4 - 1 Month Post Visit 2 Follow Up ....................................... 29 
6.2.5 
Visit 5 - 2 Months Post-Visit 2 LVRC Placement #2 .................... 30 
6.2.6 
Visit 5, cont: Post Bronchoscopy Monitoring and Evaluations ..... 30 
6.2.7 
Visit 6 - 1 Week Post Visit 5 Phone Call ...................................... 30 
6.2.8 
Visit 7 - 1 Month Post Visit 5 Follow Up ....................................... 31 
6.2.9 
Visit 8 - 6 Months Post Visit 2 Follow Up ..................................... 31 

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CLN0016.p.D 
PneumRx, Inc. 
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6.2.10 Visit 9 - 9 Months Post Visit 2 Phone Call ................................... 31 
6.2.11 Visit 10 - 12 Months Post Visit 2 Follow Up ................................. 31 
6.2.12 Visit 11 - 24 Months Post Visit 2 Follow Up ................................. 32 
6.2.13 Visit 12 - 36 Months Post Visit 2 Follow Up ................................. 32 
6.2.14 Visit 13 - 48 Months Post Visit 2 Follow Up ................................. 32 
6.2.15 Visit 14 - 60 Months Post Visit 2 Follow Up ................................. 33 
6.2.16 Unscheduled Visits ...................................................................... 33 
7 
Management of Adverse Events (AEs) and Serious Adverse Events (SAEs)33 
7.1 
Serious Adverse Events  ......................................................................... 34 
7.2 
Unanticipated Adverse Device Effect (UADE) ......................................... 34 
7.3 
Severity of AEs and SAEs ....................................................................... 35 
7.4 
Relationship of an Event .......................................................................... 35 
7.5 
Process for Assessment, Recording and Reporting of AEs .................... 35 
7.6 
Data Monitoring Committee Composition and Role ................................ 36 
8 
Administrative ................................................................................................... 36 
8.1 
Premature Termination of Study .............................................................. 36 
8.2 
Insurance Coverage ................................................................................ 37 
9 
Risks and Benefits ............................................................................................ 37 
9.1 
Potential Risks to the Subject .................................................................. 37 
9.2 
Potential Benefits to the Subject .............................................................. 39 
10 
Study Monitoring ............................................................................................... 40 
11 
Responsibilities of the Sponsor ...................................................................... 40 
12 
Responsibilities of the Principal Investigator ................................................ 41 
13 
Good Clinical Practice & Regulatory Requirements ...................................... 43 
14 
Citations and References ................................................................................. 45 
 

CONFIDENTIAL 
CLN0016.p.D 
PneumRx, Inc. 
Page 7 of 46 
 
Table of Tables 
Table 1. 6 Minute Walk Test (6MWT), Bilateral Subjects ................................................ 20 
Table 2. Residual Volume (RV), Bilateral Subjects ......................................................... 20 
Table 3. Forced Expiratory Volume in 1 Second (FEV1), Bilateral Subjects ................... 20 
Table 4. Saint George's Respiratory Questionnaire (SGRQ), Bilateral Subjects ............ 20 
Table 5. Comparison of 6-Month SAE Data Per Procedure - LVRC System vs. EASE 
Sham Control .................................................................................................................. 21 
Table 6. Visit Schedule ................................................................................................... 25 
 

CONFIDENTIAL 
CLN0016.p.D 
PneumRx, Inc. 
Page 8 of 46 
 
Table of Figures 
Figure 1. Diagram of the Lung Volume Reduction Procedure Using Coils ..................... 18 
Figure 2. Shapes and Sizes of Coils ............................................................................... 19 
Figure 3. Components of the Delivery System ................................................................ 19 
 

CONFIDENTIAL 
CLN0016.p.D 
PneumRx, Inc. 
Page 9 of 46 
 
Table of Attachments 
 
A. Investigator Agreement 
 

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CLN0016.p.D 
PneumRx, Inc. 
Page 10 of 46 
List of Abbreviations  
 
6MWT 
6 Minute Walk Test 
ABG 
Arterial Blood Gas 
AE 
Adverse Event 
BD 
Bronchodilator 
BL 
Baseline 
CAO 
Coil-Associated Opacity 
COPD 
Chronic Obstructive Pulmonary Disease 
CRF 
Case Report Form 
CT 
Computed tomography 
CXR 
Chest X-ray 
DLCO 
Diffusion Capacity of the Lung for Carbon Monoxide 
DMC 
Data Monitoring Committee / Data Safety Monitoring Board 
EC 
Ethics Committee 
EKG 
Electrocardiogram 
EDC 
Electronic Data Collection 
FEV1 
Forced Expiratory Volume (in one second) 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GOLD 
Global Initiative for Chronic Obstructive Lung Disease 
HRCT 
High Resolution Computed Tomography (CT Scan) 
IC 
Inspiratory Capacity 
IDE 
Investigational Device Exemption 
IFU  
Instructions for Use 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat population 
LRTI 
Lower Respiratory Tract Infection 
LVRC 
Lung Volume Reduction Coil  
LVRD 
Lung Volume Reduction Device 
LVRS 
Lung Volume Reduction Surgery 
mMRC 
Modified Medical Research Council 
O2 
Oxygen 
OUS 
Outside United States 
PaO2 
Partial Arterial Blood Gases Oxygen 
PaCO2 
Partial Arterial Blood Gases Carbon Dioxide 
PI 
Principal Investigator 
PFT              Pulmonary Function Test 
PP 
Per-Protocol 
QOL 
Quality of Life 
RV  
Residual Volume 
RV/TLC 
Residual Volume / Total Lung Capacity 
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedure 
SpO2 
Oxygen Saturation by pulse oximetry 
SGRQ 
St. George’s Respiratory Questionnaire 
TLC 
Total Lung Capacity 
UADE 
Unanticipated Adverse Device Effect 

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CLN0016.p.D 
PneumRx, Inc. 
Page 11 of 46 
 
1 
Protocol Synopsis 
 
Study Number 
and Title: 
CLN0016.p.D 
LVRC IDE Crossover Study 
 
Clinical Phase: 
Cross-over from Pivotal, Phase III 
 
Study Device 
PneumRx® RePneu Coil System (RePneu® Coil) 
 
Study Objectives: 
Provide LVRC procedure to qualifying subjects who were 
enrolled as Control Subjects in and completed the Lung 
Volume Reduction Coil Treatment in Patients with 
Emphysema (RENEW) Study, CLN0009, and obtain safety 
and effectiveness data on these patients. 
 
Study Design: 
This will be a prospective, multicenter, open label, single-arm 
study. 
 
Study Population: 
The study population will include all subjects who have met 
the inclusion/exclusion study criteria.  
 
Inclusion Criteria: 
1. 
Subject was enrolled as a Control Subject in and 
completed all required study assessments through 
the 12 month visit for the Lung Volume Reduction 
Coil Treatment in Patients with Emphysema 
(RENEW) Study, CLN0009. 
2. 
Subject has post-bronchodilator FEV1 ≤45% predicted.  
3. 
Subject has residual volume (RV) ≥175% predicted. 
4. 
Subject has stopped smoking for at least 8 weeks prior 
to entering the study, as confirmed by a Cotinine test 
or other appropriate diagnostic test. 
5. 
Subject has read, understood and signed the Informed 
Consent form. 
6. 
Subject has received Pneumococcal and Influenza 
vaccinations consistent with local recommendations 
and/or policy.  
 
Exclusion Criteria: 
1. 
Subject has severe homogeneous emphysema as 
determined by the Core Radiology Lab  
2. 
Subject has co-morbidities that may significantly 
reduce subject’s ability to improve exercise capacity 
(e.g. severe arthritis, planned knee surgery) or 
baseline limitation on 6MWT is not due to dyspnea.   
3. 
Subject has a change in FEV1 >20% (or, for subjects 
with pre-bronchodilator FEV1 below 1 L, a change of 
> 200 mL) post-bronchodilator unless investigator 
can confirm by other means that subject does not 
have asthma. 
4. 
Subject has DLCO <20% of predicted. 

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CLN0016.p.D 
PneumRx, Inc. 
Page 12 of 46 
5. 
Subject has severe gas exchange abnormalities as 
defined by: 
PaCO2 >55 mm Hg  
PaO2 <45 mm Hg on room air (High altitude criterion: 
PaO2 <30 mm Hg) 
6. 
Subject has a history of recurrent clinically significant 
respiratory infections, defined as 3 hospitalizations 
for respiratory infection during the year prior to 
enrollment. 
7. 
Subject has severe pulmonary hypertension. If 
pulmonary hypertension is present, “severe” is 
defined by right ventricular systolic pressure >50 mm 
Hg via right heart catheterization and/or 
echocardiogram.  
8. 
Subject has an inability to walk >140 meters (150 
yards) in 6 minutes. 
9. 
Subject has evidence of other severe disease (such as, 
but not limited to, lung cancer or renal failure), which 
in the judgment of the investigator may compromise 
survival of the subject for the duration of the study.  
10. Subject is pregnant or lactating, or plans to become 
pregnant within the study timeframe. 
11. Subject has an inability to tolerate bronchoscopy under 
moderate sedation or general anesthesia. 
12. Subject has clinically significant bronchiectasis. 
13. Subject has giant bullae >1/3 lung volume. 
14. Subject has had previous LVR surgery, lung 
transplantation, lobectomy, LVR devices or other 
devices to treat COPD in either lung. 
15. Subject has been involved in pulmonary drug or device 
studies within 30 days prior to this study, with the 
exception of the RENEW Study. 
16. Subject is taking >20 mg prednisone (or equivalent 
dose of a similar steroid) daily. 
17. Subject requires high level chronic immunomodulatory 
therapy to treat a moderate to severe chronic 
inflammatory autoimmune disorder.  
18. Subject is on an antiplatelet agent (such as Plavix) or 
anticoagulant therapy (such as heparin or Coumadin) 
which cannot be stopped for seven (7) days prior to 
procedure. 
19. Subject has a sensitivity or allergy to nitinol (nickel-
titanium) or its constituent metals. 
20. Subject has a known sensitivity to drugs required to 
perform bronchoscopy. 
21. Subject has been diagnosed with alpha-1 antitrypsin 
deficiency (AATD). 
22. Subject has any other disease, condition(s) or habit(s) 
that would interfere with completion of study and 
follow up assessments, would increase risks of 
bronchoscopy or assessments, or in the judgment of 
the investigator would potentially interfere with 
compliance to this study or would adversely affect 

CONFIDENTIAL 
CLN0016.p.D 
PneumRx, Inc. 
Page 13 of 46 
study outcomes.  
 
