Conditions: Idiopathic Pulmonary Fibrosis (IPF)
Keywords: TD139 Idiopathic pulmonary fibrosis Galectin-3 inhibitor GB0139
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 172
Healthy volunteers: no

Brief summary:
This is a randomized, double-blind, placebo-controlled phase 2b trial in subjects with IPF (idiopathic pulmonary fibrosis) investigating the efficacy and safety of GB0139.

Detailed description:
This study is designed to evaluate the efficacy and safety of GB0139, a galectin-3 inhibitor, administered by dry powder inhalation over 52 weeks. GB0139, given once per day, will be compared to placebo. GB0139 was previously known as TD139.

Arms:
arm 1: Inhalation of GB0139 arm 2: Inhalation of Placebo

Interventions: intervention 1: GB0139 intervention 2: Placebo
Intervention descriptions: intervention 1: GB0139 is a galectin-3 inhibitor designed to modulate the fibrogenic response to tissue injury. It is administered as inhalation once a day. intervention 2: Placebo is administered as inhalation once a day

Protocol document:
Prot_000.pdf: 
Galecto Biotech AB
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Galecto Biotech AB 
STUDY PROTOCOL
GALACTIC-1 - A randomized, double-blind, multicentre, parallel, placebo-controlled 
Phase 2b study in subjects with idiopathic pulmonary fibrosis (IPF) investigating the 
efficacy and safety of GB0139, an inhaled galectin-3 inhibitor administered via a dry 
powder inhaler over 52 weeks
Sponsor:
Galecto Biotech AB, Ole Maaloes Vej 3, DK-2200 Copenhagen, 
Denmark
Study Number:
GALACTIC-1
IND Number:
124075
EudraCT Number: 
2018-002664-73
Compound:
Authors:
GB0139
Jie Wang, Bertil E. Lindmark, De Phung, Rob Slack, Catherine 
McClinton, Alison MacKinnon, Lise Gravelle, Bill Russell, Agusta 
Gudjonsdottir, Hans Schambye
Version:
Date:
7.1_UK
28 January 2022
CONFIDENTIAL PROPERTY OF GALECTO BIOTECH AB
This document is a confidential communication of Galecto Biotech AB. Acceptance of this document 
constitutes the agreement by the recipient that no information contained herein will be published or disclosed 
without written authorization from Galecto Biotech AB except to the extent necessary to obtain informed 
consent from those persons to whom the drug may be administered. Furthermore, the information is only meant 
for review and compliance by the recipient, his or her staff, and applicable institutional review committee and 
regulatory agencies to enable conduct of the study.


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1.0
ADMINISTRATIVE 
Contacts 
A separate contact information list will be provided to each site.
Contact Type/Role
Europe
Contact
USA
Contact
Serious adverse 
event and pregnancy 
reporting
See Section 11.0
See Section 11.0
Medical Monitor
Dr Karina Avakova, MD, PhD
Moscow, RUSSIA
Dr Peter G. Polos,
MD, PhD, FCCP, FAASM
301 College Road East Princeton, New 
Jersey, USA 08540
Responsible Medical 
Officer 
Prof. Bertil E. Lindmark MD, 
PhD
Chief Medical Officer
Galecto Biotech AB,
Ole Maaloes Vej 3,
DK-2200 Copenhagen
Denmark
Prof. Bertil E. Lindmark MD, PhD
Chief Medical Officer
Galecto Biotech AB,
Ole Maaloes Vej 3,
DK-2200 Copenhagen
Denmark
1.1


28 January 2022


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INVESTIGATOR AGREEMENT 
I confirm that I have read and that I understand this protocol, package insert, and any other 
product information provided by the sponsor. I agree to conduct this study in accordance with 
the requirements of this protocol and also to protect the rights, safety, privacy, and well-being 
of study subjects in accordance with the following:

The ethical principles that have their origin in the Declaration of Helsinki.

International Conference on Harmonisation, E6 Good Clinical Practice: Consolidated 
Guideline.

All applicable laws and regulations, including, without limitation, data privacy laws and 
regulations.

Regulatory requirements for reporting serious adverse events defined in Section 11.2 of 
this protocol.

Terms outlined in the Clinical Study Site Agreement.

Responsibilities of the Investigator (A).
Signature of Investigator
Date
Investigator Name (print or type)
Investigator’s Title
Location of Facility (City, State/Provence)
Location of Facility (Country)


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TABLE OF CONTENTS
1.0
ADMINISTRATIVE............................................................................................2
Contacts..........................................................................................................2
Approval.........................................................................................................3
2.0
PROTOCOL SUMMARY..................................................................................10
Study Synopsis .............................................................................................10
Study Time and Events Schedule..................................................................15
3.0
STUDY REFERENCE INFORMATION ...........................................................17
Study-Related Responsibilities......................................................................17
Principal Investigator/Principal Coordinator .................................................17
List of Abbreviations ....................................................................................18
4.0
INTRODUCTION..............................................................................................20
Study Background ........................................................................................20
Study Rationale ............................................................................................21
4.2.1
Role of Galectin-3 in fibrosis ..................................................................21
5.0
STUDY OBJECTIVES ......................................................................................23
Primary Objective.........................................................................................23
Secondary Objective.....................................................................................23
6.0
STUDY DESIGN...............................................................................................24
Overall design...............................................................................................24
Number of Participants .................................................................................25
Participant - and Study completion................................................................25
Study Design Rationale.................................................................................25
Dose Justification .........................................................................................27
Dosing..........................................................................................................27
7.0
STUDY POPULATION.....................................................................................27
Inclusion Criteria..........................................................................................27
Exclusion Criteria.........................................................................................28
8.0
STUDY DRUG ..................................................................................................31
Study Drug Administration...........................................................................31
Permitted medications...................................................................................32
Prohibited Medications including approved and non-approved medications for 
IPF................................................................................................................32
8.3.1
Medications approved for IPF.................................................................32
8.3.2
Non-approved medications for IPF..........................................................32
1.2
2.1
2.2
3.1
3.2
3.3
4.1
4.2
5.1
5.2
6.1
6.2
6.3
6.4
6.5
6.6
7.1
7.2
8.1
8.2
8.3


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Management of Clinical Events ....................................................................33
Blinding and Unblinding procedures.............................................................33
8.5.1
Blinding..................................................................................................33
8.5.2
Unblinding..............................................................................................33
Description of Investigational Agents ...........................................................34
Packaging and Labeling................................................................................34
Storage, Handling, and Accountability..........................................................35
9.0
STUDY END POINTS.......................................................................................36
Primary Endpoint..........................................................................................36
Key Secondary Endpoints.............................................................................36
Secondary endpoints.....................................................................................36
Safety Endpoints...........................................................................................37
Exploratory Endpoints ..................................................................................37
9.5.1
Biomarkers .............................................................................................37
9.5.2
Initiation or termination of nintedanib and pirfenidone in the previous 
stratified study population.......................................................................37
9.5.3
Time to initiation of pirfenidone or nintedanib treatment for SoC2 
participants up to the time when SoC1 and SoC2 were removed in the 
study.Pharmacogenetics..........................................................................37
10.0
STUDY CONDUCT...........................................................................................38
Study Personnel and Organizations...............................................................38
Arrangements for Recruitment of Subjects....................................................38
Visit schedule ...............................................................................................38
10.3.1 Screening & Randomisation....................................................................38
10.3.2 Re-screening visit....................................................................................39
10.3.3 Treatment period.....................................................................................39
10.3.4 Study treatment completion and Follow-up period ..................................40
Study procedures ..........................................................................................40
10.4.1 Data collection........................................................................................40
10.4.2 Informed Consent....................................................................................41
10.4.3 Subject Demographics ............................................................................41
10.4.4 Medical History ......................................................................................41
10.4.5 Physical Examination..............................................................................42
10.4.6 Vital Signs ..............................................................................................42
10.4.7 Health-related Quality of Life Questionnaires .........................................42
10.4.8 12-Lead Electrocardiogram.....................................................................43
8.4
8.5
8.6
8.7
8.8
9.1
9.2
9.3
9.4
9.5
10.1
10.2
10.3
10.4


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10.4.9 Clinical Laboratory Evaluations..............................................................43
10.4.10
Pregnancy Test..................................................................................44
10.4.11
Biomarkers........................................................................................44
10.4.12
Genetics Sample................................................................................45
10.4.13
Spirometry ........................................................................................45
10.4.14
Pulse Oximetry..................................................................................45
10.4.15
DLCO ...............................................................................................45
10.4.16
6MWT ..............................................................................................45
10.4.17
HRCT central overread......................................................................45
10.4.18
Concomitant Medications and Procedures .........................................46
10.4.19
Adverse Events .................................................................................46
Discontinuation of study treatment................................................................46
Withdrawal of Subjects from the Study.........................................................46
Study Compliance.........................................................................................47
11.0
ADVERSE EVENTS .........................................................................................48
Definitions....................................................................................................48
11.1.1 Pretreatment Event Definition.................................................................48
11.1.2 Treatment Emergent Adverse Event........................................................48
11.1.3 Adverse Event Definition........................................................................48
11.1.4 Serious Adverse Event Definition ...........................................................48
Procedures for Recording and Reporting Adverse Events and Serious 
Adverse Events.............................................................................................50
11.2.1 SAE Reporting Contact Information: ......................................................51
Monitoring of Adverse Events and Period of Observation.............................52
Procedures for Reporting Drug Exposure During Pregnancy and Birth Events
....................................................................................................................52
Procedures for Reporting Product Complaints or Medication Errors (Including 
Overdose) .....................................................................................................53
Safety Reporting to Investigators, IRBs or IECs, and Regulatory Authorities53
12.0
SAFETY MONITORING...................................................................................54
Data and Safety Monitoring Board (DSMB) .................................................54
Event Adjudication.......................................................................................54
13.0
DATA HANDLING AND RECORD KEEPING................................................55
eCRFs...........................................................................................................55
Record Retention ..........................................................................................56
14.0
STATISTICAL METHODS...............................................................................57
10.5
10.6
10.7
11.2
11.6
12.1
12.2
13.1
13.2


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Statistical and Analytical Plans .....................................................................57
Statistical Hypothesis....................................................................................57
14.2.1 Primary efficacy endpoints......................................................................58
14.2.2 Key Secondary Efficacy Endpoints: ........................................................58
Analysis Sets ................................................................................................58
Primary Efficacy Analysis ............................................................................59
14.4.1 Analysis of Primary Efficacy Endpoint ...................................................59
14.4.2 Analysis of Secondary Endpoints............................................................60
Secondary Efficacy Analysis.........................................................................62
14.5.1 Other Analyses........................................................................................62
14.5.2 Safety Analysis .......................................................................................62
Determination of Sample Size.......................................................................64
Randomization..............................................................................................64
Handling of Missing Data.............................................................................64
15.0
QUALITY CONTROL AND QUALITY ASSURANCE....................................67
Study-Site Monitoring Visits ........................................................................67
Protocol Deviations.......................................................................................67
Quality Assurance Audits and Regulatory Agency Inspections .....................68
16.0
ETHICAL ASPECTS OF THE STUDY.............................................................69
IRB and/or IEC Approval .............................................................................69
Subject Information, Informed Consent, and Subject Authorization ..............70
Subject Confidentiality .................................................................................72
Publication, Disclosure, and Clinical Trial Registration Policy......................72
16.4.1 Publication..............................................................................................72
16.4.2 Clinical Trial Registration.......................................................................73
16.4.3 Clinical Trial Results Disclosure .............................................................73
Insurance and Compensation for Injury.........................................................73
17.0
REFERENCES...................................................................................................75
18.0
APPENDICES....................................................................................................79
Appendix 1. Plastiape DPI Inhaler Device - Instructions for Use...................79
Appendix 2. Biomarker Panel .......................................................................83
Appendix 3. Definition of Acute Exacerbations in IPF..................................94
19.0
A. RESPONSIBILITIES OF THE INVESTIGATOR.......................................104
14.1
14.2
14.3
14.4
14.5
14.6
14.7
14.8
15.1
15.2
15.3
16.1
16.2
16.3
16.4
16.5
18.1
18.2
18.3


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LIST OF TABLES
Table 1:
Study Time & Events Schedule...............................................................15
Table 2:
Clinical Chemistry and Hematology Tests...............................................43
Table 3:
Clinical Urinalysis Tests .........................................................................43
Table 4:
Biomarker Panel .....................................................................................45
Table 5:
Handling of anticipated ICEs for treatment effect of primary endpoint....65
LIST OF FIGURES
Figure 1:
Study Schematic Diagram.......................................................................24


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2.0
PROTOCOL SUMMARY
Study Synopsis
Name of Sponsor(s):
Galecto Biotech AB
Compound:
GB0139 (previously known as TD139)
Title of Protocol: 
GALACTIC-1 - A randomized, double-blind, 
multicentre, parallel, placebo-controlled phase 2b 
study in subjects with idiopathic pulmonary fibrosis 
(IPF) investigating the efficacy and safety of GB0139, 
an inhaled galectin-3 inhibitor administered via a dry 
powder inhaler over 52 weeks
IND No.: 124075
EudraCT No.: 
2018-002664-73
Study Number: GALACTIC-1
Phase: IIb
Co-ordinating Investigator
Toby Maher MD MSc PhD FRCP
Professor of Medicine and Director of Interstitial Lung 
Disease.
Keck School of Medicine of USC
University of Southern California
Department of Medicine
Division of Pulmonary, Critical Care and Sleep 
Medicine
2020 Zonal Avenue, IRD 724
Los Angeles, CA 90033
Overview (Figure 1)
Population: 
All subjects enrolled into the study will have a diagnosis of IPF established within the previous five years, and a 
diagnostic HRCT scan assessed according the ATS/ERS/Fleischner criteria available within the previous 12 
months (up to 12 months +27 days). 
Treatment:
All subjects eligible for the study will be randomised in a 2:1 ratio to one of two treatment arms:
A.
GB0139 3mg once a day (2x 1.5mg capsules) by inhalation 
B.
Placebo once a day (2x placebo capsules) by inhalation
The stratification at randomization and the following SoCs are removed in Protocol version 6.1_UK such that 
all future participants will not be treated with nintedanib or pirfenidone at screening and ranodmisation:
The two strata of Standard of Care (SoC) were as follows in the previous study design:
1.
SoC1: Subjects currently on treatment with either pirfenidone or nintedanib. 
2.
SoC2: Subjects not currently treated with pirfenidone or nintedanib.
2.1


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Evaluation and follow up:
From baseline to week 52, visits will be scheduled at weeks 0, 4, 8, 12, 26, 40 and 52 for evaluations according 
to the Time & Events Table (Section 2.2). A subject’s follow-up safety assessment will be performed via a 
phone call one week after the last study visit.
Number of Subjects
Estimated to randomize approximately 141 participants in total 
Dose Level(s)
•
GB0139 3mg once a day (2x 1.5mg capsules) by inhalation 
•
Placebo once a day (2x placebo capsules) by inhalation
Duration of Treatment & Follow up
•
52-weeks treatment after randomisation
•
Follow up via a phone call one week after 
the last study visit
Main Criteria for Inclusion
1.
Male and female subjects aged ≥ 40 years of age with a diagnosis of IPF established during the previous 
five years according to ATS/ERS/Fleischner criteria. A historical diagnostic HRCT scan assessed according 
to the ATS/ERS/Fleischner criteria must be available from within the 12 months (up to 12 months +27 
days) prior to screening. Diagnostic HRCTs will be subject to central reading for confirmation.
2.
Lung function parameters as follows:
a.
FVC > 45% of the predicted value at screening
b.
DLCO (corrected for Hb) of 30% to 79% of the predicted value at screening.
3.
Patients who currently are not being treated with nintedanib or pirfenidone; or cannot tolerate nintedanib or 
pirfenidone.
4.
Subjects must sign and date a written, IRB/EC approved informed consent form and any required 
authorization prior to initiation of any study procedures.
Main Criteria for Exclusion
Subjects meeting any of the following exclusion criteria are not to be enrolled in the study/randomized to 
treatment:
1.
Currently has significant airways obstruction: FEV1/FVC ratio of < 0.7 at screening.
2.
Has clinical evidence of active infection, including, but not limited to, bronchitis, pneumonia, sinusitis, 
urinary tract infection, and cellulitis.
3.
Has a history of malignancy within the last 2 years with the exception of basal cell carcinoma, 
squamous cell carcinoma of the skin (localised, treated or cured), chronic lymphocytic leukaemia 
(under observation) and prostate cancer requiring anti-androgens, localised treatment (minor surgery, 
radiotherapy) and/or managed by observation.
4.
Has any condition other than IPF that, in the opinion of the investigator, is likely to result in the death 
of the subject within the next 2 years.


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5.
Presence of other disease that may interfere with testing procedures or in the judgement of the 
Investigator may interfere with trial participation or may put the patient at risk when participating in 
this trial.
6.
Is likely to receive lung transplantation within the next 12 months.
7.
Currently receiving nintedanib, pirfenidone, high dose corticosteroid, cytotoxic (e.g., chlorambucil, 
azathioprine, cyclophosphamide, methotrexate), vasodilator therapy for pulmonary hypertension (e.g., 
bosentan). Also see prohibited medications (Section 8.3.2). A current dose of less than or equal to 15 
mg/day of prednisone or its equivalent is acceptable if the dose is anticipated to remain stable during 
the study. 
8.
Prior use of GB0139 or previously randomised in GALACTIC-1. 
9.
Prior use of nintedanib or pirfenidone within 7 days of initiation of screening.
10. Prior use of investigational drugs within 30 days (or 5 half-lives, whichever is longer) of initiation of 
screening.
11. Participating in another interventional clinical trial. 
12. Has a history of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within the 
previous six months, including, but not limited to, the following:
a.
Unstable angina pectoris or myocardial infarction, or percutaneous coronary intervention 
within the last 6 months
b.
Congestive heart failure requiring hospitalization 
c.
Uncontrolled clinically significant arrhythmias. 
13. If female, the subject is pregnant or lactating or intending to become pregnant before participating in 
this study during the study and within 33 days after last dose of the study drug; or intending to donate 
ova during such time period. 
14. Woman considered to be of childbearing potential who do not use highly effective birth control 
methods during the study and for 33 days after last administration of study drug. 
15. Male partners of women of child bearing potential not committing to using condoms during the course 
of the study and 90 days after last administration of study drug, unless they have undergone male 
sterilization. 
16. Hypersensitivity to the active substance (GB0139) or the excipient (lactose).
Study Objectives
Primary Objectives

Evaluate the effect of GB0139 dry powder for inhalation compared with placebo over 52 weeks 
treatment period on the annual rate of decline in FVC in participants with IPF who are not treated with 
or cannot tolerate nintedanib or pirfenidone.
Secondary Objectives

Further characterize the effect of GB0139 compared with placebo over 52 weeks treatment period on 
FVC, also on the quality of life, time to respiratory-related hospitalizations and all-cause mortality.


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Main Criteria for Evaluation and Analyses
Primary Endpoint
•
The annual rate of decline in Forced Vital Capacity (FVC; expressed in mL over 52 weeks) 
Key Secondary Endpoints
•
Proportion of subjects with an absolute decline from baseline in FVC % pred of ≤10% at w52.
•
Change from baseline in St. George’s Respiratory Questionnaire (SGRQ) total score at w52.
•
Time to first hospitalization (respiratory related, including acute exacerbation of IPF).
•
Time to death (all-causes).
Additional secondary and exploratory efficacy variables with bearing on the efficacy of GB0139 (e.g., other 
QoL) are described in detail in the Main Criteria and Evaluation and Analyses below).
Other Secondary Endpoints 
•
Proportion of subjects with an absolute decline from baseline in FVC % pred of ≤5% at w52
•
Change from baseline in 6-minute walk test (6MWT) distance over 52 weeks
•
Change in diffusion capacity of the lung for carbon monoxide (DLCO), corrected for Hb
•
Change from baseline at week 52 for dyspnoea assessment by University of California San Diego -
Shortness of Breath Questionnaire (UCSD - SOBQ)
•
Change from baseline at week 52 for HRQoL as assessed by Short Form Survey (SF-36) 
•
Percentage of subjects with Adverse Events (AE) or Serious Adverse Events (SAE)
•
Time to first hospitalization (IPF related, including acute exacerbation of IPF)
•
Time to first hospitalization (all cause)
•
Time to respiratory related death
•
Time to initatiation of nintedanib or pirfenidone
•
Change in FVC expressed in mL over 52 weeks for subjects who have never been treated with 
pirfenidone or nintedanib
Exploratory Endpoints

Biomarkers: Change from baseline of selected biomarkers. These may include but are not limited to: 
YKL-40, PAI-1, PDGF-BB, MCP-1, CCL-18, Gal-3, markers of collagen metabolism.

Time to initiation of pirfenidone or nintedanib treatment for SoC2 participants up to the time when 
SoC1 and SoC2 were removed in the study

Pharmacogenetics: The study includes a pharmacogenetic component. This is not mandatory in order 
for a subject to participate in the study.
Statistical Considerations: 
The primary efficacy analysis will be based on the comparison between the GB0139 3mg group against the 
Placebo group in patients who were not treated with nintedanib or pirfenidone at screening.


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The primary endpoint of this trial, annual rate of decline in FVC, will be analyzed by a random coefficient 
regression model including treatment group and baseline FVC (mL).
The key secondary endpoints will be analysed as follows: Proportion of participants with an absolute decline 
from baseline in FVC % predicted of ≤10% at week 52 will be analysed by logistic regression including 
treatment and baseline FVC (mL) in the model. 
Change from baseline in the SGRQ total score at week 52 will be analysed by a mixed model repeated measure.
The time to first hospitalization (any respiratory related) will be analysed by a Cox PH model.  
Time to death (all-causes) will be analysed by Cox PH model. 
Secondary and further endpoints will be analysed in an exploratory manner.
Sample size justification:
The annual decline in FVC for placebo is estimated to be 200ml. To detect a difference from placebo in the 
decline of FVC of 100ml with a standard deviation of 240ml at the significance level of 10%, a sample size of 
141, with a randomization ratio of 2:1, the study would have 75% power.


