Changes in Lung Physiology and Cardiac Performance in Patients With Emphysema Post Bilateral RePneu Coil Treatment
Conditions: Emphysema
Sponsor: Boston Scientific Corporation

CONFIDENTIAL 
NCT #: NCT02499380 
CLN0017.p.A 
PneumRx, Inc. 
Page 1 of 39 
 
 
 
 
 
CLINICAL TRIAL PROTOCOL COVER SHEET 
Device: 
PneumRx® RePneu® Coil 
System 
 
 
Study Number & Rev.: 
CLN0017.p. Rev A 
 
Study Title: 
Changes in lung physiology and cardiac 
performance in patients with emphysema post 
bilateral RePneu Coil Treatment 
 
 
Study Design: 
Post-market, multicenter, single-arm, study of the 
CE Marked PneumRx, Inc. RePneu Coil System 
whithin intended use 
 
 
Sponsor Name: 
PneumRx, Inc. 
 
 
Sponsor Address: 
530 Logue Avenue 
Mountain View, California 94043 
USA 
 
 
Study Coordination 
PneumRx, Inc. 
and Data Analysis: 
 
 
Projected Initiation Date: 
September 2014 
 
 
Projected 
Completion Date: 
December 2016 
 
 
 
 
 
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. 

CLN0017.p.A 
PneumRx, Inc. 
Page 2 of 39 
CONFIDENTIAL 
 
 
 
 
Revision History 
Revision 
DCO 
Effective Date 
Originator 
A 
2699 
19 Aug 14 

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PneumRx, Inc. 
Page 3 of 39 
CONFIDENTIAL 
 
 
 
 
STUDY ACKNOWLEDGMENT 
 
Investigator's Statement: 
 
I have read and understand Protocol No. CLN0017.p.A and agree to conduct the 
study as outlined herein. 
 
 
Investigator's Name (please print) 
 
 
Investigator’s Title 
 
 
Investigator's Signature 
 
 
Date 
 
 
Sponsor Signature, Protocol Approval: 
 
This study protocol, Protocol No. CLN0017.p.A, has been reviewed and approved 
by PneumRx, Inc., in accordance with Company policy and procedures and the 
national laws. 
 
For: 
PneumRx, Inc. 
530 Logue Avenue 
Mountain View, CA 94043 
USA 
 
 
 
Name (please print) 
 
 
Signature 
 
 
Position/Title 
 
 
Date 

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CONFIDENTIAL 
 
 
 
STATEMENT OF COMPLIANCE 
 
The Trial will be conducted in compliance with this Protocol, and with local, and national 
requirements, including Good Clinical Practices, my overseeing ethics committee 
requirements, patient privacy requirements, and all applicable regulatory requirements. 
 
 
Protocol Title: Changes in lung physiology and cardiac performance in patients 
with emphysema post bilateral RePneu Coil Treatment 
 
Version: CLN0017.p.A 
Revision Date: July 29, 2014 
 
 
 
 
Investigator's Name (please print) 
 
 
Investigator’s Title 
 
 
Investigator's Signature 
 
 
Date 

CLN0017.p.A 
PneumRx, Inc. 
Page 5 of 39 
CONFIDENTIAL 
 
 
 
Table of Contents 
1 
Protocol Synopsis ............................................................................................. 8 
2 
Introduction ...................................................................................................... 12 
2.1 
Background and Clinical Need ............................................................... 12 
2.2 
Description of the RePneu Coil System .................................................. 13 
2.3 
Historical Data ........................................................................................ 15 
3 
Study Objectives .............................................................................................. 17 
4 
Study Design .................................................................................................... 18 
4.1 
Design Overview .................................................................................... 18 
4.2 
Number of Subjects ................................................................................ 18 
4.3 
Population .............................................................................................. 18 
4.4 
Demographic and Baseline Characteristics ............................................ 18 
4.5 
Safety Evaluation ................................................................................... 18 
4.6 
Statistical analysis .................................................................................. 18 
4.7 
Brief Description of Study ....................................................................... 19 
4.7.1 CT Based Patient Selection and Treatment Planning .................. 19 
4.7.2 Treatment with RePneu Coils ..................................................... 22 
4.7.3 Pharmacological 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 
6.2 
Informed Consent ................................................................................... 27 
6.3 
Study Identification Number .................................................................... 28 
6.4 
Screening / Baseline Evaluations ........................................................... 28 
6.5 
Treatment Tx1, Tx2 and optional Tx3 ..................................................... 28 
6.6 
Post Bronchoscopy Monitoring and Evaluations ..................................... 28 
6.7 
Unscheduled Visits ................................................................................. 29 
7 
Management of Adverse Events (AEs) and Serious Adverse Events (SAEs)29 
7.1 
Serious Adverse Events (SAE) ............................................................... 29 
7.2 
Unanticipated Adverse Device Effect (UADE)......................................... 29 
7.3 
Severity of AEs and SAEs ...................................................................... 30 
7.4 
Relationship of an Event ......................................................................... 30 
7.5 
Process for Assessment, Recording and Reporting of AEs .................... 30 

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CONFIDENTIAL 
 
 
8 
Administrative .................................................................................................. 31 
8.1 
Premature Termination of Study ............................................................. 31 
8.2 
Insurance Coverage ............................................................................... 31 
9 
Risks and Benefits ........................................................................................... 31 
9.1 
Potential Risks to the Subject ................................................................. 31 
9.2 
Potential Benefits to the Subject ............................................................. 33 
10 
Study Monitoring ............................................................................................. 34 
11 
Responsibilities of the Sponsor...................................................................... 35 
12 
Responsibilities of the Principal Investigator ................................................ 36 
13 
Good Clinical Practice & Regulatory Requirements ...................................... 38 
14 
Citations and References ................................................................................ 39 