Study Treatment: 
Subjects will undergo two bronchoscopy sessions under 
general anesthesia or moderate sedation, at the discretion of 
the bronchoscopist. During the procedure, subjects will be 
treated with Coils according to the Instructions for Use. 
Subjects will receive prophylactic drugs before and after the 
procedure. Following LVRC placement (Visit 2), the subject 
will remain in the hospital under observation per standard 
hospital practice. Following hospital discharge, the subject will 
be contacted by phone one week after Visit 2 and will be seen 
at the study site at one month after the procedure. After the 
one month visit following Visit 2, the subject will be scheduled 
for the second procedure in the contralateral lung to take 
place approximately 2 months after Visit 2. Only a single lung 
will be treated during any bronchoscopy.   
 
Study Procedures 
and 
Assessments: 
The following assessments are prescribed in the protocol 
through the study period. 
 
Visit 1: Baseline evaluation after informed consent is signed. 
NOTE that SGRQ, mMRC and 6MWT, DLCO and other PFTs 
(excluding spirometry) results from the 12 month evaluation 
for RENEW will be used as baseline measures, provided that 
Visit 1 occurs within 6 weeks of the 12 month RENEW 
evaluation. Spirometry must be repeated. If Visit 1 occurs 
more than 6 weeks after the 12 month RENEW evaluation, all 
baseline measures will be taken and recorded at Visit 1. 
 
Visit 2: LVRC Placement #1   
Prescribe a prophylactic regimen of antibiotics and steroids 
before and after Coil placement. Subject to remain in the 
hospital for monitoring per standard hospital practice. 
 
Visit 3: 1 Week Follow Up Phone Call/interview to assess 
overall status. Review medications and O2 use and record 
AEs. 
 
Visit 4: 1 Month Follow Up  
Perform focused physical exam including Vital Signs (heart 
rate, blood pressure, temperature, respiratory rate, SpO2) and 
breath sounds and 6MWT, administer SGRQ and mMRC. 
Review medications and O2 use, Record AEs since last 
follow-up. 
 
Visit 5: LVRC Placement #2 (2 Months Post-Visit 2) 
Prescribe a prophylactic regimen of antibiotics and steroids 
before and after treatment. Subject to remain in the hospital 
for observation and monitoring per standard hospital practice. 
 
Visit 6: 1 Week post Visit 5 Follow Up Phone Call/interview to 
assess subject overall status. Review medications and O2 

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CLN0016.p.D 
PneumRx, Inc. 
Page 14 of 46 
use and record AEs. 
 
Visit 7: 1 Month post Visit 5Perform focused physical exam 
including Vital Signs (heart rate, blood pressure, temperature, 
respiratory rate, SpO2) and breath sounds and 6MWT, 
administer SGRQ and mMRC. Review medications and O2 
use, Record AEs since last follow-up. 
 
Visit 8: 6 Months post Visit 2 
Perform focused physical exam including Vital Signs (heart 
rate, blood pressure, temperature, respiratory rate, SpO2) and 
breath sounds, post-bronchodilator spirometry, lung volumes, 
DLCO and 6MWT; administer SGRQ and mMRC. Review 
medications and O2 use, Record AEs since last follow-up. 
 
Visit 9: 9 Months post Visit 2 Follow Up Phone Call/interview 
to assess subject overall status. Review medications and O2 
use and record AEs. 
 
Visit 10: 12 Months post Visit 2 
Perform focused physical exam including Vital Signs (heart 
rate, blood pressure, temperature, respiratory rate, SpO2) and 
breath sounds, post-bronchodilator spirometry, lung volumes, 
DLCO and 6MWT; administer SGRQ and mMRC. Review 
medications and O2 use, Record AEs since last follow-up. CT 
scan. 
 
Visit 11: 24 Months post Visit 2, Visit 12: 36 Months post Visit 
2, and Visit 13: 48 Months post Visit 2 
 
Perform focused physical exam including Vital Signs (heart 
rate, blood pressure, temperature, respiratory rate, SpO2) and 
breath sounds, post-bronchodilator spirometry, lung volumes, 
DLCO and 6MWT, administer SGRQ and mMRC. Review 
medications and O2 use, Record AEs since last follow-up. 
 
Visit 14: 60 Months post Visit 2 
Perform focused physical exam including Vital Signs (heart 
rate, blood pressure, temperature, respiratory rate, SpO2) and 
breath sounds, post-bronchodilator spirometry, lung volumes, 
DLCO and 6MWT; administer SGRQ and mMRC. Review 
medications and O2 use, Record AEs since last follow-up. 
Exit study. 
 

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CLN0016.p.D 
PneumRx, Inc. 
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Management of 
Adverse Events 
AE information will be collected throughout the study. 
Adverse events will be recorded on the AE eCRF by the 
investigator or authorized designee. Event, date of onset, 
severity, duration, and relationship to the procedure/device 
will be recorded. All adverse events will be followed until they 
are adequately resolved or stabilized or for 1 month following 
study completion or termination, whichever comes first.  
 
Statistical 
Analyses 
Descriptive statistics will be used to evaluate the data, 
including differences from Baseline to 12 months in 6MWT 
and SGRQ, and safety. 
 

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CLN0016.p.D 
PneumRx, Inc. 
Page 16 of 46 
 
2 
Introduction 
2.1 
Background 
The objective of this study is to provide the LVRC procedure and safety and 
effectiveness follow up to qualifying subjects who were enrolled as Control 
Subjects in and completed the Lung Volume Reduction Coil Treatment in 
Patients with Emphysema (RENEW) Study, CLN0009. At the time of entry into 
the RENEW trial, patients who were randomized to the Control arm were told that 
they would have the opportunity to receive insertion of the Coil at the end of one 
year, if they still fulfilled the entry criteria, did not have any exclusion criteria, and 
if the Data Monitoring Committee (DMC) did not have any major safety concerns.  
 
Physician-investigators who wish to participate in this study understand that the 
study will be conducted under all applicable regulatory requirements for the 
country where the study is being conducted. All participating investigators and 
co-investigators will be asked to sign a Study Acknowledgment (refer to page 3 
of this protocol), a Statement of Compliance (refer to page 4 of this protocol) and 
a sponsor-generated Investigator Agreement (Attachment A), as well as any 
required country-specific Investigator Agreement. 
 
This study is being conducted according to Good Clinical Practice (GCP), in 
compliance with the principles enunciated in the Declaration of Helsinki (World 
Medical Association Declaration of Helsinki, 2008), the US FDA regulations in 
accordance with 21 CFR, Parts 50, 56, and 812, applicable local regulations, and 
PneumRx, Inc. and its designee(s) Clinical Standard Operating Procedures 
(SOPs). Participating study centers in the EU and Canada are also subject to the 
clinical study investigation laws and regulations of those communities and their 
local Ethics Committees, in addition to those of the US FDA for this IDE study. 
 
2.2 
Clinical Need  
Emphysema is a chronic respiratory disease with an estimated prevalence of 
1.8% (Halbert, 2006). Emphysema is characterized by gradual destruction and 
disappearance of alveolar walls. This results in reduction in the elasticity and 
recoil pressure of the lungs, and allows the smaller airways to collapse 
prematurely during exhalation, resulting in hyperinflation, air trapping, and 
diaphragmatic 
flattening 
with 
decreased 
diaphragmatic 
efficiency. 
This 
hyperinflation worsens with rapid breathing associated with exercise. These 
effects are believed to be a primary contributor to the dyspnea experienced by 
emphysema patients (O’Donnell, 2006). The alveolar wall damage also creates 
large nonfunctional air pockets or bullae that become physiologic dead space in 
the thorax, preventing healthier portions of the lung from expanding and 
contracting normally. Patients with advanced emphysema also frequently 
demonstrate collateral ventilation both within the affected lobes and even across 
lobar fissures. As the disease progresses, the emphysema patient eventually 
becomes hypoxemic due to progressive loss of alveolar capillary membrane 
surface area. Hypoxemia and deconditioning contribute to muscle weakness and 
fatigue. The crippling effects of end-stage emphysema include severe dyspnea, 
severe limitation of activities, recurrent lung infections, and ultimately respiratory 
failure, which can result in death.  
 

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CLN0016.p.D 
PneumRx, Inc. 
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There are several treatments available for emphysema including smoking 
cessation, medications, physical therapy, supplemental oxygen, and surgery. 
Emphysema can be treated with inhaled bronchodilators, inhaled corticosteroids, 
anticholinergics, theophylline, phosphodiesterase-4 inhibitors and supplemental 
oxygen. Emphysema patients are prone to exacerbations, usually due to 
respiratory infections, which are usually treated with antibiotics and/or systemic 
corticosteroids 
and 
frequently 
require 
emergency 
room 
visits 
and/or 
hospitalizations. Emphysema patients may undergo pulmonary rehabilitation 
exercises and training. There are also two surgical procedures available for 
treatment of severe emphysema: lung transplantation and lung volume reduction 
surgery (LVRS). Lung transplantation is a seldom used option because of the 
limited availability of donor lungs, low transplantation priority for emphysema 
patients relative to other rapidly fatal pulmonary diseases, and because of the 
advanced age of most emphysema patients. Lung Volume Reduction Surgery is 
major surgery that carries the risk of morbidity and mortality. Recently, less 
invasive bronchoscopic approaches have been developed and several 
approaches are being actively investigated in human clinical trials in Europe and 
the US. 
 
The PneumRx RePneu Coil System (RePneu Coil) is designed to compress the 
areas of lung parenchyma most damaged by emphysema. This compression 
reduces air flow to treated portions of the lung allowing enhanced airflow to 
healthier untreated portions of the lung (Figure 1). The compression also reduces 
the volume of the hyperinflated emphysematous lung, resulting in lung volume 
reduction with improved diaphragmatic efficiency. Additionally, by gathering up 
the loose parenchyma of the most severely damaged segments, the Coil restores 
elasticity and recoil to the whole lung, improving expiratory flow rates, lessening 
small airway collapse with air trapping, and reducing dynamic hyperinflation. 
Because the Coil acts by a simple mechanical action these effects are achieved 
immediately in the presence or absence of collateral ventilation. This device is 
deployed using a minimally invasive approach using a simple catheter-based 
delivery system through a fiber-optic bronchoscope and requires no incision.  
 