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Study Time and Events Schedule
Table 1:
Study Time & Events Schedule
Visit
1
2
3
4
5
6
7
8
Withdrawal9
Follow up7
Screening1
Baseline
Treatment
Weeks of treatment
0
4
8
12
26
40
52
-
Day
Time window
            
6 weeks
0
29
±3
57
±3
85
±3
183
±7
281
±7
365
±7
7 days after final 
study visit (+7 
days)
Informed consent
X
HRCT sent to central review
X
Demographics (including height, weight)
X
Medical history
X
Randomization
X
ln- /exclusion criteria
X
X
Physical examination, vital signs
X
X
X
X
X
X
X
X
X
HRQoL (SGRQ, SF-36)
X
X
X
X
Dyspnoea index (UCSD-SOBQ)
X
X
X
X
12-lead ECG
X
X
X
X
X
X
X
X
Laboratory test (chemistry, haemtaology)2
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
Pregnancy test3, 4
X
X
X
X
X
X
X
X
X
Biomarker sample
X
X
X
X
X
Genetics sample 5
X
Spirometry (FVC, FEV1)
X
X
X
X
X
X
X
X
X
SpO2
X
X
DLCO
X
X
X
6MWT
X
X
X
Administer 1st study medication (at clinic) & 
inhaler training6
X
Dispense trial drug 
X
X
X
X
X
X
Compliance / drug accountability7
X
X
X
X
X
X
X
Adverse events & conc. meds8
X
X
X
X
X
X
X
X
X
X
Notes:
1. HRCT confirmation by central reading must be obtained as soon as possible following screening visit 1 and prior to visit 2
2. See Table 2 and Table 3 Section 10.4.9
2.2


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3. In women of childbearing potential only: serum b-HCG will be required at visit 1 only, followed by urinary testing at subsequent visits.
4. This is optional and separate consent must be obtained. The sample can be taken at other study visits.
5. Subjects should be observed for 1 hour after the first dose to monitor for any acute adverse effects of study drug administration (e.g., bronchospasm – see Section 8.1)
6. Includes checking the subject’s use of the DPI device (Plastiape monodose inhaler)
7. The follow-up will be performed via a phone call.
8. Events occurring prior to randomization and administration of drug are considered as pre-treatment (as defined in Section 11.1.1). Adverse events are also collected for up to the phone 
follow up.
9. FVC, DLCO and 6MWT will be performed as part of the withdrawal assessments.


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3.0
STUDY REFERENCE INFORMATION
Study-Related Responsibilities 
Syneos Health and Biorasi the CROs designated to execute the study, will perform all study-
related activities as described in this study protocol. IQVIA serves as the central vendor to 
manage SAE reporting and the study safety database.
Principal Investigator/Principal Coordinator
Galecto Biotech AB together with Syneos Health has selected a Signatory Coordinating 
Investigator from the investigators who participate in the study. Selection criteria for this 
investigator will include significant knowledge of the study protocol, the study medication, their 
expertise in the therapeutic area and the conduct of clinical research as well as study 
participation. The Signatory Coordinating Investigator will be required to review and sign the 
clinical study report and by doing so agrees that it accurately describes the results of the study.
3.1
3.2


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List of Abbreviations
6MWT
6 minute walk test
ALP
alkaline phosphatase
ALT
AM
alanine aminotransferase
alveolar macrophages
AST
ATA
aspartate aminotransferase 
American Thoracic Association
BAL
BALF
bronchoalveolar lavage
bronchoalveolar lavage fluid
CHF
CHI3L1
congestive heart failure 
chitinase-3-like protein 1
COPD
chronic obstructive pulmonary disease
eCRF
electronic case report form 
CRO
contract research organization
HRCT
high resolution computed tomography
DLCO
diffusion lung capacity for carbon monoxide
ECG
ECM
EMA
electrocardiogram
extracellular matrix
European Medicines Agency
FEV1
forced expiratory volume in 1 s
FDA
FUV
FVC
Gal-3
Food and Drug Administration 
Follow-up Visit
forced vital capacity 
galectin-3 
GCP
good clinical practice
GGT
-glutamyl transferase
ICH
International Conference on Harmonisation
IEC
ILD
IPF
independent ethics committee
interstitial lung disease
idiopathic pulmonary fibrosis
IRB
institutional review board
IVRS
interactive voice response system
IWRS
NAC
KL-6
interactive web response system 
N-acetylcysteine
Krebs’ von de Lungen-6
LSLV
MAD
last subject last visit
multiple ascending dose 
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MoA
mechanism of action
MedDRA
NOAELs
NSIP
Medical Dictionary for Regulatory Activities 
no-observed-adverse-effect-levels 
non-specific interstitial pneumonia 
MRI
magnetic resonance imaging
NYHA
OD
PAI-1
New York Heart Association
once per day
plasminogen activator inhibitor 1
PD
PDGF
PFT
progressive disease 
platelet derived growth factor
pulmonary function test
PFS
PH
p.o.
PK
progression-free survival 
pulmonary hypertension
per os (oral) 
pharmacokinetic
QoL
RT
RRT
quality of life
retention time 
relative retention time
SAE
serious adverse event 
SAD
single ascending dose
SmPC
summary of product characteristics 
SoC
standard of care
TGF
transforming growth factor β 
TLC
TID
total lung capacity 
three times per day
UIP
usual interstitial pneumonia   
WHO
WBC
YKL-40
World Health Organization  
Leukocytes (white blood cells) 
chinitnase-3-like protein 1


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4.0
INTRODUCTION
Study Background
Idiopathic pulmonary fibrosis (IPF), the most common form of the idiopathic interstitial 
pneumonias, is a chronic, progressive, irreversible, and usually lethal lung disease of unknown 
cause. IPF occurs mostly in elderly adults, is limited to the lungs, and is associated with a 
histopathological or radiological pattern typical of usual interstitial pneumonia (UIP) [1-3]. The 
disease course is heterogeneous with clinical course highly variable from one subject to another. 
In general, the clinical course can be relatively slow but progressive or very rapid with 
deterioration leading to decline in lung function and death. The clinical picture is invariably 
characterized by worsening cough and dyspnea, respiratory insufficiency and an overall poor 
prognosis with median survival between 2 to 3 years from diagnosis [4-7]. 
The cause of IPF is unknown, but it appears to be a disorder likely arising from the interplay 
between environmental and genetic factors. Cigarette smoking is the most consistent 
environmental risk factor. Genetic factors have also been strongly implicated in both sporadic 
IPF and familial pulmonary fibrosis. A growing body of evidence suggests that the disease 
process is initiated through alveolar epithelial cell microinjuries and apoptosis. Subsequently, 
fibroblasts proliferate and differentiate into myofibroblasts, leading to the excessive 
accumulation of extracellular matrix (ECM) components including collagen and fibronectin 
under the control of profibrogenic stimuli such as transforming growth factor β (TGF-β). The 
resulting fibrotic tissue is characterized by excessive scarring, organ injury, function decline and 
organ failure [8-13]. TGF-β has been assigned a clear pathogenic role by its induction of ECM 
production and apoptosis of alveolar epithelial cells (AECs) in IPF. Inhibiting TGF-β activity, in 
experimental models of lung fibrosis reduces the fibrosis. [14-23].
The natural history of IPF is heterogeneous; therefore, raising a number of challenges for 
individual patient management. There are a number of asymptomatic subjects with subclinical, 
undiagnosed disease, especially among the elderly [24, 25]. Some subjects remain relatively 
stable for a prolonged period of time, while others progress rapidly [26] and some experience 
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acute exacerbations of IPF, e.g., acute respiratory worsening [27] of unidentified cause [28] 
leading to non-elective hospitalization and frequently death [29]. IPF has a broad and profound 
impact on subjects’ health-related quality of life (HRQoL) [30, 31].
Two drug therapies, pirfenidone and nintedanib, are currently licensed for the treatment of IPF. 
Both therapies are only conditionally recommended by the current official ATS/ERS/JRS/ALAT 
clinical practice guidelines for the treatment of IPF due to the potentially significant adverse 
effects with both therapies [36]. Both drugs appear to have comparable efficacy, approximately 
halving the rate of disease progression over 52 weeks as assessed by decline in FVC when 
compared with placebo. However, neither has shown clear evidence of a survival or symptomatic 
benefit [32-35]. Moreover, tolerability limits the use of both drugs in some subjects, and it 
increasingly recognized that a number of subjects either require a reduced dose or have to stop 
treatment [36-39]. Hence there remains a significant unmet medical need in IPF.
Although they have been widely used in the past, current evidence does not support the use of 
corticosteroid or immunosuppressant as a therapy for IPF [3, 40, 41]. Indeed, long-term 
corticosteroid therapy is associated with significant treatment-related morbidity and various 
potentially severe side effects. As a result, current evidence-based guidelines [3] provide a strong 
recommendation against the use of corticosteroid monotherapy in IPF, albeit in the absence of 
any randomized placebo-controlled trial. 
Study Rationale
4.2.1
Role of Galectin-3 in fibrosis
Gal-3 is a beta-galactoside-binding mammalian lectin (a carbohydrate binding protein) of 
approximately 30 kDa which is evolutionarily highly conserved [42]. In multiple models of 
organ fibrosis, it has been demonstrated that Gal-3 is potently pro-fibrotic, modulating the 
activity of fibroblasts and macrophages in chronically injured tissues [18, 43-48]. It is 
hypothesized that increased Gal-3 expression during chronic injury leads to fibroblast activation 
via the aggregation of growth factor receptor clusters (such as TGF-ß), thereby amplifying pro-
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fibrotic signal cascades. Mice that are deficient in Gal-3, although phenotypically normal, 
develop reduced fibrosis in response to tissue injury in lung, liver, blood vessels, heart, and 
kidney, and also in response to allograft rejection [43-48]. In addition, preclinical studies using 
direct intratracheal administration of the galectin-3 inhibitor GB0139 showed that GB0139
decreased bleomycin-induced fibrosis when administered during the fibrotic phase in mice [18,
49]. Thus, Gal-3 may be an important regulator of fibrosis, and these pre-clinical studies provide 
a proof of principal that inhibition of Gal-3 in man could be a potential novel therapeutic 
strategy. Gal-3 is up-regulated in subjects with IPF with elevated levels of Gal-3 in 
bronchoalveolar lavage fluid and serum [18] but not in non-specific interstitial pneumonia 
(NSIP), suggesting that Gal-3 may be a more specifically associated with disease pathogenesis 
and outcome in IPF. Gal-3 is also upregulated during acute exacerbations of IPF. Gal-3 
expression is also up-regulated in other chronic fibroses, including fibrotic liver disease, 
regardless of etiology [44]. Together, these observations support the development of Gal-3 
selective inhibitors for IPF.
GB0139 is a small molecule lectin inhibitor designed specifically to modulate the fibrogenic 
response to tissue injury. GB0139 has been formulated for inhaled delivery to both target the 
disease site in the periphery of the lung in IPF more directly, and to limit any potential systemic 
toxicity. More details on the profile of GB0139 be found in the Investigator’s Brochure (IB).
Galecto Biotech AB conducted a phase 1 clinical study in human volunteers and in 24 subjects 
with IPF in which GB0139 was delivered once daily by dry powder inhalation using a Plastiape 
device. The trial was divided into two parts. Part 1 (single ascending dose) explored the safety 
and tolerability of GB0139 in healthy volunteers. Part 2 (IND opening study) investigated the 
safety, tolerability pharmacokinetics and pharmacodynamics in subjects with IPF. The clinical 
protocol was discussed with the FDA during a pre-IND meeting held on 03 December 2014, and 
the changes suggested by the Agency were implemented before Part 2 of the protocol was 
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The results from clinical trial GB-HV-01 confirm that GB0139 is safe and well tolerated at 
single inhaled doses up to 50 mg in healthy volunteers [Single Ascending Dose (Part 1)], and 
multiple inhaled doses up to 10 mg daily in IPF subjects during 2 weeks of treatment [Multiple 
Ascending Dose (Part 2)]. Further, GB-HV-01 demonstrated that GB0139 reaches the alveolar 
macrophages at pharmacologically relevant concentrations and causes a dose-dependent 
reduction in cell surface Galectin-3 in participants with IPF. In addition, dose-response related 
reductions were observed in the plasma levels of putative IPF biomarkers (YKL-40, PAI-1, 
PDGF-BB, and CCL18), which have been associated with IPF disease severity and all-cause 
mortality [50].
Based on both preclinical and available clinical data, GB0139 is expected to demonstrate a 
favourable risk/benefit profile compared with existing treatment options. No dose-limiting
toxicity has been observed in preclinical testing. In addition, the inhaled route of delivery targets 
the site of the disease directly, with the potential to limit systemic side effects. 
5.0
STUDY OBJECTIVES
Primary Objective
The primary objective of the study is to evaluate the effect of GB0139 dry powder for inhalation 
compared with placebo over 52 weeks treatment period on the annual rate of decline in FVC in 
participants with IPF who are not treated with or cannot tolerate nintedanib or pirfenidone. 
Secondary Objective
The secondary objective of the study is to further characterize the effect of GB0139 compared 
with placebo over 52 weeks treatment period on FVC, also on the quality of life, time to 
respiratory-related hospitalizations and all-cause mortality. 
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6.0
STUDY DESIGN
Overall design
Following a review of unblinded efficacy and safety data by the study’s DSMB in Feb2021, the 
study design is modified based on the DSMB’s recommendation. DSMB has recommended the 
participants randomised to the 10 mg GB0139 group and all those currently taking nintedanib or 
pirfenidone should be discontinued from the study. Galecto expects to continue recruiting 
participants who are not taking nintedanib or pirfenidone at screening and who would be 
randomised to receive 3 mg GB0139 or placebo.
This remains a multicenter, randomized, double-blind, placebo-controlled trial in subjects with 
IPF. The updated design based on the above DSMB’s recommendation is summarized in Figure 
1 below. 
Figure 1:
Study Schematic Diagram
6.1
GB0139 3mg (n=113)
Placebo (n=56)
S R
i 
i 
I 
I
w0
F
Final efficacy analysis
Rate of FVC decline
i i
w52
Screening 
Treatment
Up to 6 weeks 
52 weeks
S — Screening R- randomization
Phone Follow Up
7 days after last visit


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There are three study periods:
Screening Period – After signing the study inform consent form (ICF) participant will enter a 
screening period up to 6 weeks. 
Treatment Period- Following randomization, eligible participants will receive blinded treatment, 
GB0139 or placebo, for 52 weeks. Clinic visits will be performed at week 0/baseline, and then at 
weeks 4, 8, 12, 26, 40, and 52 according to the Study Time and Events Table (Section 2.2)
Follow up Period - At the end of the treatment period (week 52), a safety follow-up phone call 
will be performed 7 days after the withdrawal/last study visit. 
Number of Participants
Approximately 141 participants in total will be randomized in GALACTIC-1.
Participants are considered evaluable if they have taken at least one dose of the double-blind 
treatment. 
Participants who prematurely discontinue double-blind study treatment after randomization can 
remain in the study and complete the remaining scheduled visits, if possible.
Any participants who withdrawn from the study after randomization cannot be replaced and re-
screened. 
Participant - and Study completion
A participant is considered to have completed the study if he/she has completed all periods of the 
study including follow up visit. 
The end of study is defined as the date of the last safety follow up via phone of the last 
participant in the study. 
Study Design Rationale
Based on the DSMB’s recommendation, GALACTIC-1 can continue to randomise participants 
with IPF to receive either placebo or 3 mg GB0139 in a randomized and blinded fashion. 
6.2
6.3
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A placebo treatment arm included in the study is to allow for a quantitative assessment of the 
efficacy of 3 mg GB0139 compared with an inactive control. Use of the placebo is also essential 
in the evaluation of the GB0139 safety in this study. 
DSMB also recommended no further co-administration of GB0139 with nintedanib and 
pirfenidone. Therefore, patients who are not currently taking or cannot tolerate nintedanib or 
pirfenidone will be eligible for screening (Section 7.0). Furthermore, nintedanib and pirfenidone 
are defined as study prohibited medications in Protocol version 6.1_UK. 
Eligible participants will be randomized in a ratio of 2:1 to receive either 3 mg GB0139 or 
placebo. The updated design has maintained the ratio of active to placebo in the original study 
design, after the 10 mg GB0139 treatment group was removed in Protocol version 6.1_UK.  
The 12 months (52 weeks) treatment duration is considered optimal for evaluating the primary 
endpoint in the study.
FVC is generally accepted as a measure of disease severity and as a predictor of survival in IPF. 
FVC is also commonly used as the primary efficacy measure for clinical trials in IPF. The 
decline of lung function in IPF is punctuated by acute exacerbations which carry a substantial 
risk of hospitalization and mortality. Thus, any intervention which reduces the time to 
exacerbation represents a substantial benefit and will be evaluated. In addition to measurements 
of lung volume (FVC), diffusion capacity for carbon monoxide (DLCO) as well as oxygen 
saturation (SpO2) will be monitored and assessed as secondary lung function endpoints.
Survival is recognised as an important measure to evaluate effect of a potential treatment for IPF 
therefore, time to death (all-cause mortality) is included as one of the key secondary endpoints. 
Patients with IPF also suffer from dyspnea, cough and poor exercise tolerance, which can reduce 
the quality of life and cause a severe restriction in their activities of in every-day life. Therefore, 
a number of patient-reported outcome instruments including SGRQ will be used to document the 
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Dose Justification
In the phase Ib study in IPF patients 3 mg GB0139 administered via dry powder inhaler has 
shown to reduce alveolar macrophage (AM) Gal-3 surface expression to 42.8 % of baseline 
levels over 14 days of treatment [50]. When comparing the 3 mg GB0139 group with placebo on 
day 14, five high relevance plasma markers (PDGF-BB, PDGF-AA, PAI-1, YKL-40 and MCP 
1) associated with IPF pathogenesis were either significantly reduced or showed a trend for 
reduction [50]. In addition, there was a correlation between the change in lung Gal-3 levels and 
the change in plasma levels of the high relevance biomarkers across the 3 mg and 10 mg groups 
(see IB for details). Therefore, these reductions in plasma biomarkers were associated with the 
GB0139-induced reduction in Gal-3 expression on AMs and support the lung PK/PD as the key 
driver of the observed systemic biomarker changes. These observations, coupled with AM Gal-3 
target engagement data on 3 mg GB0139, indicated potential efficacy at this dose level in IPF 
which supports the further evaluation of 3 mg in the present study. 
The 3 mg GB0139 dose was also well tolerated in healthy participants and participants with IPF 
in the phase I study.
Dosing
Following Protocol version 6.1_UK, subjects eligible for the study will be randomised into 2:1 
ratio to one of two treatment arms:
A. GB0139 3mg once a day (2x 1.5mg capsules) by inhalation 
B. Placebo once a day (2x placebo capsules) by inhalation
7.0
STUDY POPULATION
Prospective approval of protocol deviations to enrolment criteria, also known as protocol 
waivers, is not permitted.
Inclusion Criteria
Each subject must meet all of the following inclusion criteria in order to be enrolled in the study/
randomized to treatment:
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6.6
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1. Male and female subjects aged ≥ 40 years of age with a diagnosis of IPF established 
during the previous five years according to ATS/ERS/Fleischner criteria [1-3]. A 
diagnostic HRCT scan assessed according to the ATS/ERS/Fleischner criteria should be 
available from within the 12 months (up to 12 months + 27 days) prior to screening. 
Note: a separate HRCT scan will not be performed as part of the study. Diagnostic 
HRCTs will be subject to central reading for assessing study eligibility.
2. Lung function parameters as follows:
a. FVC > 45% of the predicted value at screening
b. DLCO (corrected for Hb) of 30% to 79% of the predicted value at screening.
3. Participants who currently are not being treated with nintedanib or pirfenidone; or cannot
tolerate nintedanib or pirfenidone.
4. Subjects must sign and date a written, IRB/EC approved informed consent form and any 
required authorization prior to initiation of any study procedures.
Exclusion Criteria
Subjects meeting any of the following exclusion criteria are not to be enrolled in the 
study/randomized to treatment:
1. Currently has significant airways obstruction: FEV1/FVC ratio of < 0.7 at screening.
2. Has clinical evidence of active infection, including, but not limited to, bronchitis, pneumonia, 
sinusitis, urinary tract infection, and cellulitis.
3. Has a history of malignancy within the last 2 years with the exception of basal cell 
carcinoma, squamous cell carcinoma of the skin (localised, treated or cured), chronic 
lymphocytic leukaemia (under observation) and prostate cancer requiring anti-androgens, 
localised treatment (minor surgery, radiotherapy) and/or managed by observation.
4. Has any condition other than IPF that, in the opinion of the investigator, is likely to result in 
the death of the subject within the next 2 years.
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5. Presence of other disease that may interfere with testing procedures or in the judgement of 
the Investigator may interfere with trial participation or may put the patient at risk when 
participating in this trial.
6. Is likely to receive lung transplantation within the next 12 months.
7. Currently receiving nintedanib, pirfenidone, high dose corticosteroid, cytotoxic (e.g., 
chlorambucil, azathioprine, cyclophosphamide, methotrexate), vasodilator therapy for 
pulmonary hypertension (e.g., bosentan), also see prohibited medications (Section 8.3.2). A 
current dose of less than or equal to 15 mg/day of prednisone or its equivalent is acceptable if 
the dose is anticipated to remain stable during the study. 
8. Prior use of GB0139 or previously randomized in GALACTIC-1. 
9. Prior use of nintedanib or pirfenidone within 7 days of initiation of screening.
10. Prior use of investigational drugs within 30 days (or 5 half-lives, whichever is longer) of 
initiation of screening.
11. Participating in another interventional clinical trial. 
12. Has a history of unstable or deteriorating cardiac or pulmonary disease (other than IPF) 
within the previous six months, including, but not limited to, the following:
a.
Unstable angina pectoris or myocardial infarction, or percutaneous coronary 
intervention within the last 6 months.
b. Congestive heart failure requiring hospitalization.
c.
Uncontrolled clinically significant arrhythmias. 
13. If female, the subject is pregnant or lactating or intending to become pregnant before 
participating in this study during the study and within 33 days after last dose of the study 
drug; or intending to donate ova during such time period. 
14. Woman considered to be of childbearing potential who do not use highly effective birth 
control methods (A/B/C) during the study and for 33 days after last administration of study 
drug. Female subjects will be considered to be of childbearing potential unless surgically 


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sterilised by hysterectomy or bilateral tubal ligation, or postmenopausal for at least 12 
months.
A. Highly effective methods of birth control (when used consistently and correctly) are: 
o
intrauterine device (IUD) placed at least 4 weeks prior to the IMP administration
o
bilateral tubal occlusion.
o
vasectomised partnerB.
o
sexual abstinenceC.  
o
combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulation: oral, intravaginal, transdermal. 
o
progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, 
implantable.
o
intrauterine hormone-releasing system (IUS). 
B. Vasectomised partner is a highly effective birth control method provided that partner is 
the sole sexual partner of the woman of childbearing potential trial subject and that the 
vasectomised partner has received medical assessment of the surgical success.
C. Sexual abstinence is considered a highly effective method only if defined as refraining 
from heterosexual intercourse during the entire period of risk associated with the study 
treatments. The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the clinical trial. 
15. Male partners of women of child bearing potential not committing to using condoms 
during the course of the study and 90 days after last administration of study drug, unless 
they have undergone male sterilization (with appropriate post-vasectomy documentation 
of the absence of sperm in the ejaculate).
16. Hypersensitivity to the active substance (GB0139) or the excipient (lactose).