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CONFIDENTIAL 
 
 
 
 
List of Abbreviations 
 
6MWT 
6 Minute Walk Test 
ABG 
Arterial Blood Gas 
AE 
Adverse Event 
BD 
Bronchodilator 
BL 
Baseline 
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 
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 
IFU 
Instructions for Use 
ITT 
Intent-to-Treat population 
LRTI 
Lower Respiratory Tract Infection 
LVRS 
Lung Volume Reduction Surgery 
mMRC 
Modified Medical Research Council 
O2 
Oxygen 
PaO2 
Partial Arterial Blood Gases Oxygen 
PaCO2 
Partial Arterial Blood Gases Carbon Dioxide 
PI 
Principal Investigator 
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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CONFIDENTIAL 
 
 
 
 
1 
Protocol Synopsis 
 
Study Number 
and Title: 
CLN0017.p.A 
Changes in lung physiology and cardiac performance in 
patients with emphysema post bilateral RePneu Coil 
Treatment 
Clinical Phase: 
Post-market study with CE Marked device within intended 
use 
Study Device 
PneumRx RePneu® Coil 
Study Objectives: 
The objective of this post-marketing study is to advance the 
understanding of mechanism of action of the CE marked 
RePneu Coil by observing changes in lung physiology and 
cardiac performance in patients with emphysema treated with 
the RePneu Coils, when used as intended. 
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. Adult subjects diagnosed with emphysematous type of 
COPD. 
2. CT scan indicates bilateral emphysema, with sufficient 
lung parenchyma for coil deployment (based on PneumRx 
CT scoring criteria). 
3. Subject has post-bronchodilator FEV1 ≤45% predicted. 
4. Subject has Total Lung Capacity >100% predicted. 
5. Subject has residual volume (RV) ≥175% predicted. 
6. Subject has marked dyspnea scoring ≥2 on mMRC scale 
of 0-4. 
7. Subject read, understood and signed the Informed 
Consent form. 
8. Subject has received Pneumococcal and Influenza 
vaccinations consistent with local recommendations 
and/or policy. 

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CONFIDENTIAL 
 
 
 
Exclusion Criteria: 
1. 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 not due to dyspnea. 
2. 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. 
3. 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) 
4. Subject has severe pulmonary hypertension defined by 
right ventricular systolic pressure >50 mm Hg via right 
heart catheterization and/or echocardiogram. 
5. 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. 
6. Subject is pregnant or lactating, or plans to become 
pregnant within the study timeframe. 
7. Subject has an inability to tolerate bronchoscopy under 
moderate sedation or general anesthesia. 
8. Subject has clinically significant bronchiectasis. 
9. Subject 
has 
had 
previous 
LVR 
surgery, 
lung 
transplantation, lobectomy or other BLVR treatment in 
either lung. 
10. Subject has participated in studies to treat COPD using 
high dose radiation 
11. Subject has been involved in pulmonary drug or device 
studies within 30 days prior to this study. 
12. Subject is chronically taking >20 mg prednisone (or 
equivalent dose of a similar steroid) daily. 
13. Subject requires high level chronic immunomodulatory 
therapy to treat a moderate to severe chronic 

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CONFIDENTIAL 
 
 
 
inflammatory autoimmune disorder. 
14. Subject is on any type of antiplatelet or anticoagulant 
therapy which cannot be stopped for seven (7) days 
prior to procedure. 
15. Subject has a sensitivity or allergy to Nickel. 
16. Subject has a known sensitivity to drugs required to 
perform bronchoscopy. 
17. Subject has been diagnosed with alpha-1 antitrypsin 
deficiency (AATD). 
18. 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. 
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 treatment. Following 
RePneu Coil placement, the subject will remain in the 
hospital under observation per standard hospital practice. 
Following hospital discharge, the subject will be will be seen 
at the study site one month following the procedure. After 
the one month post-procedure visit the subject will be 
scheduled for the second procedure in the contralateral lung 
to take place within the following 4 weeks. Following hospital 
discharge, the subject will be seen at the study site one 
month following second procedure. If, at the discretion of the 
treating investigator, the patient did not respond to the 
bilateral treatment due to low coil dose, an optional 3rd 
procedure may be scheduled. 
If a patient is unable to complete these treatments for any 
reason, that patient’s data will be collected and analyzed 
separately. 
Study Procedures 
and 
Assessments: 
Baseline Visit: Participant agrees to be a part of the study 
and signs the informed consent. Baseline tests for all primary 
and secondary endpoints will be performed. Participant is 
evaluated and selected for RePneu procedure and has 
met inclusion/exclusion criteria. 
First and Second Procedure visit: Participant undergoes 
the RePneu Procedure in accordance with manufacturer 

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CONFIDENTIAL 
 
 
 
Instructions for Use. Procedure data will be collected. 
Third Optional Procedure: Patient will receive an additional 
1-3 coils in each treated lobe, at the discretion of the treating 
investigator if the initial coil dose did not bring the expected 
benefit. 
The procedures shall be performed no closer together than 4 
weeks and if possible no longer than 8 weeks apart. 
Follow up Visit (s): The follow up visits shall be performed 1 
month post each procedure and then 4 months post final 
treatment. The final study follow up visit shall be performed 1 
year post first treatment. 
Follow-up visits will occur at the hospital in which the coil 
implantation procedure was performed. 
Management of 
Adverse Events 
AE information will be collected throughout the study. 
Adverse events will be recorded on the AE CRF 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 
The endpoints will be analyzed with a paired t-test, which will 
compare baseline to 4-month post final treatment and 12- 
months post first treatment follow-up values. A p-value of 
<0.05 will be considered statistically significant. Parametric 
descriptive statistics will be used to summarize data for 
secondary effectiveness variables. Adverse events will be 
categorized into medically relevant categories and presented 
as frequency counts and percentages. 
Intention to Treat (ITT) and Per-protocol analyses will be 
performed as well as a site-specific subgroup analysis. 
Other subgroup analyses will include: 
- 
upper vs. lower lobe treatments 
multi-variate analysis of baseline characteristics, adverse 
events, and various CT and other imaging characteristics 