2.3 
Description of the RePneu Coil System 
The RePneu Coil is an implantable device, delivered through a fiber-optic 
bronchoscope, designed specifically to treat patients suffering from emphysema. 
The Coil System is a two part system that consists of 1) sterile Coils and 2) a 
sterile, disposable, single-use (single-patient) Delivery System consisting of a 
Guidewire, Catheter, Cartridge, and Forceps.  
 
The Coil is composed of nitinol (nickel-titanium), a biocompatible super-elastic 
material. The self-recovering Coil is delivered into the airway in a straight 
configuration and recovers to a non-straight, pre-determined shape upon 
deployment. The Coil is intended to compress the most damaged parenchyma 
and tension the surrounding tissue, which increases elastic recoil, reduces 
hyperinflation and redirects air to healthier portions of the lung for more effective 
ventilation. Since this therapy targets local diseased regions of the lung, more 
than one Coil may be necessary to achieve adequate effect. In previous clinical 
trials, the majority of cases involved 10 Coils per treated lung, with good safety 
and effectiveness results. The Coil will effectively reduce the volume of damaged 
parenchyma, even in the presence of collateral ventilation. 
 

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PneumRx, Inc. 
Page 18 of 46 
The Coil derives its recovery ability from the super-elastic properties of the nitinol 
wire. The Coils are available in four lengths to accommodate anticipated 
anatomical variations – the lengths are 100mm, 125mm, 150mm, and 175mm 
(Figure 2). The trailing proximal end of the Coil (most proximal 10mm) has a 
smaller diameter than the rest of the Coil to reduce rigidity, lessen pressure of 
the Coil on the airway wall, and facilitate recapture, if necessary. The distal and 
proximal ends of the Coil terminate with a smooth atraumatic ball. 
 
The Delivery System is used to safely deliver the Coils (Figure 3). The Guidewire 
serves as a specialized large and flexible guide for the Catheter, which enables 
the identification of suitable airways for treatment and supports the Catheter to 
help guide it to a delivery site. The Guidewire also facilitates the selection of the 
appropriate Coil length. The Catheter functions as a conduit to deliver the Coil 
from outside the patient to the targeted treatment area. It also can be used to 
reposition or remove the Coil. The Cartridge straightens the Coil, couples to the 
Catheter, and aids in the process of loading the Coil into the Catheter. The 
Forceps couples to the proximal end of the Coil and delivers it through the 
Catheter, enabling the clinician to control the placement and release of the 
device.  
 
The Coil can be removed by reversing the deployment procedure. For additional 
information about repositioning or Coil removal, refer to Section 9.1 of the 
protocol and the “Coil Removal Instructions” section in the Instructions for Use. 
 
The procedure is designed to be performed using a bronchoscope with a 2.8mm 
inner diameter working channel (which accommodates the Delivery System) and 
fluoroscopy for visualization beyond the viewing range of the bronchoscope. 
 
Each Coil is individually pouched in its own protective packaging shell and five 
Coils of the same size are packaged in a box. The Guidewire, Catheter, 
Cartridge, and Forceps are pouched together and packaged in a box. The LVRC 
Delivery System is sterilized by Ethylene Oxide (EO) and the Coils are sterilized 
by Electron Beam (E-Beam). 
 
Figure 1. Diagram of the Lung Volume Reduction Procedure Using Coils 
 

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CLN0016.p.D 
PneumRx, Inc. 
Page 19 of 46 
 
Figure 2. Shapes and Sizes of Coils 
 
  
100 mm 
COIL 
 
        
125mm 
COIL 
       
         
 
 
150 mm 
COIL 
 
        
175 mm 
COIL 
 
 
 
Figure 3. Components of the Delivery System 
Catheter 
 
Forceps 
 
 
Guidewire 
 
 
Cartridge 
 
 
2.4 
Historical Data 
PneumRx has conducted and analyzed data from human clinical trials of the 
RePneu Coil System in Europe, performing over 250 LVRC procedures in 142 
subjects. The data presented below are the accumulation of 3 OUS studies, each 
of which had inclusion/exclusion criteria virtually identical to those in the FDA-
approved IDE study, as well as in the present study. The combined data from all 
OUS studies, as of May 31, 2013, show statistically significant improvements in 
pulmonary function, exercise capacity and quality of life at both 6-Months and 12-
Months post treatment, as set forth below: 

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CLN0016.p.D 
PneumRx, Inc. 
Page 20 of 46 
 
Table 1. 6 Minute Walk Test (6MWT), Bilateral Subjects  
 
N 
6 Months Post 
Baseline (180 
Days) 
p-value 
N 
12 Months 
Post Baseline 
(360 Days) 
p-value 
Change in 
Meters from 
Baseline 
110 
+49.07 ± 8.26 
<.0001 
71 
+61.94 ± 12.36 
<.0001 
% Change from 
Baseline 
110 
+19.53% ± 
3.46% 
<.0001 
71 
+22.58% ± 5.27% 
0.0002 
 
Table 2. Residual Volume (RV), Bilateral Subjects 
 
N 
6 Months 
Post Baseline 
(180 Days) 
p-
value 
N 
12 Months Post 
Baseline (360 
Days) 
p-value 
Change in 
Liters from 
Baseline 
112 
-0.67 ± 0.09 
<.0001 
74 
-0.54 ± 0.11 
<.0001 
% Change from 
Baseline 
112 
-12.08% ± 1.51 
<.0001 
74 
-9.97% ± 1.98% 
<.0001 
 
Table 3. Forced Expiratory Volume in 1 Second (FEV1), Bilateral Subjects 
 
N 
6 Months 
Post Baseline 
(180 Days) 
p-value 
 
N 
12 Months Post 
Baseline (360 
Days) 
p-value 
Change in 
Liters from 
Baseline 
106 
+0.13 ± 0.02 
<.0001 
73 
+0.10 ± 0.04 
0.0178 
% Change from 
Baseline 
106 
+17.30% ± 
2.81% 
<.0001 
73 
+12.37% ± 4.37% 
0.0090 
 
Table 4. Saint George's Respiratory Questionnaire (SGRQ), Bilateral Subjects 
 
N 
6 Months 
Post Baseline 
(180 Days) 
p-value 
N 
12 Months Post 
Baseline (360 
Days) 
p-value 
Change 
from 
Baseline 
(Points) 
111 
-11.43 ± 1.41 
<.0001 
74 
-12.29 ± 2.15 
<.0001 
 
With respect to safety, the Coil has been designed to be as safe as possible, 
which is supported by the fact that the Serious Adverse Event profile of the 
device is comparable to that reported in the literature for bronchoscopy alone in a 
sham procedure, specifically, referenced in the control patient population in the 
EASE trial (Shah, 2011), which observed 107 individuals for 6 months. 
Comparing the PneumRx OUS study results to the EASE sham control group, it 
appears that the risks associated with the Coil System are largely attributable to 
the bronchoscopic procedure itself rather than to the device per se. Specifically, 
the rate of serious events of pneumothorax, hemoptysis, COPD exacerbation 
and pneumonia are comparable between the LVRC treatment population and the 
EASE sham control group. 

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Table 5. Comparison of 6-Month SAE Data Per Procedure - LVRC System vs. 
EASE Sham Control 
Reported SAE 
PneumRx OUS studies 
(up to 6 Months) 
EASE sham control 
(6 Months reported data) 
Pneumothorax 
14/238 procedures = 5.9% 
1/107 procedures = 0.9% 
Hemoptysis 
1/238 procedures = 0.4% 
0/107 procedures = 0% 
Respiratory Failure 
0/238 procedures = 0% 
0/107 procedures = 0% 
COPD exacerbation/ 
pneumonia1 
41/238 procedures = 17.2% 
18/107 procedures = 16.8% 
Death 
1*/238 procedures = 0.4% 
4/107 procedures = 3.7% 
* Not related to device or procedure 
 
With regard to a risk/benefit analysis, it is important to note that, in evaluating the 
clinical data presented in PneumRx's original IDE submission seeking approval 
for the IDE trial, the FDA determined that the risk/benefit ratio was acceptable to 
proceed with a pivotal clinical trial. As part of the approved IDE pivotal protocol, 
FDA acknowledged that "Upon completing their 12-month visit and exiting the 
[IDE] study, control subjects will be offered a crossover opportunity. An 
independent DMC will determine, based upon the safety data from the study, 
whether subjects may be allowed to enroll in a separate cross-over study." 
PneumRx has submitted this crossover protocol to the independent DMC and, 
based upon their review of the safety data as of the date of their review, has 
concluded that the risk profile since FDA's approval of the pivotal trial is similar to 
the risk profile before the RENEW study, other than one intra-operative death 
and the recognition of local tissue reaction in the region of the coil observed on 
imaging studies and termed coil-associated opacity (CAO) . As such the DMC felt 
that it was reasonable for subjects to be offered insertion of Coils, as part of the 
cross-over study, as long as they were informed of the possible risks. The DMC 
will continue to monitor the safety data from the IDE trial and will make 
recommendations regarding the continuation of this trial accordingly. 
 
The RePneu Coil System is classified as a Class III device per FDA regulations. 
The device was approved for CE Mark (Class IIa [LVRC Delivery System] and IIb 
[LVR Coil] in accordance with the Medical Device Directive) in October 2010 and 
is used commercially in Europe.  
 
A US IDE approval was granted for studying the LVRC further under the RENEW 
Study, protocol CLN0009, IDE G110066. This study protocol continues the 
research initiated under protocol CLN0009 by allowing the completed study 
Control subjects to have the opportunity to receive the LVRC under a controlled 
clinical study protocol (i.e. via crossover study design). 
 
 
This crossover study requires approval by the RENEW Study Data Monitoring 
Committee and the FDA. 
 
 
1  While PneumRx reported on COPD exacerbations and pneumonias separately, the EASE trial 
reported a single data point for "COPD exacerbation or infection."   

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3 
Study Objectives 
The primary objective of this study is to provide the LVRC procedure and safety 
and effectiveness follow up to qualifying subjects who were enrolled as Control 
Subjects in and completed the 12 month visit of the Lung Volume Reduction Coil 
Treatment in Patients with Emphysema (RENEW) Study. 
 