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8.0
STUDY DRUG
Study Drug Administration 
Both GB0139 (3 mg) as well as the placebo will be administered via inhalation once a day using
the Plastiape RS01 Monodose DPI device (a CE marked device).
All subjects must be trained in the use of the inhaler device at w0/baseline, according to the 
instructions provided with the device (Appendix 1 in Section 18.0). Placebo capsules and inhaler 
devices will be provided for training and demonstration purposes. Site staff should be assured the 
subject will be able to administer the drug at home safely and competently. The same DPI 
devices can be used for training throughout the study but must not be used for dosing. Study site 
personnel will dispense the IMPs, and site personnel will facilitate administration when the 
subject is in the clinic, at the time of w0/baseline, however subjects themselves will hold the DPI 
device during inhalation. At subsequent visits up until study completion/withdrawal the subject’s 
technique with the DPI device should be assessed to ensure correct usage and further instruction 
given if required/requested.
Capsules will be loaded into the DPI device as per the instructions provided with the device (and 
included in Appendix 1). A single device will be used per two weeks of dosing. The device will 
be dispensed with the IMP. One (1) to three (3) inhalations from the DPI device will be 
performed with each capsule. Any problems with drug administration will be noted in the CRF.
Site staff will instruct the subject on how to take the drug, including the number of capsules to be 
inhaled each day and the timing of dose administration. On administration of the first dose the 
subject should be monitored at the site for 1 hour to observe any acute adverse reaction to study 
medication (e.g., bronchospasm). The PI/attending physician may perform additional spirometry 
as part of their assessment if, in their opinion, it is safe to do so and would be helpful in the 
assessment of any such events. For daily doses taken at home, subjects should be advised to 
administer the study drug at approximately the same time of day. Subjects will be given DPI 
devices and enough supplies until their next visit (plus one week). Subjects will be encouraged to 
contact the site for additional advice and support if they have an issue whilst using the inhaler. 
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Subjects will also be instructed to bring back unused medication. All used and unused blister
should be returned to site for accountability purposes. Individual used capsules can be discarded 
by the participant at home. 
Permitted medications
Vaccines that are available to study participants including but not limited to COVID-19, 
influenza and pneumonia vaccines.
Prohibited Medications including approved and non-approved medications for IPF
8.3.1
Medications approved for IPF

Nintedanib 

Pirfenidone
Following the most recent DSMB recommendation, the above approved medications for IPF are 
prohibited in GALACTIC-1, and if taken, should result in immediate exclusion from screening 
for the study, or withdrawal from the study treatment.
Under caring physician’s medical judgement, if deemed appropriate, patients with IPF may 
discontinue nintedanib or pirfenidone and be considered for screening after a wash out period of 
minimum 7 days. 
Following randomization, study participants are only permitted to take nintedanib or pirfenidone 
after withdrawals of the inhaled study treatment. 
8.3.2
Non-approved medications for IPF
Current guidelines recommend against use of a number of drugs, either alone or in combination, 
to modify disease progression in idiopathic pulmonary fibrosis, and the use of the following 
should be result in exclusion from the study: 
•
N-acetylcysteine
•
Azathioprine
•
Ambrisentan
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8.3


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•
Bosentan
•
Macitentan
•
Mycophenolate mofetil
•
Warfarin (disallowed only when prescribed solely for the treatment of IPF and is 
permitted for other recognised indications such as Atrial Fibrillation)
Management of Clinical Events 
Management of all types of adverse events, regardless of the possible underlying cause is the 
responsibility of the treating physician/investigator. 
Blinding and Unblinding procedures
8.5.1
Blinding
This study is a double-blind study which will be maintained throughout the study, including the 
follow-up period. Study medication is identified by a medication code number. Packaging and 
labelling will be otherwise identical. Subjects, Investigators and everyone involved in analysing 
or with an interest in this double- blind study (Sites, Study team, CROs, other service providers) 
will remain blinded with regard to the randomised treatment assignments until after database 
lock. Only the DSMB will have access to unblinded information. An IVRS/IWRS will be used to 
assign subjects to treatment groups at study start. The randomisation code will be kept 
undisclosed up to database lock. 
8.5.2
Unblinding
If the Investigator believes that knowledge of the IMP received by a subject is essential for 
appropriate treatment of an AE, the Investigator should ideally consult with the CRO/Galecto 
before breaking the code. In any event, the Investigator should inform Galecto Biotech AB 
(subsequently referred to as Galecto) as soon as possible whenever the code has been broken for 
a subject. In the event that the site requires emergency access to an individual subject code and 
personnel from Galecto are not available, each site may break the blind without any prior 
consultation. In such an event, the Chief Investigator, Principal Investigator or delegate would 
8.4
8.5


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notify Galecto as soon as possible via email or fax. If the Investigator needs to break the blind 
for an individual subject, the date and reason will be recorded in the subject’s CRF. The 
IVRS/IWRS will provide a telephone/web procedure for unblinding the code to the Investigator / 
Pharmacist / investigational drug storage Manager. The Investigator will not reveal the unblinded 
treatment code to any other member of the clinical team involved in the study or to the Study 
Monitor. If the code is broken for any individual subject, the subject will be withdrawn from the 
study and the procedures accompanying the withdrawal visit performed. If the code is broken 
without justification, this will be deemed a serious protocol violation.
To avoid unblinding of the study team through drug safety reports which are to be unblinded as 
per regulatory requirements, a procedure will be maintained to keep code-breaking in these cases 
unknown to the study team.
Description of Investigational Agents 
The planned dose levels (3 and 10 mg GB0139) have been selected in the original study design 
(Protocol version 5.1_UK) following review of non-clinical pharmacokinetic, safety 
pharmacology and toxicology data. Pharmacokinetic, toxicokinetic and toxicology studies in 
mice, rats and dogs indicate the drug is readily bioavailable via the inhaled route with little or no 
accumulation after 14-day dosing and is excreted in the faeces with a t1/2 of approximately 6 h.
Given the lack of adverse effects seen in the two species as well as the favourable safety profile 
seen in the phase I/IIa in healthy volunteers and IPF subjects, no direct anticipated adverse drug 
specific side effects are expected in the current study, nor are any drug interactions anticipated 
given the clear cytochrome profiling. Further details regarding non-clinical pharmacokinetic, 
safety pharmacology and toxicology data can be found in the IB.
Packaging and Labeling 
The IMPs will be prepared by the sponsor and supplied to the Investigator. The Sponsor must 
ensure that the Investigator is notified prior to dispatch of IMP supplies, and of the anticipated 
date of their arrival. The IMP is shipped upon first screening, then arrives on site prior to dosing.
8.6
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The IMPs must be received at each Investigational site by a designated person, handled and 
stored safely and properly, and kept in a secured location to which only the Investigator and 
designated staff have access. After a review of the temperature monitors included with shipments 
the Sponsor/CRO must ensure that it is confirmed that the transportation conditions were 
acceptable.
Storage, Handling, and Accountability 
Following the Sponsor’s approval, all remaining IMP will either be returned to the Sponsor or 
sent for destruction within 8 weeks of completion of the study-dosing period.
All used IMP containers and unused IMP will be held under quarantine in the investigator site 
facility pending accountability/return/destruction.
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9.0
STUDY END POINTS
Primary Endpoint
•
The annual rate of decline in Forced Vital Capacity (FVC; expressed in mL over 52 
weeks).
Key Secondary Endpoints
•
Proportion of subjects with an absolute decline from baseline in FVC (% pred) of ≤10% 
at Week 52.
•
Change from baseline in SGRQ total score at Week 52.
•
Time to first hospitalization (respiratory related, including acute exacerbation of IPF).
•
Time to death (all-causes). 
Secondary endpoints 
•
Proportion of subjects with an absolute decline from baseline in FVC % pred of ≤5% at 
w52.
•
Change from baseline in 6-minute walk test (6MWT) distance over 52 weeks.
•
Change from baseline in diffusion capacity of the lung for carbon monoxide (DLCO), 
corrected for HB, over 52 weeks.
•
Change from baseline at week 52 for dyspnoea assessment by University of California 
San Diego - Shortness of Breath Questionnaire (UCSD - SOBQ).
•
Change from baseline at week 52 for HRQoL as assessed by Short Form Survey (SF-36).
•
Percentage of subjects with Adverse Events (AE) or Serious Adverse Events (SAE).
•
Time to first hospitalization (IPF related, including acute exacerbation of IPF).
•
Time to first hospitalization (all cause).
•
Time to respiratory-related death.
•
Time to initiation of nintedanib or pirfenidone.
•
Change in FVC expressed in mL over 52 weeks for subjects who have never been treated 
with pirfenidone or nintedanib.
9.1
9.2
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Safety Endpoints
•
The following measure of safety will be assessing throughout the study:
•
Vital signs 
•
Physical examination 
•
Weight 
•
Clinical laboratory tests (haematology, clinical chemistry and urinalysis) 
•
Adverse events (see Section 11.0)
•
12-lead electrocardiogram (ECG)
Exploratory Endpoints
9.5.1
Biomarkers
Change from baseline in selected biomarkers including but not limited to: YKL 40, PAI 
1, PDGF-BB, MCP-1, CCL-18, KL-6, CA-125, CA-19, Gal-3 and collagen neoepitopes –
described in Appendix 2 (Section 18.0) – over time up to week 52 in all subjects.
9.5.2
Initiation or termination of nintedanib and pirfenidone in the previous stratified 
study population 
9.5.3
Time to initiation of pirfenidone or nintedanib treatment for SoC2 participants up 
to the time when SoC1 and SoC2 were removed in the study.Pharmacogenetics
The study includes a pharmacogenetic component including but not limited to analysis of 
GAL-3 and IPF disease related genes of interest that might relate to the efficacy and/or 
safety of GB0139. 
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10.0
STUDY CONDUCT
This trial will be conducted in compliance with the protocol, Good Clinical Practice (GCP), 
applicable regulatory requirements, and International Conference on Harmonisation (ICH) 
guidelines.
Study Personnel and Organizations
The contact information for the project clinician for this study, the clinical laboratories, the 
coordinating investigator for each member state/country, the interactive voice response system 
(IVRS)/interactive web response system (IWRS) provider, the contract research organization 
(CRO) team may be found in the Investigator Site File. A full list of investigators is available in 
the sponsor’s investigator database.
Arrangements for Recruitment of Subjects
Recruitment and enrollment strategies for this study may include recruitment from the 
investigator’s local practice/hospital or referrals from other physicians. If advertisements become 
part of the recruitment strategy, they will be reviewed by the institutional review board 
(IRB)/independent ethics committee (IEC). 
Enrollment strategies for this study may include the following:

Review of local practice/hospital database

Communication with other physicians/colleagues and cooperating health care facilities 
that regularly refer subjects for further diagnosis and care
Visit schedule 
There is a screening visit and 7 study visits planned over the 52 weeks treatment period. A safety 
follow up will be conducted via phone 7 days after the final visit.
10.3.1 Screening & Randomisation
After giving his/her Informed Consent, the patient may be selected based on inclusion and 
exclusion criteria for the study at visit 1. The shipment or transfer of HRCT for review can be 
10.1
10.2
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organised before the screening visit provided the participant has given and signed his Informed 
Consent. The screening is up to 6 weeks. 
The participants will be randomised at visit 2 if all inclusion and exclusion criteria are fulfilled.  
The results of laboratory parameters from visit 2 may only become available 24 to 72 hours after 
visit 2. Therefore, laboratory results from visit 2 cannot qualify as exclusion criteria. However, in 
case these results would retrospectively fulfil an exclusion criterion, the patient will be 
withdrawn unless continuation is justified in writing by the Investigator. 
10.3.2 Re-screening visit
If a subject fails to meet the screening criteria for reasons which the Principal Investigator judges 
to be anomalous or the result of a temporary factor, those test(s) may be repeated once at an ad 
hoc visit(s), providing the subjects is still within the six weeks screening window. Subjects who 
fail screening and are outside the six weeks screening window, whom the Principal Investigator 
judges to now meet the screening criteria will be permitted to undergo rescreening one additional 
time, with advanced approval from Syneos Health Medical Monitors.
If a re-screening visit occurs within 12 weeks of initial screening it is not required to repeat PFT 
and DLCO, if the PFT and DLCO measured at the initial screening have met study inclusion 
criteria.  
10.3.3 Treatment period
There will be seven study visits during the treatment period as follows: at randomization/baseline 
(w0), w4, w8, w12, w26, w40, and w52. Details for the data collected at each visit are given in 
the time and events table (Section 2.2). Visits 3, 4 and 5 should occur within ± 3 days of the 
scheduled time point. Visits 6 and 7 should occur within 7 days of the scheduled time point. 
10.3.3.1 Participants randomized prior to Protocol version 6.1_UK and eligible to continue 
participation 
Participants who were already randomised and eligible to remain in GALACTIC-1 and continue 
to receive blinded study treatment (3 mg GB0139 or placebo) should attend visits as required by 


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Protocol version 5.1_UK until Protocol version 6.1_UK is approved. Once the amended ICF is 
approved they should be re-consented. Participants who have completed w52 visit by the time 
the Protocol version 6.1_UK is approved should attend a withdrawal visit as soon as possible 
followed by a phone call follow up as specified in the Protocol version 6.1_UK. 
10.3.4 Study treatment completion and Follow-up period
Subjects will be considered to have completed the study treatment period if assessments 
according to the protocol at week 52 have been performed. At the end of the treatment period 
subjects will enter a follow-up period. Follow-up phone call can be performed from 7 days and 
up to 14 days after the last study visit or withdrawal visit.
Additional individual visits may be scheduled by the treating physician on a case by case basis.
Data collected at these visits will be recorded as unscheduled visits in the eCRF.
At all scheduled visits, study site staff will collect treatment patterns and outcomes, vital status, 
clinical events, AE/SAE data from the charts of study subjects followed at the participating sites. 
Study procedures
10.4.1 Data collection
An electronic case report form (eCRF) system will be utilized for data collection, monitoring, 
and quality control. Data validation will be programmed in the eCRF system to automate data 
queries. The physician or assigned study personnel will complete the eCRFs at every visit, and as 
required by the protocol.
If clarifications are needed, queries will be raised either by the monitor of the study or the 
assigned data management team, through the built-in query management functionality in the 
eCRF. The physician or assigned study personnel will be required to respond to these queries 
through the eCRF system.
Subject data collected on eCRFs during the study will be recorded in an anonymous fashion to 
ensure subject confidentiality. The physician must maintain source documents where relevant for 
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each subject in the study, consisting of all demographic and medical information, and keep the 
written informed consent form. All information on the eCRFs must be traceable to these source 
documents in the subject’s medical file. 
Initiation of the participating sites will be performed by the designated CROs. Before study 
initiation, a CRO representative will review the protocol, the CRF and the eCRF system with the 
physicians and their staff. CROs will follow streamlined SOPs that have been reviewed and 
approved by Galecto.
Concomitant or prior medications entered into the database will be coded using the World Health 
Organization (WHO) Drug Reference List. Medical history/current medical conditions and 
adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
terminology.
10.4.2 Informed Consent
Each subject must provide written informed consent before any study-required procedures are 
conducted, and before the diagnostic HRCT can be sent for central review.
10.4.3 Subject Demographics
Subject demographics will be collected at screening visit 1.
•
Age at baseline
•
Gender
•
Height and body weight (for BMI computation)
10.4.4 Medical History
During the Screening period, a complete medical history will be compiled for each subject. The 
following variables will be collected:
•
Smoking history, recorded in pack-years
•
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•
Time of IPF diagnosis by HRCT or surgical lung biopsy
•
Time of start of treatment with pirfenidone or nintedanib (as appropriate)
•
Time point and reason for discontinuation of treatment with pirfenidone or nintedanib (as 
appropriate)
•
Any episode of acute exacerbation in the subject’s IPF context during three months prior 
to randomization
•
Any  medication used prior to screening including vaccinations
10.4.5 Physical Examination
A physical examination will be completed as per standard of care at all visits.
10.4.6 Vital Signs
Vital sign measurements include supine (after at least 5 minutes in this position) measurements 
of diastolic and systolic blood pressure, heart rate, and body temperature. They will be conducted 
at all visits.
10.4.7 Health-related Quality of Life Questionnaires
Three patient-reported assessments related to symptoms and quality of life will be collected 
during the study. A version of each will be to the site and will be completed by each subject at 
the visits as per the T&E table Section 2.2

St George’s Respiratory Questionnaire (SGRQ) a validated QoL for IPF 

The Short Form Health-36 survey 

The University of California San Diego, shortness of breath questionnaire (UCSD-
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10.4.8 12-Lead Electrocardiogram
Safety monitoring by ECG will be performed using site local equipment. PR interval, QRS 
duration, QT interval and QTcF are required to be evaluated.
10.4.9
Clinical Laboratory Evaluations
Clinical laboratory evaluations will be performed by a central laboratory as outlined below.
Blood samples for analysis of the clinical chemistry and hematological parameters, urinalysis 
and biomarkers are shown in Table 2, Table 3 and Table 4.
Table 2:
Clinical Chemistry and Hematology Tests
Hematology
Serum Chemistry
Hematocrit
Hemoglobin
Leukocytes with differential count
Platelet (count)
Albumin
Alkaline phosphatase (ALP)
Aspartate transaminase (AST)
Alanine transaminase (ALT)
Bilirubin (total)
Calcium
Creatinine
Glucose
Potassium
Sodium
Table 3:
Clinical Urinalysis Tests
                            Urinalysis
Bilirubin
Glucose
Ketones
Leukocytes
Nitrite
Occult blood
pH
Protein
Specific gravity
Turbidity and color
Urobilinogen
Results are recorded qualitatively as:  -, +, ++, +++


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10.4.10 Pregnancy Test
A serum pregnancy (choriogonadotropin beta) test will be completed by all females of 
child-bearing potential during screening; this test must be negative for the subject to be enrolled. 
Urinary pregnancy tests will then be repeated at various times during the study as specified in the 
Time & Events table. 
Any occurrence of a pregnancy in a subject undergoing treatment in the GALACTIC-1 study 
must be reported according to the rules agreed upon with the designated CRO within 24 hours of 
learning of its occurrence. The pregnancy should be followed-up via fax or email to determine
outcome, including spontaneous or voluntary termination, details of the birth, and the presence or 
absence of any birth defects, congenital abnormalities, or maternal and/or new-born 
complications.
Pregnancy should be recorded on a Pharmacovigilance Pregnancy Form and reported by the
treating physician or other involved health care professional to Galecto’s Pharmacovigilance 
(PV) representative. In case of any congenital abnormality, birth defect or maternal and new-
born complications, the possible relationship to the Galecto drug should be reported.
Additionally, any SAE experienced during pregnancy must be reported into the eCRF system.
Note: should the eCRF system become non-operational, the site must complete the appropriate
paper Serious Adverse Event Form. The completed form is then faxed/mailed within 24 hours of 
the Investigator’s or site’s awareness; however, the reported information must be entered into the 
eCRF system once it becomes operational. Please see Section 11.2 for PV reporting information.
10.4.11 Biomarkers 
A serum sample for the assessment of biomarkers will be collected at baseline (visit 2) and 
weeks 4, 12, 26 and 52. The list in Table 4 gives examples of biomarkers potentially related to 
Galectin-3 activity and/or IPF disease severity/prognosis. More detail on the rationale for 
including such biomarkers is described in Appendix 2 (Section 18.0). Ultimately, individual 
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Table 4:
Biomarker Panel
                                                                  Serum Biomarkers 
Gal-3
Collagen neoepitopes
YKL-40    
MCP-1
CA-125
                                           KL-6
PAI-1
PDGF-BB
CCL-18
CA-19
10.4.12 Genetics Sample
All subjects will be asked for a blood sample for genetic assessment. However, this is not 
mandatory for the subject to participate in the study. A single sample will be taken at visit 2 or at 
any visit throughout the study and processed or stored after separate informed consent is given in 
accordance with local ethical and regulatory requirements. The sample will be anonymised, 
meaning there will be no way to trace back to the identity of the donor. Samples will be stored 
for up to 15 years after the end of the study or until there is no more material available for tests.
10.4.13 Spirometry
Equipment and manual will be provided by Clario (previously ERT). Data will be centrally 
evaluated by Clario. 
10.4.14 Pulse Oximetry  
Pulse oximetry will be measured using sites local equipment. 
10.4.15 DLCO
Sites use local equipment to measure DLCO using a manual provided by Clario. Data will be 
centrally overread by Clario. 
10.4.16 6MWT
Test manual will be provided by Clario. 
10.4.17HRCT central overread
HRCT will be reviewed by an independent Chest radiologist, assigned byClario, who will assess 
according to the ATS/ERS/Fleischner criteria [1-3].


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10.4.18 Concomitant Medications and Procedures
Medications including vaccination used by the subject will be recorded in the electronic case 
report form (eCRF) to cover screening period and then prospectively at all study visits (treatment 
and follow up periods) until study completion/withdrawal. See Section 8.3.2 for a list of 
medications and therapies that are prohibited during the study.
10.4.19 Adverse Events
Monitoring of AEs, serious and nonserious, will be conducted throughout the study as specified 
in the Time and Events Table (Section 2.2). Refer to Section 11.0 for details regarding 
definitions, documentation, and reporting of pretreatment events (PTEs), AEs, and SAEs. 
Discontinuation of study treatment 
Temporary discontinuation of GB0139 for <2 weeks will be permitted, if for reasons other than 
those stated below. The reason for discontinuation should be documented in the eCRF.
Treatment with study drug may be permanently discontinued for any of the following reasons:
•
Persistent non-adherence by subject
•
Adverse event assigned to the investigational drug
•
Overall unsatisfactory therapeutic response
•
Study terminated by sponsor
•
Withdrawal by subject
•
Lost to follow-up
•
Other (cause to be elaborated on in the subject’s file)
In all cases, participants should be encouraged to discuss any potential study treatment 
discontinuation with the investigator prior to stopping treatment. If considered medically 
appropriate by the PI, participants who have been withdrawn from study treatment can remain in 
the study, resume their usual standard of care treatment for IPF, if applicable, and complete 
scheduled visits and study assessments up to the follow up phone call.
Withdrawal of Subjects from the Study
Subjects may withdraw for the following reasons:
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•
Lost to follow-up
•
Study terminated by sponsor
•
Withdrawal by subject
•
Completed study
•
Death
•
Lung transplant
•
Other (cause to be elaborated on in the subject’s file)
All study procedures outlined for the withdrawal visit will be completed as specified in the Time 
and Events Table (Section 2.2). The primary reason for study drug discontinuation will be 
recorded on the eCRF. 
Following the study withdrawal, no new information will be collected from the withdrawn 
subject and added to the existing data or any database.
Study Compliance
Study drug will be administered or dispensed only to eligible subjects under the supervision of 
the investigator or identified sub-investigator(s). The appropriate study personnel will maintain 
records of study drug receipt and dispensing.
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11.0
ADVERSE EVENTS
Definitions
11.1.1 Pretreatment Event Definition
A pretreatment event (PTE) is any untoward medical occurrence in a subject who has signed 
informed consent to participate in a study but before administration of the first dose of study 
medication; it does not necessarily have to have a causal relationship with study participation.
11.1.2 Treatment Emergent Adverse Event
A treatment emergent adverse event (TEAE) is any untoward medical occurrence that emerges 
during treatment, having been absent pre-treatment or worsens relative to the pre-treatment state.
11.1.3 Adverse Event Definition
Adverse Event (AE) means any untoward medical occurrence in a subject or subject 
administered a pharmaceutical product; the untoward medical occurrence does not necessarily 
have a causal relationship with this treatment. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal (investigational) product whether or not it is related to the 
medicinal product. This includes any newly occurring event, or a previous condition that has 
increased in severity or frequency since the administration of study drug.
An abnormal laboratory value will not be assessed as an AE unless that value leads to 
discontinuation or delay in treatment, dose modification, therapeutic intervention, or is 
considered by the investigator to be a clinically significant change from baseline.
11.1.4 Serious Adverse Event Definition
Serious Adverse Event (SAE) means any untoward medical occurrence that at any dose:

Results in death.


