A Feasibility Study: A Safety Evaluation of RheOx on Patients With Chronic Bronchitis in the United States
Phase: NA
Conditions: Chronic Bronchitis, Copd Bronchitis
Sponsor: Gala Therapeutics, Inc.

A Feasibility Study: A Safety Evaluation of the RheOx™ on Patients with 
Chronic Bronchitis in the United States 
Study Number: CS003 
 Version: 19APR2019 
Study Sponsor: Gala Therapeutics, Inc. (Corporate Headquarters) 
230 Park Ave., Suite 2800 
New York, NY 10169 
Gala Therapeutics, Inc. (Manufacturing Site) 
155 Jefferson Drive, Suite 100 
Menlo Park, CA USA 94025 
Study Device: RheOx™ 
IRB Approved at the 
Protocol Level 
May 28, 2019
20181490

PROTOCOL REVISION HISTORY 
Revision Date 
DESCRIPTION 
28MAY2018 
Original Issue 
25JUN2018 
Updates made to address FDA questions as follows: 
• 
Section 3.2.1 added sustained (> 30 seconds) ventricular tachycardia 
• 
Section 7.1 added IVY heart rate alarm limits 
• 
Sections 7.2.2 and 7.2.4 added 6-section 3-lead EKG recording prior to initiation 
of energy delivery 
• 
Section 7.6.1 clarified arrhythmia stopping rule 
27JUN2018 
Updates made to address FDA questions as follows: 
• 
Section 3.2.1 added Respiratory Failure 
• 
Section 6.1 Inclusion Criteria added Subject has a SGRQ score of 
greater than or equal to 25 and CAT score of greater than or equal to 10. 
• 
Section 6.2 added exclusions for Asthma, Bronchiectasis, Uncontrolled 
GERD, severe Pulmonary Hypertension and infectious drug resistant 
infectious airway diseases 
• 
Section 7.2 Description of Visits including Figure 7.1 Study Procedures 
and Table 7.1 to include 1 week and 1-month post procedure follow-ups 
• 
Section 7.6.1 Study Stopping Rules added Pulmonary Hemorrhage and 
modified the pneumothorax criteria to require 3 or more subjects  
• 
Section 10.2 List of foreseeable adverse events added significant 
pulmonary bleeding and death as low occurrence 
28JUN2018 
Updates made to address FDA questions as follows: 
• Section 6.1 Inclusion Criteria added Subject has 1 or more COPD 
exacerbations, defined as an acute worsening in respiratory symptoms 
that requires additional treatment, in the 12-months prior to enrollment 
12NOV2018 
• 
Cover Page: Updated address for Gala Menlo Park Office 
• 
Synopsis: Revised number of clinical sites from 5 to 7 
• 
Throughout Document: Replaced Gala Airway Treatment (GATS) with 
RheOx to reflect trademarked device name and minor punctuation/page 
formatting corrections 
• 
Schedule of Events Table 7.1: Changed Follow-up CT scan from 3 
months to 6 months post-bronchoscopy #2; updated sections 7.2.7 and 
7.2.8 accordingly.  Removed ‘phone call’ from Visit #5 in table header to 
clarify the visit is in-office; this is consistent with section 7.2.5 and Figure 
7.1.  Changed the time period for the daily diary from entire study period 
(5 years) to only the first year. 
31JAN2019 
• 
Section 7.2.4 Visit 4/Bronchoscopy #2 added CT scan 
• 
Table 7.1 Schedule of Events: Added CT at Visit 4 prior to 
Bronchoscopy #2; removed Induced Sputum from Visit 2/Bronchoscopy 
#1 and Visit 4/Bronchoscopy #2 and moved superscripts to individual 
activities for additional clarity 
19APR2019 
• 
Synopsis: Revised number of clinical sites from 7 to 10 

PROTOCOL REVISION HISTORY 
Revision Date 
DESCRIPTION 
• 
Synopsis: Revised number of patients from 15 to 30 
• 
Synopsis:  Revised Other (tertiary) endpoints to include the Insomnia 
Sleep Index (ISI) and cough count 
• 
Section 3.2.3 was updated to include the Insomnia Sleep Index (ISI) and 
cough count 
• 
Section 7.2 clarified wording regarding rescheduling of follow-up visits 
due to COPD exacerbations 
• 
Section 7.4 schedule of events added visit windows, ISI and selected, 
optional polysomnography, cough counting monitor, and clarified 
wording regarding rescheduling of follow up visits due to COPD 
exacerbations 
• 
Section 10.2 added urinary retention to minor complications associated 
with anesthesia 
• 
References: added reference 21 
 
 
 
 
 

STUDY ACKNOWLEDGMENT 
 
Investigator's Statement: 
I have read and understand Protocol No. CS003 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. CS003, has been reviewed and approved by Gala 
Therapeutics, Inc., in accordance with Company policy and procedures and the US FDA, as 
warranted, under IDE requirements per 21 CFR part 812. 
 
For: 
Gala Therapeutics, Inc.  
 
 
230 Park Ave., Suite 2800 
New York, NY 10169 
 
 
 
 
 
Name (please print) 
 
 
 
 
Signature 
 
 
 
 
Position/Title 
 
 
 
 
Date  

STATEMENT OF COMPLIANCE 
 
The clinical trial referenced herein will be conducted in compliance with this Protocol, and 
with local, State, and Federal requirements, including Good Clinical Practices, the 
overseeing IRB requirements, patient privacy requirements, and all applicable regulatory 
requirements. 
 
Protocol Version: CS003 
Revision Date:  19 April 2019 
 
 
 
 
 
Investigator's Name (please print) 
 
 
 
 
Investigator’s Title 
 
 
 
 
Investigator's Signature 
 
 
 
 
 
Date 
 
 

TABLE OF CONTENTS 
1.0 
INTRODUCTION ................................................................................................................................ 14 
1.1 
Background ...................................................................................................................................... 14 
1.2 
Trial Justification .............................................................................................................................. 15 
1.2.2 
Opportunity for Intervention ........................................................................................................... 15 
1.3 
Supporting Rationale – First-In-Human Trial (FIH) Overview .................................................. 16 
2.0 
DEVICE DESCRIPTION ................................................................................................................... 18 
2.1 
Device Identification ........................................................................................................................ 18 
2.2 
Device Manufacturer ....................................................................................................................... 18 
2.3 
Device Description .......................................................................................................................... 18 
2.4 
Intended Purpose and Study Population ..................................................................................... 21 
2.5 
Anticipated Changes During Investigation .................................................................................. 21 
3.0 
STUDY OBJECTIVES ....................................................................................................................... 21 
3.1 
Study Objective ................................................................................................................................ 21 
3.2 
Outcome Measures ......................................................................................................................... 21 
4.0 
INVESTIGATIONAL SITES .............................................................................................................. 22 
5.0 
STUDY DURATION ........................................................................................................................... 23 
6.0 
SUBJECT ELIGIBILITY ..................................................................................................................... 23 
6.1 
Inclusion Criteria .............................................................................................................................. 23 
6.2 
Exclusion Criteria ............................................................................................................................ 24 
7.0 
STUDY PROCEDURES .................................................................................................................... 25 
7.1 
Treatment Plan ................................................................................................................................ 27 
7.2 
Description of Visits ........................................................................................................................ 27 
7.3 
Concomitant Medications / Treatments ....................................................................................... 30 
7.4 
Schedule of Events (Table 7.1) ..................................................................................................... 32 
7.5 
Removal of Subjects ....................................................................................................................... 33 
7.6 
Early Termination or Suspension of Study .................................................................................. 33 
8.0 
STATISTICAL CONSIDERATIONS ................................................................................................ 34 
8.1 
Study Design .................................................................................................................................... 34 
8.2 
Sample Size ..................................................................................................................................... 34 
8.3 
Evaluable Cohort ............................................................................................................................. 34 
8.4 
Outcome Analysis ........................................................................................................................... 34 
9.0 
DATA MANAGEMENT ...................................................................................................................... 35 

9.1 
Data Entry ......................................................................................................................................... 35 
9.2 
Subject Data Protection .................................................................................................................. 35 
9.3 
Data Retention ................................................................................................................................. 35 
9.4 
Monitoring ......................................................................................................................................... 35 
10.0 
ADVERSE EVENTS .......................................................................................................................... 36 
10.1 
Reporting Requirements ................................................................................................................ 36 
10.2 
List of foreseeable adverse events related to investigational therapy and/or study 
procedure: ........................................................................................................................................................ 37 
11.0 
RISK-BENEFIT ASSESSMENT ....................................................................................................... 38 
11.1 
Anticipated Risks ............................................................................................................................. 38 
11.2 
Anticipated Benefits ........................................................................................................................ 38 
12.0 
STUDY MANAGEMENT ................................................................................................................... 38 
12.1 
Statement of Compliance ............................................................................................................... 38 
12.2 
Institutional Review Board (IRB) ................................................................................................... 38 
12.3 
Investigator Responsibilities .......................................................................................................... 39 
12.4 
Study Initiation ................................................................................................................................. 39 
12.5 
Amendments to the Clinical Investigational Plan (CIP) ............................................................. 40 
12.6 
Deviations from the Clinical Investigational Plan ....................................................................... 40 
12.7 
Informed Consent Process ............................................................................................................ 40 
12.8 
Device Accountability ...................................................................................................................... 40 
12.9 
Publication Policy ............................................................................................................................ 41 
13.0 
BIBLIOGRAPHY ................................................................................................................................. 42 
 
 
 

 
 