Descriptive statistics will be used to evaluate the data, including differences from 
Baseline to 12 months in 6MWT and SGRQ, and safety. 
 
4 
Study Design 
4.1 
Design Overview 
This will be a prospective, multicenter, single-arm study.  
 
4.2 
Number of Subjects 
The number of subjects in this study will be limited by the number of subjects 
who were randomized to the Control Group in the Lung Volume Reduction Coil 
Treatment in Patients with Emphysema (RENEW) Study, who completed the 
RENEW Study, and wish to participate in this crossover study, who provide 
written informed consent for this study, and who meet the inclusion and exclusion 
criteria of this study. 
 
4.2.1 Pharmacological Treatment 
As recommended by the GOLD guidelines, each subject will continue 
maintenance bronchodilator therapy, which will include an inhaled long-
acting beta-agonist, inhaled anticholinergic, or both. These drugs may 
also be combined with theophylline and/or inhaled corticosteroids at the 
discretion of the treating physician. The physician will be allowed to adjust 
the subject’s pharmacological regimen as needed during the course of 
the study to deal with variations in the subject’s condition (e.g., COPD 
exacerbations). However, the subject’s medical regimen should be 
optimized at the pre-Treatment Visit, prior to completing the baseline Six 
Minute Walk Test and pulmonary function tests. From then on, changes 
to their medical regimen should be discouraged during the follow-up 
period. Changes in medications or dosages will be recorded in the eCRF. 
 
All subjects enrolled in the study must have current influenza and 
pneumococcus vaccinations consistent with local recommendations 
and/or policy. 
 
4.3 
Population 
The 
study 
population 
will 
include 
all 
subjects 
who 
have 
met 
the 
inclusion/exclusion study criteria defined in this protocol. 
 
4.4 
Demographic and Baseline Characteristics 
Demographics and subject characteristics at baseline will be summarized to 
include age at enrollment, sex, and ethnic origin.  
 

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4.5 
Safety Evaluation 
Safety will be evaluated by collection of AEs and SAEs from entry into the study 
(Visit 1) until Visit 10 (12 months Follow-up from Visit 2) or until the subject has 
completed or terminated from the study.  
 
Prior to discharge after treatments and at each phone call or follow-up visit, 
subjects will be instructed to report to the investigator any adverse physical or 
mental changes they experienced since the previous visit/interview. All such 
AEs/SAEs reported by the subjects or observed by the investigators will be 
recorded. 
 
Safety data from the various OUS studies that PneumRx has conducted to date 
have been collected and analyzed. A summary of the safety data is provided in 
Section 2.4, above. 
 
4.6 
Brief Description of Study 
The complete Study and its required visits, procedures, and assessments will be 
carefully discussed with the study subjects using an Institutional Review Board 
(IRB) or an Ethics Committee (EC) approved Informed Consent Form (ICF). The 
ICF will contain all essential elements including a description of the research, 
expected duration and procedures, alternative treatments including lung volume 
reduction surgery, statement of the subject’s right to decline to participate or to 
withdraw from the study at any time and for any reason without fear of retribution. 
The ICF will also include potential risks, discomforts or adverse effects, potential 
benefits, limits of confidentiality, reimbursement of certain expenses for 
participation, timely dissemination of any new information that becomes 
available, and contact information of the research personnel. All patients will sign 
an ICF prior to any additional procedures being performed to evaluate their 
eligibility for participation in the Study. 
 
End of study data from the 12 Month Visit of the RENEW Study will be obtained 
to complete RENEW participation. At the end of the 12 Month Visit, RENEW 
participants who meet inclusion and exclusion criteria for this study will be offered 
participation that begins with signing a new ICF. Medical history, physical exam, 
and smoking history will be collected to ensure the subject meets inclusion and 
exclusion criteria. Spirometry must be repeated after the RENEW Study 12 
Month visit as both pre- and post-bronchodilator data must be collected at 
Baseline for the Crossover Study. Only post-bronchodilator spirometry is 
collected at the 12 Month visit for the RENEW Study. However, the PFT 
excluding spirometry, DLCO, 6MWT, mMRC, and SGRQ data collected for the 
12 Month Visit of the RENEW Study will be reviewed and used as Baseline data 
for this Study, unless the 12 Month RENEW data was taken more than 6 weeks 
previously, in which case such tests/questionnaires are be performed again, and 
data collected. If the subject does not meet the inclusion / exclusion criteria the 
subject will be excluded from the study. 
 
If the subject has met the inclusion / exclusion criteria for this study, the subject 
will continue the screening evaluation to ensure they meet the remaining 
inclusion / exclusion criteria. The investigator will perform other tests such as 
spirometry, CT scan, X-ray, echocardiogram, EKG, and blood tests. 
 

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Once the subject has completed the pre-treatment tests and meets all inclusion / 
exclusion criteria, the subject will proceed to treatment.  
 
4.6.1 Treatment 
 
For each treatment, subjects will undergo bronchoscopy under general 
anesthesia or moderate sedation, at the discretion of the bronchoscopist. 
During both procedures, subjects will be treated with Coils according to 
the Instructions for Use. Subjects will receive prophylactic drugs pre-
procedure and post-procedure. 
 
Following LVRC placement (Visit 2), the subject will remain in the hospital 
under observation per standard hospital practice. Following hospital 
discharge, the subject will be contacted by phone one week after Visit 2 
and will be seen at the study site at one month after Visit 2. After the one 
month visit following Visit 2, the subject will be scheduled for the second 
LVRC placement in the contralateral lung to take place approximately 2 
months after Visit 2. Only a single lung will be treated during any 
bronchoscopy.   
 
After the subject’s second LVRC placement procedure (Visit 5), the 
subject will remain in the hospital under observation per standard hospital 
practice. Following hospital discharge, the subject will be contacted by 
phone one week after Visit 5 and will be seen for the tests, procedures 
and follow-up described in Table 6. Subjects will be followed up annually 
for 5 years. After the 5 year visit, the subject will exit the study.  
 

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Table 6. Visit Schedule 
Procedure / 
Assessment 
Visit 1 
Pre-Treatment 
(Screening) 
 
Visit 2 LVRC 
Placement #1 
 
Visit 3 
1 Week post 
Visit 2a 
(Phone Call) 
Visit 4 
1 Month post 
Visit 2b 
(Office Visit) 
Visit 5  LVRC 
Placement#2 
(2 Month post 
Visit 2) 
Visit 6 
1 Week post  
Visit 5a 
(Phone Call) 
Visit 7 
1 Month post 
Visit 5b 
(Office Visit) 
Visit 8 
6 Months post 
Visit 2c (Office 
Visit) 
Visit 9 
9 Months post 
Visit 2a (Phone 
Call) 
Visit 10 
12 Months post  
Visit 2c 
(Office Visit) 
Visit 11 
24 Months post 
Visit 2c 
(Office Visit) 
Visit 12 
36 Months post 
Visit 2c 
(Office Visit) 
Visit 13 
48 Months post 
Visit 2c 
(Office Visit) 
Visit 14 
60 Months post 
Visit 2c 
(Office Visit) 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ Exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Focused physical exam 
including vital Signs 
andSpO2 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
Record the following 
measures from the 12 
Month RENEW Visit in 
the eCRF as baseline 
measurements:  
Spirometry, Lung 
Volumes and Diffusing 
Capacity, 6MWT, 
SGRQ, mMRC*  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Spirometry 
X 
 
 
 
 
 
 
X 
 
X 
X 
X 
X 
X 
Lung Volumes and 
Diffusing Capacity 
X* 
 
 
 
 
 
 
X 
 
X 
X 
X 
X 
X 
6MWT 
X* 
 
 
X 
 
 
X 
X 
 
X 
X 
X 
X 
X 
SGRQ 
X* 
 
 
X 
 
 
X 
X 
 
X 
X 
X 
X 
X 
mMRC 
X* 
 
 
X 
 
 
X 
X 
 
X 
X 
X 
X 
X 
Blood panel and ABG   
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
EKG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Echocardiogram‡ 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medication 
/ O2 Use 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy Testing 
X 
X 
 
 
X 
 
 
 
 
X 
 
 
 
 
CT Scan  
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Chest X-Ray  
X 
X† 
 
 
X† 
 
 
 
 
 
 
 
 
 
Bronchoscopy / Coil 
Placement 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
Take subject statusd 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 Exit Study 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
     a ±3 days 
     b Minus 2 weeks to plus 4 weeks 
     c  ±4 weeks 
     * If 12 Month RENEW Visit occurred within 6 weeks of Visit 1, use 12 Month RENEW values for lung volumes, diffusing capacity, SGRQ, 6MWT, and mMRC as baseline measurements. If 12 Month RENEW Visit occurred more than 6 weeks before Visit 1, perform these tests and record results as baseline 
measurements. 
     † Chest x-ray #1 is done immediately post-procedure and chest x-ray #2 is done prior to discharge. 
     d includes a review of subject's medicines, O2 use and AE assessment 
     ‡ May use any echocardiogram taken within 6 months of Visit 1 
 

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5 
Study Subject Recruitment 
All study subjects will be patient volunteers who completed the Lung Volume 
Reduction Coil Treatment in Patients with Emphysema (RENEW) Study as 
Control Subjects and who meet the inclusion / exclusion criteria including a 
willingness to read, understand, and sign the Informed Consent.  
 
5.1 
Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be entered into the 
study: 
 
1. Subject was enrolled as a Control Subject in and completed all required study 
assessments through the 12 Month visit for the Lung Volume Reduction Coil 
Treatment in Patients with Emphysema (RENEW) Trial, CLN0009. 
2. Subject has post-bronchodilator FEV1 ≤45% predicted.  
3. Subject has residual volume (RV) ≥175% predicted. 
4. Subject has stopped smoking for at least 8 weeks prior to entering the study, 
as confirmed by a Cotinine test or other appropriate diagnostic test. 
5. Subject read, understood and signed the Informed Consent form. 
6. Subject has received Pneumococcal and Influenza vaccinations consistent 
with local recommendations and/or policy.  
 