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
Is life-threatening (refers to an AE in which the subject was at risk of death at the time 
of the event. It does not refer to an event which hypothetically might have caused death if 
it were more severe).

Requires subject hospitalization or prolongation of an existing hospitalization (see 
clarification in the paragraph in Section 11.2 on planned hospitalizations).

Results in persistent or significant disability or incapacity. (Disability is defined as a 
substantial disruption of a person’s ability to conduct normal life functions).

Is a congenital anomaly/birth defect?

Is a medically important event. This refers to an AE that may not result in death, be 
immediately life threatening, or require hospitalization, but may be considered serious 
when, based on appropriate medical judgment, may jeopardize the subject, require 
medical or surgical intervention to prevent one of the outcomes listed above, or involves 
suspected transmission via a medicinal product of an infectious agent. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in subject 
hospitalization, or the development of drug dependency or drug abuse; any organism, 
virus, or infectious particle (e.g., prion protein transmitting transmissible spongiform 
encephalopathy), pathogenic or nonpathogenic, is considered an infectious agent.
Clarification should be made between an SAE and an AE that is considered severe in intensity 
(Grade 3 or 4), because the terms serious and severe are NOT synonymous. The general term 
severe is often used to describe the intensity (severity) of a specific event; the event itself, 
however, may be of relatively minor medical significance (such as a Grade 3 headache). This is 
NOT the same as serious, which is based on subject/event outcome or action criteria described 
above and is usually associated with events that pose a threat to a subject’s life or ability to 
function. A severe AE (Grade 3 or 4) does not necessarily need to be considered serious. For 
example, a white blood cell count of 1000/mm3 to less than 2000 is considered Grade 3 (severe) 


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but may not be considered serious. Seriousness (not intensity) serves as a guide for defining 
regulatory reporting obligations.
Procedures for Recording and Reporting Adverse Events and Serious 
Adverse Events
All AEs spontaneously reported by the subject and/or in response to an open question from study 
personnel or revealed by observation, physical examination, or other diagnostic procedures will 
be recorded on the appropriate page of the eCRF (see Section 11.3 for the period of observation).  
Any clinically relevant deterioration in laboratory assessments or other clinical finding is 
considered an AE. When possible, signs and symptoms indicating a common underlying 
pathology should be noted as 1 comprehensive event.
Regardless of causality, SAEs and serious pretreatment events (as defined in Section 11.1) must 
be reported (see Section 11.3 for the period of observation) by the investigator to Galecto’s 
pharmacovigilance representative or designee (contact information provided below). This should 
be done by faxing/mailing the paper SAE Form within 24 hours after becoming aware of the 
event before recording the SAE into the eCRF system. Follow-up information on the SAE or 
serious pretreatment event may be requested by Galecto. SAE report information must be 
consistent with the data provided on the eCRF. The SAE Form, created specifically by Galecto 
(or by the designated CRO), will be provided to each clinical study site.
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11.2.1 SAE Reporting Contact Information:
E-mail: PhV_ZZA31672_SO@IQVIA.com
Fax number: 
Country
Toll-Free Fax No. 
INDIA
000-800001-6750 
Planned hospital admissions or surgical procedures for an illness or disease that existed before 
the subject was enrolled in the trial or before study drug was given are not to be considered AEs 
unless the condition deteriorated in an unexpected manner during the trial (e.g. surgery was 
performed earlier or later than planned).
For both serious and nonserious AEs, the investigator must determine both the severity (toxicity 
grade) of the event and the relationship of the event to study drug administration. For serious 
pretreatment events, the investigator must determine both the severity (toxicity grade) of the 
event and the causality of the event in relation to study procedures.
Relationship of the event to study drug administration (i.e., its causality) will be determined by 
the investigator responding yes (related) or no (unrelated) to this question: “Is there a reasonable 
possibility that the AE is associated with the study drug?”


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Monitoring of Adverse Events and Period of Observation
AEs, both nonserious and serious, will be monitored throughout the study as follows: 
•
AEs will be reported from the signing of informed consent through 30 days after 
administration of the last dose of study drug and recorded in the eCRFs.    
•
SAEs.
•
Serious pretreatment events will be reported to the Galecto pharmacovigilance 
representative or designee from the time of the signing of the informed consent form up 
to first dose of study drug and will also be recorded in the eCRF. 
•
Related and unrelated treatment-emergent SAEs will be reported to the Galecto 
pharmacovigilance representative or designee from the first dose of study drug through 
30 days after administration of the last dose of study drug and recorded in the eCRF. 
After this period, only related SAEs must be reported to the Galecto pharmacovigilance 
representative or designee. SAEs should be monitored until they are resolved or are 
clearly determined to be due to a subject’s stable or chronic condition or intercurrent 
illness(es).
Procedures for Reporting Drug Exposure During Pregnancy and Birth Events
If a woman becomes pregnant or suspects that she is pregnant while participating in this study, 
she must inform the investigator immediately and permanently discontinue study drug. The 
sponsor must also be contacted immediately by faxing a completed Pregnancy Form to the 
Galecto pharmacovigilance representative or designee (see Section 11.2). The pregnancy must be 
followed for the final pregnancy outcome.
If a female partner of a male subject becomes pregnant during the male subject’s participation in 
this study, the sponsor must also be contacted immediately by emailing a completed Pregnancy 
Form to the Galecto pharmacovigilance representative or designee (see Section 11.2). Every 
effort should be made to follow the pregnancy for the final pregnancy outcome.
11.3
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Procedures for Reporting Product Complaints or Medication Errors (Including 
Overdose)
A product complaint is a verbal, written, or electronic expression that implies dissatisfaction 
regarding the identity, strength, purity, quality, or stability of a drug product.  Individuals who 
identify a potential product complaint situation should immediately report this via the phone 
numbers or e-mail addresses provided below.
A medication error is a preventable event that involves an identifiable subject and that leads to 
inappropriate medication use, which may result in subject harm. Whereas overdoses and 
underdoses constitute medication errors, doses missed inadvertently by a subject do not. 
Individuals who identify a potential medication error (including overdose) situation should 
immediately report this via the phone numbers or e-mail addresses provided in Section 11.2.1.
Product complaints in and of themselves are not AEs.  If a product complaint results in an SAE, 
an SAE form should be completed and sent to IQVIA (refer to Section 11.2).
Safety Reporting to Investigators, IRBs or IECs, and Regulatory Authorities
A designated CRO will be responsible for reporting all suspected unexpected serious adverse 
reactions (SUSARs) and any other applicable SAEs to regulatory authorities, including the 
European Medicines Agency (EMA), investigators and IRBs or IECs, as applicable, in 
accordance with national regulations in the countries where the study is conducted. Relative to 
the first awareness of the event by/or further provision to the sponsor or sponsor’s designee, 
SUSARs will be submitted to the regulatory authorities as an expedited report within 7 days for 
fatal and life-threatening events and 15 days for other serious events, unless otherwise required 
by national regulations. The sponsor will also prepare an expedited report for other safety issues 
where these might materially alter the current benefit-risk assessment of an investigational 
medicinal product or that would be sufficient to consider changes in the investigational 
medicinal product’s administration or in the overall conduct of the trial. The investigational sites 
will also forward a copy of all expedited reports to their IRB or IEC in accordance with national 
regulations.
11.5
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12.0
SAFETY MONITORING
Data and Safety Monitoring Board (DSMB)
An independent Data and Safety Monitoring Board (DSMB) will be implemented. Members of 
the DSMB selected and appointed by the sponsor will be fully independent of any ties to the 
trial, the sponsor, or any other activity or entity that might affect their objectivity. The 
establishment and management of the DSMB is prescribed by a charter and provides reports to 
the study team, sponsor, CRO. The minutes of all DSMB meetings will be stored in the Trial 
Master File (TMF).
The DSMB will continue to conduct regular review of the trial safety data, with the focus on the 
following safety information: 
• Death cases 
• Serious adverse events 
• Adverse events leading to withdrawal from study
The DSMB will recommend continuing, modifying or stopping the study based on these reviews. 
The DSMB is committed to meet and to make timely decisions. The DSMB will inform the 
coordinating Investigator of the trial, the Sponsor, and the Trial team if any urgent decision has 
to be implemented. 
Event Adjudication
Following study read-out, Galecto may decide to employ an independent adjudication panel to 
review, in a blinded manner, events reported in the study including but not limited to all cases of 
death (the primary cause of death) and reported acute IPF exacerbations (based on written 
clinical reports, for diagnostic confirmation). See Appendix 3 (Section 18.0) for a definition of 
acute exacerbation in IPF. 
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13.0
DATA HANDLING AND RECORD KEEPING 
The full details of procedures for data handling will be documented in the Data Management 
Plan. If selected for coding, AEs, PTEs, medical history, and concurrent conditions will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA). Drugs will be coded using 
the World Health Organization (WHO) Drug Dictionary.
eCRFs 
The designated CRO will supply investigative sites with access to eCRFs and will make 
arrangements to train appropriate site staff in the use of the eCRF. The data collection forms are 
used to transmit the information collected to ensure quality and performance of this study to the 
sponsor, CRO partners, and regulatory authorities. Investigative sites must complete eCRFs in 
English.
After completion of the entry process, computer logic checks will be run to identify items, such 
as inconsistent data, missing data, and questionable values. Queries may be issued by the CRO 
personnel and will be answered by the site. Issues will be reconciled with Galecto.
Any change of, modification of, or addition to the data on the eCRFs should be made by the 
investigator or appropriate site personnel. Corrections to eCRFs are recorded in an audit trail that 
captures the old information, the new information, identification of the person making the 
correction, the date the correction was made, and the reason for change.
The principal investigator must review the eCRFs for completeness and accuracy and must sign 
and date the appropriate eCRFs as indicated. Furthermore, the principal investigator must retain 
full responsibility for the accuracy and authenticity of all data entered on the eCRFs.
eCRFs will be reviewed for completeness and acceptability at the study site during periodic 
visits by study monitors. The sponsor or its designee will be permitted to review the subject’s 
medical and hospital records pertinent to the study to ensure accuracy of the eCRFs. The 
completed eCRFs are the sole property of the sponsor and should not be made available in any 
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form to third parties, except for authorized representatives of appropriate governmental health or 
regulatory authorities, without written permission of the sponsor.
Record Retention
The investigator agrees to keep the records stipulated in Section 13.1 and those documents that 
include (but are not limited to) the study-specific documents, the identification log of all 
participating subjects, medical records, temporary media such as thermal sensitive paper, all 
original signed and dated informed consent forms, subject authorization forms regarding the use 
of personal health information (if separate from the informed consent forms), electronic copy of 
eCRFs, including the audit trail, and detailed records of drug disposition to enable evaluations or 
audits from regulatory authorities, the sponsor or its designees. Any source documentation 
printed on degradable thermal sensitive paper should be photocopied by the site and filed with 
the original in the subject’s chart to ensure long term legibility. Furthermore, International 
Conference on Harmonisation (ICH) E6 Section 4.9.5 requires the investigator to retain essential 
documents specified in ICH E6 (Section 8) until at least 2 years after the last approval of a 
marketing application for a specified drug indication being investigated or, if an application is 
not approved, until at least 2 years after the investigation is discontinued and regulatory 
authorities are notified. No study document is to be destroyed without prior written agreement 
between Sponsor and the Investigator. Should the Investigator wish to assign the study records to 
another party or move them to another location, he/she must notify the Sponsor in writing of the 
new responsible person and/or the new location.
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14.0
STATISTICAL METHODS
As part of Protocol version 6.1_UK study design and objectives have been amended to focus on 
comparisons between GB0139 3 mg and Placebo within the SoC2 strata (participants not 
currently treated with pirfenidone or nintedanib). All relevant subsections within this section 
have been amended accordingly.
Statistical and Analytical Plans
A blinded data review will be conducted prior to database lock. This review will assess the 
accuracy and completeness of the study database, subject evaluability, and appropriateness of the 
planned statistical methods.
A statistical analysis plan (SAP) will be prepared and finalized prior to database lock. This 
document will provide further details regarding the definition of analysis variables and analysis 
methodology to address all study objectives.
For descriptive statistics categorical data will be presented as frequencies and percentages. 
Percentages will be based on the number of subjects with non-missing values for the 
corresponding categorical variable. Continuous data will be presented as number of subjects with 
non-missing values, mean standard deviation, median, minimum and maximum, as well as the 
25th and 75th percentile.
All statistical tests as well as the confidence intervals will be two-sided. The study-wise type I 
error probability for the confirmatory analyses is set to 10%. 90% confidence intervals are to be 
calculated, if feasible.
Covariates for the primary analyses will be pre-specified. For secondary analyses these are 
anticipated to be broadly similar to primary analysis but will be fully specified in the Statistical 
Analysis Plan (SAP).
Statistical Hypothesis
The primary efficacy analyses are based on data from SoC2 only.
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14.2.1 Primary efficacy endpoints
The superiority of GB0139 3 mg compared to Placebo (Plc) will be tested for the annual rate of 
decline in FVC in mL.
The null hypothesis is:
H0: There is no difference in the annual rate of decline in FVC in mL between GB0139
3 mg and Plc.
The alternative hypotheses are:
Ha: There is a difference in the annual rate of decline in FVC in mL between GB0139
3 mg and Plc.
14.2.2 Key Secondary Efficacy Endpoints:
The superiority of GB0139 3 mg compared to Plc will be tested for the proportion of subjects 
with a decline ≤10% from baseline in predicted %FVC at week 52. The superiority of GB0139
3 mg compared to Plc will be tested for the change from baseline in SGRQ total score at Week 
52.The superiority of GB0139 3 mg compared to Plc will be tested for the time to first 
hospitalization (any respiratory related, including acute exacerbation of IPF) during treatment.
The superiority of GB0139 3 mg compared to Plc will be tested for time to death from all causes 
from date of randomization where time to death will be death at any time up to Week 52.
Analysis Sets
The following analysis sets will be used in this trial

Intention-to-Treat (ITT) Analysis Dataset - this includes all randomized subjects

Modified Intention-to-Treat Analysis Dataset (mITT) - this includes all randomized 
subjects with at least one application of study drug, and will be grouped according to the 
treatment they were randomised to.

Safety Analysis Dataset- this includes all randomized subjects with at least one 
application of study drug, and will be grouped according to the treatment they received.
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
Per-Protocol Analysis Dataset - this includes a subset of the subjects in the ITT analysis 
set who complied with the protocol sufficiently to ensure that these data would be likely 
to represent the effects of study intervention according to the underlying scientific model 
(e.g., subjects who took at least 80% of study intervention treatment for at least 80% of 
the initial 52 weeks).
Primary Efficacy Analysis
The primary efficacy analysis will be based on data from SoC2 only. 
14.4.1 Analysis of Primary Efficacy Endpoint
The primary endpoint is described in Section 9.1. The primary efficacy analysis is a random 
coefficient regression (random slopes and intercepts) model. Treatment and baseline FVC (mL) 
will be included as a covariate in the analysis model. Other covariates such as age, and gender 
will be included as covariates unless their inclusion violates model assumptions or impacts 
stability. Baseline FVC is defined as the FVC result recorded at Visit w0/baseline, unless 
missing in which case the latest FVC before randomization in the subject’s chart result will be 
used.
The decrease in FVC is assumed to be linear within each subject over 52 weeks. The intercepts 
and slopes will be assumed to be normally distributed with arbitrary covariance matrix. The 
within-subject error will be assumed to be independent and normally distributed with mean zero 
and a common variance. The Kenward-Roger approximation will be used to estimate 
denominators degrees of freedom. 
Section 14.8 details of the approaches to handling of missing data are given.
Significance tests will be based on least-squares means; p-values and two-sided 90% confidence 
intervals for the difference between the treatment groups will be presented. An intent-to-treat 
principle will be used. Analyses will be implemented using SAS® Version 9.4 or higher. The 
assumptions for the primary analysis of decline in FVC will be tested; details will be provided in 
the SAP. The primary analysis will be based on observed data (but including retrieved drop out 
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measurements) and will assume remaining missing data are missing at random. The effect of 
missing data will be investigated using multiple imputation methods which assume that subjects 
who discontinue treatment will no longer benefit from it in the future. See Section 14.8 for 
further details of these sensitivity analyses. 
Subgroup analyses will be fully specified in the SAP and will include: 
•
Age
•
Gender
•
Race
•
Ethnicity
•
Previous treatment with pirfenidone and/or nintedanib
•
Recruitment cohort (e.g., pre- or post- DSMB cutoff, and pre- or post-Protocol version 
6.1_UK)
A cumulative distribution plot will be provided, showing the percentage of subjects by change 
from baseline in FVC in mL at week 52. 
Data will be summarized graphically and using summary statistics.
14.4.2 Analysis of Secondary Endpoints 
For all secondary endpoints, an intent-to-treat principle will be used.
14.4.2.1 Key Secondary Endpoints
The key secondary analysis will be based on data from SoC2 only. Data will be summarized 
graphically and using summary statistics. The multiplicity procedure used for the key secondary 
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Comparisons between treatment groups regarding the binary endpoint variable based on an 
absolute decline from baseline in FVC % predicted of ≤10% will be performed using a logistic 
regression model. Treatment and baseline FVC (mL) will be included in the model along with 
any other covariates included in the analysis of the primary endpoint. The likelihood-ratio test 
will be used to test for differences between treatments. Odds ratios together with 90% confidence 
intervals will be used to quantify the effect of treatment, comparing GB0139 3 mg to placebo as 
the reference.
The change from baseline in the SGRQ total score at Week 52 will be analysed using a mixed 
model repeated measures with covariates treatment, baseline total score along with any other 
covariates included in the analysis of the primary endpoint.
The time to first hospitalization (respiratory related, including acute exacerbation of IPF) will be 
analysed using a Cox proportional hazards model with covariates treatment, baseline FVC (mL) 
along with any other covariates included in the analysis of the primary endpoint. The equality of 
the hazard rates between the GB0139 3 mg and placebo group will be tested by the Wald test for 
the treatment effect. The model will include treatment as covariates. Breslow’s method for 
handling ties will be used. Kaplan-Meier plots by treatment group will also be presented. 
Time to death from all causes (plus death from respiratory-related causes if numbers allow) will 
be analysed using a Cox proportional hazards model. The equality of the hazard rates between 
the GB0139 3 mg group and placebo will be tested by the Wald test for the treatment effect. The 
model will include treatment, baseline FVC (mL) as covariates along with any other covariates 
included in the analysis of the primary endpoint. Breslow’s method for handling ties will be 
used. Kaplan-Meier plots by treatment group will also be presented. If the proportion of deaths is 
less than 5%, then only frequencies of deaths by treatment group will be provided for the key 
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14.4.2.2 Other Secondary Endpoints
All further endpoint analyses will be considered exploratory in nature. 
Data will be summarized graphically and using summary statistics. 
Any p-values presented for the secondary endpoints will be considered nominal in nature and no 
adjustment for multiplicity will be made. 
Further details are given in the SAP.
Secondary Efficacy Analysis
Secondary efficacy analysis of subgroups will be based on:

Strata (i.e. analysing available data from SoC1)