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CONFIDENTIAL 
 
 
 
2 
Introduction 
 
2.1 
Background and Clinical Need 
Emphysema is a chronic respiratory disease with an estimated prevalence of 
1.8% 
[1]. 
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 [2]. 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. 
 
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 seldomly 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 but none of them are indicated for use in homogeneous type of 
emphysema. 
 
The PneumRx 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 

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CONFIDENTIAL 
 
 
 
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. 
 
2.2 
Description of the RePneu Coil System 
The RePneu System is approved for CE Mark (Class IIa [Delivery System] and 
IIb [RePneu Coil] in accordance with the Medical Device Directive) since 
October 2010 and is used commercially in Europe. 
 
The RePneu Coil is an implantable device, delivered through a fiber-optic 
bronchoscope, 
designed 
specifically 
to 
treat 
patients 
suffering 
from  
emphysema. It 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, 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. 
 
The Coil derives its recovery ability from the super-elastic properties of the 
Nitinol wire. The Coils are available in three lengths to  accommodate  
anticipated anatomical variations – the lengths are 100mm, 125mm, and 150mm 
(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 rounded 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 procedure is designed to be performed using a bronchoscope with a 2.8mm 
working channel (which accommodates the Delivery System) and fluoroscopy for 
visualization beyond the viewing range of the bronchoscope. 

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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 
Delivery System is sterilized by Ethylene Oxide (EO) and the RePneu Coils are 
sterilized by Electron Beam (E-Beam). 
 
Figure 1. Diagram of the Endoscopic Emphysema Treatment Procedure Using 
Coils 
 
 
Figure 2. Shapes and Sizes of Coils 
 
100 mm 
COIL 
 
125mm 
COIL 
 
 
 
150 mm 
COIL 
 

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CONFIDENTIAL 
 
 
 
Figure 3. Components of the Delivery System 
 
 
 
Catheter 
 
Forceps 
 
Guidewire 
 
Cartridge 
 
 
 
2.3 
Historical Data 
PneumRx has conducted and analyzed data from human clinical trials of the 
RePneu Coil in Europe. The data presented below are the accumulation of 4 
completed studies[3-7], each of which had inclusion/exclusion criteria virtually 
identical to each other as well as to the present study . The results are presented 
in the summary below: 
 
Table 1. Effectiveness summary of completed studies 
 
 
Study # 
Publication 
Trea 
ted 
pati 
ents 
3 Months 
6 Months 
12 Months 
FEV1 
% or L 
RV 
% or L 
6MWT 
m 
SGRQ 
pts 
FEV1 
% or L 
RV 
% or L 
6MWT 
m 
SGRQ 
pts 
FEV1 
% or L 
RV 
% or L 
6MWT 
m 
SGRQ 
pts 
CLN0006 
Herth, 2010 
11 
-5.0% 
+ 3.3 
% 
+5.6 % 
-6.1 
Slebos, 2012 
16 
+14.9 
% 
-11.4 
% 
+84.4 
-14.9 
CLN0008 
(RESET) 
Shah, 2013 
23 
+14.29 
% 
-0.51 L 
+51.2 
-8.11 
Submitted 
May 2014 
45 
+0.07 
L 
-0.34 L 
+54.6 
-7.3 
+0.06 
L 
-0.32 L 
+34.1 
-6.1 
CLN0011 
Deslee 2014, 
60 
+0.11 
L 
-0.65 
L 
+29.7 
-12.1 
+0.11L 
-0.71 
L 
+51.4 
-11.1 
CLN0012 
Klooster 2014 
10 
+0.11 
L 
-0.6 L 
+61 
-15 

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CONFIDENTIAL 
 
 
 
With respect to safety, the RePneu Coils have shown an excellent safety profile 
to date. 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 [8], 
which observed 107 individuals for 6 months. Comparing the RePneu Coil 
combined study results to the EASE sham control group, it appears that the risks 
associated with the RePneu System are largely attributable to the bronchoscopic 
procedure itself rather than to the device per se. Specifically, the rate of serious 
events of hemoptysis, COPD exacerbation and pneumonia are comparable 
between the RePneu Coil treatment population and the EASE sham control 
group (Table 2). 
 
Table 2. Comparison of 6-Month SAE Data per Procedure – RePneu System vs. 
EASE Sham Control 
 
Reported SAE 
PneumRx 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 
2*/238 procedures = 0.8% 
4/107 procedures = 3.7% 
* Not related to device or procedure 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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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CONFIDENTIAL 
 
 
 
3 
Study Objectives 
 
The objective of this post-marketing study is to advance the understanding of the 
mechanism of action of the CE marked RePneu Coil by observing changes in 
lung physiology and cardiac performance in patients with emphysema treated 
with the RePneu Coils, when used as intended. 
 