PROTOCOL SYNOPSIS 
Protocol Title 
A Feasibility Study: A Safety Evaluation of the RheOx™ on Patients with 
Chronic Bronchitis in the United States 
Study Number 
CS003 
Study Sponsor 
Gala Therapeutics, Inc. 
Menlo Park, CA USA 
Study Device 
RheOx™ 
Design 
Prospective, single-arm feasibility study 
Objective 
Primary: To assess the safety of the RheOx in patients with chronic 
bronchitis 
Secondary: To assess the clinical utility of the RheOx in patients with 
chronic bronchitis 
Study Population 
The study will treat up to 30 adult patients with chronic bronchitis at up to 
10 clinical study sites in the United States 
Gala will conduct an interim safety analysis after 5 subjects complete the 
second RheOx procedure to assess the safety profile of the device and 
procedure and ensure it is safe to continue the study.   
Study Period 
Subjects receive treatment in the right lung first, followed by treatment of 
the left lung approximately 4-weeks later. The follow-up period will extend 
to 5 years following treatment of the second lung. Study follow-up visits 
will occur at 6-months, 12-months, 2, 3, 4 and 5 years after the second 
treatment. 
Outcome 
Measures 
The primary outcome of the study is safety. The primary safety analysis 
will be the incidence of serious adverse events of interest through 12 
months defined as the following; 
• 
Death 
• 
COPD exacerbation, as defined as an acute worsening in 
respiratory symptoms requiring additional therapy, that requires a 
hospital stay of greater than 24 hours 
• 
Pneumothorax within 2 days of either Gala Treatment procedure 
• 
Pneumonia within 7 days of either Gala Treatment procedure, as 
defined as an increase in respiratory symptoms, fever, sputum 
production and or purulence with radiographic confirmation 
• 
Respiratory Failure as defined as a requirement for mechanical 
ventilatory support for > 24 hours 
• 
Arrhythmia requiring intervention or sustained (> 30 seconds) 
ventricular tachycardia 
 
 

The secondary outcome measures of clinical utility will be assessed by; 
• 
The change from baseline at 6 and 12 months in St. George’s 
Respiratory Questionnaire (SGRQ) 
• 
The change from baseline at 6 and 12 months in COPD 
Assessment Test (CAT)  
Hospitalization rates (not including the planned bronchoscopy 
procedures) from discharge from the initial RheOx Bronchial Rheoplasty 
procedure (Visit 2) through 12 months 
Other (tertiary) 
endpoints 
Other, tertiary and exploratory endpoints will also be assessed including 
changes from baseline to follow-up in:  
• 
Responder rates utilizing established clinically meaningful thresholds 
for SGRQ (4 points)17 and CAT (2 points)16 
• 
Change in other QOL measures including CASA-Q and EXACT-PRO 
• 
Change in lung function as measured by FEV1 and FVC  
• 
Change in sleep patterns as assessed by the Insomnia Sleep Index 
(ISI)  
• 
Change in cough count as assessed by a cough counting monitor 
• 
Mucin concentrations (MUC5AC, MUC5B) from induced sputum 
samples 
• 
Quantitative High Resolution CT Scan (HRCT) metrics including 
airway volume, total airway count, and lobar volumes 
• 
Device performance  
 
In addition to the endpoints described above, additional safety analyses 
in support of the primary study outcome and to assess the totality of 
safety profile of RheOx, will be conducted. 
Adverse events reported from the day of the index procedure through 
completion or termination of the study will be assessed. AEs and SAEs 
will be summarized using a standard medical coding dictionary 
(MedDRA). AEs and SAEs will be also analyzed by severity, relatedness 
to the device and/or procedure and within discrete time periods in relation 
to the index procedure.  
COPD exacerbations will also be analyzed by severity (mild, moderate, 
and severe) based on commonly accepted clinical definitions as defined 
in GOLD 2018 Report18. 
  
Statistical 
Considerations 
As this is a feasibility study, endpoints will not be powered for statistical 
significance.  Descriptive statistics will be utilized to summarize and 
report on data for all subject and outcome variables.  
Categorical data (e.g., age, gender) will be reported in frequency 
distributions. Certain dichotomous data (e.g., Adverse Events) will also 
be presented as rates. Continuous data (e.g., age, FEV1) will be 

summarized using mean, standard deviations, medians, minimums, 
maximums, and interquartile ranges.  
All patients that enter the procedure room for the index RheOx Bronchial 
Rheoplasty procedure (Visit 2) will be included in the analysis.  
Additional subgroup and other multivariable analyses may be performed 
including examination of the association between subject risk factors 
(e.g., age, gender) and trial outcomes, and the potential contributions of 
these factors.  
 

LIST OF ABBREVIATIONS 
6MWT 
Six Minute Walk Test 
AE 
Adverse Event 
ARDS 
Acute Respiratory Distress Syndrome 
BAL 
Bronchoalveolar lavage 
CASA-Q 
Cough and Sputum Assessment Questionnaire 
CAT 
COPD Assessment Test 
CBC 
Complete Blood Count 
CIP 
Clinical Investigational Plan 
COPD 
Chronic Obstructive Pulmonary Disease 
CRF 
Case Report Form 
CT scan 
Computed Tomography scan; also referred to as CAT scan 
EC 
Ethics Committee 
EDC 
Electronic Data Capture (electronic database) 
EKG 
Electrocardiogram; also referred to as ECG 
EXACT-
PRO 
EXAcerbations of Chronic pulmonary disease Tool (EXACT) Patient Reported 
Outcomes 
FEV1 
Forced Expiratory Volume in 1 Second 
FVC 
Forced Vital Capacity 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
HHS 
Depart of Health and Human Services 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Board 
IRE 
Irreversible Electroporation 
ISI 
Insomnia Sleep Index 
MCID 
Meaningful Clinically Important Difference 
mMRC 
Modified Medical Research Council Dyspnea Scale 
MRI 
Magnetic Resonance Imaging 

PFT 
Pulmonary Function Test(s) 
PI 
Principal Investigator 
RF 
Radiofrequency 
RFE 
Radiofrequency Energy 
SAE 
Serious Adverse Event 
SGRQ 
St. George Respiratory Questionnaire 
Tx 
Gala Bronchoscopy Treatment 
UADE 
Unanticipated Adverse Device Effect 
 
 

 
DEFINITIONS 
Adverse Event (AE): any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, user or other persons, whether or 
not related to the investigational medical device [Reference ISO 14155:2011] 
 
COPD Exacerbation: An acute worsening in respiratory symptoms that requires additional 
treatment 
 
Mild: Treated with short acting bronchodilators only (SABDs) 
Moderate: Treated with SABDs plus antibiotics and/or oral corticosteroids 
Severe: Requires hospitalization and or visits to the emergency room. Severe exacerbations 
may also be associated with acute respiratory failure 
Chronic Bronchitis: One form of COPD defined by GOLD guidelines and characterized by chronic 
productive cough for three months in each of two successive years in a patient in whom other 
causes of productive cough have been excluded 
 
Serious Adverse Event (SAE): an adverse event that a) led to death, b) lead to serious 
deterioration in the health of the subject that either resulted in 1) a life-threatening illness or injury, 
or 2) a permanent impairment of a body structure or a body function, or 3) in-patient or prolonged 
hospitalization, or 4) medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function, or c) led to fetal distress, fetal death 
or a congenital abnormality or birth defect [Reference ISO 14155:2011] 
 
Unanticipated Adverse Device Effect (UADE): any serious adverse effect on health or safety or 
any life-threatening problem or death cause 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 [Reference 21 CFR 812.3(s)] 
 
 

1.0 
INTRODUCTION 
1.1 
Background 
Approximately 12 million patients in the United States, 13 million in the European 
Union and 4 million in Japan are diagnosed with Chronic Obstructive Pulmonary 
Disease (COPD) and millions more may have the disease without a diagnosis.  
COPD is the third leading cause of death in the United States. COPD causes serious 
long-term disability and early death. Currently, there is no cure for COPD and 
treatment aims simply to reduce exacerbations, reduce hospitalization and improve 
quality of life. 
COPD severity is diagnosed by degree of FEV1 reduction. FEV1 is the volume of air 
exhaled by a patient in the first second when exhaling as hard as possible into a 
spirometer.  Once diagnosed with COPD, drugs are prescribed based on standard 
guidelines (see Figure 1.1).   
COPD is, however, most likely several different physiologic conditions that have 
been combined into one category.  Most simply, emphysema and chronic bronchitis 
are two examples of subsets of COPD that vary physiologically. 
 