Previous treatment with pirfenidone and/or nintedanib

Cohort (e.g. pre- or post- DSMB cutoff, and pre- or post-Protocol version 6.1_UK)
The same endpoints as for the primary and key secondary efficacy analysis will be analysed in an 
exploratory manner with the same methods as described for the primary efficacy analysis. No 
formal statistical hypotheses will be tested.
14.5.1 Other Analyses
Intervention groups should be compared on baseline characteristics, including demographics and 
laboratory measurements, using descriptive statistics. No inferential statistics will be used. The 
primary and key secondary endpoints will be analysed by age, gender, race and ethnicity. Models 
as described for the primary and key secondary endpoints will be used including the covariates 
defining the subgroup in the model and a covariate-by-treatment interaction factor. Individual 
subject data will be listed by treatment group and time point.
14.5.2 Safety Analysis
The primary assessment of benefit-risk of GB0139 3 mg compared to Plc will be based on 
efficacy and safety data over 52 weeks. All safety assessments described below will focus on 
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data collected within the first 52 weeks of the study. In addition, selected safety analyses will be 
repeated to include data collected beyond 52 weeks; further details will be specified in the SAP. 
All treated subjects will be included in the safety analysis. The primary safety assessment will be 
based on the participants who received 3mg or placebo as study treatments.  A separate safety 
assessment will be made for the participants who received study treatment in combination of 
nintedanib or pirfenadone. The particular tables and figures to be split in this way will be 
specified in the SAP. In general, safety analyses will be descriptive in nature. No hypothesis 
testing is planned. 
Kaplan-Meier plots will be produced for the time to premature treatment discontinuation. 
Statistical analysis and reporting of adverse events will concentrate on treatment-emergent 
adverse events. All adverse events occurring between start of treatment and end of the residual 
effect period will be considered ‘treatment-emergent’. The residual effect period is defined as the 
28 days after the date of the last dose of trial medication. Adverse events that start before first 
drug intake and deteriorate under treatment will also be considered ‘treatment-emergent’. 
Frequency, severity, and causal relationship of adverse events will be tabulated by system organ 
class and preferred term after coding according to the current version of MedDRA. 
Laboratory data will be analysed both quantitatively as well as qualitatively. The latter will be 
done via comparison of laboratory data to their reference ranges. Values outside the reference 
range as well as values defined as clinically relevant will be highlighted in the listings. Treatment 
groups will be compared descriptively with regard to distribution parameters as well as with 
regard to frequency and percentage of subjects with abnormal values or clinically relevant 
abnormal values. 
Vital signs, physical examinations, or other safety-relevant data observed at screening, baseline, 
during the course of the treatment and at the end-of-treatment evaluation will be assessed with 
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Determination of Sample Size
The null hypothesis for the treatment difference between GB0139 at 3 mg and placebo for the 
two doses is tested using a type I error of 10% for a 2-side test. The power for detecting a 
statistically significant difference in the treatment effect (annual rate of decline in FVC or the 
FVC change from baseline to 52 weeks) is dependent on the effect size (mean treatment 
difference/ standard deviation) and the number of subjects per treatment group.
To detect an average difference from placebo in decline in FVC of at least 100 ml and with a 
standard deviation of 240 ml then a final sample size of 141 subjects would provide 75% power, 
assuming that future subjects are randomised into the study on a 1:2 randomisation allocation so 
that for every subject randomised to placebo 2 subjects will be randomised to 3 mg GB0139.
Randomization
Following the Protocol version 6.1_UK participants will be randomised in blocks to double-blind 
treatment in a 1:2 ratio (Placebo : GB0139 3 mg). The unbalanced randomisation is to maintain 
the same probability of allocation to placebo post-Protocol version 6.1_UK since this may 
impact participant enrolment. Note that prior to Protocol version 6.1_UK participants were
randomized in blocks to double-blind treatment in a 1:1:1 ratio (GB0139 3 mg : GB0139 10 mg : 
Placebo) stratified by SoC. 
The Sponsor will arrange for the randomization and the packaging and labelling of trial
medication. The randomization list will be generated using a validated system, which involves a 
pseudo-random number generator so that the resulting treatment will be both reproducible and 
non-predictable. The block size will be documented in the CTR. Access to the codes will be 
controlled and documented.
Handling of Missing Data
This section describes the estimands approach for the primary analysis and associated sensitivity 
analyses using the Detailed Clinical Objectives framework described by Bell [51].
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The trial will compare GB0139 3 mg with Placebo in patients with IPF not currently treated with 
pirfenidone or nintedanib. The primary objective is to demonstrate superiority of GB0139 3 mg 
for the mean annual rate of decline in FVC in mL. A composite strategy will be taken to patient 
deaths with FVC attributed the lowest value recorded in the trial when a patient dies.
Three specific inter-current events (ICEs) are anticipated during the trial: death, treatment 
discontinuation, and initiation of pirfenidone or nintedanib. The handling of these ICEs for the 
treatment effect of primary interest and planned sensitivity analyses for the primary endpoint are 
described in Table 5.
Table 5:
Handling of anticipated ICEs for treatment effect of primary endpoint
Treatment 
effect
Description
Death
Treatment 
discontinuation
Initiation of IPF 
therapy
Primary (ICEs 
of treatment 
discontinuation 
or additional 
IPF therapy)
Randomized and 
treated patients 
with treatment 
policy applied 
for intercurrent 
events other than 
death
FVC attributed 
the lowest 
value recorded 
in the trial 
when a patient 
dies
Analysis will include 
all available FVC 
measurements after 
randomised treatment 
discontinuation
Analysis will include 
all available FVC 
measurements after 
initiation of additional 
IPF therapy
Sensitivity 1 
(on-treatment)
Randomized and 
treated patients 
while on 
randomised 
treatment
FVC attributed 
the lowest 
value recorded 
in the trial 
when a patient 
dies
Analysis will exclude 
any FVC 
measurements after 
randomised treatment 
discontinuation
Analysis will exclude 
any FVC 
measurements after 
initiation of additional 
IPF therapy
Sensitivity 2 
(ICE of Death)
Randomized and 
treated patients 
while on 
FVC attributed 
value of 0 
Analysis will exclude 
any FVC 
measurements after 
Analysis will exclude 
any FVC 
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randomised 
treatment
when a patient 
dies
randomised treatment 
discontinuation
initiation of additional 
IPF therapy
Sensitivity 3 
(Tipping point 
for ICE of 
Death will only 
be performed if 
sensitivity 2 
indicates a 
different 
conclusion to 
primary 
analysis)
Randomized and 
treated patients 
while on 
randomised 
treatment
When a patient 
dies FVC 
attributed a 
series of values 
between 0 and 
the lowest 
value recorded 
in the trial 
Analysis will exclude 
any FVC 
measurements after 
randomised treatment 
discontinuation
Analysis will exclude 
any FVC 
measurements after 
initiation of additional 
IPF therapy
Further details for the tipping point analysis can be found in the SAP.


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15.0
QUALITY CONTROL AND QUALITY ASSURANCE
Study-Site Monitoring Visits
Monitoring visits to the study site will be done periodically during the study to ensure that all 
aspects of the protocol are followed, and according to the monitoring plan. Source documents 
will be reviewed for verification of data recorded on the eCRFs. Source documents are defined 
as original documents, data, and records. The investigator and institution guarantee access to 
source documents by the sponsor or its designee (CRO) and by the IRB or IEC.
All aspects of the study and its documentation will be subject to review by the sponsor or 
designee (as long as blinding is not jeopardized), including but not limited to the Investigator’s 
Binder, study medication, subject medical records, informed consent documentation, 
documentation of subject authorization to use personal health information (if separate from the 
informed consent forms), and review of eCRFs and associated source documents. It is important 
that the investigator and delegated study personnel are available during the monitoring visits and 
that sufficient time is devoted to the process.
Protocol Deviations
The investigator should not deviate from the protocol, except where necessary to eliminate an 
immediate hazard to study subjects. Should other unexpected circumstances arise that will 
require deviation from protocol-specified procedures, the investigator should consult with the 
sponsor or designee (and IRB or IEC, as required) to determine the appropriate course of action. 
There will be no exemptions (a prospectively approved deviation) from the inclusion or 
exclusion criteria.
The site must document all protocol deviations in the subject’s source documents. In the event of 
a significant deviation, the site must notify the sponsor or its designee (and IRB or EC, as 
required). Significant deviations include, but are not limited to, those that involve fraud or 
misconduct, increase the health risk to the subject, or confound interpretation of primary study 
assessment. Protocol Deviations are recorded by the CRO's CRA in their clinical trial 
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management system. All recorded Protocol Deviations will be shared with the investigator in 
writing following each monitoring visit, and period reports will be made available as required for 
submission to the EC/IRB. Recorded Protocol Deviations will also be reviewed regularly with 
Galecto.
The investigator can deviate and change from the protocol for any medically unavoidable reason, 
for example, to eliminate an immediate hazard to study subjects, without a prior written 
agreement from the sponsor or a prior approval from IRB. In the event of a deviation or change, 
the principal investigator should notify the sponsor and the head of the site of the deviation or 
change as well as its reason in a written form, and then retain a copy of the written form. When 
necessary, the principal investigator may consult and agree with the sponsor on a protocol 
amendment. If the protocol amendment is appropriate, the amendment proposal should be 
submitted to the head of the site as soon as possible and an approval from IRB should be 
obtained.
The investigator must document all protocol deviations.
Quality Assurance Audits and Regulatory Agency Inspections
The study site also may be subject to quality assurance audits by the sponsor or designees. In this 
circumstance, the sponsor-designated auditor will contact the site in advance to arrange an 
auditing visit or remote auditing. The auditor may ask to visit the facilities where laboratory 
samples are collected, where the medication is stored and prepared, and any other facility used 
during the study. In addition, there is the possibility that this study may be inspected by 
regulatory agencies, including those of foreign governments (e.g., the FDA, the United Kingdom 
Medicines and Healthcare products Regulatory Agency). If the study site is contacted for an 
inspection by a regulatory body, the sponsor should be notified immediately. The investigator 
and institution guarantee access for quality assurance auditors to all study documents as 
described in Section 15.1.
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16.0
ETHICAL ASPECTS OF THE STUDY
This study will be conducted with the highest respect for the individual subjects (i.e., subjects) 
according to the protocol, the ethical principles that have their origin in the Declaration of 
Helsinki, and the ICH Harmonised Tripartite Guideline for GCP. Each investigator will conduct 
the study according to applicable local or regional regulatory requirements and align his or her 
conduct in accordance with the “Responsibilities of the Investigator” that are listed in Section 
18.0. The principles of Helsinki are addressed through the protocol and through appendices 
containing requirements for informed consent and investigator responsibilities.
IRB and/or IEC Approval
IRBs and IECs must be constituted according to the applicable requirements of each 
participating region. The sponsor or designee will require documentation noting all names and 
titles of members who make up the respective IRB or IEC. If any member of the IRB or IEC has 
direct participation in this study, written notification regarding his or her abstinence from voting 
must also be obtained. Those American sites unwilling to provide names and titles of all 
members due to privacy and conflict of interest concerns should instead provide a Federal Wide 
Assurance Number or comparable number assigned by the Department of Health and Human 
Services.
The sponsor or designee will supply relevant documents for submission to the respective IRB or 
IEC for the protocol’s review and approval. This protocol, the Investigator’s Brochure, a copy of 
the informed consent form, and, if applicable, subject recruitment materials and/or 
advertisements and other documents required by all applicable laws and regulations, must be 
submitted to a central or local IRB or IEC for approval. The IRB’s or IEC’s written approval of 
the protocol and subject informed consent must be obtained and submitted to the sponsor or 
designee before commencement of the study (i.e., before shipment of the sponsor-supplied drug 
or study specific screening activity). The IRB or IEC approval must refer to the study by exact 
protocol title, number, and version date; identify versions of other documents (e.g., informed 
consent form) reviewed; and state the approval date. Once the sponsor or designee has confirmed 
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the adequacy of site regulatory documentation and, when applicable, the sponsor or designee has 
received permission from competent authority to begin the trial, it will notify investigative sites 
meaning that protocol activities and screening may occur.
Sites must adhere to all requirements stipulated by their respective IRB or IEC. This may include 
notification to the IRB or IEC regarding protocol amendments, updates to the informed consent 
form, recruitment materials intended for viewing by subjects, local safety reporting requirements, 
reports and updates regarding the ongoing review of the study at intervals specified by the 
respective IRB or IEC, and submission of the investigator’s final status report to IRB or IEC. All 
IRB and IEC approvals and relevant documentation for these items must be provided to the 
sponsor or its designee.
Subject incentives should not exert undue influence for participation. Payments to subjects must 
be approved by the IRB or IEC and sponsor.
Subject Information, Informed Consent, and Subject Authorization
Written consent documents will embody the elements of informed consent as described in the 
Declaration of Helsinki and the ICH Guidelines for GCP and will be in accordance with all 
applicable laws and regulations. The informed consent form describes the planned and permitted 
uses, transfers, and disclosures of the subject’s personal health information for purposes of 
conducting the study. The informed consent form further explains the nature of the study, its 
objectives, and potential risks and benefits, as well as the date informed consent is given. The 
informed consent form will detail the requirements of the subject and the fact that he or she is 
free to withdraw at any time without giving a reason and without prejudice to his or her further 
medical care.
The designated CROs are responsible for the preparation, content, and IRB or IEC approval of 
the informed consent form. The informed consent form must be approved by both the IRB or 
IEC and the sponsor prior to use.
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The informed consent form must be written in a language fully comprehensible to the 
prospective subject. It is the responsibility of the investigator to explain the detailed elements of 
the informed consent form to the subject. Information should be given in both oral and written 
form whenever possible and in the manner deemed appropriate by the IRB or IEC. In the event 
the subject is not capable of rendering adequate written informed consent, then the subject’s 
legally acceptable representative may provide such consent for the subject in accordance with 
applicable laws and regulations.
The subject, or the subject’s legally acceptable representative, must be given ample opportunity 
to: (1) inquire about details of the study and (2) decide whether or not to participate in the study. 
If the subject, or the subject’s legally acceptable representative, determines he or she will 
participate in the study, then the informed consent form must be signed and dated by the subject, 
or the subject’s legally acceptable representative, at the time of consent and prior to the subject 
entering into the study. The subject or the subject’s legally acceptable representative should be 
instructed to sign using their legal names, not nicknames, using blue or black ballpoint ink. The 
investigator must also sign and date the informed consent form at the time of consent and prior to 
subject entering into the study; however, the sponsor may allow a designee of the investigator to 
sign to the extent permitted by applicable law.
Once signed, the original informed consent form will be stored in the investigator’s site file. The 
investigator must document the date the subject signs the informed consent in the subject’s 
medical record. Copies of the signed informed consent form shall be given to the subject.
All revised informed consent forms must be reviewed and signed by relevant subjects or the 
relevant subject’s legally acceptable representative in the same manner as the original informed 
consent. The date the revised consent was obtained should be recorded in the subject’s medical 
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Subject Confidentiality
The sponsor and designees affirm and uphold the principle of the subject’s right to protection 
against invasion of privacy. Throughout this study, a subject’s source data will only be linked to 
the sponsor’s clinical study database or documentation via a unique identification number. As 
permitted by all applicable laws and regulations, limited subject attributes, such as sex, age, or 
date of birth, and subject initials may be used to verify the subject and accuracy of the subject’s 
unique identification number.
To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the 
sponsor requires the investigator to permit its monitor or designee’s monitor, representatives 
from any regulatory authority (e.g., FDA, Medicines and Healthcare products Regulatory 
Agency, Pharmaceuticals and Medical Devices Agency), the sponsor’s designated auditors, and 
the appropriate IRBs and IECs to review the subject’s original medical records (source data or 
documents), including, but not limited to, laboratory test result reports, ECG reports, admission 
and discharge summaries for hospital admissions occurring during a subject’s study 
participation, and autopsy reports. Access to a subject’s original medical records requires the 
specific authorization of the subject as part of the informed consent process (see Section 16.2).
Copies of any subject source documents that are provided to the sponsor must have certain 
personally identifiable information removed (i.e., subject name, address, and other identifier 
fields not collected on the subject’s eCRF).
Publication, Disclosure, and Clinical Trial Registration Policy
16.4.1 Publication 
The investigator is obliged to provide the sponsor with complete test results and all data derived 
by the investigator from the study. During and after the study, only the sponsor may make study 
information available to other study investigators or to regulatory agencies, except as required by 
law or regulation. Except as otherwise allowable in the clinical study site agreement, any public 
16.3
16.4


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disclosure (including publicly accessible websites) related to the protocol or study results, other 
than study recruitment materials and/or advertisements, is the sole responsibility of Galecto.
The sponsor may publish any data and information from the study (including data and 
information generated by the investigator) without the consent of the investigator. Manuscript 
authorship for any peer-reviewed publication will appropriately reflect contributions to the 
production and review of the document. All publications and presentations must be prepared in 
accordance with this section and the Clinical Study Site Agreement. In the event of any 
discrepancy between the protocol and the Clinical Study Site Agreement, the Clinical Study Site 
Agreement will prevail.
16.4.2 Clinical Trial Registration
In order to ensure that information on clinical trials reaches the public in a timely manner and to 
comply with applicable laws, regulations and guidance, Galecto will, at a minimum register 
interventional clinical trials it sponsors anywhere in the world on ClinicalTrials.gov or other 
publicly accessible websites on or before start of study. Galecto contact information, along with 
investigator’s city, state (for Americas investigators), country, and recruiting status will be 
registered and available for public viewing. 
As needed Galecto and Investigator/site contact information may be made public to support 
subject access to trials via registries. Once subjects receive investigator contact information, they 
may call the site requesting enrollment into the trial. The investigative sites are encouraged to 
handle the trial inquiries according to their established subject screening process.
16.4.3 Clinical Trial Results Disclosure
Galecto Biotech will post the results of clinical trials on ClinicalTrials.gov or other publicly 
accessible websites (including the Galecto corporate site) and registries. 
Insurance and Compensation for Injury
Each subject in the study must be insured in accordance with the regulations applicable to the 
site where the subject is participating. If a local underwriter is required, then the sponsor’s 
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designee will obtain clinical study insurance against the risk of injury to clinical study subjects. 
Refer to the Clinical Study Site Agreement regarding the sponsor’s policy on subject 
compensation and treatment for injury. If the investigator has questions regarding this policy, he 
or she should contact the sponsor or sponsor’s designee.


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17.0
REFERENCES
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Ryu JH, Wells AU. Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society 
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American Thoracic Society/European Respiratory Society. International multidisciplinary 
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Raghu G, Collard HR, Egan J, et al. An official ATS/ERS/JRS/ALAT statement: 
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Kim HJ, Perlman D, Tomic R. Natural history of idiopathic pulmonary fibrosis. Respir 
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King TE Jr, Tooze JA, SchwarzMI, Brown K, Cherniack RM. Predicting survival in 
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Latsi PI, du Bois RM, Nicholson AG, Colby TV, Bisirtzoglou D, Nikolakopoulou A, 
Veeraraghavan S, Hansell DM, Wells AU. Fibrotic idiopathic interstitial pneumonia: the  
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Lancet  2011; 378:1949–61.
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Friedman SL, Sheppard D, Duffield JS, and Violette S. Therapy for fibrotic diseases: 
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Speca S, Giusti I, Rieder F, and Latella G. Cellular and molecular mechanisms of 
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Kuhn C III, Boldt J, King TE Jr, Crouch E, Vartio T, McDonald JA. An  
immunohistochemical study of architectural remodeling and connective tissue synthesis in  
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King TE Jr, Pardo A, Selman M. Idiopathic pulmonary fibrosis. Lancet 2011; 
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14.
Kim KK, Kugler MC, Wolters PJ, Robillard L, Galvez MG, Brumwell AN, SheppardD, 
and Chapman HA. Alveolar epithelial cell mesenchymal transition develops in vivo during 
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Sureshbabu A, Tonner E, Allan GJ, and Flint DJ. Relative roles of TGF-b and IGFBP-5 
in idiopathic pulmonary fibrosis. Pulm Med 2011:517687.
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Mizushima T. Ameliorative effect of mepenzolate bromide against pulmonary fibrosis. J 
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antiinflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of 
lung fibrosis. J Pharmacol Exp Ther 2014; 349:209–220.
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Mackinnon AC, Gibbons MA, Farnworth SL, Leffler H, Nilsson UJ, Delaine T, Simpson 
AJ, Forbes SJ, Hirani N, and Gauldie J, et al. Regulation of transforming growth factor b1-driven 
lung fibrosis by galectin-3. Am J Respir Crit Care Med 2012; 185:537-546.  
19.
Kasper M and Hughes RC. Immunocytochemical evidence for a modulation of galectin 3 
(Mac-2), a carbohydrate binding protein, in pulmonary fibrosis. J Pathol 1996; 179:309–316.
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Lee BS, Margolin SB, Nowak RA. Pirfenidone: a novel pharmacological agent that 
inhibits leiomyoma cell proliferation and collagen production. J Clin Endocrinol Metab  1998; 
83(1):219–223.
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Oku H, Shimizu T, Kawabata T, et al. Antifibrotic action of pirfenidone and 
prednisolone: different effects on pulmonary cytokines and growth factors in bleomycin-induced 
murine pulmonary fibrosis. Eur J Pharmacol 2008; 590(1–3):400–408.
22.
Iyer SN, Gurujeyalakshmi G, Giri SN. Effects of pirfenidone on transforming growth 
factor-beta gene expression at the transcriptional level in bleomycin hamster model of lung  
fibrosis. J Pharmacol Exp Ther 1999; 291(1):367–373.
23.
Iyer SN, Gurujeyalakshmi G, Giri SN. Effects of pirfenidone on procollagen gene 
expression at the transcriptional level in bleomycin hamster model of lung fibrosis. J  Pharmacol 
Exp Ther 1999; 289(1):211–218.
24.
Copley SJ, Wells AU, Hawtin KE, et al. Lung morphology in the elderly: comparative 
CT  study of subjects over 75 years old versus those under 55 years old. Radiology 2009; 251: 
566–573.
25.
Washko GR, Hunninghake GM, Fernandez IE, et al. Lung volumes and emphysema in  
smokers with interstitial lung abnormalities. N Engl J Med 2011; 364:897–906.
26.
Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic  
pulmonary fibrosis. Am J Respir Crit Care Med 2011; 183:431–440.


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27.
Ryerson CJ, Cottin V, Brown KK, et al. Acute exacerbation of idiopathic pulmonary 
fibrosis: shifting the paradigm. Eur Respir J 2015; 46:512–520.
28.
Collard HR, Moore BB, Flaherty KR, et al. Acute exacerbations of idiopathic pulmonary  
fibrosis. Am J Respir Crit Care Med 2007; 176:636–643.
29.
Martinez FJ, Safrin S, Weycker D, et al. The clinical course of subjects with idiopathic   
pulmonary fibrosis. Ann Intern Med 2005; 142:963–967.
30.
Swigris JJ, Gould MK, Wilson SR. Health-related quality of life among subjects with  
idiopathic pulmonary fibrosis. Chest 2005; 127:284–294.
31.
Noble PW, Barkauskas CE, Jiang D. Pulmonary fibrosis: patterns and perpetrators. J Clin 
Invest 2012; 122:2756–2762.
32.
Borie R, Justet A, Beltramo G, Manali ED, Pradere P, Spagnalo P, Crestani B. 
Respirology 2016; 21(4):615-625. 
33.
Richeldi L, du Bois RM, Raghu G, et al; INPULSIS Trial Investigators. Efficacy and 
safety  of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014;370(22):2071–2082.
34.
Noble PW, Albera C, Bradford WZ, et al; CAPACITY Study Group. Pirfenidone in  
subjects with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet 2011; 
377(9779):1760–1769.
35.
King TE Jr, BradfordWZ, Castro-Bernardini S, et al; ASCEND Study Group. A phase 3  
trial of pirfenidone in subjects with idiopathic pulmonary fibrosis. N Engl J Med 2014; 
370(22):2083–2092.
36.
Raghu G, Rochwerg B, Zhang Y, et al. An official ATS/ERS/JRS/ALAT clinical practice 
guideline: treatment of idiopathic pulmonary fibrosis. an update of the 2011 clinical  practice 
guideline. Am J Respir Crit Care Med 2015; 192:e3–19.  
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Wuyts WA, Antoniou KM, Borensztajn K, et al. Combination therapy: the future of 
management for idiopathic pulmonary fibrosis? Lancet Respir Med 2014; 2:933–942.
38.
Collard HR, Bradford WZ, Cottin V, et al. A new era in idiopathic pulmonary fibrosis: 
considerations for future clinical trials. Eur Respir J 2015; 46:243–249.
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Wells A. Combination therapy in idiopathic pulmonary fibrosis: the way ahead will be 
hard. Eur Respir J 2015; 45:1208–1210.
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Richeldi L, Davies HR, Ferrara G, et al. Corticosteroids for idiopathic pulmonary 
fibrosis.     Cochrane Database Syst Rev. 2003; 3:CD002880.
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Davies HR, Richeldi L, Walters EH. Immunomodulatory agents for idiopathic pulmonary 
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Dumic, J., S. Dabelic, and M. Flogel, Galectin-3: an open-ended story. Biochim Biophys 
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43.
Mackinnon AC, Gibbons MA, Farnworth SL, Leffler H, Nilsson UJ, Delaine T, et al.., 
Regulation of transforming growth factor-beta1-driven lung fibrosis by galectin-3. Am J Respir 
Crit Care Med, 2012. 185(5): p. 537-46.
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Henderson NC, Mackinnon AC, Farnworth SL, Poirier F, Russo FP, Iredale JP, et al 
Galectin-3 regulates myofibroblast activation and hepatic fibrosis. Proc Natl Acad Sci U S A, 
2006. 103(13): p. 5060-5.
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Henderson NC, Mackinnon AC, Farnworth SL, Kipari T, Haslett C, Iredale JP, et al. 
Galectin-3 Expression and Secretion Links Macrophages to the Promotion of Renal Fibrosis. Am 
J Pathol, 2008. 172(2): p. 288-298.
46.
Farnworth SL, Henderson NC, Mackinnon AC, Atkinson KM, Wilkinson T, Dhaliwal K, 
et al., Galectin-3 reduces the severity of pneumococcal pneumonia by augmenting neutrophil 
function. Am J Pathol, 2008. 172(2): p. 395-405.
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Dang Z, MacKinnon A, Marson LP, & Sethi T. Tubular atrophy and interstitial fibrosis 
after renal transplantation is dependent on galectin-3. Transplantation, 2012. 93(5): p. 477-84.
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MacKinnon AC, Liu X, Hadoke PW, Miller MR, Newby DE, & Sethi T. Inhibition of 
galectin-3 reduces atherosclerosis in apolipoprotein E-deficient mice. Glycobiology, 2013. 23(6): 
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Delaine T, Collins P, MacKinnon A, Sharma G, Stegmayr J, Rajput VK, et al. (2016). 
Galectin-3-Binding Glycomimetics that Strongly Reduce Bleomycin-Induced Lung Fibrosis and
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biology 17: 1759-1770.
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Hirani, H., MacKinnon, A.C., Nicol, L., Ford, P., Schambye, H., Pedersen, A., Nilsson,
U.J., Leffler, H., Sethi, T., Tantawi, S., Gavelle, L., Slack, R.J., Mills, R., Karmakar, U.,
Humphries, D., Zetterberg, F., Keeling, L., Paul, L., Molyneaux, P.L., Li, F., Funston, W.,
Forrest, I.A., Simpson, A.J., Gibbons, M., Maher, T.M., 2020. Target-inhibition of Galectin-3 by
Inhaled TD139 in Patients with Idiopathic Pulmonary Fibrosis. Eur J Respir (in press).
51. Bell J, Hamilton A, Sailer O, Voss F. The detailed clinical objectives approach to designing
clinical trials and choosing estimands.Pharmaceutical Statistics. 2021;1–13.