Primary Endpoint: 
 
Changes at 4 months post final treatment and 12 months post first treatment in: 
• 
6 Minute Walk Distance (6MWD) 
 
Secondary Endpoints: 
Changes prior and post procedure at Tx1, Tx2 and optional Tx3 in: 
• 
Geometry (roundness) of major lung airways as defined by the ratio of major 
versus minor diameter measured from 3 bronchoscopic still images prior and 
post procedure taken in the lobar airway of the carina leading to segmental 
airways or while in any segmental airways of the same lobe of the carina 
leading to sub-segmental airways) 
• 
Static and dynamic pulmonary compliance measurement prior to and post 
treatment including closing volumes, closing capacity and small airways 
function 
 
 
Changes at 4 months post final bilateral treatment and 12 months post first 
treatment in: 
• 
 Physical activity and energy expenditure measured over a period of a week 
using multi-axial accelerometer. 
• 
Forced expiratory volume in one second (FEV1) 
• 
St. George's respiratory questionnaire (SGRQ) 
• 
Residual volume (RV) 
• 
Residual volume/total lung capacity (RV/TLC) 
• 
Diffusion capacity (DLCO) 
• 
mMRC dyspnea scale 
• 
Cardiovascular parameters such as heart rate, heart ejection fraction, 
systemic blood pressure 
• 
Body composition including BMI, fat per mass 
Changes at 12 months post first treament in: 
• 
Ventilation and perfusion single photon emission tomography (V/P SPECT) 
or Quantitative lung perfusion scintigraphy (LPS) 
• 
Diaphragm position during exhalation (Comparison of diaphragm apex to rib 
landmarks using frontal HRCT) 
• 
Lung density distribution (post CT image data processing and reconstruction) 

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CONFIDENTIAL 
 
 
 
 
4 
Study Design 
 
4.1 
Design Overview 
This will be a post-market prospective, multicenter, single-arm study. 
 
 
4.2 
Number of Subjects 
Thirty subjects will be enrolled into the study from each participating site. 
Subjects who completed only a unilateral treatment, for any reason will be 
replaced and not considered in the ITT analysis. Two sites will be recruiting 
subjects resulting in at least 60 enrolled and bilaterally treated subjects. 
 
 
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 
Subject demographics and baseline characteristics will be summarized including 
age at enrollment, sex, and ethnic origin. 
 
 
4.5 
Safety Evaluation 
Safety will be evaluated by collection of AEs and SAEs from entry into the study 
through the 12 months follow-up visit, or until the subject has terminated 
participation in the study. 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. 
 
 
4.6 
Statistical analysis 
The endpoints will be analyzed with a paired t-test, which will compare baseline 
to 4-month post final treatment and 12-monhts post first treatment follow-up 
values. A p-value of <0.05 will be considered statistically significant. Parametric 
descriptive statistics will be used to summarize data for secondary effectiveness 
variables. Adverse events will be categorized into medically relevant categories 
and presented as frequency counts and percentages. 
 
Intention to Treat (ITT) and Per-protocol analyses will be performed as well as a 
site-specific subgroup analysis. 
 
Other subgroup analyses will include: 
• 
upper vs. lower lobe treatments 
• 
multi-variate analysis of baseline characteristics, adverse events, and 
various CT and other imaging characteristics 

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CONFIDENTIAL 
 
 
 
 
 
4.7 
Brief Description of Study 
The details of this post-market study and its required visits, procedures, and 
assessments will be carefully discussed with the study patients using an Ethics 
Committee (EC) approved Informed Consent. The Informed Consent 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 patient’s right to decline to participate or to withdraw 
from the study at any time and for any reason without fear of retribution. It will  
be clearly stated that the patient will be eligible for treatment with RePneu Coils 
without agreeing to participate in this post-market study and will receive the 
same medical attention. The Informed Consent Form will include potential risks, 
discomforts or adverse effects, potential benefits, limits of confidentiality, 
incentive for participation, and timely dissemination of any new information that 
becomes available, and contact information of the research personnel. All 
patients will sign an Informed Consent prior to any procedure being performed to 
evaluate their eligibility for participation in the Study. 
 
Subjects who agree to participate in the study will sign a new Informed Consent 
and then will be evaluated to determine whether they meet inclusion and 
exclusion criteria for this study. Medical history, physical exam, and smoking 
history will be collected to ensure the subject meets inclusion and exclusion 
criteria. If the subject does not meet the inclusion / exclusion criteria the subject 
will be exited from the study. 
 
Once the subject meets all inclusion / exclusion criteria and completes the 
baseline tests the subject will be scheduled for treatment. 
 
 
4.7.1 CT Based Patient Selection and Treatment Planning 
CT based visual assessments and the PneumRx lobar damage scoring method will 
be used to select patients and plan the coil treatment. A character score (0-5) is 
assigned for each of the 4 main lobes (UL, UR, LL, and LR) that best matches 
the damage seen in the CT image. This is the method employed for CT-based 
patient selection and treatment planning in the FDA-pivotal RENEW trial. 
 
Background 
The RePneu Coil technology causes local airway distortion that restores tension 
(recoil properties) in the lung. Coils provide distortion of the airway path which 
produces the same effect as if the airway is shortened. The coils work best in 
lobes with continuous structure so tension can be maintained over a large 
volume. Lungs with preserved continuous tissue structure present better patient 
outcomes. An example of non-continuous structure would be patients with a 
giant bulla. In this case, a coil may successfully distort tissue adjacent to the 
bulla but the tension may never be developed throughout the lobe or lung 
because the bulla can simply expand. In this case, the tension is not maintained 
across the volume. 

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Lobe Scores 
Lobe score will be determined by visual evaluation of the lobe to identify the 
single axial slice with the greatest severity of damage (largest total area of tissue 
defects). The average damage observed in the slice (not the single largest 
defect in the slice) will be compared to the provided visual standards of lung 
damage to assign a score for the lobe. This method characterizes the slice with 
the greatest combination of tissue defects that can possibly interrupt the 
transmission of tension across the lobe of interest. Each lobe should be 
examined individually. 
 