Figure 1.1: COPD Severity and Interventions  
 
 
Emphysema.  Emphysema is a disease of the alveoli which are responsible for 
oxygen and carbon dioxide exchange.  Inhaled toxins, from cigarette smoke in most 
cases, activate proteases leading to alveolar tissue destruction.  As more alveoli are 
destroyed, patients cannot adequately oxygenate and carbon dioxide retention leads 
to chronic respiratory acidosis, which symptomatically manifests as shortness of 
breath. 
Chronic Bronchitis. Chronic bronchitis is defined as the presence of cough with 
productive sputum for three months in duration for two consecutive years.  It is a 

disease of the airways, unlike emphysema which is a disease of the parenchyma 
(lung tissue) and alveoli.  The pathophysiology of chronic bronchitis is not completely 
understood, but the leading theory extends from the British Hypothesis1.  Noxious 
gases and particles are introduced into the respiratory tract by inhalation of cigarette 
smoke, leading to innate and adaptive inflammatory responses of the airway 
mucosa.  Over time, the chronic inflammation leads to abnormal tissue repair and 
remodeling of the bronchial walls, most notably with an increase in the number and 
size of the bronchial mucus glands, defective cilia, and disruption of the epithelial 
barrier2.  Abnormal, thick mucus is secreted into the airways that cannot easily be 
cleared and provides fertile ground for bacteria and other pathogens that would have 
otherwise been cleared.  As more mucus accumulates in the airways, it obstructs air 
delivery to the alveoli resulting in decreased FEV13. 
1.2 
Trial Justification  
1.2.1 Chronic Bronchitis Is Associated with Worse Outcomes 
Mucus hypersecretion is not only a histologic finding but also leads to worse clinical 
outcomes regardless of GOLD stage.  In the Copenhagen City Heart Study, which 
followed 9,400 smokers, mucus hypersecretion was associated with FEV1 decline4.  
Mortality was at least ten times greater for a patient with mucus hypersecretion for 
any given FEV1 value as compared to a patient that did not have hypersecretion.  
Chronic bronchitis in GOLD 2 to 4 patients has also been associated with more 
frequent exacerbations, more severe exacerbations and poorer quality of life.  This is 
consistent with literature showing, that while CB and airflow restriction (as measured 
by FEV1) are both hallmarks of COPD20, CB and airflow restriction are two distinct, 
albeit commonly associated disorders18,19,20.  In fact, one study showed that airflow 
limitation was accompanied by chronic mucus hypersecretion in only 30% of airflow 
restricted patients aged 60 to 64 years19. Kim et. al. also showed that nearly 20% of 
GOLD 0 and GOLD 1 subjects and 30% of GOLD 2 subjects met the clinical criteria 
for chronic bronchitis. 
In another study of patients who received lung volume reduction surgery for 
emphysema, the patients with the least mucus hypersecretion had the longest 
cumulative survival: 82% at 72 months as compared to 18% for the patients with the 
most severe mucus hypersecretion5.  Therefore, a therapy to treat the mucus glands 
may lead to a relative reduction in the risk of death, improve quality of life, and ease 
the burden associated with frequent exacerbations in chronic bronchitis patients. 
Several groups have proposed chronic antibiotics for patients with mucus 
hypersecretion to reduce the frequency of exacerbations due to bacterial infection.  A 
study of azithromycin in COPD patients showed that use of this macrolide antibiotic 
as prophylaxis for one year increased the time to first exacerbation from 174 days to 
266 days (p<.001) as compared to patients taking a placebo6.  Besides the 
antibiotic’s antimicrobial effect, other mechanisms of action of macrolides are well 
known including reduced mucus secretion, the inhibition of chloride secretion, and 
the direct inhibition of MUC5AC (the most common mucin in human airway mucus) 
production.  The reduction in mucus secondary to azithromycin may have contributed 
to improvement in these outcomes. 
1.2.2 Opportunity for Intervention 
The standard guidelines, summarized in Figure 1.1, outline the recommended 
treatment algorithm for patients diagnosed with COPD.  At all stages of disease, 

reduction of risk factors including smoking and influenza vaccine are strongly 
recommended. Increasing pharmacological therapies are prescribed as the disease 
progresses.  Despite the benefits of drug therapy, none are disease modifying even 
though healthcare systems spend over $25 billion per year on these therapies.  
While the drugs treat the symptoms of the disease, no therapy exists to reverse the 
pathophysiology of mucus hypersecretion. 
Mucus hypersecretion is not only a prognosticator for worse morbidity and mortality, 
but also an opportunity for intervention.  A device-based therapy to treat chronic 
bronchitis may reset chronic inflammation in the airways.  Selective ablation of the 
mucus glands may improve daily cough, shortness of breath, frequency of 
exacerbations and overall morbidity and mortality11.  The other cells and layers of the 
airway should be kept intact to maintain the barrier function, defend against 
pathogens, and expel mucus.  The extracellular matrix should be left unchanged to 
allow for regeneration of all cell layers.  Since these patients are frail, minimizing 
inflammation and acute exacerbations after the procedure are also priorities.   
In a 21 patient trial, CryoSpray Ablation demonstrated sloughing of the epithelium 
and submucosal glands while some sections recovered after the initial treatment 
period showed regenerative changes12.  This study establishes the proof of concept 
for ablating airway tissue for the treatment of chronic bronchitis. 
To this end, Gala Therapeutics, Inc. (herein ‘Gala’) is developing RheOx using 
irreversible electroporation (IRE) to ablate the abnormal mucus glands of the 
epithelium and reduce the submucosal glands.  Postoperatively, the therapy should 
allow for normal, healthy regeneration rather than a return to mucus hypersecretion 
and metaplasia.   
1.3 
Supporting Rationale – First-In-Human Trial (FIH) Overview 
Gala initiated a FIH trial using the Gala System in March 2017.  As of May 3, 2018, 
25 patients were treated at 5 clinical sites in Australia, Chile and Austria (see Table 
1.1 below).  
 
 

 
Table 1.1: FIH Clinical Study Sites  
Clinical Site 
Location 
Primary Investigators 
# of 
Treated 
Patients 
Otto Wagner Spital 
Vienna, Austria 
A. Valipour, MD 
9 
Clinica Alemana 
Santiago, Chile 
S. Fernandez-Bussy, MD 
6 
Macquarie 
University Hospital 
Sydney, Australia 
A. Ing, MD 
J. Williamson, MD 
6 
Royal Melbourne 
Hospital 
Melbourne, Australia D. Steinfort, MD 
L. Irving, MD 
3 
The Alfred Hospital 
Melbourne, Australia G. Snell, MD 
1 
Note: Data reported as of May 3, 2018 
This study is currently under way and patients continue to be enrolled and treated. 
 
Patients with a smoking history of at least 10 pack years and diagnosed with chronic 
bronchitis and moderate to severe chronic obstructive disease for a minimum of two 
years were considered for inclusion in the study.  Consented patients were screened 
for eligibility and scheduled for bronchoscopy if eligible. Three bronchoscopies were 
performed per patient.  Patients were treated in the right side airways using RheOx, 
previously referred to as the Gala Airway Treatment System (GATS), during the first 
bronchoscopy and then in the left side airways during the second bronchoscopy 
approximately one month later.  The third bronchoscopy was for research purposes 
only and did not include RheOx Bronchial Rheoplasty. Brushings and BALs were 
collected prior to any treatments being delivered in all bronchoscopy procedures for 
assessment of changes from pre to post-treatment. A physical exam, pulmonary 
function tests, six-minute walk test, EKG and Quality of Life questionnaires (i.e., CAT 
and SGRQ) were completed at screening/baseline and all post-treatment follow-up 
assessments (i.e., bronchoscopy #2, bronchoscopy #3, 6-months and 12-months). 
Additionally, a CT scan is taken at screening/baseline and again at 3 months post-
treatment Tx2.  
 
Table 1.2: Bronchoscopy Schedule 
Airway 
Bronchoscopy #1 
(Day 0) 
Bronchoscopy #2 
(Day 30) 
Bronchoscopy #3 
(Day 120) 
Right 
Treatment 
No Treatment 
Sample Collection 
Only 
Left 
No Treatment 
Treatment 
Sample Collection 
Only 
 

A total of 47 bronchoscopies were completed where the Gala therapy was 
administered; 25 in the right side airways and 22 in the left side airways.  The 
average age of the treatment patients was 66.3 years, ranging from 53 to 78, with a 
median 40 pack years smoking and FEV1 % predicted of 59 with a range of 30 to 
over 90%. The patients averaged 428 meters on the six-minute walk test (6MWT) at 
screening.  Despite the high 6MWT, the subjects still had severe symptoms of cough 
and mucus hypersecretion yet the impact on exercise performance was less 
pronounced, which may be indicative of this patient population. 
Data reported as of May 3, 2018 supports a favorable safety profile with no device-
related serious adverse events. There were no reported cases of sustained cardiac 
arrhythmias during or after the procedure.  The data also supports favorable clinical 
utility with an average CAT score improvement of approximately 8 points at 3 and 6 
months post-treatment. For reference, the Minimally Clinically Important Difference 
(MCID) is a reduction of 2 points.  Similarly, the average SGRQ score improved by 
nearly 20 points at 3 and 6-months post-treatment. For reference, the MCID is a 
reduction of 4 points. Based on these results further clinical study is warranted. 
2.0 
DEVICE DESCRIPTION 
2.1 
Device Identification 
RheOx™ 
Model: GTI-004-02 
2.2 
Device Manufacturer 
Gala Therapeutics, Inc. 
Menlo Park, California USA 
2.3 
Device Description 
2.3.1 Principles of Operation 
RheOx is designed to ablate abnormal mucus glands of the epithelium and reduce 
the mucus production of the submucosal glands.  Postoperatively, the therapy should 
allow for normal, healthy regeneration of the epithelium rather than a return to mucus 
hypersecretion. 
This device-based energy delivery system delivers high frequency short duration 
energy to the airway epithelium and submucosal tissue layers. By delivering energy 
to the mucus producing cells within these layers of the airway, mucus producing cell 
membranes become porous resulting in cell death.  The death of these cells reduces 
mucus hypersecretion within the airways.  This mechanism of inducing cell death is 
called Irreversible Electroporation (IRE).   IRE is a well-characterized ablation 
technology that creates an electric field with ultra-short, high voltage current that 
non-thermally kills cells but maintains the extracellular matrix.  IRE technology is 
commercially available and sold by Angiodynamics as the NanoKnife® Tissue 
Ablation System for the surgical ablation of soft tissue and is used for the treatment 
of various inoperable or difficult-to-reach tumors. 
2.3.2 Description of Components 
RheOx consists of two main components – a RheOx Generator (Figure 2.3.1) and a 
RheOx Catheter (Figure 2.3.2).  Accessories include a cable to connect the catheter 

to the generator, power supply cord, foot pedal, commercially available medical 
grade isolation transformer, and a data acquisition computer. 
 