5.2 
Exclusion Criteria     
Subjects will be excluded from the study if any of the following conditions apply: 
 
1. Subject has severe homogeneous emphysema as determined by the Core 
Radiology Lab 
2. Subject has co-morbidities that may significantly reduce subject's ability to 
improve exercise capacity (e.g. severe arthritis, planned knee surgery) or 
baseline limitation on 6MWT is not due to dyspnea. 
3. Subject has a change in FEV1 >20% (or, for subjects with pre-bronchodilator 
FEV1 below 1 L, a change of > 200 mL) post-bronchodilator, unless 
investigator can confirm by other means that subject does not have asthma. 
4. Subject has DLCO <20% of predicted. 
5. Subject has severe gas exchange abnormalities as defined by: 
PaCO2 >55 mm Hg  
PaO2 <45 mm Hg on room air (High altitude criterion: PaO2 <30 mm Hg) 
6. Subject has a history of recurrent clinically significant respiratory infections, 
defined as 3 hospitalizations for respiratory infection during the year prior to 
enrollment. 
7. Subject has severe pulmonary hypertension. If pulmonary hypertension is 
present, “severe” is defined by right ventricular systolic pressure >50 mm Hg 
via right heart catheterization and/or echocardiogram.  
8. Subject has an inability to walk >140 meters (150 yards) in 6 minutes. 
9. Subject has evidence of other severe disease (such as, but not limited to, 
lung cancer or renal failure), which in the judgment of the investigator may 

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compromise survival of the subject for the duration of the study.  
10. Subject is pregnant or lactating, or plans to become pregnant within the study 
timeframe. 
11. Subject has an inability to tolerate bronchoscopy under moderate sedation or 
general anesthesia. 
12. Subject has clinically significant bronchiectasis. 
13. Subject has giant bullae >1/3 lung volume. 
14. Subject has had previous LVR surgery, lung transplantation, lobectomy, LVR 
devices or other device to treat COPD in either lung. 
15. Subject has been involved in pulmonary drug or device studies within 30 days 
prior to this study, with the exception of the RENEW Study. 
16. Subject is taking >20 mg prednisone (or equivalent dose of a similar steroid) 
daily. 
17. Subject requires high level chronic immunomodulatory therapy to treat a 
moderate to severe chronic inflammatory autoimmune disorder. 
18. Subject is on an antiplatelet (such as Plavix) or anticoagulant therapy (such 
as heparin or Coumadin) which cannot be stopped for seven (7) days prior to 
procedure. 
19. Subject has a sensitivity or allergy to nitinol (nickel-titanium) or its constituent 
metals. 
20. Subject has a known sensitivity to drugs required to perform bronchoscopy. 
21. Subject has been diagnosed with alpha-1 antitrypsin deficiency (AATD). 
22. Subject has any other disease, condition(s) or habit(s) that would interfere 
with completion of study and follow up assessments, would increase risks of 
bronchoscopy or assessments, or in the judgment of the investigator would 
potentially interfere with compliance to this study or would adversely affect 
study outcomes.  
 
6 
Study Plan 
6.1 
Investigator Training 
Investigators will have been trained in the proper use and operation of the Coil 
System and may have performed Coil procedures as part of the Lung Volume 
Reduction Coil Treatment in Patients with Emphysema (RENEW) Study before 
initiation of any treatment. If necessary, additional training will be provided.  
 
PneumRx personnel will be available to provide any additional technical support 
during treatment sessions until the investigator and his/her team feel comfortable 
with the use of the device. 
 
NOTE: All assessments by investigators or other healthcare professionals will be 
performed to the same standards (ATS Guidelines) as those in the pivotal 
protocol as detailed in the Study Operational Instructions. 
 
6.1.1 Informed Consent  
• 
Provide information to the potential subject and review Informed 
Consent Form details. Obtain Informed Consent in writing from the 
subject as part of Pre-treatment/Baseline Screening (Visit 1). 

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• 
Provide the subject with a copy of the signed Informed Consent Form 
for their records. 
6.1.2 Study Identification Number  
• 
Assign the subject a unique study identification number (Study ID 
number) after signing of Informed Consent. 
6.1.3 Pre-treatment/Screening Evaluations  
 
Perform the following evaluations during the Pre-treatment Screening (Visit 1): 
• 
Detailed medical history, to include the number of years the subject 
has been diagnosed with emphysema, other significant illnesses, 
current smoking status and history, medications, O2 use, etc. 
• 
Vital signs and pulmonary assessment, including SpO2 and breath 
sounds. 
• 
Resting Electrocardiogram (EKG). 
• 
Echocardiogram, or review echocardiogram taken within the past 6 
months. 
• 
Blood panel to assess inclusion exclusion criteria and ability to 
undergo anesthesia (to include Hemoglobin, Hematocrit, White Blood 
Cell 
(WBC), 
Platelet 
count, 
Prothrombin 
Time/International 
Normalized Ratio (PT/INR), Sodium, Potassium, Chloride, Glucose, 
Total Protein, Albumin, Blood Urea Nitrogen (BUN), and Creatinine.). 
• 
Cotinine or other appropriate diagnostic test 
• 
Pregnancy test for females of child-bearing potential prior to 
radiographic procedures. 
• 
Room air Arterial Blood Gasses (ABG). 
• 
Chest x-ray. 
• 
CT Scan collected per guidelines provided by the Core (Radiology) 
Lab Protocol. 
• 
Pre- and post-bronchodilator spirometry 
 
If screening performed more than 6 weeks after subject's 12 Month Visit in the 
RENEW study, also perform the following: 
• 
Pre- and post-bronchodilator spirometry 
• 
Post-bronchodilator lung volume measurements by plethysmography 
• 
Diffusing Capacity (DLCO) 
• 
Modified Medical Research Council (mMRC) dyspnea scale 
• 
6 Minute Walk Test 
• 
St. George's Respiratory Questionnaire (SGRQ) 
 
6.2 
Treatment 
6.2.1 Visit 2 - LVRC Placement 
• 
Perform pregnancy test for females of child bearing potential prior to 
radiographic procedures.  
• 
Prepare subject for bronchoscopy per standard hospital practice. 

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• 
Unless contraindicated, prescribe a prophylactic regimen of antibiotics 
to be taken for at least seven (7) days after the procedure and 
steroids to be taken two (2) days before and at least seven (7) days 
after the procedure.  
• 
Administer general anesthesia or sedation to perform Coil placement. 
All local institutional policies relevant to general anesthesia and/or 
sedation should be observed. 
• 
Insert the bronchoscope per the manufacturer’s instructions. 
• 
If not already documented, perform bronchoalveolar lavage and send 
sample for culture and Gram stain to document any host pathogens. 
• 
Navigate the bronchoscope and identify the airways in one of the 
lobes identified by the CT Core Lab as a lobe to be treated.  
• 
Deliver the Coils in accordance with RePneu Coil System Instructions 
for Use. 
• 
Only place the devices unilaterally. DO NOT place the devices in both 
the right and left lungs during one bronchoscopy session.  
• 
Allow the Subject to recover from anesthesia and monitor as per 
standard hospital practice.  
 
6.2.2 Visit 2, cont: Post Bronchoscopy Monitoring and Evaluations 
• 
Complete a chest x-ray post-procedure. 
• 
Record AEs (See Section 7). 
• 
Maintain subject in hospital for observation per standard hospital 
practice. 
• 
Complete a second chest x-ray prior to discharge 
• 
Discuss maintenance rehabilitation activity plan with subject. 
• 
Provide detailed instructions to Subject on expected effects of Coil 
procedure and instruct the Subject to contact the Site and Principal 
Investigator immediately should any of the effects be experienced. 
 
6.2.3 Visit 3 - 1 Week Post Visit 2 Follow Up Phone Call  
• 
Contact Subject via telephone 1 week after Visit 2 to assess status.  
• 
Review medications and O2 use.  
• 
Record AEs (See Section 7). 
• 
Discuss maintenance rehabilitation activity plan. 
 
6.2.4 Visit 4 - 1 Month Post Visit 2 Follow Up 
• 
Perform focused pulmonary assessment including Vital Signs (heart 
rate, blood pressure, temperature, respiratory rate, SpO2) and breath 
sounds. 
• 
Perform 6MWT 
• 
Administer SGRQ 
• 
Administer mMRC 
• 
Review medications and O2 use. 

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• 
Record AEs since last follow-up (See Section 7). 
• 
Discuss maintenance rehabilitation activity plan. 
 
6.2.5 Visit 5 - 2 Months Post-Visit 2 LVRC Placement #2 
• 
During Coil placement procedure #2, the investigator will treat the 
contra-lateral lung. 
• 
Perform pregnancy test for females of child-bearing potential prior to 
radiographic procedures. 
• 
Unless contraindicated, prescribe a prophylactic regimen of antibiotics 
to be taken for at least seven (7) days post-procedure and steroids to 
be taken two (2) days before and at least seven (7) days after 
treatment.  
• 
Prepare subject for bronchoscopy per standard hospital practice. 
• 
Administer general anesthesia or sedation to perform Coil placement. 
All local institutional policies relevant to general anesthesia and/or 
sedation should be observed. 
• 
Insert the bronchoscope per manufacturer’s instructions. 
• 
Navigate the bronchoscope and identify the airways in one of the 
lobes identified by the CT Core Lab as a lobe to be treated 
• 
Deliver the Coils in accordance with the RePneu Coil System 
Instructions for Use. 
• 
Only place the Coils unilaterally. DO NOT place the devices in both 
the right and left lungs during one bronchoscopy session.  
• 
Allow the Subject to recover from anesthesia and monitor as per 
standard hospital practice.  
 
6.2.6 Visit 5, cont: Post Bronchoscopy Monitoring and Evaluations 
• 
Conduct chest x-ray. 
• 
Record AEs (See Section 7). 
• 
Maintain Subject at the hospital for observation per standard hospital 
practice. 
• 
Conduct another chest x-ray prior to discharge. 
• 
Discuss maintenance rehabilitation activity plan with Subject. 
• 
Provide detailed instructions to Subject on expected effects of Coil 
procedure and instruct the Subject to contact the Site and Principal 
Investigator immediately should any of the effects be experienced. 
 
6.2.7 Visit 6 - 1 Week Post Visit 5 Phone Call 
• 
Contact Subject via telephone 1 week after Visit 5 to assess status.  
• 
Review medications and O2 use.  
• 
Record AEs (See Section 7). 
• 
Discuss maintenance rehabilitation activity plan with Subject. 
 