This method is not based on densitometry or other analytical metrics that have 
been found to be overly sensitive to diffuse patterns of low damage (diffuse 
damage sometimes looks like total destruction when there is still substantial 
preserved structure). 
 
Scores 0-5 are patterns of damage that should be scored using the average ( 
>50% of the area) of the most severely damaged axial CT slice in the lobe. 
Additionally, the apical and basilar 10mm of each lobe should be excluded from 
consideration while scoring each lobe. 
 
The following are general descriptions of the patterns of damage that relate to 
each character score; however, comparisons with the provided visual standard 
images should be used as the predominant means to assign a score: 
 
#0 score – The majority of the slice presents with low attenuation lung that may 
present visually as normal tissue or having damage limited to scattered 
small centrilobular emphysematous holes. The tissue  presents  as 
relatively healthy and the majority of the parenchyma appears normal and 
fully connected throughout the lobe. 
 
If any single bulla is present that exceeds 8cm in length or any 
single paraseptal defect is present (a defect that is completely 
without internal structure or septi) that exceeds 10cm in length 
within the axial plane, the patient should be excluded from the 
study. 
 
We have seen this pattern in emphysema patients who still present with post- 
bronchodilator residual volumes in excess of 250% predicted. Some patients 
present with large amounts of air trapping even when only low levels of tissue 
destruction can be visualized on the CT images. These patients have 
relatively preserved structure and still benefit very much from the treatment. 
 
#1 score – The majority of the slice presents with more obvious 
centrilobular disease. Many small (approximately 1-3mm diameter) 
lung parenchyma tissue defects are present but the parenchyma is 
still extensively connected and preserved. If any single bulla is 
present that exceeds 8cm in length or any single paraseptal defect 
is present (a defect that is completely without internal structure or 
septi) that exceeds 10cm in length within the axial plane, the patient 
should be excluded from the study. 

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CONFIDENTIAL 
 
 
 
#2 score – The majority of the slice presents with more advanced centrilobular 
emphysema. Defects (approximately 3-10mm diameter) can be seen 
making up the majority of the damage however the periphery of 
secondary pulmonary lobule and the interstitium remain intact. If 
any single bulla is present that exceeds 8cm in length or any single 
paraseptal defect is present (a defect that is completely without 
internal structure or septi) that exceeds 10cm in length within the 
axial plane, the patient should be excluded from the study. 
 
#3 score – The majority of the slice presents with mostly non-coalescent bullous 
centriobular emphysema with 2-3cm parenchymal defects. The lung tissue 
is still globally connected (the interstitium and boundary of the secondary 
pulmonary lobule can still be seen. This will look similar to the #2 score but 
with larger defects. If any single bulla is present that exceeds 8cm in 
length or any single paraseptal defect is present (a defect that is 
completely without internal structure or septi) that exceeds 10cm in 
length within the axial plane, the patient should be excluded from 
the study. 
 
#4 score – The majority of the slice presents with panlobular emphysema or 
coalescent emphysema with parenchyma defects 3-5cm in size and 
complete loss of secondary pulmonary lobular structure. If any single 
bulla is present that exceeds 8cm in length or any single paraseptal 
defect is present (a defect that is completely without internal structure 
or septi) that exceeds 10cm in length within the axial plane, the 
patient should be excluded from the study. 
 
#5 score – The majority of the slice presents with confluent defects that 
are larger than 5cm or the slice presents with more than one 
paraseptal defect longer than 7.5cm along the perimeter of the 
lobe. If any single bulla is present that exceeds 8cm in length or 
any single paraseptal defect is present (a defect that is completely 
without internal structure or septi) that exceeds 10cm in length 
within the axial plane, the patient should be excluded from the 
study. 

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4.7.2 Treatment with RePneu Coils 
 
Subjects will undergo bronchoscopy 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, according to CE Mark intended use. Subjects will 
receive prophylactic drugs as prescribed by the protocol. 
 
Following RePneu Coil placement at Treatment 1 (Tx1) and Treatment 
2 (Tx2), the subject will remain in the hospital under observation per 
standard hospital practice. Following hospital discharge, the subject 
will be seen at the study site at one month after Tx1. After the one 
month visit following Tx1, the subject will complete the Tx2. Only a 
single lung will be treated during either of the first 2 bronchoscopies. 
 
After Tx2, the subject will remain in the hospital under observation per 
standard hospital practice. Following hospital discharge, the subject 
will be seen at the study site at one month post Tx2. 
 
If, at the discretion of the treating investigator and in consulation with 
the patient, the patient did not respond to the bilateral treatment 
possibly due to low coil dose determined at Visit 3 (1 month post Tx2), 
an optional Tx3 may be scheduled to place an additional 1-3 coils 
bilaterally. The investigator will determine wheather the patient 
anatomy (large lung, large lobe, diffuse large volume damage) 
warrants an additional 1-2 coils in each upper lobe or 1-3 additional 
coils in each lower lobe. The exact number of addition coils is at the 
discretion of the investigator. 
 
The procedures shall be performed no closer together than 4 weeks 
and if possible no longer than 8 weeks apart. 
 
The follow up visits should be performed at 4 months post final 
treatment and1 year post treatment 1. 
 
Follow-up visits will occur at the hospital which performed the coil 
implantation procedure. 
 