 
 
Figure 2.3.1: RheOx Generator (Front Panel) 
 
 
 
 
Figure 2.3.2 (A): RheOx Catheter 
Figure 2.3.2 (B): Distal tip of RheOx 
Catheter.  These images illustrate how 
the electrode contact area changes with 
airway diameter. 
 
 
RheOx Generator.  The RheOx Generator is a transportable non-sterile electrical 
device compatible for use in a bronchoscopy suite or operating room environments.  
It consists of hardware, software, a display touch screen user interface, a power 
supply cord and a foot switch. The RheOx Generator power supply may be detached 
and provides the means to safely and reliably connect to and disconnect from the 
hospital electrical system.  It features controls to initiate and stop treatment as well 
as indicators to monitor the treatment and alert users. 
The RheOx Generator interfaces with a commercially available cardiac monitoring 
device, such as the Ivy, to ensure reliable energy delivery synchronization with the 
patient’s cardiac cycle thereby reducing risk of cardiac rhythm disturbances.  The 
Generator’s software algorithm tracks the cardiac cycle, only delivering energy 
during the S-T segment of a normal cardiac cycle.  The Generator creates high 

frequency short duration energy which is delivered to the airway cells via the RheOx 
Catheter. 
 
RheOx Catheter.   The RheOx Catheter is a sterile, single-use catheter designed for 
use by pulmonologists familiar with bronchoscopic techniques.  The Catheter is 
designed with a single monopolar electrode at the distal tip which when expanded 
via the handle mechanism contacts the airway wall to deliver the energy to the 
targeted location.  It is designed to treat airway diameters ranging from 5mm to 
18mm. 
 
 
 
Figure 2.3.3: The RheOx system depicted in the clinical setting.  The physician 
introduces the RheOx Catheter into the airway through a bronchoscope using standard 
bronchoscopic catheter techniques and then expands the electrode to contact the airway 
wall.  Using the foot pedal, the RheOx Generator is activated, and monopolar energy is 
delivered in conjunction with a commercially available dispersive electrode applied to the 
patient’s skin. The physician then moves the Catheter slightly up the airway to slightly 
overlap with the previous activation site and delivers the next energy pulse.  The 
procedure is repeated until all target airway sites have been treated. Each activation 
lasts approximately 5 seconds.  
The total number of activations is at the discretion of the treating physician in order to 
completely treat accessible airways in the designated treatment areas. The number of 
activations is dependent upon patient anatomy including airway diameter, airway length 
EKG leads from 
Cardiac Monitor to 
Patient 

and airway accessibility and typically range between 30 and 60 activations per lung. In 
some cases, bronchoscopists may be able to access more distal subsegmental airways, 
delivering additional activations occasionally totaling over 100 activations.  
2.4 
Intended Purpose and Study Population 
RheOx is an investigational device intended to reduce mucus production and cough 
in patients with chronic bronchitis. Patients with a smoking history of at least 10 pack 
years who are diagnosed with chronic bronchitis for a minimum of two years will be 
considered for inclusion in the study.   
The investigational device is to be used only in accordance with the approved 
Clinical Investigational Plan and IFU on subjects who have completed an informed 
consent form.  Device use is limited to approved study investigators who have 
completed the requisite procedure and device training. Additional detail on the 
training program can be found in Section 4.2. 
2.5 
Anticipated Changes During Investigation 
The feasibility of various components (e.g., ease of use) of the device system will be 
assessed during this clinical investigation.  Modifications to device components may 
be made by the study sponsor to optimize device performance. Any changes that 
impact therapy delivery or instructions for use of the device system shall be 
communicated by the Sponsor to the clinical investigator(s) prior to implementation. 
3.0 
STUDY OBJECTIVES 
3.1 
Study Objective 
Primary: To assess the safety of RheOx Bronchial Rheoplasty in patients with 
chronic bronchitis 
Secondary: To assess the clinical utility of RheOx Bronchial Rheoplasty in patients 
with chronic bronchitis 
3.2 
Outcome Measures 
3.2.1 Primary Outcome Measure:  Safety 
The primary outcome of the study is safety. The primary safety analysis will 
be the incidence of serious adverse events of interest through 12 months 
defined as the following; 
• 
Death 
• 
COPD exacerbation, as defined as an acute worsening in respiratory 
symptoms requiring additional therapy, that requires a hospital stay of 
greater than 24 hours 
• 
Pneumothorax within 2 days of either Gala Treatment procedure 
• 
Pneumonia within 7 days of either Gala Treatment procedure, as 
defined as an increase in respiratory symptoms, fever, sputum 
production and or purulence, with radiographic confirmation 
• 
Respiratory Failure as defined as a requirement for mechanical 
ventilatory support for > 24 hours 
• 
Arrhythmia requiring intervention or sustained (> 30 seconds) 
ventricular tachycardia 

 
3.2.2 Secondary Outcome Measure: Clinical Utility 
The secondary outcome measures of clinical utility will be assessed by: 
• 
The change from baseline at 6 and 12 months in St. George’s 
Respiratory Questionnaire (SGRQ) 
• 
The change from baseline at 6 and 12 months in COPD Assessment 
Test (CAT) 
• 
Hospitalization rates (not including the planned bronchoscopy 
procedures) discharge from the initial RheOx Bronchial Rheoplasty 
procedure (Visit 2) through 12 months 
3.2.3 Other Endpoints 
Other, tertiary and exploratory endpoints will also be assessed including 
changes from baseline to follow-up in;  
• 
Responder rates utilizing established clinically meaningful thresholds for 
SGRQ (4 points)17 and CAT (2 points)16 
• 
Change in other QOL measures including CASA-Q and EXACT-PRO 
• 
Change in lung function as measured by FEV1 and FVC  
• 
Change in sleep patterns as assessed by the Insomnia Sleep Index (ISI)  
• 
Change in cough count as assessed by a cough counting monitor 
• 
Mucin concentrations (MUC5AC, MUC5B) from induced sputum samples 
• 
Quantitative High Resolution CT Scan (HRCT) metrics including airway 
volume, total airway count, and lobar volumes 
• 
Device performance  
 
In addition to the endpoints described above, additional safety analyses in 
support of the primary study outcome and to assess the totality of safety 
profile of the RheOx Bronchial Rheoplasty, will be conducted. 
Adverse events reported from the day of the index procedure through 
completion or termination of the study will be assessed. AEs and SAEs will 
be summarized using a standard medical coding dictionary (MedDRA). AEs 
and SAEs will be also analyzed by severity, relatedness to the device and/or 
procedure and within discrete time periods relative to the index procedure.  
COPD exacerbations will also be analyzed by severity (mild, moderate, and 
severe) based on commonly accepted clinical definitions as defined in GOLD 
2018 Report18. 
 
4.0 
INVESTIGATIONAL SITES 
4.1 
Site Selection 
Clinical sites and investigators will be chosen to participate in this study based on 
their qualifications and experience including;   
• 
Expertise in the field of pulmonology and bronchoscopic techniques 
• 
Study staff with appropriate credentials and or experience to accommodate 
the needs of the study 

• 
Geographical location of site for representativeness 
• 
Clinical experience with other studies or devices for bronchoscopic use 
The site principal investigator is required to sign an Investigator’s Agreement prior to 
initiating the study.   
The study sponsor will maintain a listing of investigational sites and principal 
investigators, along with the names and addresses of all institutions where the 
investigation, or any part of the investigation, may be conducted.  The current listing 
will be made available to the FDA at least annually or upon request.  The study 
sponsor will also provide the FDA a with a list of all the IRB names and addresses 
and the associated IRB chairperson for each respective site. 
4.2 
Required Training 
All sites and study personnel will be required to undergo protocol training prior to 
participation in the study. Completed training shall be documented in the study file.  
Training will be conducted at the site initiation visit and as needed throughout the 
study to ensure proper execution of the protocol. It is the investigators responsibility 
to ensure proper training is administered and documented prior to delegation of any 
tasks to study staff. 
Gala will also provide training to the designated research staff on the proper use of 
RheOx. Device training will be in accordance with the approved device IFU and 
study training plan and consist of both didactic and hands on training modules. 
Procedures for collection of biologic samples (i.e. induced sputum) will also be 
reviewed during the training.  The training will supplement the information provided in 
the User’s Manual.  Training material will be provided to the site and stored for future 
reference in the study file or operational instructions binder. 
Gala representatives will be available in clinic during all treatment procedures to 
answer any questions and to support the clinician and designated research staff 
upon request. Additional training will also be available upon request if there is a 
change in staff, or if procedural difficulties that require additional training are 
identified during the course of the study.   
5.0 
STUDY DURATION 
This study is anticipated to be conducted over a six-year period encompassing site initiation 
and enrollment through completion of follow-up of the last enrolled patient.   
6.0 
SUBJECT ELIGIBILITY 
6.1 
Inclusion Criteria 
6.1.1 Subject is at least 40 years of age.  
6.1.2 Subject has had chronic bronchitis for a minimum of two years, where chronic 
bronchitis is defined clinically as chronic productive cough for three months in 
each of two successive years in a patient in whom other causes of productive 
cough have been excluded.   
6.1.3 Subject’s responses to the first two questions of the COPD Assessment Test 
(CAT) must sum to at least 7 points.  If the sum of the first two CAT questions 
is 6 points and the subject’s total CAT score is greater than 20 points, the 

subject may be enrolled.  The first two questions of the CAT questionnaire 
are as follows: 
“For each item below, place a mark (X) in the box that best describes you currently." 
 