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18.0
APPENDICES
Appendix 1. Plastiape DPI Inhaler Device - Instructions for Use
1. Remove the protective cap from the 
Plastiape inhaler.
2. Open mouthpiece to access
the capsule housing.
3. Peel back foil from the 
blister strip and remove 
capsule from the blister. 
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4. Load capsule into housing and then shut 
the mouthpiece.
5. Pierce the capsule:
• Hold the inhaler upright with the mouthpiece 
pointing up.
• Pierce the capsule by firmly pressing together 
both side buttons at the same time. Do this 
only once.
• You should hear a “click” as the capsule is being pierced.
6. Breathe out:
Before placing the mouthpiece in your mouth, breathe out fully and do not blow into the 
mouthpiece.


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7. Inhalation
To breathe the medicine deeply into your 
airways:
• hold the inhaler so the side buttons are facing 
left and right, and do not press the side buttons.
• place the mouthpiece in your mouth and close 
your lips firmly around it.
• breathe in rapidly but steadily and as deeply as they can.
8. Note:
As you breathe in through the inhaler, the capsule spins around in the chamber and you should  
hear a whirring noise. 
9. Breath hold:
After you have inhaled the medicine:
• Hold your breath for at least 5-10 seconds or as long as you comfortably can. 
• Then breathe out. Open the inhaler to see if any powder is left in the capsule.
If there is powder left in the capsule:
• Close the inhaler.
• Repeat steps 6 to 9 (second inhalation)


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If there is powder left in the capsule:
• Close the inhaler.
• Repeat steps 6 to 9 (third inhalation)
Most people are able to empty the capsule with one or two inhalations, but a maximum of 3 
inhalations can be performed. Please note that 2 capsules are used per dose so steps 3-10 are 
repeated with the second capsule. 
Please ensure you return all unused medication to your study staff at each visit, including all 
blister packs. 
Please ensure you contact study staff if you have further questions. You will receive training 
prior to your first drug administration by a member off your clinical team. Please ask any 
questions to your study throughout the study, as required. 


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Appendix 2. Biomarker Panel
Biomarkers have the potential to impact all aspects of the clinical care of IPF patients including 
diagnosis and prognosis. The identification of serum biomarkers that are diagnostic for IPF would 
be helpful for both clinicians and patients, particularly in cases where a surgical lung biopsy had 
not been obtained or access to dedicated interstitial lung disease/IPF physicians is limited. 
Secondly, the discovery of peripheral blood biomarkers that reflect disease activity would allow 
for serial monitoring as well as an objective marker to assess treatment efficacy. Lastly, a 
biomarker that provides prognostic information about disease course and/or mortality would be 
valuable for both clinical care and future research study design.
In the context of Galactic-1 study a number of serum biomarkers will be explored:
These may include but are not limited to YKL-40, PAI-1, PDGF-BB, MCP-1, CCL-18, KL-6, 
CA-125, CA-19, Gal-3 and collagen neoepitopes. Testing will be performed at time points 
indicated in the Time and Events Table.
Galectin - 3
Galectins are a group of soluble β-galactoside-binding lectins that play many important regulatory 
roles in inflammation, immunologic response and cancer. A total of 15 galectins have been 
identified. Galectin-3 is the most widely studied member of the galectin protein family [1, 2].
Galectin-3 is a mid-size protein (29 to 35 kDa) consisting of an N-terminal domain with tandem 
repeats of short amino acid segments (a total of approximately 120 amino acids) linked to a single 
C-terminal carbohydrate-recognition domain (CRD) of about 130 amino acids. It can interact with 
carbohydrates, which involves the C-terminal domain, and with unglycosylated molecules, such 
as cell surface and extracellular receptors, which involves the N-terminal domain [3].
As other galectins, galectin-3 does not contain a signal sequence, therefore it is localized primarily 
in the cytoplasm, and occasionally, in the nucleus and mitochondria. Galectin-3 is found in 
epithelial cells, fibroblasts, dendritic cells and inflammatory cells. In addition, galectin-3 can be 
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secreted and function in extracellular space. It can form pentamers upon binding to multivalent 
carbohydrates, therefore it is capable of crosslinking glycans on the cell surface, and in this manner 
initiating transmembrane signaling events and affecting various cellular functions [4].
Galectin-3 is known for its role in tumorigenesis and progression through regulating cell 
proliferation, apoptosis, cell adhesion, invasion, angiogenesis and metastasis. Expression of 
galectin-3 is modulated in many different cancers. Measurement of serum galectin-3 can be helpful 
in diagnosis and prognosis for specific cancer types, such as thyroid and prostate [5].
One of the more interesting and well characterized effects is the role of galectin-3 in the promotion 
of fibrosis. Fibrogenesis or scarring is a consequence of certain types of injury and inflammation, 
which are central pathophysiological mechanisms in the development and progression to heart 
failure. Expression of galectin-3 is low in a healthy human heart; however, as heart failure 
progresses galectin-3 becomes significantly up-regulated. It is released by activated cardiac 
macrophages stimulating additional macrophages, pericytes, myofibroblasts, and fibroblasts, 
which in response signal cellular proliferation and secretion of procollagen I. Procollagen I 
irreversibly crosslinks to form collagen and results in cardiac fibrosis [6 -10].
Involvement of galectin-3 in fibrosis has also been demonstrated in liver [11] and kidney [12].
Inhibition of galectin-3 appears to prevent progression of fibrosis. Recent publications describe 
the tetrapeptide, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) that causes inhibition of cardiac 
fibroblast proliferation and collagen synthesis. Ac-SDKP is a naturally occurring anti-
inflammatory and antifibrotic peptide that is hydrolyzed almost exclusively by angiotensin-
converting enzyme (ACE), and plasma concentration of Ac-SDKP is increased substantially by 
ACE inhibitors. Rats overexpressing cardiac ACE have decreased Ac-SDKP concentration and 
increased fibrosis in heart tissue [13]. Other studies include galectin-3 knock-out mice, use of small 
interfering RNA that can silence galectin-3 gene activity and use of carbohydrate molecules, which 
can deactivate galectin-3.


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Because of the unambiguous association of galectin-3 with the disease development, progression 
and poor outcome, measurement of galectin-3 in patients diagnosed with IPF, pulmonary 
hypertension, acute and chronic heart failure may have diagnostic and therapeutic implications.
Recently, the FDA has approved for market an assay manufactured by BG Medicine, Inc. 
(Waltham, MA) for galectin-3 to supplement standard risk assessment in patients with chronic 
heart failure [14]. BGM Galectin-3 is currently available at Pacific Biomarkers. The test is based 
on the common ELISA utilizing two monoclonal antibodies against galectin-3. One rat monoclonal 
anti-mouse galectin-3 antibody is coated onto the surface of wells as a capture antibody to bind 
galectin-3 molecules in samples, while the other mouse monoclonal anti-human galectin-3 
antibody is provided in solution and functions as the tracer antibody for detecting galectin-3 
molecules bound to the capture antibody [15].
Galectin-3 results should be interpreted with caution. Levels may be increased in patients with 
certain forms of cancer, in other conditions associated with organ fibrosis, and in patients with a 
history of therapeutic use of murine monoclonal antibodies (IgG) or fragments, or who have known 
autoimmune disorders. Additionally, specimens with high levels of gamma globulins (>2.5 g/dL) 
may cause false elevation in results.
References:
1. Barondes SH, Castronovo V, Cooper DN, et al. A family of animal beta-galactoside-binding 
lectins. Cell. 1994;76:597-8.
2. Yang RY, Rabinovich GA, Liu FT. Galectins: structure, function and therapeutic 
potential. Expert Rev Mol Med. 2008;13:e17-e39.
3. Barboni EA, Bawumia S, Henrick K, and Hughes RC. Molecular modeling and mutagenesis 
studies of the N-terminal domains of galectin-3: evidence for participation with the C-terminal 
carbohydrate recognition domain in oligosaccharide binding. Glycobiology. 2000;10(11):1201-8.
4. Ochieng J, Furtak V, and Lukyanov P. Extracellular functions of galectin-3. Glycoconj J. 


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2004;19(7-9): 527-35.
5. Balan V, Nangia-Makker P, and Raz A. Galectins as Cancer Biomarkers. Cancers 2010;2:592-
598.
6. de Boer RA, Yu L, van Veldhuisen DJ. Galectin-3 in cardiac remodeling and heart 
failure Curr Heart Fail Rep. 2010;7:1-8.
7. de Boer RA, Voors AA, Muntendam P, et al. Galectin-3: a novel mediator of heart failure 
development and progression Eur J Heart Fail. 2009;11:811-17.
8. deFilippi CR, Felker GM. Galectin-3 in heart failure-linking fibrosis, remodeling, and 
progression US Cardiology. 2010;7:67-70
9. Lok D, van der Meer P, de La Porte PM, et al. Galectin-3, a novel marker of macrophage 
activity, predicts outcome in patients with stable chronic heart failure J Am Coll Cardiol. 
2007;49:98A
10. Shah RV, Chen-Tournoux AA, Picard MH, et al. Galectin-3, cardiac structure and function, 
and long-term mortality in patients with acutely decompensated heart failure Eur J Heart Fail. 
2010;12:826-32.
11. Henderson NC, Mackinnon AC, Farnworth SL, et al. Galectin-3 regulates myofi broblast 
activation and hepatic fibrosis. Proc Natl Acad Sci. 2006;103:5060-65.
12. Henderson NC, Mackinnon AC, Farnworth SL, et al. Galectin-3 expression and secretion 
links macrophages to the promotion of renal fibrosis. Am J Pathol. 2008;172:288-98.
13. Liu H, D‘Ambrosio M, Liao T, et al. N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac 
remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory 
lectin Am J Physiol Heart Circ Physiol. 2009;296:H404-12.
14. McCullough P, Olobatoke A, Vanhecke TE. Galectin-3: a novel blood test for the evaluation 
and management of patients with heart failure. Rev Cardiovasc Med.  2011;12:200-10
15. Galectin-3 Product Insert (US), BG Medicine, Inc., March 2011.


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YKL-40
Several studies have demonstrated elevated levels of YKL-40, human chitinase-like glycoprotein, 
in the serum and BALF of IPF patients, with a significant correlation between its serum levels and 
clinical parameters, including PaO2, DLCO, and serum concentrations of KL-6. Additionally, 
enhanced expression of YKL-40 protein was found in bronchiolar epithelial cells and alveolar 
macrophages adjacent to fibrotic lesions by immuno-histochemistry [1-4]. Although the detailed 
biological function of YKL-40 has not been fully elucidated, recent studies have shown that this 
glycoprotein has an important role in tissue remodelling processes leading to fibrosis. YKL-40 
potently promotes the growth of fibroblasts, endothelial cells, synovial cells, and chondrocytes [5-
7].
In the lung, a recent study showed elevated serum YKL- 40 levels in patients with severe asthma, 
and its levels correlated with thickening of the subepithelial basement membrane and pulmonary 
function [5, 6]. Taken together, these findings suggest that, besides etiology, YKL-40 can be 
increased under pathological conditions leading to chronic inflammation and tissue remodelling in 
the lung. Collectively, these data suggest that increased production of YKL-40 in IPF lungs 
contributes to tissue remodelling and fibrosis, possibly through its fibrogenic capacity [8-18]. 
References:
1. Furuhashi K, Suda T, Nakamura Y, et al. Increased expression of YKL-40, a chitinase-like 
protein, in serum and lung of patients with idiopathic pulmonary fibrosis. Respir Med. 
2010;104:1204–1210. 
2. Korthagen NM, van Moorsel CH, Barlo NP, et al. Serum and BALF YKL-40 levels 
arepredictors of survival in idiopathic pulmonary fibrosis. Respir Med. 2011;105:106–113.
3. Korthagen NM, van Moorsel CH, Zanen P, Ruven HJ, Grutters JC. Evaluation of circulating 
YKL-40 levels in idiopathic interstitial pneumonias. Lung. 2014;192:975–980.


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4. Chen G, Yang T, Gu Q, Ni XH, Zhao ZH, Ye J, Meng XM, Liu ZH, He JG, Xiong CM.
Elevated plasma YKL-40 as a prognostic indicator in patients with idiopathic pulmonary 
arterial hypertension. Respirology 2014;19:608–615.
5. Chupp GL, Lee CG, Jarjour N, Shim YM, Holm CT, He S, Dziura JD, Reed J, Coyle AJ, 
Kiener P, Cullen M, Grandsaigne M, Dombret MC, Aubier M, Pretolani M, Elias JA. A 
chitinase-like protein in the lung and circulation of patients with severe asthma. N Engl J 
Med 2007;357:2016–2027.
6. Tang H, Fang Z, Sun Y, Li B, Shi Z, Chen J, Zhang T, Xiu Q. YKL-40 in asthmatic patients, 
and its correlations with exacerbation, eosinophils and immunoglobulin E. Eur Respir J 
2010;35:757–760.
7. De Ceuninck F, Gaufillier S, Bonnaud A, Sabatini M, Lesur C, Patoureau P. YKL-40 
(Cartilage gp-39) induces proliferative events in cultured chondrocytes and synoviocytes and 
increases glycosaminoglycan synthesis in chondrocytes. Biochem Biophys Res Commun
2001;285:926e31.
8. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. 
International consensus statement: American Thoracic Society and the European Respiratory 
Society. Am J Respir Crit Care Med 2000;161:646e64.
9. Bigg HF, Wait R, Rowan AD, Cawston TE. The mammalian chitinase-like lectin, YKL-40, 
binds specifically to type I collagen and modulates the rate of type I collagen fibrilformation. 
J Biol Chem 2006;281:21082e9.
10. Johansen JS, Stoltenberg M, Hansen M, et al. Serum YKL-40 concentrations in patients with 
rheumatoid arthritis: relation to disease activity. Rheumatology 1999; 38:618e26.
11. Johansen JS, Milman N, Hansen M, Garbarsch C, Price PA, Graudal N. Increased 
serumYKL-40 in patients with pulmonary sarcoidosis e a potential marker of disease 
activity? Respir Med 2005;99:396e402.


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12. Kruit A, Grutters JC, Ruven HJ, Moorsel CC, van den Bosch JM. A CHI3L1 gene 
polymorphismis associated with serumlevels of YKL-40, a novel sarcoidosis marker. Respir 
Med 2007;101:1563e71.
13. Nordenbaek C, Johansen JS, Halberg P, et al. High serum levels of YKL-40 in patients with 
systemic sclerosis are associated with pulmonary involvement. Scand J Rheumatol
2005;34:293e7.
14. Le´tuve´ S, Kozhich A, Arouche N, et al. YKL-40 is elevated in patients with chronic 
obstructive pulmonary disease and activates alveolar macrophages. J Immunol
2008;181:5167e73.
15. Furuhashi K, Suda T, Nakamura Y, et al. Increased expres¬sion of YKL-40, a chitinase-Like 
protein, in serum and lung of patients with idiopathic pulmonary fibrosis. Respir Med.
2010;104:1204–1210.
16. Korthagen NM, van Moorsel CH, Barlo NP, et al. Serum and BALF YKL-40 levels are 
predictors of survival in idiopathic pulmonary fibrosis. Respir Med. 2011;105:106–113
KL-6/mucin 1 (MUC-1)
KL-6/mucin 1 (MUC-1) is a circulating glycoprotein belonging to the MUC-1 class and is
expressed on alveolar epithelial cells and bronchiolar epithelial cells. KL-6 exerts antifibrotic and
antiapoptotic effects on lung fibroblasts [1]. KL-6 is probably the most extensively studied serum 
biomarker in ILD, at least in Japan, where it has been used to assess patients in the clinical routine 
[2]. Serum KL-6 shows good correlation with disease severity, although it does not discriminate 
between different ILD patterns. Serum levels of KL-6 are significantly elevated in IPF and are 
associated with increased mortality. A serum cut-off value of ⩾1000 U·mL−1 has been associated 
with poor prognosis [3]. The presence of the MUC1 568 adenosine to guanine polymorphism 
(rs4072037) has been found to influence serum KL-6 levels in Caucasian and Japanese subjects, 
and may need to be considered in the calculation of normal upper limits and cut-off values [4,5].


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References:
1. Ohshimo S, Yokoyama A, Hattori N, et al. KL-6, a human MUC1 mucin, promotes 
proliferation and survival of lung fibroblasts. Biochem Biophys Res Commun 2005;338: 
1845–1852.
2. Ishikawa N, Hattori N, Yokoyama A, et al. Utility of KL-6/MUC1 in the clinical  
management of interstitial lung diseases. Respir Investig 2012;50:3–13.
3. Satoh H, Kurishima K, Ishikawa H, et al. Increased levels of KL-6 and subsequent 
mortality in patients with interstitial lung diseases. J Intern Med 2006;260:429–434.
4. Horimasu Y, Hattori N, Ishikawa N, et al. Different MUC1 gene polymorphisms in  
5. German and Japanese ethnicities affect serum KL-6 levels. Respir Med 2012;106:1756–
1764.
6. Janssen R, Kruit A, Grutters JC, et al. The mucin-1 568 adenosine to guanine 
polymorphism influences serum Krebs von den Lungen-6 levels. Am J Respir Cell Mol 
Biol 2006;34:496–499.
PAI-1
Plasmin is a key protease involved in the repair of the damaged alveolar epithelium and the 
plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of plasminogen activators in 
plasma and the alveolar space. PAI-1 is one of the most important target genes in the TGF-
β/Smad signaling pathway, which can hinder the degradation of ECM composition and promote 
cell invasion and migration.  Multiple reports using preclinical models suggest that PAI-
1 deficiency or inhibition of PAI-1 activity attenuates fibrosis. [1]. Mice overexpressing PAI-1 
show increased bleomycin-induced lung fibrosis whilst mice deficient in PAI-1 show reduced 
fibrosis in this model [2,3].  PAI-1 has been shown to be elevated in the BALf in IPF patients 
compared to control [4,5].


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References:
1. Flevaris P, Vaughan D. The Role of Plasminogen Activator Inhibitor Type-1 in Fibrosis.
Semin Thromb Hemost. 2017 Mar;43(2):169-177.
2. Eitzman DT, McCoy RD, Zheng X, Fay WP, Shen T, Ginsburg D, Simon RH.
Bleomycin-induced pulmonary fibrosis in transgenic mice that either lack or overexpress 
the murine plasminogen activator inhibitor-1 gene. J Clin Invest. 1996 (1):232-7.
3. Hattori N, Degen JL, Sisson TH, Liu H, Moore BB, Pandrangi RG, Simon RH, Drew AF.
Bleomycin-induced pulmonary fibrosis in fibrinogen-null mice. J Clin Invest. 2000 
Dec;106(11):1341-50.
4. Lison et al., 1999 Biomarkers : biochemical indicators of exposure, response, and 
susceptibility to chemicals 4, 361-372.
5. Willems S, Verleden SE, Vanaudenaerde BM, Wynants M, Dooms C, Yserbyt J, Somers 
J, Verbeken EK, Verleden GM, Wuyts WA. Multiplex protein profiling of 
bronchoalveolar lavage in idiopathic pulmonary fibrosis and hypersensitivity 
pneumonitis. Ann Thorac Med. 2013 Jan;8(1):38-45.
CCL18
CCL18 is a CC chemokine produced mainly by antigen-presenting cells including alveolar 
macrophages, and is elevated in BALf and serum in patients with IPF [1,2]. CCL18 can stimulate 
pulmonary fibroblasts and increase collagen production in vitro [3]. In GB-HV-01 10 mg GB0139
treatment trended to reduce serum CCL-18 levels compared to the placebo group.
References:
1. Cai M Bonella F, He X, Sixt SU, Sarria R, Guzman J, Costabel U. CCL18 in serum, BAL 
fluid and alveolar macrophage culture supernatant in interstitial lung diseases. Respir 
Med. 2013 Sep;107(9):1444-52.


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2. Zhang Y, Kaminski N. Biomarkers in idiopathic pulmonary fibrosis. Curr Opin Pulm 
Med. 2012 (5):441-6.
3. Prasse A, Pechkovsky DV, Toews GB, Jungraithmayr W, Kollert F, Goldmann T, 
Vollmer E, Müller-Quernheim J, Zissel G. A vicious circle of alveolar macrophages and 
fibroblasts perpetuates pulmonary fibrosis via CCL18. Am J Respir Crit Care Med. 2006 
(7):781-92.
MCP-1
CC 
chemokines 
such 
as 
MCP-1 
play 
important 
roles 
in 
the 
pathogenesis 
of 
interstitial lung diseases. Elevated CC chemokine levels have been observed in BALf of patients 
with IPF (reviewed in [1]). Elevated levels of MCP-1 in BALf may be predictive of a poor outcome 
in patients with IPF [2]. A deficiency in MCP-1 has been shown to protect mice from bleomycin-
induced lung fibrosis [2]. In the GB-HV-01 patient cohort there was a dose dependent trend for a 
reduction in plasma MCP-1 with GB0139.  
References:
1. Osafo-Addo AD, Herzog EL. CCL2 and T cells in pulmonary fibrosis: an old player gets 
a new role. Thorax. 2017 (11):967-968.
2. Baran CP, Opalek JM, McMaken S, Newland CA, O'Brien JM Jr, Hunter MG, 
Bringardner BD, Monick MM, Brigstock DR, Stromberg PC, Hunninghake GW, Marsh 
CB. Important roles for macrophage colony-stimulating factor, CC chemokine ligand 2, 
and mononuclear phagocytes in the pathogenesis of pulmonary fibrosis. Am J Respir Crit 
Care Med. 2007 Jul 1;176(1):78-89.
As well as the biomarkers described above there are several biomarkers of note which have shown 
to be elevated in IPF compared to control and have suggested prognostic significance for disease 
progression.  These include the Nordic collagen neo-epitopes (Jenkins et al., 2015, Lancet. Respir 
Med. 3(6):462472) as well as epithelial markers SPD, SPA, KL-6, CA-125, CA-19) and matrix 


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remodeling markers MMP7 and MMP1 (reviewed in Guiot et al., Lung. 2017 Jun;195(3):273-280; 
Maher et al., 2017, Lancet Respir Med. (12):946-955).  In addition, we would like to incorporate 
the flexibility to measure new analytes as evidence for new biomarkers may evolve during the 
course of the study. 