Treatment Planning Chart 
 
Upper Lobe Character Score 
Lower Lobes 
Character Score 
0 
1 
2 
3 
4 
5 
0 U 
U 
U 
U 
U 
NT 
1 L 
U 
U 
U 
U 
NT 
2 L 
L 
U 
U 
U 
NT 
3 L 
L 
L 
U 
NT 
NT 
4 L 
L 
L 
NT 
NT 
NT 
5 NT 
NT 
NT 
NT 
NT 
NT 
 
U – Upper lobe treatment with approximately 10 coils per lobe 
L – Lower lobe treatment generally between 11 and 14 coil per lobe 
NT – Patient not eligible, do not treat 

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A) Evaluate the CT independent data to diagnose COPD and possibly 
exclude the patient from safe use of the coil technology. 
B) Review the patient’s CT for indicators of disease that may exclude the 
patient from treatment (study site responsibility) such as: 
a. Clear visible bronchiectasis in the treatment lobe 
b. Scarring/ fibrosis in the treatment lobe 
c. Unstable or suspicious nodule in any lobe 
d. Severe bullous disease 
 
 
Steps C-E will be performed by PneumRx and by the treating site. 
Decisions related to treatment planning will be by agreement 
between the site investigator and PneumRx. 
 
C) Review the patient’s CT and assign a character score for each lobe. 
The right upper, left upper, right lower and left lower lobe should be 
evaluated and a character score should be recorded for each lobe. The 
score should be based on a review of all the slices that comprise the 
lobe. The score should characterize the average damage of the most 
severe slice within each lobe as detailed above (not an average of the 
entire lobe). 
 
D) Interpret the character score to recommend a treatment plan or to 
exclude the patient using the following guideline: 
a. If the any of the 4 major lobes receive a score of 5, the patient 
should be excluded from the study. 
b. If either lung presents with a score of 4 and 4 or a combination of 3 
and 4, the lung is in a severely damaged homogeneous condition 
and the patient should be excluded. 
c. The treatment planning chart should be reviewed to determine a 
treatment plan for each lung. Treatments should be upper or lower 
lobes, or opposite upper/lower lobe pairs (i.e. left-upper and right- 
lower lobes) but not both lobes in a single lung, except for the 
optional Tx3. The treatment plan should recommend treatment in 
the lobe with the highest character score in each lung as indicated 
by the treatment planning chart. 
E) Heterogeneous or Homogeneous? 
 
Patients will be classified as heterogeneous or homogeneous by 
comparing the character score of the evaluable lobes in each lung. A 
character score difference between the upper versus lower lobe 
greater than 1 (2 and above) indicates heterogeneous damage in that 
lung. A lung with character scores that match or are different by 1 
point is considered homogeneous. A patient that presents both lungs 
as homogenous is considered homogeneous. All other patients are 
considered heterogeneous (a patient with both types is considered 
heterogeneous). 

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4.7.3 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. Medically necessary changes in medications or dosages will be 
recorded in the CRF. Supplemental oxygen utilization should be 
recorded and monitored throughout the Study. 
 
All subjects enrolled in the study must have current influenza and 
pneumococcus vaccinations consistent with local recommendations 
and/or policy. 
 
Prophylactic anti-inflammatory treatment with steroids 50mg/day shall 
be given 1 day prior, during and after each treatment for up to 15 
days. Prophylactic treatment with antibiotics can be considered for at 
lease 5 days if some bleeding occurs during the implantation and 
there are infiltrations on chest x-ray post Tx or patient has an excess 
secretion or sputum culture shows pathologic concentration. 
Pseudomonades effective antibotics are needed only in case of 
positive culture in sputum. 

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CONFIDENTIAL 
 
 
 
 
 
 
Table 3.  Visit Schedule 
 
Procedure / Assessment 
Visit 1 
Baseline 
Screening (at 
least 7 days 
prior to Tx1) 
Tx1 RePneu 
Placement 
Visit 2 
1 month post 
Tx1 
Tx2 RePneu 
Placement 
(4-8 weeks post 
Tx1) 
Visit 3 
1 month post 
Tx2 
Optional Tx3 
RePneu 
Placement 
(4-8 weeks post 
Tx2) 
Visit 3 
4 months post 
final Tx 
Visit 4 
12 months post 
Tx1 
Informed Consent 
X 
Inclusion/ Exclusion 
X 
Focused physical exam including vital Signs and SpO2 
X 
X 
X 
X 
X 
X 
X 
X 
Spirometry 
X 
X 
X 
Lung volumes 
X 
X 
X 
6MWT 
X 
X 
X 
SGRQ 
X 
X 
X 
mMRC 
X 
X 
X 
Concomitant medication / O2 Use 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testing 
X 
X 
X 
X 
Physical activity and energy expenditure for 6-8 days 
X 
X 
X 
Bronchoscopic still images 
X 
X 
X 
Static and dynamic pulmonary compliance prior and post Tx 
X 
X 
X 
Echocardiogram 
X 
X 
X 
Body composition 
X 
X 
X 
V/P SPECT or Lung perfusion scintigraphy 
X 
X 
High Resolution CT 
X 
X 
Chest X-Ray 
X 
X 
X 
X 
Bronchoscopy / Coil Placement 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 

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5 
Study Subject Recruitment 
 