 
 
6.1.4 Subject has a pre-procedure post-bronchodilator FEV1 percent predicted of 
greater than or equal to 30% and less than or equal to 80% within three 
months of enrollment.  
6.1.5 Subject has had 1 or more COPD exacerbations, defined as an acute 
worsening in respiratory symptoms that requires additional treatment, in the 
12-months prior to enrollment 
6.1.6 Subject has a SGRQ score of greater than or equal to 25 and CAT score of 
greater than or equal to 10. 
6.1.7 Subject has a cigarette smoking history of at least ten packs years. 
6.1.8 Subject is, in the opinion of the principal investigator, able to adhere to and 
undergo two bronchoscopies. 
6.1.9 Subject has provided signed informed consent. 
6.2 
Exclusion Criteria 
6.2.1 Subject has lower respiratory tract infection (e.g., pneumonia, mycobacterium 
avium-intracellulare infection (MAI), tuberculosis, or severe COPD 
exacerbation (as defined per GOLD 2018 guidelines18) within the six weeks 
prior to the initial treatment bronchoscopy or mild or moderate COPD 
exacerbation (per GOLD guidelines) within 4 weeks of the procedure. 
6.2.2 Subject is taking > 10 mg of prednisolone or prednisone per day. 
6.2.3 Subject has an implantable cardioverter defibrillator or pacemaker. 
6.2.4 Subject has a history of arrhythmia within past two years which include tachy-
atrial arrhythmias, any sustained ventricular tachy-arrhythmias, or sinus 
bradycardia with heart rate less than 45 beats per minute. 
6.2.5 Subject has history of unresolved lung cancer in last 5 years. 
6.2.6 Subject has bullous disease as defined by bullae exceeding 3 cm in diameter 
on HRCT. 
6.2.7 Subject has a pulmonary nodule or cavity that in the judgement of the 
investigator may require intervention during the course of the study. 
6.2.8 Subject has prior lung surgery, such as lung transplant, LVRS, lung 
implant/prosthesis, metal stent, valves, coils or bullectomy.  Prior 

pneumothorax without lung resection is acceptable. Pleural procedures 
without surgery are acceptable.  
6.2.9 Subject has emphysema of greater than or equal to 20% as quantified on 
baseline HRCT scan (low attenuation area less than -950HU). 
6.2.10 Subject has clinically significant cardiomyopathy. 
6.2.11 Subject has a change in FEV1 >12% (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. 
6.2.12 Subject has severe bronchiectasis as outlined in the report of the CT scan of 
the chest by the interpreting radiologist or in the view of the PI, those findings 
bronchiectasis or any other significant second lung disease, are the main 
drivers of the patient’s clinical symptoms. 
6.2.13 Subject actively smoked (including tobacco, marijuana, e-cigarettes, vaping, 
etc.) within the last 6 months. 
6.2.14 Subject has the inability to walk over 100 meters in 6 minutes. 
6.2.15 Subject has clinically significant serious medical conditions, such as: 
congestive heart failure, angina or myocardial infarction in the past year, 
renal failure, liver disease cerebrovascular accident within the past 6 months, 
uncontrolled diabetes, uncontrolled hypertension or autoimmune disease. 
6.2.16 Subject has uncontrolled GERD.   
6.2.17 Subject has severe pulmonary hypertension. 
6.2.18  Subject has a known sensitivity to medication required to perform 
bronchoscopy (such as lidocaine, atropine, and benzodiazepines). 
6.2.19 Subject is pregnant, nursing, or planning to get pregnant during study 
duration. 
6.2.20 Subject has received chemotherapy within the past 6 months or is expected 
to receive chemotherapy during participation in this study. 
6.2.21 Subject receive treatment in another clinical study within 6 weeks of baseline. 
6.2.22 Subject is on anticoagulation for cardiovascular indications and, at the 
discretion of the investigator, is unable to have anticoagulants (i.e., Aspirin, 
Plavix, Coumadin) withheld for the bronchoscopy procedure per institution’s 
standard of care. 
6.2.23 Subject has known airway colonization with resistant organisms, such as 
pseudomonas, methicillin-resistant Staphylococcus aureus (MRSA), 
Burkholderia cepacia complex, Mycobacterium Tuberculosis (MTB), 
Mycobacterium abscessus mucor or significant fungus. 
7.0 
STUDY PROCEDURES 
Figure 7.1 contains a flowchart of the study procedures. This research protocol does not 
require withholding or postponing any medically indicated customary health care.  Subjects 
will be carefully monitored during the course of the trial. If complications occur, the 
investigator will use good clinical judgment and administer all necessary clinical care. 
Note: 
Patients are considered enrolled in the study when informed consent is signed, all screening 
criteria have been met, and the first RheOx treatment activation is administered. 

Figure 7.1: Study Procedures 
  
 
 
 
 
Identify potential study subject. 
If subject appears qualified for study, obtain informed consent and complete medical history. 
Complete initial screening testing per Schedule of Activities. Exclude subject from study if the study 
inclusion criteria are not met or if any exclusion criteria is met. 
Within 90 days after screening, admit subject for investigational procedure. Obtain pre-op tests (see 
Schedule of Activities).   
Bronchoscopy #1 / Treatment Session #1.  Administer anesthesia in accordance with the institution’s 
standard protocol. Using bronchoscopy, visualize airways and complete BAL. Prior to energy delivery, 
record 6 second 3-lead EKG strip. Complete investigational therapy on right bronchial side in 
accordance with instructions for use. Recover subject and discharge when appropriate. 
1-week post- Bronchoscopy #1.  Complete physical examination and testing per Schedule of Activities.   
Pre-Bronchoscopy #2 Obtain pre-op tests (see Schedule of Activities).  
If any complications that preclude treatment, halt additional investigational therapy. If subject has not 
experienced any complication that precludes treatment, then prepare subject for second treatment 
session.  
1-month post- Bronchoscopy #2.  Complete physical examination and testing per Schedule of 
Activities. 
3 months, 6 months and 1, 2, 3, 4 and 5-years post- Bronchoscopy #2.  Complete physical examination 
and testing per Schedule of Activities.   
10 months post-Bronchoscopy #2.  Study coordinator / research nurse follows up with subject via 
phone call. 
Bronchoscopy #2 / Treatment Session #2. Administer anesthesia in accordance with the institution’s 
standard protocol. Using bronchoscopy, visualize airways and complete BAL. Prior to energy delivery, 
record 6 second 3-lead EKG strip. Complete investigational therapy on left bronchial side in 
accordance with instructions for use. Recover subject and discharge when appropriate. 
1-week post- Bronchoscopy #2.  Complete physical examination and testing per Schedule of 
Activities. 

 
7.1 
Treatment Plan 
Following screening and enrollment, subjects will undergo two bronchoscopic 
procedures (Visit 2 and Visit 4) both of which include treatment with the 
investigational device. Bronchoalveolar Lavage (BAL) will also be completed during 
the bronchoscopy prior to the initiation of RheOx treatment.  
Investigational treatment with RheOx will be administered to the right lung during 
bronchoscopy #1 (Visit 2) and to the left lung during bronchoscopy #2 (Visit 4).  Each 
activation will deliver 5 packets of electrical pulses synchronized with the cardiac 
cycle such that 1 packet is delivered with each cardiac cycle.   
The IVY cardiac monitor will be utilized to monitor cardiac activity during the RheOx 
Bronchial Rheoplasty in this study. The IVY will be set with heart rate alarm limits of 
less than 30 beats per minute (BPM) and greater than 130 BPM. Anesthesiologists 
assigned to the study will be trained on IVY alarm signal and its indication. 
Anesthesiologists will be instructed to use their best clinical judgement and follow 
standard of care procedure should the IVY monitor alarm during the bronchoscopy 
procedure.   
The total number of activations is at the discretion of the treating physician in order to 
completely treat accessible airways in the designated treatment areas. The number 
of activations is dependent upon patient anatomy including airway diameter, airway 
length and airway accessibility and typically range between 30 and 60 activations per 
lung. In some cases, bronchoscopists may be able to access more distal 
subsegmental airways, delivering additional activations occasionally totaling over 
100 activations.  
Note: 
A therapeutic bronchoscope having at least a 3.0 mm working channel, such as the 
Olympus model 1T180, is required for use with the RheOx Catheter. 
Specimen/fluid from the BAL is used to assess pathogens and cell composition in the 
airways as well as markers for inflammation.  Samples will be collected at each 
bronchoscopy and compared to determine whether any changes occur after the use 
of RheOx.  BAL instructions are included in the study operational instruction manual.  
7.2 
Description of Visits 
7.2.1 Visit #1. Screening and Enrollment 
Subjects who meet the eligibility criteria and have signed an informed 
consent form may be enrolled in the study.  Assessments performed 
exclusively to determine eligibility for this study will be done only after 
obtaining signed informed consent from the subject.  Assessment performed 
for clinical indications (i.e., not exclusively to determine study eligibility) may 
be used for screening evaluation even if the studies were completed before 
informed consent was obtained. 
 
All screening procedures must be completed within 90 days prior to start of 
study treatment.  

Note: If the subject experiences a COPD exacerbation or other change in 
functional status between screening and the first bronchoscopy, screening 
procedures should be repeated as appropriate at the investigator’s discretion. 
Refer to the Table 7.1 Schedule of Events for listing of required screening 
procedures. 
 
General Screening Notes: 
High Resolution CT Scan 
High resolution computed tomography (HRCT) is incorporated as a tool to 
define subject inclusion criteria and to assess post treatment changes. CT 
acquisition will be per the CT Core Manual provided separately to each site 
upon completion of training by the designated CT core lab for this study. 
 