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6.2.8 Visit 7 - 1 Month Post Visit 5 Follow Up 
• 
Perform focused pulmonary assessment including Vital Signs (heart 
rate, blood pressure, temperature, respiratory rate, SpO2) and breath 
sounds. 
• 
Perform 6MWT 
• 
Administer SGRQ 
• 
Administer mMRC 
• 
Review medications and O2 use. 
• 
Record AEs since last follow-up (See Section 7). 
• 
Discuss maintenance rehabilitation activity plan with Subject. 
 
6.2.9  Visit 8 - 6 Months Post Visit 2 Follow Up 
• 
Perform focused pulmonary assessment including Vital Signs (heart 
rate, blood pressure, temperature, respiratory rate, SpO2) and breath 
sounds. 
• 
Perform post-bronchodilator spirometry. 
• 
Perform Lung Volumes and DLCO 
• 
Perform 6MWT 
• 
Administer SGRQ 
• 
Administer mMRC 
• 
Review medications and O2 use. 
• 
Record AEs since last follow-up (See Section 7). 
• 
Discuss maintenance rehabilitation activity plan with Subject. 
 
6.2.10 Visit 9 - 9 Months Post Visit 2 Phone Call 
• 
Contact Subject via telephone 1 week after bronchoscopy session / 
LVRC procedure to assess status.  
• 
Review medications and O2 use.  
• 
Record AEs (See Section 7). 
• 
Discuss maintenance rehabilitation activity plan with Subject. 
 
6.2.11 Visit 10 - 12 Months Post Visit 2 Follow Up  
• 
Perform focused pulmonary assessment including Vital Signs (heart 
rate, blood pressure, temperature, respiratory rate, SpO2) and breath 
sounds. 
• 
Perform pregnancy test for females of child-bearing potential prior to 
radiographic procedures. 
• 
Perform post-bronchodilator spirometry. 
• 
Perform Lung Volumes and DLCO 
• 
Perform 6MWT 
• 
Administer SGRQ 
• 
Administer mMRC 

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• 
Review medications and O2 use. 
• 
Record AEs since last follow-up (See Section 7). 
• 
Discuss maintenance rehabilitation activity plan with Subject. 
• 
Take Chest CT 
 
6.2.12 Visit 11 - 24 Months Post Visit 2 Follow Up 
• 
Perform focused pulmonary assessment including Vital Signs (heart 
rate, blood pressure, temperature, respiratory rate, SpO2) and breath 
sounds. 
• 
Perform post-bronchodilator spirometry. 
• 
Perform Lung Volumes and DLCO 
• 
Perform 6MWT 
• 
Administer SGRQ 
• 
Administer mMRC 
• 
Review medications and O2 use. 
• 
Record AEs since last follow-up (See Section 7). 
• 
Discuss maintenance rehabilitation activity plan with Subject. 
 
6.2.13 Visit 12 - 36 Months Post Visit 2 Follow Up 
• 
Perform focused pulmonary assessment including Vital Signs (heart 
rate, blood pressure, temperature, respiratory rate, SpO2) and breath 
sounds. 
• 
Perform post-bronchodilator spirometry. 
• 
Perform Lung Volumes and DLCO 
• 
Perform 6MWT 
• 
Administer SGRQ 
• 
Administer mMRC 
• 
Review medications and O2 use. 
• 
Record AEs since last follow-up (See Section 7). 
• 
Discuss maintenance rehabilitation activity plan with Subject. 
 
6.2.14 Visit 13 - 48 Months Post Visit 2 Follow Up 
• 
Perform focused pulmonary assessment including Vital Signs (heart 
rate, blood pressure, temperature, respiratory rate, SpO2) and breath 
sounds. 
• 
Perform post-bronchodilator spirometry. 
• 
Perform Lung Volumes and DLCO 
• 
Perform 6MWT 
• 
Administer SGRQ 
• 
Administer mMRC 
• 
Review medications and O2 use. 
• 
Record AEs since last follow-up (See Section 7). 

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• 
Discuss maintenance rehabilitation activity plan with Subject. 
 
6.2.15 Visit 14 - 60 Months Post Visit 2 Follow Up  
• 
Perform focused pulmonary assessment including Vital Signs (heart 
rate, blood pressure, temperature, respiratory rate, SpO2) and breath 
sounds. 
• 
Perform pregnancy test for females of child-bearing potential prior to 
radiographic procedures. 
• 
Perform post-bronchodilator spirometry. 
• 
Perform Lung Volumes and DLCO 
• 
Perform 6MWT 
• 
Perform SGRQ 
• 
Perform mMRC 
• 
Review medications and O2 use. 
• 
Record AEs since last follow-up (See Section 7). 
• 
The subject can be exited from the study. 
 
6.2.16 Unscheduled Visits 
 
It is expected that some subjects may present during the follow-up period 
with complaints (e.g., COPD exacerbation). These visits and the findings 
should all be recorded on the appropriate eCRFs. Notify the Sponsor if an 
unscheduled visit occurs. 
 
7 
 Management of Adverse Events (AEs) and Serious Adverse Events (SAEs)  
An adverse event (AE) is any untoward medical occurrence in a study subject. 
This may include symptom(s), illness, clinically significant abnormal laboratory 
value or change in value, or worsening in a subject during a clinical study.  
 
It is the responsibility of the investigator to report when he/she becomes aware 
that an AE has occurred. AE information will be collected throughout the study. 
Adverse events will be recorded on the eCRF by the investigator or authorized 
designee. Event/diagnosis, date of onset, severity, duration, and relationship to 
the procedure/device will be recorded, as well as a detailed description of the 
Event. All AEs will be followed until they are adequately resolved or stabilized, or 
for 1 month following study completion or termination, whichever comes first. 
 
Due to the similarity in reported symptoms between an infectious pneumonia and 
the occurrence of post-Coil implant response (the localized tissue reaction 
sometimes referred to as “tension induced opacity” and hereafter as Coil 
Associated Opacity or CAO), the DMC has recommended that Subjects be 
instructed to immediately contact the PI or authorized designee if the Subject 
experiences any chest or pleuritic pain/discomfort, fatigue, or increased 
dyspnea/shortness of breath within approximately  two (2) months following each 
Coil treatment. These symptoms may or may not be accompanied by fever, chills 
and/or night sweats. Recommendations on diagnosis, treatment and follow-up of 
these events are provided in the Study Operational Instructions. 
 

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Safety data from the various OUS studies that PneumRx has conducted to date 
have been collected and analyzed. A summary of the safety data is provided in 
Section 2.4, above. 
 
7.1 
Serious Adverse Events  
In accordance with 21 CFR Parts 803 and 812, a Serious Adverse Event (SAE) 
is defined as any untoward medical occurrence that: 
1. results in death, 
2. is life-threatening, 
3. requires inpatient hospitalization or prolongation of existing hospitalization, 
4. results in persistent or significant disability/incapacity, 
5. is a congenital anomaly/birth defect, or 
6. requires intervention to prevent permanent impairment or damage. 
In addition, Major Complications, as defined below (which will be adjudicated by 
the Medical Monitor based on AE/SAE documentation in the eCRFs):  
• 
Death; 
• 
Pneumothorax that requires a chest drainage tube for more than 7 days (from 
time of chest drainage tube insertion to the time of chest drainage tube 
removal); 
• 
Hemoptysis requiring an intervention (e.g., blood transfusion(s), arterial 
embolization, or surgical/endoscopic procedure); 
• 
COPD exacerbation that becomes life-threatening or disabling as a result of 
an increase in respiratory symptoms requiring in-patient hospitalization of >7 
days with or without mechanical ventilation; 
• 
Lower Respiratory Infections (including pneumonia) defined by new or 
increased clinical symptoms such as fever, chills, productive cough, chest 
pain, dyspnea or an infiltrate on plain chest x-ray and hospitalization for 
administration of intravenous antibiotics and/or steroids; 
• 
Respiratory failure defined as a requirement for mechanical ventilatory 
support (whether via endotracheal tube or mask) for >24 hours; and 
• 
An unanticipated bronchoscopy in order to remove one or more Coils due to 
a device-related AE. (Note: This definition does not include re-positioning, 
replacement or removal of the Coil(s) during the procedure.)  
 
All SAEs must be reported to the PneumRx Clinical Affairs immediately 
(within one working day) using the AE eCRF. To maintain subject 
confidentiality, the subject shall only be identified by the subject number used on 
the eCRFs. Further written reports through final resolution of the event, study 
completion or termination or, in case of permanent impairment, until the event 
stabilizes and the overall clinical outcome has been ascertained shall be 
provided to PneumRx, Inc. Clinical Affairs via the eCRF. 
   
7.2 
Unanticipated Adverse Device Effect (UADE)   
An Unanticipated Adverse Device Effect (UADE) is defined as any serious 
adverse effect on health or safety or any life-threatening problem or death 
caused by, or associated with, a device, if that effect, problem, or death was not 

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previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), 
or any other unanticipated serious problem associated with a device that relates 
to the rights, safety, or welfare of subjects.  
 
7.3 
Severity of AEs and SAEs 
The following general definitions for rating severity should be used for this study: 
 
1. Mild: Awareness of signs or symptoms, but easily tolerated and transient; 
causing no loss of time from normal activities; symptoms may not require 
medication or a medical treatment; signs and symptoms are transient. 
 
2. Moderate: Marked symptoms and discomfort severe enough to cause 
moderate interference with the subject’s usual activities. Symptomatic 
treatment is possible. 
 
3. Severe: Incapacitating with inability to do work or usual activities; signs and 
symptoms may be of systemic nature or require medical intervention and/or 
treatment. Hospitalization may be required or prolonged. 
 
7.4 
Relationship of an Event 
The relationship of an AE or SAE to the underlying disease or to the procedure 
will be attributed using the following definitions: 
 
1. Not Related: There is no evidence that the event has a relationship to the 
procedure performed. 
 
2. Possibly Related: The event has a timely relationship to the procedure 
performed. However, a potential alternative etiology may be responsible for 
the adverse event.  
 
3. Probably Related: The event has a timely relationship to the study 
procedure performed and the causative relationship can clearly be 
established. No potential alternative etiology is apparent. 
 