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Appendix 3. Definition of Acute Exacerbations in IPF
Acute respiratory worsening occurs in a small minority of patients with IPF annually 
(approximately 5–10%) [1-3]. These episodes may occur secondary to common conditions such 
as pneumonia, pulmonary embolism, pneumothorax, or cardiac failure [4]. When a cause cannot 
be identified for the acute respiratory decline, the term acute exacerbation of IPF has been used 
[3, 5-15]. It is presently unclear if acute exacerbation of IPF is simply a manifestation of an 
unidentified respiratory complication (such as pulmonary emboli, infection) contributing to an 
acute worsening in a patient with IPF or represents an inherent acceleration in the 
pathobiological processes involved in IPF. 
Regarding the definition of AE in IPF, a revised "conceptual framework" was proposed by an 
international working group in 2016 [16].
The 2007 proposed definition of an "acute exacerbation" (AE) of IPF included all of the 
following:

A previous or concurrent diagnosis of IPF

Deterioration within 30 days

New bilateral ground glass opacities and/or consolidation on a background of 
reticular or honeycomb pattern consistent with usual interstitial pneumonia (UIP)

No evidence of pulmonary infection by endotracheal aspiration or 
bronchoalveolar lavage

Exclusion of alternative causes including left heart failure, pulmonary embolism, 
or an identifiable cause of acute lung injury
The 2016 revised criteria more accurately reflect today's knowledge of AE-IPF and should allow 
for better insights into the etiology, treatment, and outcomes of this process [17]. Similar to the 
definition in 2007, this newly proposed framework defines an AE as "an acute, clinically 
significant respiratory deterioration characterized by evidence of new widespread alveolar 
18.3


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abnormality," but does not set an exact 30 day limit for symptom onset and does not require 
exclusion of infection. The following diagnostic criteria are proposed:

A known diagnosis of IPF (diagnosis may be made at the time of acute respiratory 
deterioration)

Acute worsening, "typically less than one month's duration"

Computed tomography of the chest with new bilateral ground glass opacification 
and/or consolidation superimposed on a background of findings consistent with 
usual interstitial pneumonia (bibasilar reticular opacities associated with 
honeycomb changes and traction bronchiectasis) 

Heart failure or fluid overload does not fully explain the worsening.
Based on our understanding that these events may be triggered similar to acute lung injury in the 
non-IPF patient population, events are further classified into "triggered" (ie, postprocedure, drug 
toxicity, infection, aspiration) versus "idiopathic" (ie, no inciting event identified). This new 
classification will allow for a more complete picture of these patients.
Pathophysiology and risk factors - While our current understanding of the pathophysiology of 
AE-IPF is limited, AE has clinical similarities to acute respiratory distress syndrome (ARDS). 
Both have increased oxygen needs, bilateral ground glass opacities and/or consolidation on 
imaging, and histopathology demonstrating diffuse alveolar damage [19-22]. It is known that 
there are multiple causes for ARDS and it is likely the same for those with AE-IPF. Further, IPF 
patients likely have maladaptive responses to lung injury, demonstrated by altered responses of 
IPF versus control fibroblasts to stimuli in vitro [23, 24]. 
There are multiple examples of lung injury that subsequently develop into an AE-IPF [25-28]. 

Microaspiration of gastric contents – Microaspiration of gastric contents is a 
proposed risk factor for exacerbations and progression of IPF, based on a meta-
analysis of clinical trials that demonstrated patients who received treatment for 


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gastric reflux had slower decline of forced vital capacity (FVC), although there 
was no difference in mortality [29].

Surgery and thoracic procedures – Thoracic procedures, such as surgical lung 
biopsy, lung cancer resection, and bronchoscopy, have been associated with the 
development of IPF exacerbations [30-34]. Nonthoracic surgical procedures have 
also been implicated in development of exacerbations [33]. Potential mechanisms 
include administration of high concentrations of oxygen and volutrauma or 
barotrauma during mechanical ventilation. However, a causal relationship 
between IPF exacerbations and procedures is difficult to ascertain due to the 
retrospective analysis of the studies. 

Advanced lung disease – Clinical factors of physiologically advanced IPF are 
associated with increased rates of AE, including: lower FVC, diffusing capacity 
of the lung for carbon monoxide (DLCO), and six-minute walk distance [27, 35, 
36]. 

Other – A number of other potential contributors have been implicated, such as 
evidence of pulmonary hypertension, higher body mass index, coronary artery
disease, and treatment with immunosuppressive therapy [36-38].
Clinical manifestations - In patients with IPF, an acute exacerbation typically presents with 
shortness of breath or worsening exercise tolerance that develop over days to weeks, but 
generally less than one month [17,39]. In a small series of 11 patients, the time from onset of 
symptoms to hospital admission averaged approximately 13 days [18]. Cough (with or without 
sputum production) is common; fever and flu-like symptoms may also be present.
On physical examination, the patient may be tachypneic and will typically have bibasilar 
crackles consistent with the underlying diagnosis of IPF.


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Patients typically demonstrate impaired gas exchange, as evidenced by an arterial oxygen tension 
to fraction of inspired oxygen ratio (PaO2/FiO2) of less than 225 mmHg or a decrease in the PaO2 
of 10 mmHg or more from baseline.
High resolution computed tomography (HRCT) reveals bilateral ground glass or consolidative 
opacities superimposed on a background of typical HRCT features of IPF (eg, bibasilar reticular 
opacities, honeycomb changes, traction bronchiectasis).
Diagnosis - The diagnosis of AE-IPF is generally made in a patient with known or concurrently 
diagnosed IPF and the following features [17]:

An acute, clinically significant respiratory deterioration typically <1 month in 
duration

High resolution computed tomography (HRCT) demonstrating new bilateral 
ground glass opacification and/or consolidation superimposed on a background of 
findings consistent with usual interstitial pneumonia

Exclusion of heart failure and fluid overload as significant contributors to the 
deterioration
Flexible bronchoscopy with bronchoalveolar lavage (BAL) is used to identify infectious agents 
and exclude malignancy. While the 2007 criteria for AE-IPF required the exclusion of infection, 
the 2016 criteria do not exclude potential triggers, such as infection, lung procedures/operations, 
drug toxicity, and aspiration [16, 17]. These potential triggers should be noted, but do not 
exclude AE-IPF.
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of AE-IPF includes venous 
thromboembolism, infection, and heart failure. A pneumothorax can complicate IPF, but would 
usually be recognized on a conventional chest radiograph. Pulmonary hypertension developing 
as a consequence of IPF is also in the differential diagnosis of worsening dyspnea, but would not 
have the new radiographic opacities associated with AE-IPF.


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
Venous thromboembolism – IPF is associated with a significantly increased risk 
of venous thromboembolism (VTE) [40-42]. The suspicion for VTE is increased 
in patients with obesity, immobilization, malignancy, and prior or family history 
of VTE. 

Infection – For patients who can tolerate the procedure, our standard practice is to 
perform a full investigation for potential lung infection and to initiate empiric 
antibiotics for pneumonia while studies are pending, as described. The choice of 
antibiotics for community-acquired pneumonia is described separately. 

Heart failure – Given the average age of individuals with IPF, careful cardiac 
assessment for heart failure or myocardial infarction is appropriate. We typically 
begin with serial troponin, brain natriuretic peptide (BNP), and an 
electrocardiogram. An echocardiogram is not typically a first line assessment, but 
may be useful to evaluate for heart failure in a subset of patients, such as those 
with extrathoracic clinical features of heart failure or an elevated BNP. 

Pulmonary hypertension – Pulmonary hypertension (group 3), a well-known 
complication of IPF, also presents with worsening dyspnea, but without increased 
radiographic opacities. The diagnosis is often suspected in patients with 
worsening gas transfer without evidence of worsening interstitial lung disease.
Plasma BNP is often increased, and Doppler echocardiography can provide an 
estimate of pulmonary artery systolic pressure. A firm diagnosis requires right 
heart catheterization. 
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19.0
A. RESPONSIBILITIES OF THE INVESTIGATOR
Clinical research studies sponsored by the sponsor are subject to ICH GCP and all the applicable 
local laws and regulations. The responsibilities imposed on investigators by the FDA are 
summarized in the “Statement of Investigator” (Form FDA 1572 – A).
By signing the Form FDA 1572, the investigator agrees to assume the following responsibilities:
1. Conduct the study in accordance with the protocol.
2. Personally conduct or supervise the staff who will assist in the protocol.
3. Ensure that study related procedures, including study specific (non routine/non standard
panel) screening assessments are NOT performed on potential subjects, prior to the receipt of 
written approval from relevant governing bodies/authorities.
4. Ensure that all colleagues and employees assisting in the conduct of the study are informed 
of these obligations.
5. Secure prior approval of the study and any changes by an appropriate IRB/IEC that conform 
to 21 CFR Part 56 (for IND only), ICH, and local regulatory requirements.
6. Ensure that the IRB/IEC will be responsible for initial review, continuing review, and 
approval of the protocol. Promptly report to the IRB/IEC all changes in research activity and 
all anticipated risks to subjects. Make at least yearly reports on the progress of the study to 
the IRB/IEC, and issue a final report within 3 months of study completion.
7. Ensure that requirements for informed consent, as outlined in 21 CFR Part 50 (only for IND), 
ICH and local regulations, are met.
8. Obtain valid informed consent from each subject who participates in the study, and document 
the date of consent in the subject’s medical chart. Valid informed consent is the most current 
version approved by the IRB/IEC. Each informed consent form should contain a subject 
authorization section that describes the uses and disclosures of a subject’s personal 
information (including personal health information) that will take place in connection with 


Galecto Biotech AB
Page 105 of 105
GALACTIC-1 v7.1_UK
28 January 2022
the study. If an informed consent form does not include such a subject authorization, then the 
investigator must obtain a separate subject authorization form from each subject or the 
subject’s legally acceptable representative.
9. Prepare and maintain adequate case histories of all persons entered into the study, including 
eCRFs, hospital records, laboratory results, etc, and maintain these data for a minimum of 
2 years following notification by the sponsor that all investigations have been discontinued or 
that the regulatory authority has approved the marketing application. The investigator should 
contact and receive written approval from the sponsor before disposing of any such 
documents.
10. Allow possible inspection and copying by the regulatory authority of GCP-specified essential 
documents.
11. Report adverse reactions to the sponsor promptly. In the event of an SAE, notify the sponsor 
within 24 hours.

SAP_001.pdf: 
 
 
Plus-Project Statistical Analysis Plan 
 
Protocol Number: GALACTIC-1 
Version: 1 
 
1 
 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN (SAP)  
 
 
 
 
 
Study treatments: GB0139 3mg, GB0139 10mg, Placebo 
 
 
Study Phase: Phase 2b 
 
 
Study Title: GALACTIC-1 - A randomized, double-blind, multicentre, parallel, placebo-
controlled Phase 2b study in subjects with idiopathic pulmonary fibrosis (IPF) investigating 
the efficacy and safety of GB0139, an inhaled galectin-3 inhibitor administered via a dry 
powder inhaler over 52 weeks 
 
 
 
  
 
SAP Version Number: Version 1 
Date:  
 
07 July 2023 
Author: 
 
Debbie Adkins 
  
 
 
Principal Statistician, Statistics 
Plus-Project Ltd 
 
 
 
 
 
 
 








 
 
Plus-Project Statistical Analysis Plan 
 
Protocol Number: GALACTIC-1 
Version: 1 
 
3 
 
Table of Contents 
 
LIST OF ABBREVIATIONS ................................................................................................................................... 5 
1. 
INTRODUCTION ....................................................................................................................................... 6 
1.1 
TRIAL DESIGN ............................................................................................................................................ 6 
1.2 
DATABASE LOCK ........................................................................................................................................ 8 
1.3 
STUDY POPULATIONS .................................................................................................................................. 8 
2. 
STUDY OBJECTIVES AND OUTCOME MEASURES ...................................................................................... 9 
2.1 
PRIMARY EFFICACY OBJECTIVE AND OUTCOME MEASURES .............................................................................. 10 
2.2 
SECONDARY OBJECTIVES AND OUTCOME MEASURES ...................................................................................... 10 
2.3 
EXPLORATORY OUTCOME MEASURES .......................................................................................................... 11 
2.4 
SAFETY ................................................................................................................................................... 12 
3. 
STUDY DESIGN ...................................................................................................................................... 12 
3.1 
SAMPLE SIZE DETERMINATION .................................................................................................................... 12 
3.2 
RANDOMIZATION AND BLINDING ................................................................................................................ 12 
4. 
ANALYSIS SETS ...................................................................................................................................... 13 
4.1 
SCREENED SET ......................................................................................................................................... 13 
4.2 
INTENTION-TO-TREAT (ITT) SET .................................................................................................................. 13 
4.3 
MODIFIED ITT (MITT) SET ........................................................................................................................ 13 
4.4 
SAFETY ANALYSIS SET (SS) ......................................................................................................................... 14 
4.5 
PER PROTOCOL SET (PPS) ......................................................................................................................... 14 
4.6 
PROTOCOL DEVIATIONS AND BLIND DATA REVIEW MEETING ........................................................................... 14 
5. 
GENERAL METHODS AND PRINCIPLES ................................................................................................... 15 
5.1 
STANDARD DESCRIPTIVE STATISTICS ............................................................................................................. 16 
5.2 
DEFINITION OF ANALYSIS VISITS .................................................................................................................. 16 
5.3 
DESCRIPTION OF BASELINE ......................................................................................................................... 18 
5.4 
TABLES, LISTINGS AND FIGURES PRESENTATION ............................................................................................. 18 
6. 
DEMOGRAPHIC AND BASELINE CHARACTERISTICS ................................................................................ 20 
6.1 
SUBJECT DISPOSITION ............................................................................................................................... 20 
6.2 
DEMOGRAPHY AND BASELINE CHARACTERISTICS ............................................................................................ 21 
6.3 
PRIOR AND CONCOMITANT MEDICATION (EXCLUDING PIRFENIDONE AND NINTEDANIB) ......................................... 22 
6.4 
PREVIOUS USE OF PIRFENIDONE AND NINTEDANIB .......................................................................................... 22 
6.5 
PRIOR AND CONCOMITANT PROCEDURES ...................................................................................................... 23 
7. 
STATISTICAL METHODS AND PRINCIPLES .............................................................................................. 23 
7.1 
GENERAL METHODS AND PRINCIPLES ........................................................................................................... 23 
7.1.1 
Analysis of Subgroups ............................................................................................................ 23 
7.1.2 
Methods for Handling Missing Values ................................................................................... 24 
7.1.3 
Multiplicity ............................................................................................................................. 24 
7.1.4 
Pooling of Sites....................................................................................................................... 24 
7.2 
EFFICACY ................................................................................................................................................ 24 
7.2.1 
Primary Efficacy Endpoint Analysis ........................................................................................ 24 
7.2.2 
Main Estimand and Analysis .................................................................................................. 24 
7.2.3 
Key Secondary Efficacy Endpoints Analysis............................................................................ 28 
7.2.4 
Other Secondary Endpoint Analysis ....................................................................................... 32 
7.2.5 
Exploratory Endpoints............................................................................................................ 35 
7.3 
SAFETY ................................................................................................................................................... 36 
7.3.1 
Exposure and Treatment Compliance .................................................................................... 36 


 
 
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7.3.2 
Adverse Events ....................................................................................................................... 37 
7.3.3 
Major Adverse Cardiovascular Events (MACE) ...................................................................... 40 
7.3.4 
Laboratory Data ..................................................................................................................... 40 
7.3.5 
Vital Signs (including Pulse Oximetry) .................................................................................... 41 
7.3.6 
ECG ......................................................................................................................................... 42 
7.3.7 
Physical Examination ............................................................................................................. 42 
7.3.8 
Time to Premature Treatment Discontinuation .................................................................... 42 
7.3.9 
COVID-19 ................................................................................................................................ 43 
8. 
REFERENCES .......................................................................................................................................... 43 
9. 
CHANGES TO STATISTICAL ANALYSIS FROM PROTOCOL ........................................................................ 44 
10. 
AMENDMENT HISTORY OF SAP ............................................................................................................. 44 
11. 
APPENDICES .......................................................................................................................................... 45 
11.1 FIGURE 3: TRIAL DESIGN SCHEMATIC, ORIGINAL DESIGN ................................................................................. 45 
11.2 TABLE 4: SCHEDULE OF ASSESSMENTS.......................................................................................................... 46 
11.3 PRIMARY ESTIMAND SENSITIVITY AND TIPPING POINT ANALYSES ....................................................................... 48 
11.4 MULTIPLE IMPUTATION PROCEDURE ............................................................................................................ 49 
11.5 SAS CODE .............................................................................................................................................. 51 
11.5.1 Primary analysis ..................................................................................................................... 51 
11.6 SGRQ SCORING ...................................................................................................................................... 52 
11.6.1 Item Weights .......................................................................................................................... 52 
11.6.2 Scoring ................................................................................................................................... 55 
11.7 UCSD - SOBQ ....................................................................................................................................... 56 
11.8 SF-36 SCORING....................................................................................................................................... 57 
 


 
 
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LIST OF ABBREVIATIONS 
 
AE 
 
Adverse event 
ALP 
 
Alkaline phosphatase 
ALT 
 
Alanine transaminase  
AST  
 
Aspartate transaminase 
ATC 
 
Anatomical Therapeutic Chemistry 
BID 
 
Twice-daily 
BDRM  
Blinded Data Review Meeting 
BMI 
 
Body Mass Index 
BUN 
 
Blood urea nitrogen 
CI  
 
Confidence interval 
CRF  
 
Case report form (electronic/paper) 
CSP 
 
Clinical Study Protocol  
 
CSR 
 
Clinical Study Report 
DBL 
 
Database Lock 
DMP 
 
Data Management Plan 
DSMB  
Data Safety Monitoring Board 
EoS 
 
End of Study 
EoT 
 
End of Treatment 
 
FV 
 
Final Visit  
Hb 
 
Hemoglobin 
HCT 
 
Hematocrit 
ICF 
 
Informed Consent Form  
ICH  
 
International Conference on Harmonization 
IMP 
 
Investigational Medicinal Product 
IPF 
 
Idiopathic Pulmonary Fibrosis 
ITT 
 
Intention-to-treat 
LLOD 
 
Lower Limit of Detection 
LLOQ  
Lower Limit of Quantification 
MACE  
Major Adverse Cardiovascular Event 
MedDRA 
Medical dictionary for regulatory activities 
mITT 
 
Modified intention-to-treat 
PPS  
 
Per protocol set 
PT 
 
Preferred Term 
SAE  
 
Serious adverse event 
SAP  
 
Statistical Analysis Plan 
SD 
 
Standard deviation 
SoC 
 
Standard of Care 
SOC 
 
System Organ Class 
SOP 
 
Standard Operating Procedure 
SS 
 
Safety Set 
TEAE 
 
Treatment emergent adverse event 
TFL 
 
Tables, Figures and Listings 
ULN 
 
Upper Limit of Normal 
ULOD  
Upper Limit of Detection 
ULOQ  
Upper Limit of Quantification 
WHO-DD 
World Health Organisation Drug Dictionary 
 
 
 


 
 
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1. INTRODUCTION 
This Statistical Analysis Plan (SAP) describes the statistical methods to be used during the 
reporting and analyses of data collected under protocol GALACTIC-1 (EudraCT Number 2018-
002664-73 / IND 124075).  
 
 
This SAP should be read in conjunction with the Clinical Study Protocol (CSP). This version of 
the plan has been developed using CSP version 7.0 dated 28 January 2022 [1] and Case 
Report Form (CRF) version 156 dated Nov 2021 [2]. Any further changes to these documents 
may necessitate updates to the SAP. 
 
1.1 
Trial design 
 
A randomized, double-blind, multicentre, parallel, placebo-controlled phase 2b study in 
subjects with idiopathic pulmonary fibrosis (IPF). All subjects enrolled into the study should 
have a diagnosis of IPF established within the previous five years, and a diagnostic HRCT scan 
assessed by central independent radiologists according the ATS/ERS/Fleischner criteria 
available within the previous 12 months prior to screening. 
 
The original design consisted of 3 treatment groups, placebo, GB0139 3mg and GB0139 
10mg, with patients randomized in a 1:1:1 ratio. Stratification in the original version of the 
study was according to the patient’s standard of care treatment at enrollment;  
 
• SoC1 being patients currently treated with either pirfenidone or nintedanib,  
• SoC2 being patients not currently treated with pirfenidone or nintedanib.  
A subject’s SoC must have been deemed as stable by the Principal Investigator or treating 
physician before their enrollment in the study.  
 
It was initially planned to randomize approximately 450 patients to this design across 
approximately 70 sites from the European Union and 30 sites from the United States.  This 
design was intended to evaluate the efficacy and safety of GB0139 over 52 weeks of dosing 
in addition to the subject’s current standard of care (SoC) (including treatment with either 
pirfenidone or nintedanib).  It was planned to continue blinded treatment beyond week 52 
and up to week 104 to provide further safety follow-up information.  
 
Following a review of unblinded efficacy and safety data by the study’s DSMB in February 
2021, the study design has been modified based on the DSMB’s recommendation. 
Participants randomized to the 10mg GB0139 group, and all those taking nintedanib or 
pirfenidone, have been discontinued from the study. In addition, subjects who had already 


 
 
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completed 52 weeks of treatment were discontinued. In total, about 320 subjects had been 
randomized under the original design, and approximately 200 were discontinued.  
 
In the revised version of the study, post the changes following the DSMB recommendations, 
participants who are not taking nintedanib or pirfenidone at screening and during the study 
continue in the study. New patients are recruited and randomized to receive either 3mg 
GB0139 or placebo in a 2:1 ratio, to ensure the same proportion of patients on active drug as 
in the original design. Approximately 141 patients are expected to be enrolled into the 
modified design. Both nintedanib and pirfenidone are prohibited in the revised version of 
the study. 
 