7.2.2 Visit #2. Bronchoscopy #1 / Treatment Session #1 
Eligible subjects are scheduled for the first bronchoscopy and treatment 
session within 90 days of completing screening procedures. Pre-operative 
procedures (e.g., physical exam, complete blood count) are completed in 
accordance with the Schedule of Events table prior to the bronchoscopy.   
Note:  Pre and post-bronchoscopy care (including medications) should be 
administered at the discretion of the treating physician per the institution’s 
standard of care.  
Upon successful completion of the preoperative procedures, the subject 
undergoes a bronchoscopy procedure in accordance with standard 
institutional protocol.  Anesthesia is administered.  The airways are 
visualized, and BAL completed.  If any complications that preclude continued 
participation in the study are revealed, then the treatment is halted. If subject 
has not experienced any complications that precludes continued participation 
in the study, then RheOx therapy is administered to the target sites in the 
right lung in accordance with the instructions for use.  The clinical investigator 
ensures FiO2 does not exceed 40% during energy delivery. Prior to the 
initiation of energy delivery and during at least one energy delivery a 6 
second 3 lead EKG strip is recorded.  An EKG rhythm strip from anesthesia 
monitoring is adequate.  
The subject is recovered in accordance with standard institutional 
procedures. The study investigator determines whether an overnight stay is 
clinically warranted, and the subject is discharged at the investigator’s 
discretion.   Any observed adverse events are reported accordingly.   
Note:  Subjects may be excluded or treatment delayed at the investigator’s 
discretion if the patient has an active respiratory infection (e.g., common cold, 
pneumonia, MAI), COPD exacerbation or any other significant adverse event 
that may compromise the procedure.  
Likewise, if at the time of the scheduled procedure the study physician 
determines the patient has clinical signs or findings (i.e., pulmonary nodule 
requiring follow-up, abnormal cardiac rhythm) that may adversely impact the 

safety of the procedure, the procedure will be postponed pending treatment 
of the condition and reassessment of the patient.  
7.2.3 Visit #3.  1-week Follow-up Visit 
Subjects are scheduled for follow-up one week (7 days ± 3 days) following 
Bronchoscopy #1.  The visit will include a physical exam and assessment of 
AEs and medications in accordance with the Schedule of Events table.  
7.2.4 Visit #4. Bronchoscopy #2 / Treatment Session #2 
Subjects are scheduled for follow-up 3-6 weeks following Bronchoscopy #1.  
Pre-operative procedures (e.g. CT Scan, physical exam, CBC) are completed 
in accordance with the Schedule of Events table prior to the bronchoscopy.  
Any observed adverse events are reported accordingly.  If the subject has 
experienced any complications that preclude continued participation in the 
study, then additional treatment is halted.  
Upon successful completion of the pre-operative procedures, the subject 
undergoes a bronchoscopy procedure in accordance with standard 
institutional protocol.  Anesthesia is administered.  The airways are 
visualized, and BAL completed.  The RheOx Bronchial Rheoplasty is 
administered to the target sites in the left side lung in accordance with the 
instructions for use.  The clinical investigator ensures FiO2 does not exceed 
40% during energy delivery.  Prior to the initiation of energy delivery and 
during at least one energy delivery a 6 second 3 lead EKG strip is recorded. 
An EKG rhythm strip from anesthesia monitoring is adequate.  
The subject is recovered in accordance with standard institutional procedures 
and observed overnight at the discretion of the study investigator.  The 
subject is then discharged at the investigator’s discretion.  Any observed 
adverse events are reported accordingly. 
Note: Bronchoscopy #2 may be delayed or halted at the investigator’s 
discretion if the patient has an active respiratory infection (e.g., common cold, 
pneumonia, MAI), COPD exacerbation since treatment session #1 or any 
other significant clinical symptom that may compromise the procedure.   
7.2.5 Visit #5.  1-week Follow-up 
Subjects are scheduled for follow-up one week (7 days ± 3 days) following 
Bronchoscopy #2.  The visit will include a physical exam and assessment of 
AEs and medications.  
7.2.6 Visit #6.  1-month Follow-up 
Subjects are scheduled for follow-up one month (1 month ± 7 days) following 
Bronchoscopy #2.  The visit will include a physical exam and assessment of 
AEs and medications. 

7.2.7 Visits #7 In-office Follow-up Visit (3 months post Bronchoscopy # 2) 
Subjects will return for follow-up visits at 3 months ± 2 weeks after 
Bronchoscopy #2 (Visit 4).    Refer to the Schedule of Events table for a 
complete listing of required tests. 
7.2.8 Visits #8 In-office Follow-up Visit (6 months post Bronchoscopy # 2) 
Subjects will return for follow-up visits at 6 months ± 4 weeks after 
Bronchoscopy #2 (Visit 4). A CT Scan will be performed as part of this visit. 
Refer to the Schedule of Events table for a complete listing of required tests. 
7.2.9 Visit # 9 Phone Call Visit (10 months post Bronchoscopy # 2) 
The study coordinator / research nurse calls the subject on the telephone 10 
months ± 2 weeks. Any adverse events or changes in medication are 
reported accordingly. A study visit may be scheduled if clinically warranted. 
7.2.10 Visits # 10, 11, 12, 13 and 14 In-office Follow-up Visits (Annual Follow-up 
post Bronchoscopy # 2)  
Subjects will return for follow-up visits at 12 months ± 4 weeks after 
Bronchoscopy #2 (Visit 4) and annually thereafter for 5 years (± 4 weeks). 
Refer to the Schedule of Events table for a complete listing of required tests. 
 
Note: If the subject experiences a COPD exacerbation or other change in functional status 
within 6 weeks of any scheduled follow-up visit, the investigator should consider 
rescheduling study follow-up visits based on his or her best medical judgement to allow for a 
true assessment of the patient’s stable condition once the subjects symptoms have returned 
to normal. It is recommended that subjects return to clinical baseline for a minimum of two-
weeks prior to undergoing study specific follow-up testing. 
 
7.3 
Concomitant Medications / Treatments 
Subjects should be treated for COPD before enrollment according to the appropriate 
ATS guidelines at the discretion of the study investigator and will remain on current 
(pre-investigational treatment) bronchitis/COPD medications (e.g., long-acting 
bronchodilators (LABA), long-acting muscarinic antagonists (LAMA), inhaled 
corticosteroids (ICS)) through the 1-year evaluation unless adjustment is deemed 
appropriate or medically necessary by the study investigator.  Effort should be made 
to hold dosing constant.  
Subjects who are treated with more than 10 mg oral corticosteroids (prednisolone/ 
prednisone) daily are excluded.   Patients treated with oral corticosteroids 
(prednisolone/ prednisone) ≤ 10mg per day may be enrolled in the study. Pre-
procedural, peri-procedural or post-treatment corticosteroids (IV or oral) may be 
administered if medically necessary at the discretion of the study investigator. 
If applicable, it is recommended subjects temporarily stop taking anticoagulants (e.g., 
warfarin, Xarelto) prior to each bronchoscopy, as directed by the study investigator.  
Aspirin may be taken at the discretion of the study investigator.  
Perioperative antibiotics are not recommended unless deemed medically necessary 
by the study investigator.  If necessary, a non-macrolide antibiotic (e.g., Cipro, 
Augmentin) is preferred. 

 
 

7.4 
Schedule of Events (Table 7.1) 
Table 7.1: Schedule of Events 
 
Visit #1: Screening
Visit #2: Bronchoscopy #1
Visit #3: Follow-up 
1 week Post-Bronchscopy #1
Visit #4: Bronchoscopy #2
Visit #5: Follow-up 
1 week Post-Bronchoscopy #2
Visit #6: Follow-up 
1 month Post-Bronchscopy #2
Visit #7: Follow-up 
3 month Post-Bronchscopy #2
Visit #8: Follow-up
6 month Post-Bronchscopy #2 
Visit #9: Follow-up Phone Call
10 month Post-Bronchscopy #2
Visit #10-14: Annual Follow-up
1 - 5 years Post-Bronchscopy #2
Window
± 3 days -3 to +6 weeks ± 3 days ± 7 days ± 2 weeks ± 4 weeks ± 2 weeks ± 4 weeks
Informed Consent
X
Inclusion/Exclusion Criteria
X
Medical History
X
Exacerbations History
X
X
X
X
X
X
X
X
X
X
Concomitant Meds
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
Physical Exam
X
X1
X
X1
X
X
X
X
X
CBC & Blood Panel
X
X1
X1
X
X
X
Cotinine Test
X
EKG
X
X4
X4
X
X
X
Spirometry
X
X1
X
X
X
DLCO/Body Pleth
X
X1
X
X
X
Six Minute Walk Test
X
CT Scan
X
X1
X
Bronchoscopy 
X
X
Bronchoalveolar lavage
X
X
RheOx Bronchial Rheoplasty
X
X
Induced Sputum Sample
X
X
X
X
SGRQ
X
X1
X
X
X
CAT Score
X
X1
X
X
X
CASA-Q
X
X1
X
X
X
ISI5
X
X1
X
X
X
Cough Counting Monitor6
X
X
X
X7
EXACT-PRO8
X
Note 1:
Note 2:
Note 3:
Note 4:
Note 5:
Note 6:
Note 7:
Note 8:
12-month visit only
In this study, VitaloJAK cough monitor is an exploratory outcome measure. Patients willing to 
participate are encouraged to wear the 24 hour cough monitor at the 4 visits specified, but it is not 
mandatory.
DAILY
In this study, EXACT-PRO is an exploratory outcome measure to quantify and measure exacerbations of 
COPD.  Patients are encouraged to complete the questionnaire daily during the first year (up to Visit 
#10), but it is not mandatory. Daily patient compliance will not be a reason for removal from the study.
Adverse Events are noted before and after bronchscopy.
Noted activities are completed prior to bronchoscopy.
Overnight Hospital Stay at discretion of PI
An EKG is recorded prior to the initiation of RheOx procedure and during at least one energy delivery; 
anesthesia EKG may be used.
Subjects with clinically significant insomnia at baseline as defined by a ISI score of > 8 points21, may be 
asked to complete optional polysomnography testing at baseline and 3-months follow-up. 