All study subjects will be patient volunteers who are diagnosed with 
emphysema 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. Adult subjects diagnosed with emphysematous type of COPD. 
2. CT scan indicates bilateral emphysema, with sufficient lung parenchyma 
for coil deployment (based on PneumRx CT scoring) criteria. 
3. Subject has post-bronchodilator FEV1 ≤45% predicted. 
4. Subject has Total Lung Capacity >100% predicted. 
5. Subject has residual volume (RV) ≥175% predicted. 
6. Subject has marked dyspnea scoring ≥2 on mMRC scale of 0-4. 
7. Subject read, understood and signed the Informed Consent form. 
8. 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 co-morbidities that may significantly reduce subject’s ability to 
improve exercise capacity (e.g. severe arthritis, planned knee surgery) or 
baseline limitation not due to dyspnea. 
2. 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. 
3. Subject has severe gas exchange abnormalities as defined by: 
a. PaCO2 >55 mm Hg 
b. PaO2 <45 mm Hg on room air (High altitude criterion: PaO2 
<30 mm Hg) 
4. Subject has severe pulmonary hypertension defined by right ventricular 
systolic pressure >50 mm Hg via right heart catheterization and/or 
echocardiogram. 
5. 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. 
6. Subject is pregnant or lactating, or plans to become pregnant within the 
study timeframe. 
7. Subject has an inability to tolerate bronchoscopy under moderate 
sedation or general anesthesia. 
8. Subject has clinically significant bronchiectasis. 

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9. Subject has had previous LVR surgery, lung transplantation, lobectomy or 
other BLVR treatment in either lung. 
10. Subject has participated in studies to treat COPD using high dose 
radiation. 
11. Subject has been involved in pulmonary drug or device studies within 30 
days prior to this study. 
12. Subject is chronically taking >20 mg prednisone (or equivalent dose of a 
similar steroid) daily. 
13. Subject requires high level chronic immunomodulatory therapy to treat a 
moderate to severe chronic inflammatory autoimmune disorder. 
14. Subject is on any type of antiplatelet or anticoagulant therapy which 
cannot be stopped for seven (7) days prior to procedure. 
15. Subject has a sensitivity or allergy to Nickel. 
16. Subject has a known sensitivity to drugs required to perform 
bronchoscopy. 
17. Subject has been diagnosed with alpha-1 antitrypsin deficiency (AATD). 
18. 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 and/or re-trained in the proper use and 
operation of the RePneu System, and will have performed several  
commercial procedures prior to initiation of any treatment. 
 
PneumRx personnel will be present at the first five treatments for each 
implanter to provide any additional technical support during treatment 
sessions, and/or 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/ERS Guidelines) as those in the 
pivotal protocol as detailed in the Study Operational Instructions. 
 
 
6.2 
Informed Consent 
• 
Provide information to the potential subject and review Informed 
Consent Form details. Obtain a signed Informed Consent from the 
subject as part of Pre-treatment/Baseline Screening (Visit 1). 
• 
Provide the subject with a copy of the signed Informed Consent for 
their records. 

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6.3 
Study Identification Number 
• 
Assign the subject a unique study identification number (Study ID 
number) after signing of Informed Consent. 
 
 
6.4 
Screening / Baseline Evaluations 
 
• 
Perform all screening and baseline assessments according to the 
schedule. 
 
 
6.5 
Treatment Tx1, Tx2 and optional Tx3 
• 
Perform pregnancy test for females of child bearing potential prior 
to radiographic procedures. 
• 
Prepare subject for bronchoscopy per standard hospital practice. 
• 
Prescribe a prophylactic regimen of antibiotics and steroids before 
and after treatment. 
• 
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 into the subject per the bronchoscope 
manufacturer’s instructions. 
• 
Navigate the bronchoscope and identify the airways leading to the 
diseased parenchyma via fluoroscopy. 
• 
Insert the Catheter into the working channel of the bronchoscope 
and deliver the device per the RePneu Coil Instructions for Use. 
• 
Navigate the Catheter to the distal airways and verify the position 
via fluoroscopy. 
• 
Deliver the Coil into the Catheter and deploy the Coil while 
monitoring the position via fluoroscopy in accordance with RePneu 
Coils Instructions for Use. 
• 
Only place the devices unilaterally. DO NOT place the devices in 
both the right and left lungs during one bronchoscopy session 
(except for Tx3). 
• 
Allow the subject to recover from anesthesia and monitor as per 
standard hospital practice. 
 
 
6.6 
Post Bronchoscopy Monitoring and Evaluations 
• 
Subject will be monitored per standard hospital practice. 
• 
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. 

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6.7 
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 CRFs. 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 adverse event has occurred. AE information will be collected 
throughout the study. Adverse events will be recorded on the CRF 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. 
 
 
7.1 
Serious Adverse Events (SAE) 
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. 
 
All SAEs must be reported to the PneumRx Clinical Affairs Group 
within two working days using the SAE CRF form. To maintain subject 
confidentiality, the subject shall only be identified by the subject number used 
on the CRFs. 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 CRF. 
 
 
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 previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or 

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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 would 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, as assigned. 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 CRF. The Ethics Committee(s) will be informed if the Serious or 
unexpected adverse event, in the opinion of the Investigator, or the Medical 

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Monitor, is likely to affect the safety of the subjects or the conduct of the 
study. 
 
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 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 
Ethics Committee approval from any site. The investigators are responsible 
for informing their Ethics Committees regarding premature trial termination. 
Subjects who experienced any SAEs that result in trial termination will be 
followed to resolution or stabilization. 
 
 
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 [9], pneumothorax [10], 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. 
 
• 
Infection including Pneumonia 
There is a risk of developing pneumonia (confirmed by positive culture) as 
a result of the RePneu Coils 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 [11]. 
 
• 
Hemoptysis 
Hemoptysis is defined as coughing up blood > 5ml, which results in more 
than occasional blood-streaked sputum. There is also an increased risk of 

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hemoptysis in patients with emphysema over those who do not have 
emphysema [12]. 
 