7.5 
Process for Assessment, Recording and Reporting of AEs 
Subjects will be instructed at the beginning of the study to report to the 
investigator any adverse physical or mental changes they experience and they 
will be asked about adverse events at each visit, including those experienced at 
the baseline visit prior to, during, or immediately following treatment. All such 
adverse events reported by the subjects or observed by the investigators will be 
reported to the Sponsor. 
 
As described in Section 7.0, if the event is deemed to be Serious, such events 
will be reported to the Sponsor via the completion of the Adverse Event eCRF. 
The IRB/EC(s) will be informed if the Serious or unexpected adverse event, in 
the opinion of the Investigator, or the Medical Monitor, is likely to affect the safety 
of the subjects or the conduct of the study. 
 

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An independent DMC will be engaged to provide independent benefit/risk 
oversight during the conduct of the study. The DMC or a subcommittee dedicated 
to review of Clinical Events will: 
 
• 
Review and evaluate Serious Adverse Events on an “as needed” basis 
and all adverse events on a quarterly basis or on an as needed basis, if 
the Sponsor requests an unscheduled review. 
 
• 
Recommend discontinuation of the study in the event of the occurrence of 
Serious or Unexpected Adverse Events that are determined by the DMC 
to pose a significant safety concern. 
The DMC will notify the Sponsor, who will in turn notify the FDA or other 
regulatory bodies, of safety outcome information from the DMC meetings. This 
information will also be reported as part of required regulatory progress update 
reports. 
 
7.6 
Data Monitoring Committee Composition and Role   
An independent DMC will be engaged prior to the enrollment of the first subject. 
The DMC will be comprised of at least four members, including but not limited to 
a pulmonary doctor with expertise in COPD, a statistician, a thoracic surgeon, 
and a Regulatory Affairs Advisor. 
 
The DMC's role will be to review and evaluate safety events and monitor study 
safety data; and to recommend discontinuation of the study according to the 
Study Stopping Rules, in Section 8, below. 
 
8 
Administrative 
8.1 
Premature Termination of Study 
The clinical study may be terminated at any time in the event of the occurrence of 
serious or unanticipated AEs that are determined by the DMC to pose a 
significant safety concern. In addition, the clinical study may be terminated at any 
time in the event that information indicates that the device will not be 
commercially viable, or in the event that the sponsor can no longer fund the 
study. 
 
PneumRx will notify all investigators in the event of a premature withdrawal of 
IRB/EC approval from any site. The investigators are responsible for informing 
their IRBs/ECs regarding premature trial termination. Subjects who experienced 
any SAEs that result in trial termination will be followed to resolution or 
stabilization. 
 
Study Stopping Rules: 
Treatment of  subjects will be suspended to allow time for analysis of the safety 
of the Coil and the LVRC procedure if any of the following are observed: 
1. Two or more deaths, as deemed by the Investigator to be possibly or 
probably related to the Coil device or the LVRC procedure, occur within 30 
days following Coil treatment.   
2. Any of the following during the immediate post-procedure period (3 days): 

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 
Hemoptysis >200 ml, in 2 subjects at a single center. 
 
Respiratory failure requiring mechanical ventilation for >24 hours in 2 
subjects at a single center. 
 
Pneumothorax requiring chest tube drainage for >7 days that occurs in 2 
subjects at a single center, or greater than 4 of the first 20 subjects 
treated, regardless of center. 
 
PneumRx shall notify FDA within 24 hours of stopping the study based on the 
stopping rules. 
 
8.2 
Insurance Coverage 
If a device- or procedure-related incident occurs, the study Sponsor has a 
products liability insurance policy to cover damages within the legally prescribed 
scope. 
 
9 
Risks and Benefits 
9.1 
Potential Risks to the Subject 
Participation in this clinical study may expose the subject to the following 
potential risks associated with the device and/or the procedure:  
 
• 
Bronchoscopy 
 
With any bronchoscopic procedure, there is the possibility of exacerbation of 
emphysema symptoms, fever, bleeding, laryngospasm, bronchospasm, 
irregular heartbeat, shortness of breath, infection, transient infiltrates, 
pneumonia (Djukanovic, 1998), pneumothorax (Bleeker, 1992), death or 
syncope. In the event that any of these were to occur, the subject will be 
treated for the condition. Some subjects may experience wheezing, coughing, 
or shortness of breath during the first few days following a bronchoscopy 
procedure. Of over 1300 LVRC procedures performed to date, there has 
been one reported death that was deemed related to the device or the 
procedure. 
 
• 
Infection including Pneumonia 
 
There is a risk of developing pneumonia as a result of the LVRC being placed 
in the airway, excess mucus production, or impairment of the ability of the 
lung to clear mucus and/or microorganisms from the airways. There is also 
an increased risk of infection in patients with emphysema over those who do 
not have emphysema (Zalacain, 1999). 
 
• 
Hemoptysis  
Hemoptysis is defined as coughing up blood > 5ml, which requires more than 
occasional blood-streaked sputum. There is also an increased risk of 
hemoptysis in patients with emphysema over those who do not have 
emphysema (Bidwell, 2005). 
 
• 
Moderate Sedation/Anesthesia  
 
There is a potential risk of developing side effects associated with the use of 
sedation and/or anesthesia. The risks of anesthesia depend on the agents 

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and/or gases used. The risks of anesthesia include respiratory acidosis and 
possible respiratory failure, postoperative pain, nausea and vomiting, 
dizziness, drowsiness, shivering, liver toxicity and/or cardiovascular events. 
 
 
Trained professionals with extensive experience and expertise who routinely 
administer general anesthesia or local anesthesia with moderate sedation to 
subjects requiring multiple procedures will be responsible for the induction 
and associated monitoring required for this study. In addition, study subjects 
will be monitored throughout the recovery period as well after the recovery 
period, as indicated. 
 
• 
Coil Removal  
A Coil(s) may be removed up to 2 months following the treatment for 
medically indicated safety reasons (e.g., due to a persistent air leak or poor 
Coil location that may pose a safety risk). Other than during the LVRC 
treatment procedures (Study Visits 2 and 5), Coils should only be removed or 
repositioned for safety reasons, and Coils may not be replaced post-
procedure. If the decision is made to remove a Coil(s), refer to the “Coil 
Removal Instructions” section in the Instructions for Use for details. The 
Investigator will notify the Sponsor of the need for removal prior to removing 
any Coil(s) and return the Coil(s) to PneumRx Quality Assurance for 
inspection.  
 
In prior PneumRx OUS Feasibility Studies, numerous Coils have been 
bronchoscopically repositioned or removed during treatment procedures to 
improve placement or to deploy a different size Coil. All attempts to remove 
or reposition Coils during the over 200 procedures performed in the OUS 
studies have been successful and easy to perform as determined by the 
Investigator There have been no reported complications or adverse events 
associated with the bronchoscopic removal or repositioning of the Coils 
during the LVRC procedures.  
 
Coil(s) can and may be repositioned, replaced or removed during the 
treatment procedure (Study Visits 2 and 5). Coils can be removed 
bronchoscopically up to 2 months after the LVRC procedure, but only if 
medically indicated. Such medically indicated post-procedure removal would 
be considered a Major Complication, and will be recorded in the eCRF AE 
page. Although Coils have been removed as late as 4 months post-procedure 
in animal studies, the need to remove Coils in human trials is not anticipated 
based on safety data from European clinical trials. Note that the Coil removal 
procedure has not been tested after time periods longer than 4 months post-
procedure. 
 
• 
Pneumothorax  
Pneumothorax is defined as the presence of air within the pleural space, 
which may or may not require chest tube insertion. There is also an increased 
risk of pneumothorax in patients with emphysema over those who do not 
have emphysema (Guo, 2005). 
 
• 
Reaction 

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Reaction to the study device, including (1) an allergic reaction to the metal 
(nickel-titanium) that may require removal of the study device, and (2) an 
opacity on chest x-ray that may be difficult to differentiate from infectious 
pneumonia. 
 
The following are potential risks that are associated with the tests required as 
part of the study conduct: 
 
• 
Blood draws 
The risks of blood draws include temporary pain and discomfort from the 
needle stick, and/or tenderness, redness or bruising at the site, bleeding, 
fainting and lightheadedness. While rare, there is a possibility of infection or a 
local blood clot. 
 
 
• 
Pulmonary function tests 
Pulmonary function tests are low risk procedures. They may occasionally 
cause dizziness and/or slight chest discomfort due to muscle soreness, but 
these are self-limited. There is a risk of fainting during forced exhalation. 
 
• 
Chest X-rays, CT Scans and Fluoroscopy 
Study subjects will have radiation exposure as a result of the chest X-rays, 
CT scans and fluoroscopy required as part of the protocol. 
 
• 
Medications required to perform bronchoscopy 
Drugs required for bronchoscopy could include lidocaine, atropine, narcotics, 
and one of the benzodiazepines. Although these drugs each have a number 
of potentially significant side effects, they are commonly used safely to 
perform bronchoscopy (Djukanovic, 1998). 
 
Lidocaine toxicity has been described in association with bronchoscopy. At 
least one death has been reported in the literature as a result of lidocaine 
toxicity in a research Subject who underwent bronchoscopy (Clinical Trials 
Advisory Newsletter, 1996). Amounts of topical lidocaine given will be 
monitored and recorded and at all times will be less than 400 mg. Moderate 
sedation can be associated with respiratory suppression resulting in 
hypoxemia and the need for increased supplemental oxygen or the need for 
intubation with mechanical ventilation. In addition, moderate sedation can 
result in cardiovascular compromise with hypotension. To minimize these 
complications, sedation will be given in accordance with moderate sedation 
protocols applicable at the participating hospital and administered by trained 
professionals with experience in moderate sedation and ventilation. 
 
Subjects with known sensitivity to drugs required to perform bronchoscopy 
are excluded from study participation. Should a subject experience a 
significant side effect for which there is concern, s/he will be managed as 
appropriate. 
 
9.2 
Potential Benefits to the Subject 
It is possible that a study subject will not receive any benefits from treatment with 
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Potential benefits of the Coil treatment that may be realized by study subjects 
include overall reduction in number or severity of symptoms related to 
emphysema and improved quality of life.  
Another potential benefit to subjects participating in the study is the ability to 
learn more about their emphysema based on the assessments that will be 
performed throughout the course of the study.  
For subjects with Medicare, Medicaid and/or third party insurance (private 
insurance) required to comply with the US Medicare Clinical Trial Policy rules for 
clinical trial coverage, many of the tests and procedures necessary for study 
completion will be billed to them. Tests and services required by the study that 
are not covered by the Medicare Clinical Trial Policy rules will be paid by 
PneumRx, Inc., the study sponsor. 
The results of this study may help other emphysema subjects to gain access to a 
device that may improve their quality of life and general health. 
 