  
Additional Notes on Schedule of Events: 
Note: If Bronchoscopy #2 cannot be completed the subject should continue follow-up 
at 3 months, 6 months, 12 months and annually through 5 years following 
Bronchoscopy #1 (i.e., last treatment session). 
Note: If the subject experiences a COPD exacerbation or other change in functional 
status within 6 weeks of any scheduled follow-up visit, the investigator should 
consider rescheduling study follow-up visits based on his or her best medical 
judgement  to allow for an accurate assessment of the patient’s stable condition once 
the subjects symptoms have returned to normal. It is recommended that subjects 
return to clinical baseline for a minimum of two-weeks prior to undergoing study 
specific follow-up testing. 
7.5 
Removal of Subjects 
Subjects may be taken off the study treatment and/or removed from the study at any 
time at their own request. Subjects may also be withdrawn at the discretion of the 
investigator for safety, behavioral (e.g., subject not compliant with study treatment for 
more than two continuous weeks) or administrative reasons.   
The reason(s) for discontinuation will be documented on the End of Study eCRF. 
Reasons for withdrawal may include: 
• 
Patient voluntarily withdraws from treatment (follow-up permitted); 
• 
Patient withdraws consent (termination of treatment and follow-up); 
• 
Patient is unable to comply with protocol requirements; 
• 
Patient experiences adverse reaction that makes continuation in the protocol 
unsafe; 
• 
Investigator determines continuation on the study would not be in the 
patient’s best interest; 
• 
Patient becomes pregnant during treatment period; 
• 
Patient is lost to follow-up.  
7.6 
Early Termination or Suspension of Study  
7.6.1 Study Stopping Rules 
Study enrollment and further treatment of any subject will be halted if any of 
the following serious adverse events are observed in a given subject; 
 
• 
Death associated with the study investigational therapy or procedure 
• 
Three or more subjects with a pneumothorax within 2 days of either 
Gala Treatment procedure 
• 
Device related arrhythmias requiring cardioversion or sustained VT 
regardless of intervention 
• 
Acute pulmonary hemorrhage requiring surgical intervention or 
embolization 
• 
Unanticipated adverse device effect 
 
The study may not resume enrollment until the study medical monitor, the 
sponsor and principal investigator have reviewed the observation and events 

surrounding the observation to determine if the study should be halted or may 
continue. 
7.6.2 Interim Safety Analysis 
In addition to the study stopping rules, an interim safety analysis will be 
conducted after 5 subjects complete the second treatment (Visit 4) to ensure 
it is safe to continue study treatments. Enrollments and planned study 
visits/treatments should continue per the study protocol while the interim 
analysis is being conducted. The interim analysis will consist of a review of all 
AE and SAE data collected in the study at that point including an assessment 
of device and procedure relatedness. The data will be reviewed by the study 
medical monitor and a subcommittee of three Gala Therapeutics Scientific 
Advisory Board members, composed of experts in chronic bronchitis and 
interventional bronchoscopy procedures to ensure it is safe to continue the 
study. Patient demographics and procedural characteristics will also be 
included in the review. The review should confirm that the safety profile of the 
study is consistent with expectations set forth at the start of the study. 
Recommendations may include: 
1. Continue the study without modification  
2. Continue the study with modification or  
3. Terminate the study 
8.0 
STATISTICAL CONSIDERATIONS 
8.1 
Study Design 
This is a prospective, single arm feasibility study of RheOx in patients with chronic 
bronchitis.  Neither subjects nor investigators will be blinded.   
8.2 
Sample Size 
As this is an early feasibility study, up to 30 subjects will be enrolled and treated with 
the study device to assess the effect of the investigational device in the target 
population.  
8.3 
Evaluable Cohort 
All subjects who have entered the treatment room for Visit #2 will be included in the 
safety endpoint analysis (Safety Population). Subjects who have received at least 
one treatment will be included in the evaluable cohort for clinical utility.   
8.4 
Outcome Analysis 
Descriptive statistics will be utilized to summarize and report on data for all 
subject and outcome variables. Categorical data (e.g., age, gender) will be 
reported in frequency distributions. Certain dichotomous data (e.g., subjects with 
Serious Adverse Events) will also be presented as rates. Continuous data (e.g., 
age, FEV1) will be summarized using mean, standard deviations, medians, 
minimums, maximums, and interquartile ranges. Additional subgroup and other 
multivariable analyses may be performed including examination of the 
association between subject risk factors (e.g., age, gender) and trial outcomes, 
and the potential contributions of these factors.  

9.0 
DATA MANAGEMENT 
9.1 
Data Entry 
Source documents shall be maintained by the investigational sites throughout the 
course of the investigation. All findings in this investigation must be documented as 
source data, and therefore can be verified and audited. Source documentation may 
be paper or electronic and is defined as the first time the data appears and may 
include for example; all questionnaires, phone interview notes, clinical records, 
hospital records, surgery reports, death/autopsy reports, and any other material that 
contains original information used for clinical study data collection or adverse event 
reporting. It should be possible to verify the inclusion and exclusion criteria for the 
investigation from available source data. Source documents must include the subject 
identification number and a date. 
Data obtained from each subject during the clinical trial will be entered in the 
electronic data capture (EDC) database within five working days of the report date.  
All applicable sections of the EDC case report forms (eCRFs) must be filled out 
completely. The EDC system and associated data collected over the course of the 
study will be managed per the approved study Data Management Plan.  
9.2 
Subject Data Protection 
Upon enrollment in the study, each subject will be assigned a unique identifier in 
accordance with GCP.  Subject data will be recorded using the unique identifier.  The 
subject’s name or any other identifying label will not be recorded on the CRFs.   
In accordance with applicable regulations (e.g., HIPAA), subjects who have provided 
written informed consent must also sign a subject authorization to release medical 
information to the study sponsor and/or their representatives and allow regulatory 
authorities such as FDA access to subject’s medical information relevant to the 
study. 
9.3 
Data Retention 
Study documentation includes all CRFs, data correction forms or queries, source 
documents, correspondence, monitoring logs and letters, and regulatory documents 
(e.g., CIP and amendments, IRB correspondence and approval, signed patient 
consent forms).  Source documents include all recordings of observations or 
notations of clinical activities and all reports necessary for the evaluation and 
reconstruction of the clinical research study.   
The study sponsor or investigator(s) must retain all study documentation pertaining 
to the conduct of the study in accordance with applicable regulations.  These 
documents shall be retained during this investigation and for a period of at least two 
years after the later of the following two dates: the date on which the investigation is 
terminated or completed, or the date of the last approval of marketing application in 
an ICH region. 
9.4 
Monitoring 
The Sponsor, or designee, will monitor the clinical investigation in accordance with 
GCP and all applicable regulations.  The Monitor must ensure that the investigation 
is conducted in accordance with the signed Investigator Agreement, the Clinical 
Investigational Plan, any conditions imposed by the IRB, and applicable regulations. 

Monitoring intervals will occur as described in the clinical monitoring plan.  The 
Monitor will notify the Sponsor within 24 hours upon becoming aware of any UADE 
not previously reported to the Sponsor. In the event the investigator is not complying 
with the study requirements, it is the Sponsor’s responsibility to secure compliance. 
10.0 
ADVERSE EVENTS 
10.1 
Reporting Requirements  
10.1.1 Adverse Events 
Adverse events will be reported on the adverse event eCRF. All adverse events will 
be graded according to Medical Dictionary for Regulatory Activities (MedDRA).   
Adequate information related to the adverse event must be supplied to the Sponsor 
to determine whether the adverse event is related to use of the investigational 
device.  The study investigator should assess to the best of their ability relatedness 
of each AE to the study device and study procedure(s) according to the following 
categories; not related, possibly related, and probably related.  
AE severity is assessed by the study investigator and recorded on the AE eCRF 
according to the following definitions; 
• 
Mild (Grade 1): the event causes discomfort without disruption of normal daily 
activities. 
• 
Moderate (Grade 2): the event causes discomfort that affects normal daily 
activities. 
• 
Severe (Grade 3): the event makes the patient unable to perform normal daily 
activities or significantly affects his/her clinical status. 
• 
Life-threatening (Grade 4): the patient was at risk of death at the time of the 
event. 
• 
Fatal (Grade 5): the event caused death. 
 
AEs collected over the course of the study will be regularly monitored by the study 
medical monitor and/or other company representatives or consultant advisors (if 
deemed necessary) to ensure the ongoing safety of the study. 
 
10.1.2 Serious Adverse Events 
All serious adverse events must be reported to the Sponsor within 24 hours after the 
investigator first learns of the event, regardless of presumed relationship to the 
device or trial.  In addition, the investigator and the Sponsor will comply with IRB and 
FDA reporting requirements, inclusive of reporting requirements defined in 21 CFR 
812.150. 
 
10.1.3 Unanticipated Adverse Device Effect 
An investigator shall submit to the sponsor a report of any unanticipated adverse 
device effect occurring during an investigation as soon as possible, but in no event 
later than 10 working days after the investigator first learns of the effect. 
Reports relating to the patient's subsequent medical course must be submitted to the 
Sponsor via the study eCRFs until the event has subsided or, in case of permanent 

impairment, until the event stabilizes, and the overall clinical outcome has been 
ascertained.  For reported deaths, the investigator should supply the Sponsor and 
the IRB with any additional requested information (e.g., autopsy reports and terminal 
medical reports). 
 