• 
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 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 
RePneu Coil treatment procedures 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 Studies, numerous Coils have been bronchoscopically 
repositioned or removed during treatment procedures to improve 
placement or to deploy a different size Coil. There have been no reported 
complications or adverse events associated with the bronchoscopic 
removal or repositioning of the Coils during the procedures. 
 
Coil(s) can and may be repositioned, replaced or removed during the 
treatment procedure. Coils can be removed bronchoscopically up to 2 
months after the procedure, but only if medically indicated. Such  
medically indicated post-procedure removal would be considered a Major 
Complication, and will be recorded in the CRF 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 [13]. 

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• 
Reaction 
Reaction to the study device that could require emergency intervention to 
remove the study device. 
 
The following are potential risks that are associated with the tests required 
as part of the study conduct: 
 
 
• 
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. 
 
The following risks are associated with the use of certain drugs that are 
required as part of the study conduct: 
 
• 
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 [9]. 
 
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 the Coil. 
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. 

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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. 
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 CRFs (case report forms) 
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. 
For example, all safety data and primary and secondary endpoint measures 
as defined by the protocol will be 100% monitored to SDV. 
 
PneumRx and its designee(s) will qualify investigative study sites to review 
the adequacy of the subject population, facilities, equipment and resource 
needs of the study, and to familiarize the investigator with the study protocol. 
 
At the time of enrollment, 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. 

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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 (2013), as well as with any local laws, regulations or 
requirements applicable to any particular study site. 
 
• 
Protecting the rights, health, safety and welfare of study subjects; the 
sponsor is responsible for obtaining and reviewing copies of Ethics 
Committee 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 CRFs 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. 
 
• 
Provision of SAE reports to National Health Authorities as required per 
reportability and support of investigators as needed. 
 
• 
Review CTs for treatment reccomendation and give feedback to the 
Investigator within 24 hours of receipt. 

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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 investigator will affirm by his/her signature 
on the Investigator's 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. 
o The Investigator will send CTs to PneumRx for treatment 
recommendation and wait for the feedback before proceeding with 
the treatment. 
• 
Ethics Committee Approval 
The investigator is responsible for obtaining Ethics Committee 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 
Ethics Committee for approval prior to initiation of the study. The 
investigator is also responsible for providing any other additional 
documentation relevant to the study as required by Ethics Committee for 
complete review of the study. Written assurance of Ethics Committee 
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 Informed 
Consent form to be used should be that version of the document 
approved by the Ethics Committee. The signed Informed Consent form 
will be maintained in the subject’s medical record, and a copy of the 
signed Informed Consent form will become an integral part of each case 
report file retained by the Investigator. A copy of the signed Informed 
Consent form shall also be given to the subject who signed the form. 
 
The approved Informed Consent Form specific to each responsible Ethics 
Committee 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 
case report forms (CRFs). 
 
All information generated by the subject evaluations is to be transferred 
from the source documentation and recorded using CRFs provided by the 
sponsor. Paper CRFs 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. 

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Correction fluid may not be used. The investigator will review, correct as 
needed, and sign off on the accuracy and completeness of the CRF data 
entered on the forms. 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 CRFs or electronically entered, as appropriate. 
 
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 CRFs. 
 
The investigator is also responsible for submitting reports to PneumRx, 
Inc. and the reviewing Ethics Committee 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 Ethics 
Committee of any deviation from the protocol intended to protect the life  
or physical well-being 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 Ethics Committee 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. 
 
• 
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. 

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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 Informed  Consent 
form with information that would meaningfully add to the protection of the 
rights and welfare of subjects. Prior to submitting the revised Informed 
Consent form to the EC for review, the investigator is to receive authorization 
of the revisions by PneumRx Inc. Clinical Affairs staff. The EC at each clinical 
site will then review and approve the Informed Consent prior to study 
initiation. The investigator at each institution shall submit the approved 
Informed Consent to the sponsor who shall review it to ensure compliance 
with applicable regulations. 
 
EC Approval 
This Study may not be initiated at any site until the 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 
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 
 
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O'Donnell, D.E., et al., Effect of fluticasone propionate/salmeterol on lung 
hyperinflation and exercise endurance in COPD. Chest, 2006. 130(3): p. 647- 
56. 
3. 
Herth, F.J., et al., Bronchoscopic lung volume reduction with a dedicated coil: 
a clinical pilot study. Ther Adv Respir Dis, 2010. 4(4): p. 225-31. 
4. 
Slebos, D.J., et al., Bronchoscopic lung volume reduction coil treatment of 
patients with severe heterogeneous emphysema. Chest, 2012. 142(3): p. 
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5. 
Shah, P.L., et al., Endobronchial coils for the treatment of severe emphysema 
with hyperinflation (RESET): a randomised controlled trial. The Lancet 
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6. 
Klooster, K., et al., Lung Volume Reduction Coil Treatment in Chronic 
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7. 
Deslee, G., et al., Lung volume reduction coil treatment for patients with 
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8. 
Shah, P.L., et al., Bronchoscopic lung-volume reduction with Exhale airway 
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Djukanovic, R., et al., Safety of biopsies and bronchoalveolar lavage. Eur 
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Bleecker, E.R., et al., Investigative bronchoscopy in subjects with asthma and 
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11. 
Zalacain, R., et al., Predisposing factors to bacterial colonization in chronic 
obstructive pulmonary disease. Eur Respir J, 1999. 13(2): p. 343-8. 
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Bidwell, J.L. and R.W. Pachner, Hemoptysis: diagnosis and management. Am 
Fam Physician, 2005. 72(7): p. 1253-60. 
13. 
Guo, Y., et al., Factors related to recurrence of spontaneous pneumothorax. 
Respirology, 2005. 10(3): p. 378-84.