10 
Study Monitoring  
PneumRx and its designee(s) for Data Management and Biostatistics will be 
responsible for coordinating and conducting the handling of clinical study data.  
 
Before acceptance of the clinical data, PneumRx and its assigned Clinical 
Monitor designee(s) will review the data entered on eCRFs for completeness and 
adherence to the protocol based upon source documentation verification (SDV). 
Procedures to be followed and the data to be fully monitored to SDV will be 
described in detail in the Monitoring Plan.  
 
PneumRx and its designee(s) will meet with the investigator to ensure that 
subjects will be properly selected and enrolled, that the methods described in the 
study protocol are thoroughly understood and that the method(s) surrounding 
clinical data collection and capture are understood.  
 
Assigned Clinical Monitors of PneumRx will visit the clinical site(s) periodically 
during the course of the study to perform SDV and perform device reconciliation. 
The Investigator and Institution must guarantee direct access to associated 
medical records by designated monitors and appropriate regulatory authorities. 
 
The study may be subject to a quality assurance audit by either PneumRx or by 
appropriate regulatory authorities. It is important that the Investigator and the 
assigned authorized study personnel are available during monitoring visits and 
possible audits and that sufficient time is dedicated to the process. 
 
11 
Responsibilities of the Sponsor  
The sponsor of this clinical trial is PneumRx, Inc. of Mountain View, CA, U.S.A. 
The sponsor is committed to: 
• 
Conducting this clinical trial in compliance with Good Clinical Practice (GCP) 
Guidelines as required by United States Food and Drug Administration Code 
of Federal Regulations and the Declaration of Helsinki (2008), as well as with 
any local laws, regulations or requirements applicable to any particular study 
site. 
 

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• 
Protecting the rights, health, safety and welfare of study subjects; the sponsor 
is responsible for obtaining and reviewing copies of IRB/Research Ethics 
Board approvals and will verify that appropriate subject Informed Consent is 
obtained. 
 
• 
Informing the clinical investigator of any new information about the study that 
may affect the health, safety or welfare of the subjects, or which may 
influence their decision to continue participating in the study. 
 
• 
Providing the clinical investigator with the study protocol and the eCRFs on 
which to document the study evaluation variables for each subject entered 
into the Study. 
 
• 
Providing the data collection and management, statistical analysis and study 
report-writing resources necessary to complete reporting of the study results. 
 
• 
Ensuring proper investigative site training and monitoring. 
 
• 
Selecting qualified investigators with adequate facilities to conduct this clinical 
trial and establishing written Investigator's Agreements. 
 
• 
Maintaining copies of correspondence, records of shipment and disposition of 
devices, adverse device effects, records related to the signed investigator 
agreements, and other records related to the clinical study.  
 
• 
Securing and maintaining US FDA IDE approval prior to treatment of any 
subjects. 
 
• 
Provision of SAE reports to FDA as required per DMC determination of 
reportability and support of investigators as needed. 
 
12 
 Responsibilities of the Principal Investigator 
The Principal Investigator (PI) participating in this clinical trial must hold a current 
medical license as a physician in his/her country of employment for the full 
duration of the study. The PI will affirm by his/her signature on the Investigator 
Agreement that he/she will fulfill his/her responsibilities relative to this clinical 
trial. 
 
• 
Subject Selection 
The investigator is responsible for ensuring that all subjects entering the 
study conform to the subject inclusion criteria and that no exclusion criteria 
apply. 
 
• 
IRB/EC Approval 
The investigator is responsible for obtaining IRB/EC approval from the 
institution at which he or she shall perform the procedure, prior to consenting 
or enrolling any subjects in the study. The Informed Consent document to be 
used will also be submitted by the Investigator to the IRB/EC for approval 
prior to initiation of the study. The investigator is also responsible for 
providing any other additional documentation relevant to the study as 

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required by IRB/EC for complete review of the study. Written assurance of 
IRB/EC approval of the trial plan and the Informed Consent document must 
be provided to the sponsor prior to initiation of the study. 
 
• 
Informed Consent 
The investigator is responsible for fully discussing the nature of the study, the 
possible risks, and the alternative treatments (including lung volume 
reduction surgery) with prospective subjects prior to their enrollment in the 
study. The investigator is responsible for obtaining written Informed Consent 
from each subject prior to enrollment in the trial. The ICF to be used should 
be the version of the document approved by the IRB/EC. The signed ICF will 
be maintained in the subject’s medical record, and a copy of the signed ICF 
will become an integral part of each case report file retained by the 
Investigator. A copy of the signed ICF shall also be given to the subject who 
signed the form. 
 
The approved ICF specific to each responsible IRB/EC will be used by the 
Investigator for this study. 
 
• 
Subject Evaluations and Data Reporting 
The investigator’s designee is responsible for performing the subject 
evaluations as described in this trial plan. Regulations require that the study 
investigator maintain information in the study subject’s medical records (i.e. 
source documentation) to corroborate data collected on the eCRFs. 
 
All information generated by the subject evaluations is to be transferred from 
the source documentation and recorded using EDC. Paper source 
documents should be completed in blue or black ink or should be typewritten. 
Any necessary corrections should be made by a single strikethrough in ink, 
initialed and dated by study site personnel. Correction fluid may not be used. 
The investigator will review, correct as needed, and sign off on the accuracy 
and completeness of the data entered on the eCRFs. Subject casebooks may 
be printed for review by authorized regulatory bodies. Original laboratory 
reports are to be retained by the Investigator, and the resulting data shall be 
entered onto the appropriate eCRFs. 
 
The sponsor will routinely monitor the subject data on an ongoing basis to 
support data quality and integrity. Source records will be reviewed as 
necessary to support assessment of data collected and reported using study 
eCRFs. 
 
The investigator is also responsible for submitting reports to PneumRx, Inc. 
and the reviewing IRB/EC as specified in this protocol. 
 
• 
Protocol Deviations 
The study investigator should not deviate from this protocol unless the trial 
plan poses unacceptable risks to the health or welfare of the involved 
individual subject. 
 
The investigator shall notify PneumRx Inc. and the reviewing IRB/EC of any 
deviation from the protocol intended to protect the life or physical well-being 

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of a subject in an emergency. Such notice shall be given as soon as possible, 
but in no event later than five working days after the emergency occurred. 
Except in such an emergency, prior approval of PneumRx Inc. is required for 
any deviation from the protocol. Approval from the IRB/EC also is required if 
these changes or deviations are expected to affect the rights, safety or 
welfare of human subjects. 
 
• 
Record Retention 
The investigator shall maintain all original records as required by local 
regulation or law and at a minimum shall maintain documents until after FDA 
has approved the RePneu Coil System.  
 
• 
Investigational Device Accountability 
The investigator must maintain accurate records of the receipt of all 
investigational devices shipped by the sponsor, including the date and lot 
numbers of devices received. In addition, accurate records must be kept 
regarding the date and quantities of investigational devices received, 
dispensed and returned. Information regarding the specific identification 
numbers for investigation devices used is to be recorded onto the appropriate 
device accountability log for each subject undergoing the treatment 
procedure throughout the course of the study. The investigator must assure 
that study supplies are dispensed only to subjects properly enrolled in the 
study and under the direct supervision of the investigator or co-investigators. 
 
All used and unused investigational supplies, as well as all labeled 
containers, are to be returned to the sponsor as soon as practical upon 
request by the sponsor or designee or upon completion of the study. 
Investigational material accounting procedures must be completed before the 
study is considered terminated. 
 
13 
Good Clinical Practice & Regulatory Requirements 
 
 
Informed Consent 
 
Written Informed Consent for the study must be obtained from all subjects who 
will participate in this clinical trial prior to their participation.  
 
 
Individual institutions may revise the sponsor-provided ICF with information that 
would meaningfully add to the protection of the rights and welfare of subjects. 
Prior to submitting the revised ICF to the IRB/EC for review, the investigator is to 
receive authorization of the revisions by PneumRx Inc. Clinical Affairs staff. The 
IRB/EC at each clinical site will then review and approve the ICF prior to study 
initiation. The investigator at each institution shall submit the approved ICF to the 
sponsor who shall review it to ensure compliance with applicable regulations. 
 
 
IRB/EC Approval 
 
This Study may not be initiated at any site until the IRB/EC has reviewed and 
approved the study protocol and the Informed Consent documents. Written 
committee approval is required prior to study initiation. The sponsor will review all 
documents and notify the site when screening and enrollment may begin. 
 
 
Subject Confidentiality 

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Subject confidentiality shall be maintained at all times throughout the conduct of 
this trial, and all subject data shall be maintained secure against unauthorized 
access. The subject’s records may be reviewed and/or photocopied by 
Regulatory Authorities and/or the study Sponsor (PneumRx Inc.) and its 
representatives. Copies (electronic or hard copy) of the subject’s CT Scans will 
be collected as study data. In the event a subject’s data are used for educational, 
presentation, and/or publication purposes, subject identity will be masked to 
protect the subject’s confidentiality. 
 
 

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14 
Citations and References 
 
American Thoracic Society. ATS Statement: Guidelines for the Six-Minute Walk 
Test. Am J Respir Crit Care Med. 2002. 166; 111-117. 
Bidwell JL, Pachner RW, Hemoptysis:  Diagnosis and Management, Am Fam 
Physician, 2005 Oct 1:72(7) 1253-60. 
Bleeker ER, ER McFadden, et al. Editorial - Investigative bronchoscopy in 
subjects with asthma and other obstructive pulmonary diseases, whether and 
when. Chest 1992; 101(2): 297-298. 
Brown CD, et al. National Emphysema Treatment Trial Research Group. 
Exercise testing in severe emphysema:  association with quality of life and lung 
function. COPD. 2008 Apr; 5(2): 117-24. 
Celli, B. et al; "Improvements in Resting Inspiratory Capacity and Hyperinflation 
with Tiotropium in COPD Patients with Increased Static Lung Volumes." 
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