The Sponsor is responsible for reporting all serious and unexpected adverse device 
effects to FDA in an expedited manner, and in accordance with all applicable federal 
regulations.   The Sponsor will expedite the reporting in compliance with ICH GCP to 
all concerned investigators.  The investigator will report to the IRB in accordance with 
institutional requirements, but no later than 7 calendar days of first knowledge.   
10.2 
List of foreseeable adverse events related to investigational therapy and/or study 
procedure: 
 
• 
Sore throat (likely occurrence) 
• 
Coughing (likely occurrence) 
• 
Hemoptysis (likely occurrence) 
• 
Minor complications associated with anesthesia (moderate likely occurrence) 
including nausea, vomiting, bruising at the site of injections, sore throat or 
hoarse voice, urinary retention 
• 
Infection (moderately likely occurrence) including fever, pain or soreness  
• 
Exacerbation (moderately likely occurrence) including shortness of breath, 
increased color and/or quantity of phlegm 
• 
Bronchial perforation (low occurrence) 
• 
Lung abscess (low occurrence) 
• 
Gastroparesis (low occurrence) 
• 
Pneumothorax (low occurrence) including severe chest pain, trouble 
breathing, death 
• 
Airway stenosis (low occurrence) including wheezing, hoarseness, shortness 
of breath and/or respiratory distress 
• 
Abnormal cardiac rhythm function (low occurrence) including arrhythmia, 
atrial fibrillation, ventricular fibrillation, death 
• 
Allergic reaction (low occurrence) including abnormal breathing, difficulty 
swallowing, anxiety, chest pain, severe cough, lightheadedness or dizziness, 
sweating or fainting, swelling of the face, eyes or tongue 
• 
Significant pulmonary bleeding (low occurrence) 
• 
Significant complications associated with anesthesia (low occurrence) 
including damage to teeth, aspiration, respiratory failure, brain damage, and 
death 
• 
Death (low occurrence) 
 
Note: Likely occurrence is estimated to occur in more than 1 in 2 patients. 
Moderately likely occurrence is estimated to occur in 1 in 10 to 1 in 100 patients. Low 
occurrence is estimated to occur in less than 1 in 100 patients. 
 

11.0 
RISK-BENEFIT ASSESSMENT 
11.1 
Anticipated Risks 
Refer to section 10.2 of this protocol for a detailed listing of potential risks (i.e., 
adverse events) of this clinical investigation.  This protocol does not withhold or 
postpone any medically necessary treatment.  If any complications are experienced, 
the study investigator will use good clinical judgment in the treatment of adverse 
events. 
Based on prior literature, and preclinical and clinical studies completed, RheOx is 
expected to be safe for use in this clinical study.   
As this is a feasibility study, unanticipated events may occur, however, every effort 
will be undertaken to ensure risks are minimized. The study is designed with a 
conservative, step-wise approach to treating each subject.  Patients will be first 
treated in only the right airways and fully recovered for 30 days to allow for sufficient 
healing.  The right airways will be visualized and assessed prior to further treatment 
on the left side.  If the subject has experienced any complications that preclude 
continued participation in the study, then additional treatment is halted. 
The study also has a planned interim analysis and stopping rules, discussed earlier, 
to ensure safety concerns are addressed throughout the study.  
11.2 
Anticipated Benefits 
Gala’s Chief Medical Officer, the Scientific Advisory Board (SAB) and the study 
Investigators have determined that this research study is justified because the overall 
potential benefit to the population outweighs its attendant risks. If the investigational 
treatment is successful, participating subjects may experience a reduction in 
symptoms, an improved quality of life and potentially reduced exacerbations 
associated with chronic bronchitis. All subjects will be symptomatic at baseline (per 
the study inclusion criteria), despite standard of care pharmacotherapy. Thus, 
additional benefit from the treatment may reduce the burden of disease on the 
healthcare system. Additionally, results of this study may lead to further development 
of a new, minimally invasive therapy, RheOx, which could lead to an alternative 
therapy to chronic bronchitis. 
12.0 
STUDY MANAGEMENT 
12.1 
Statement of Compliance 
The study will be conducted in accordance with applicable regulations for clinical 
research, 21 CFR Part 812, ISO 14155, the ICH guidelines for good clinical practice 
and company standard operating procedures (SOPs).  The study will be registered 
on www.clinicaltrials.gov. 
12.2 
Institutional Review Board (IRB) 
The clinical investigational plan and site informed consent must be approved by the 
IRB for the given institution prior to any study-related activity.  The investigator is 
responsible for complying with all applicable requirements established by the IRB. 
 
The study sponsor will maintain a list of the names, addresses, and chairpersons of 
all IRBs that have or will be asked to review the investigation and a certification of 
IRB action concerning the investigation (when available). 

12.3 
Investigator Responsibilities 
The Principal Investigator is responsible for ensuring that the clinical investigation is 
conducted according to the Investigator Agreement, this study protocol, the Clinical 
Trial Agreement, all applicable federal and local regulations, and any conditions of 
approval imposed by the reviewing IRB and/or FDA.  
The Principal Investigator shall: 
• 
Indicate acceptance of this study protocol in writing by signing the Investigator 
Signature page of this study protocol and any applicable amendments; 
• 
Conduct this study in compliance with this study protocol and any applicable 
amendments; 
• 
Create and maintain adequate source documentation throughout this study and 
make source documentation available as requested for monitoring visits or 
audits; 
• 
Ensure the investigational device is used solely by authorized users at the site;  
• 
Ensure the investigational device is used in accordance with this study protocol 
and product labeling; 
• 
Refrain from implementing any modifications to this study protocol without 
agreement from Gala, the applicable IRB, and national regulatory authority as 
required;  
• 
Promptly document and explain any deviation from the approved study protocol 
during the course of this study; 
• 
Ensure the investigational site has an adequate staff, resources and training, and 
document delegations of duties throughout the study; 
• 
Ensure study staff members have document study protocol training; 
• 
Ensure adequate facilities exist and are maintained during this study; 
• 
Ensure that maintenance and calibration of all equipment relevant to the clinical 
investigation is appropriately performed and documented as requested; 
• 
Ensure the accuracy, completeness, legibility, and timeliness of all data reported 
to Gala (including source documentation as well as CRFs);  
• 
Maintain accurate and complete device accountability records; 
• 
Allow and participate monitoring and auditing activities as requested; 
• 
Allow and participate in FDA inspection activities; 
• 
Ensure all study-related records are retained as required; and 
• 
Ensure accurate and timely preparation of reports required by applicable 
regulations. 
 
Gala retains the right to terminate participating investigational sites for failure to 
comply with investigator responsibilities, or requirements imposed by applicable IRBs 
and the FDA.   
12.4 
Study Initiation 
Prior to the initiation of the clinical investigation, the qualifications of the site Principal 
Investigator and staff, and adequacy of the clinical investigation sites shall be verified 
and documented. Prior to initiating patient enrollment at the investigational site, Gala 

will conduct a Site Initiation Visit inclusive of training on the clinical investigation plan 
and operation of the device and procedure for the Principal Investigator and research 
staff.  Study enrollment may not begin until the site receives notification that it has 
been activated by Gala and has received IRB approvals and completed SIV training. 
12.5 
Amendments to the Clinical Investigational Plan (CIP) 
All amendments to the CIP will be agreed upon between the Sponsor and the clinical 
investigator(s) and will be recorded with a justification for the changes. The 
investigator is responsible for submitting all amendments of the CIP to their IRB in 
accordance with IRB procedures. 
The study may be amended to expand the study to include additional subjects and/or 
longer therapy periods (i.e., > 6 months) if subjects are positively responding to the 
investigational therapy. 
12.6 
Deviations from the Clinical Investigational Plan 
Protocol deviations should be avoided unless deemed necessary by the investigator 
to protect the life or physical well-being of a subject in an emergency. The site 
principal investigator shall notify the sponsor and the reviewing IRB of any deviation 
from the investigational plan 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 5 working days after the emergency occurred.  
All deviations from the approved CIP should be documented in the study file and 
reported to IRB as necessary per governing IRB policy and in accordance with 
§812.35(a).  Except in an emergency, the sponsor should be made aware if any 
deviation from the CIP is anticipated that may affect the scientific soundness of the 
CIP or the rights, safety, or welfare of human subjects  
All study variances will be reviewed by the Medical Monitor and study sponsor to 
determine the need to amend the CIP or to terminate the investigation.   
12.7 
Informed Consent Process 
The investigator is responsible for obtaining and documenting informed consent from 
each participating subject in accordance with applicable regulatory requirements and 
the institution’s procedures for clinical research.  Informed consent should adhere to 
GCP and to ethical principles that have their origin in the Declaration of Helsinki.  
Only an IRB-approved ICF for this CIP may be used to document a subject’s 
consent. 
12.8 
Device Accountability 
Upon receipt of investigational products from the study sponsor, the Investigator is 
responsible for accountability of the investigational devices in accordance with 
applicable regulations.  A device accountability log will be used to track device 
receipt, use, and return/disposal of the devices.   
Study device should be stored in a secure environment with access provided only to 
key study personnel who have the appropriate authorization. It is investigator’s 
responsibility to ensure that the study device is used only for study subjects under 
PI’s personal supervision or under the supervision of a properly trained sub-
Investigator.  Study Device Accountability Log should be updated every time a 
device is received at the site, used in a subject, disposed of or returned to the 

sponsor. During the study, devices that are intended to be disposable (e. g. catheter) 
may be disposed of at the site or returned to the study sponsor if requested.   
Monitors will routinely verify that investigational product documentation is accurate 
and complete throughout the study including at the close-out visit. 
The investigator must return unused devices to the sponsor at study completion, 
closing of the study site, or as requested by the sponsor.  
12.9 
Publication Policy 
Any proposed publication or presentation (including a manuscript, abstract or poster) 
will be published, or submitted for publication, in accordance with the terms of the 
Clinical Trial Agreement. 
 

13.0 
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