The revised study design consists of a screening period up to 6 weeks, a 52-week double-
blind treatment period and a safety follow-up call 7 days post last visit. The duration of the 
entire trial for each subject will be approximately 59 weeks from first screening to the final 
safety follow up.   
  
After giving Informed Consent, the subject may be selected for the study at Visit 1. Subjects 
who fail screening may be permitted to undergo re-screening one additional time. If they are 
successfully re-screened then they will be allocated a new unique subject ID number.  If all 
exclusion and inclusion criteria are fulfilled then randomization occurs at Visit 2 (Week 0). 
Further visits are scheduled at Week 4 (V3), Week 8 (V4), Week 12 (V5), Week 26 (V6), Week 
40 (V7), and Week 52 (V8). Visits 3, 4 and 5 should occur within ± 3 days of the scheduled 
time point. Visits 6 and 7 should occur within ± 7 days of the scheduled time point.  
  
Details for the data collected at each visit are given in the time and events table in Section 
11.2. 
 
The revised design is shown in Figure 1 below. For reference, the original design is shown in 
Section 11.1.  
 


 
 
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1.2 
Database Lock 
 
The end of the study is defined as the date of the last safety follow up via phone call of the 
last participant in the study.  
 
A Blind Data Review Meeting (BDRM) will take place prior to Database Lock (DBL) and 
Analysis Sets will be agreed.  
 
1.3 
Study Populations 
 
There are 3 populations of interest. These are as follows: 
 
• Primary Population : Subjects recruited under the new design, plus those from the 
original design recruited to SoC2 (not being treated with nintedanib or pirfenidone 
prior to screening) and randomized to either placebo or 3mg GB0139. 
• SoC1 Population/Combination: Subjects recruited under the original design to SoC1 
(current treatment at baseline with nintedanib or pirfenidone). 
• SoC2 Population/Monotherapy: Those subjects from the original design in the SoC2 
stratum (not receiving nintedanib or pirfenidone at baseline), plus all subjects from 


 
 
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the new design.   SOC2/Monotherapy Population is the Primary Population plus SoC2 
10 mg. 
These populations are described visually in Figure 2 below. 
 
Figure 2: Populations for analysis 
 
 
 
 
 
Randomized treatment and randomization strata will be identified per the randomization 
schedule post-unblinding. 
 
Unless otherwise stated, all analyses will be conducted in the Primary Population. Analysis 
will be repeated in the SoC1 / Combination and / or SoC2 / Monotherapy Population where 
specified. For the SoC1 / Combination and SoC2 / Monotherapy Populations, there is an 
additional treatment arm and therefore an extra column will be displayed in the 
corresponding outputs.  
 
A summary table showing the composition of the three populations by population, part and 
treatment group will be provided.  
 
For further details on selection of subjects for analysis, see Section 4, Analysis Sets.  
 
2. STUDY OBJECTIVES AND OUTCOME MEASURES 
Primary and key secondary endpoints that refer to the 52 week timepoint will also be 
analyzed at the 26 week timepoint for the SoC1 /Combination and SoC2 / Monotherapy 
Populations. 
 


 
 
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2.1 
Primary Efficacy Objective and Outcome Measures 
 
Primary Efficacy Objective: 
Primary Outcome Measures:  
To evaluate the effect of GB0139 dry 
powder for inhalation compared with 
placebo over 52 weeks treatment period on 
the annual rate of decline in FVC in 
participants with IPF who are not treated 
with or cannot tolerate nintedanib or 
pirfenidone. 
The annual rate of decline in Forced Vital 
Capacity (FVC; expressed in mL over 52 
weeks) in those receiving 3mg or placebo 
and who are not being treated with 
nintedanib or pirfenidone. 
 
2.2 
Secondary Objectives and Outcome Measures 
 
Secondary Efficacy Objective: 
Key Secondary Outcome Measure:  
To further characterize the effect of 
GB0139 compared with placebo over 52 
weeks treatment period on FVC, quality of 
life, time to respiratory-related 
hospitalizations and all-cause mortality.  
Proportion of subjects with an absolute 
decline from baseline in FVC (% pred) of 
≤10% at Week 52. 
 
Change from baseline in St George’s 
Respiratory Questionnaire (SGRQ) total 
score at Week 52. 
 
Time to first hospitalization (respiratory 
related, including acute exacerbation of 
IPF). 
 
Time to death (all causes). 
 
Other secondary outcome measures: 
 
Proportion of subjects with an absolute 
decline from baseline in FVC (% pred) of 
<=5% at week 52. 
 
Change from baseline in 6-minute walk test 
(6MWT) distance over 52 weeks. 
 
Change from baseline in diffusion capacity 
of the lung for carbon monoxide (DLCO), 
corrected for HB, over 52 weeks. 
 
Change from baseline at week 52 for 
dyspnea assessment by University of 


 
 
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California San Diego - Shortness of Breath 
Questionnaire (UCSD - SOBQ). 
 
Change from baseline at week 52 for HRQoL 
as assessed by Short Form Survey (SF-36). 
 
Percentage of subjects with Adverse Events 
(AE) or Serious Adverse Events (SAE). 
 
Time to first hospitalization (IPF related, 
including acute exacerbation of IPF). 
 
Time to first hospitalization (all cause). 
 
Time to respiratory-related death. 
 
Change in FVC expressed in mL over 52 
weeks for subjects who have never been 
treated with pirfenidone or nintedanib. [a] 
[a] Only to be considered for the Primary and the SoC2 / Monotherapy Population. 
 
2.3 
Exploratory Outcome Measures 
 
• Change from baseline in selected biomarkers including but not limited to: YKL 40, 
PAI1, PDGF-BB, MCP-1, CCL-18, KL-6, CA-125, CA-19, Gal-3, MMP7 and collagen 
neoepitopes over time up to week 52 in all subjects.  
 
• Time to initiation of pirfenidone or nintedanib treatment for SoC2 / Monotherapy 
subjects recruited to the original study design (prior to Protocol V6.0). 
 
• Time to termination of pirfenidone or nintedanib treatment [b].  
 
• Analysis of GAL-3 and IPF disease related genes of interest that might relate to the 
efficacy and/or safety of GB0139.  
 
[b] Only for the SoC1 /Combination Population. 
 
 


 
 
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2.4 
Safety  
The following measures of safety will be assessed throughout the study: 
• Vital signs 
• Physical examination 
• Weight 
• Clinical laboratory tests (haematology and clinical chemistry ) 
• Adverse events 
• 12-lead electrocardiogram (ECG) 
3. STUDY DESIGN 
Full details of the study design can be found in the CSP Section 6. 
 
3.1 
Sample Size Determination 
 
In the original design, the planned 150 subjects per arm (randomized 1:1:1 to the 3 
treatment arms) provided approximately 87% power to detect a true mean difference of 100 
ml between treatment arms in the FVC decline at Week 52, assuming a between subject 
standard deviation of 280ml, based on a two-sided 5% significance level.  
 
For the updated design, the randomization ratio was changed to 2:1 (GB0139 3mg: Placebo). 
To detect a difference from placebo in the decline of FVC of 100ml with a standard deviation 
of 240ml at the significance level of 10%, a sample size of 141 would give 75% power.  The 
lower standard deviation in the updated design was based on a blinded review of the data.  
 
3.2 
Randomization and Blinding 
In the original design, within each SoC subpopulation (SoC1: subjects on 
nintedanib/pirfenidone at baseline, SoC2: subjects not treated with nintedanib/pirfenidone), 
subjects were randomized in blocks to double-blind treatment in a 1:1:1 ratio (GB0139 3 mg: 
GB0139 10 mg: Placebo).  
 
For the updated design, there is no stratification and subjects are randomized in a 2:1 ratio 
GB0139 3mg: Placebo. The unbalanced randomization is to maintain the same probability of 
allocation to placebo post design change, since it is considered that this may facilitate 
participant enrollment. 
 
The Sponsor arranged for the randomization and the packaging and labelling of trial 
medication. The randomization list will be generated using a validated system, which 
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reproducible and non-predictable. The block size will be documented in the Clinical Study 
Report (CSR). Access to the codes will be controlled and documented.  
 
This study is a double-blind study which will be maintained throughout the study, including 
the follow up period. The only exception to this is at the point of the design change, when 
the 10mg group in the SoC2 stratum had to be unblinded in order to withdraw them from 
the study early. Study medication is identified by a medication code number. Packaging and 
labelling will be otherwise identical. An Integrated Web Response System (IWRS) will be 
used to assign subjects to treatment groups at study start. The randomization code will be 
kept undisclosed up to database lock.  
 
Other than designated unblinded team members at Syneos Health to support DSMB review, 
all subjects, Investigators and everyone involved in analyzing or with an interest in this 
double- blind study (Sites, Study team, Plus-Project, other service providers) will remain 
blinded to the randomized treatment assignments from both the original and the updated 
design until after database lock. A team from Syneos Health Biostatistics will have access to 
unblinded information to perform analyses for the DSMB (using controlled restricted folder 
access). DSMB members will receive outputs using coded treatments, so that summaries are 
separated by treatment, but it cannot be deduced which treatment code represents which 
treatment. The DSMB will have the option to request direct unblinding information at any 
point in line with the DSMB charter. 
4. ANALYSIS SETS 
In accordance with International Conference on Harmonisation (ICH) E3 [3] and E9 [4] 
guidelines, the analysis sets are defined as follows: 
4.1 
Screened Set 
The Screened Set will include all subjects who provide informed consent for the study. This 
set will be used for subject listings and summaries of subject disposition.   
4.2 
Intention-to-treat (ITT) Set 
All randomized subjects regardless of treatment received. Subjects will be analyzed based on 
the treatment to which they were randomized. The ITT set will be used for presentation of 
subjects in listings of demographic data and efficacy data. 
4.3 
Modified ITT (mITT) Set 
This will comprise all randomized subjects who have had at least one dose of trial 
medication. Again, the subjects in this set will be analyzed according to the treatment to 
which they were randomized. The mITT set will be used for analysis of efficacy and 
biomarker endpoints and will be the primary analysis set of the study used for the primary 
and key secondary endpoints.   


 
 
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4.4 
Safety Analysis Set (SS) 
All subjects who have had at least one dose of trial treatment will be analyzed for safety. 
For all safety summaries, subjects with at least one dose of GB0139 or Placebo will be 
analyzed according to the first study treatment they received.   
4.5 
Per Protocol Set (PPS)  
The PPS is a subset of the mITT set consisting of subjects who complied with the protocol 
sufficiently to ensure that these data would be likely to represent the effects of study 
intervention according to the underlying scientific model (e.g., subjects with at least 80% 
treatment compliance as defined in Section 7.3.1). It is used for efficacy sensitivity analyses 
and will only apply to the Primary Population. 
 
It consists of all randomized and dosed subjects who meet key inclusion/exclusion criteria, 
only received the treatment they were randomized to, and did not have protocol deviations 
that were considered to impact efficacy. Subjects recruited under the original study design 
and who started nintedanib or pirfenidone whilst still on randomized treatment and prior to 
52 weeks (i.e., in combination with study treatment) will be excluded from the PP Set. The 
following list of criteria will be used to exclude subjects from the Primary Population:- 
 
• 
Not in Primary Population 
• HRCT not done 
• Treatment compliance not 80-120% 
• FVC (%pred) <=45% at Baseline 
• DLCO (corrected for Hb) <30% or >79% of predicted at Baseline 
• FEV1/FVC <0.7 at Baseline 
• Use of nintedanib or pirfenidone during study 
 
The final classification of protocol deviations relative to Week 52 will be made during a 
blinded data review prior to DBL, and all decisions, including exclusions from the PP Analysis 
Set, will be made blinded to study treatment. 
 
4.6 
Protocol Deviations and Blind Data Review Meeting 
 
Protocol Deviations and Non-Compliances will be handled and reviewed regularly during the 
study according to a study specific ‘Protocol Deviation and Non-compliance Management 
Plan’ created in line with Syneos Health controlled document ‘Processing and Management 
of Protocol Deviations (3101.W02)’. All Protocol Deviations and Non-Compliances will be 
consolidated into one workbook outside of the eCRF for regular review of each entry in 
terms of its classification of Minor or Major and any effect on efficacy.  


 
 
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Shortly prior to database lock and unblinding of subject’s treatment assignment, a BDRM will 
take place to adjudicate SAP definitions, protocol deviations and any other non-compliances, 
and agree on exclusions from the PP Set. Additionally, any further actions related to the 
database, SAP and/or Protocol Deviations and Non-Compliances workbook may be discussed 
and actioned. Decisions and actions agreed at the BDRM (including any follow-up notes) will 
be documented.  
 
The strategy for the presentation of results by the ‘treatment received group’ will be 
discussed and agreed at the BDRM.  
5. GENERAL METHODS AND PRINCIPLES 
The SAP will be finalized and signed-off prior to DBL and unblinding. Any post-hoc analysis 
(analyses performed post DBL that are different from those described in the final version of 
the SAP) will be documented in the final clinical study report (CSR) as changes to the planned 
analysis.   
  
All data collected will be listed, sorted by strata/treatment group, Subject ID, visit and time, 
with the Primary Population listed first as follows:- 
• 
SoC2/Monotherapy Placebo,  
• 
SoC2/Monotherapy GB0139 3 mg,  
• 
SoC2/Monotherapy GB0139 10mg,  
• 
SoC1/Combination Placebo,  
• 
SoC1/Combination GB0139 3 mg,  
• 
SoC1/Combination GB0139 10mg, 
• 
Screening Failures.   
 
Data on screening failures will be listed only.  
  
Tabulations and data analyses will be performed using SAS® software, version 9.4 or later 
(SAS Institute, Inc.). 
  
Unless otherwise specified, efficacy analyses will be performed in the mITT Analysis Set, with 
sensitivity analyses of the primary endpoints and secondary endpoints conducted using the 
PPS. Safety summaries will be performed using the SS Analysis Set. The ITT Analysis Set will 
be used to describe demographics, baseline characteristics and medical history.  
 
The populations will be split according to SOC1 / Monotherapy and SOC2 / Combination, as 
well as per treatment group.  
 


 
 
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P-values will be generated for all efficacy treatment comparisons, in all populations, as an 
exploratory tool for detection of potential contrasts in the material. P-values will not be 
generated for subgroup analyses.  
 
5.1 
Standard Descriptive Statistics 
Continuous variables 
Unless specified otherwise, the following standard descriptive statistics by treatment group 
will be obtained for continuous variables: number of subjects with non-missing values, 
mean, standard deviation, median, 25th percentile, 75th percentile, minimum and maximum 
value.   
 
Categorical variables 
Unless specified otherwise, the following standard descriptive statistics by treatment group 
will be presented for categorical values: total number, number of values in each category 
and the corresponding percentage of the total number of non-missing values will be 
calculated. 
 
5.2 
Definition of Analysis Visits 
Assessments will be mapped to analysis visits for a variable as follows:  
• Find the closest non-missing, within time-window (as per Table 1 below) result taken 
to the scheduled day as per the protocol schedule of assessments.  
• If two assessments are equal distance either side of the scheduled day, then take the 
earlier result.   
 
 


 
 
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Table 1: Study visits and analysis visit windows 
[a] Subjects recruited under original design only. 
[b] Subjects recruited under the updated design only.  
Note: For the updated design, at the Follow up visit 7 days after the final study day visit only 
adverse events and concomitant medications are collected (does not require analysis visit 
windows). 
 
All efficacy data will be considered for efficacy summary tables (i.e. summary tables by visit 
will include Week 76 and Week 104) but all data post Day 453 will be omitted from the 
efficacy analysis tables and any efficacy figures presented by visit will only be up to Week 52. 
 
For time to event endpoints, Day 379 (Week 52 plus 2 weeks) will be considered the end of 
the period under consideration. 
 
All safety data collected will be included in summaries. 
 
In the proceeding sections of this SAP visit will mean analysis visit assignment per Table 1 
unless stated otherwise. 
Visit 
Description 
Scheduled 
Day 
Analysis 
window, 
Primary 
Population 
Analysis 
window, 
SoC1 / 
Combination 
and SoC2 / 
Monotherapy 
Populations  
Analysis 
Visit 
V2 
Baseline / 
Randomization 
1 
n/a 
n/a 
Baseline 
V3 
Visit 3 / Week 4 
29 
2-43 
2-43 
Week 4 
V4 
Visit 4 / Week 8 
57 
44-71 
44-71 
Week 8 
V5 
Visit 5 / Week 12 
85 
72-134 
72-134 
Week 12 
V6 
Visit 6 / Week 26 
183 
135-232 
135-232 
Week 26 
V7 
Visit 7 / Week 40 
281 
233-323 
233-323 
Week 40 
V8 [a] 
Visit 8 / Week 52 
365 
324-453 
324-453 
Week 52 
V8 [b] 
Visit 8 / Week 52 
365 
>=324 
324-453 
Week 52 
FUV1 [a] 
Follow-up 1 / Week 
76 
541 
 454-635 
 
454-635 
Week 76 
FUV2 [a] 
Follow-up 2 / Week 
104 
728 
 >=636 
 
>=636 
Week 104 


 
 
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5.3 
Description of Baseline 
For all treatment groups and under both designs, the baseline is defined as the last available, 
non-missing, value before or on Study Day 1.  Study Day 1 is defined as the day of dosing  (or 
the day of randomization for subjects randomized and not dosed).   
 
At Week X, absolute change from baseline will be defined as value at Week X – baseline 
value. 
 
5.4 
Tables, Listings and Figures Presentation 
All outputs will be incorporated into PDF files, sorted and labelled according to the ICH 
recommendations, and formatted to the appropriate page size(s). 
 
For all outputs, the order and labels of the treatment groups will be displayed as per Table 2 
below:  
 
 
Table 2: Ordering and labelling of treatment groups for each population 
 
Primary Population 
SoC1 / Combination 
Population 
SoC2 / Monotherapy 
Population 
Placebo 
GB0139 3mg 
Total * 
Placebo 
GB0139 3mg 
GB0139 10mg 
Total* 
 
Placebo 
GB0139 3mg 
GB0139 10mg 
Total* 
 
 
*Where applicable. 
 
Table 3 shows the study visit labels to be used in the listings. 
  
 
 


 
 
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Table 3: Study visit labels 
 
Visit Number (Title) 
Visit Label 
Visit 1 (Screening) 
Screening 
Visit 2 (Baseline / Randomization) 
Baseline 
Visit 3 (Week 4) 
Week 4 
Visit 4 (Week 8) 
Week 8 
Visit 5 (Week 12) 
Week 12 
Visit 6 (Week 26) 
Week 26 
Visit 7 (Week 40) 
Week 40 
Visit 8 (Week 52) 
Week 52 
Follow-up Visit 1 (Week 76) [a] 
Week 76 (FUV1) 
Follow-up Visit 2 (Week 104) [a] 
Week 104 (FUV2) 
Follow up telephone call [b] 
Follow-up call 
Unscheduled 
Unscheduled 
[a] Applicable to subjects in the SoC1 / Combination and SoC2 / Monotherapy 
Populations only 
[b] Applicable to subjects in the Primary Population only 
 
The listings will display all the data contained in the EDC system. All screen failure 
information will be listed separately. The listings will be ordered by strata, treatment group, 
site, subject, visit and visit date unless otherwise stated. All AE listings will contain age, sex, 
weight and race.  
 
Summaries for continuous variables will use the descriptive statistics as described in Section 
5.1. The number of decimal places to be displayed for each will be as follows: 
- Mean, median, 25th percentile and 75th percentile: one more decimal place than 
source data. 
- Standard deviation, coefficient of variation: two more decimal places than data. 
- Minimum and maximum: same number of decimal places as data. 
- Confidence intervals: 2 decimal places. 
- P-value: 3 decimal places, if less than 0.001 then display as “<0.001“. 
 
Categorical variables will be presented as frequency counts and percentages.  Percentages 
will be displayed to one decimal place throughout in the Tables, Figures and Listings (TFLs).  
If the count is 0, the percentage will not be displayed. 
 
All dates will be displayed in the format DDMONYYYY.  


 
 
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Calculations using dates will follow these conventions: 
• The relative study day of the event (DAY) is calculated as the difference between the 
date of the event of interest (EVENT DATE) and reference start date, where reference 
start date is defined as the date of first dose of study medication for all subjects, i.e.  
DAY = EVENT DATE – REFERENCE START DATE + 1 for EVENT DATE ≥ REFERENCE DATE 
DAY = EVENT DATE – REFERENCE START DATE for EVENT DATE < REFERENCE DATE 
• Durations will be calculated by: DURATION = (STOP DATE – START DATE) + 1 
 
6. DEMOGRAPHIC AND BASELINE CHARACTERISTICS 
6.1 
Subject Disposition 
Subject disposition data will be presented by randomized treatment group. 
 
The following will be summarized for each of the populations based on the ITT Analysis Set 
unless otherwise stated: 
 
• Subjects screened, screen failed (including reasons), randomized, randomized after 
re-screening, randomized and not dosed, and dosed (Screened Set). For this output 
only, a  total column will also be included. 
• Treatment completion (including reasons for discontinuation). 
• Study completion (including reasons for discontinuation). 
• Major protocol deviations will be summarized by category and whether they lead to 
exclusion from the PP Set.  
• Analysis sets (including reasons for exclusion). 
 
Specific details related to study treatment discontinuation and study discontinuation 
captured as free text fields in the CRF will be listed only. 
 
Supportive listings will be provided for all subjects (including screen failures); date of 
informed consent, date of informed re-consent, randomization (yes/no), date of 
randomization and, where available, reasons for non-randomization will be included. 
 
Violation of inclusion/exclusion criteria will be listed. 
 
 


 
 
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6.2 
Demography and Baseline Characteristics 
 
The following demographic and baseline characteristic variables will be summarized (with 
unit for continuous variables or categories for categorical variables) for the ITT, mITT and PP 
Sets: 
• Age (complete years) from eCRF 
• Age group (<70 years / >= 70 years)  
• Gender (Male/ Female)  
• Race (American Indian or Alaska Native/ Asian/ Black or African American/ Native 
Hawaiian or Other Pacific Islander/ White/ Other) 
• Ethnicity (Hispanic or Latino/ Not Hispanic or Latino) 
• Country (Australia/ Belgium/ Canada/ France/ Georgia/ Germany/ Ireland/ Israel/ 
Italy/ Poland/ Russia/ Spain/ Ukraine/ United Kingdom/ United States). This will be 
derived from the country code in the subject number. 
• Height (cm) 
• Weight (kg) 
• Body Mass Index (kg/m2) [derived in the eCRF] 
• Smoking Status (Current-smoker/ Ex-smoker/ Never smoked) 
• Diagnosis Confirmed from HRCT for Fleischner criteria (Yes/ No) 
• Pirfenidone or Nintedanib Usage at Screening (Current/ Previous/ Never) 
• SoC Randomized Strata (SoC1 / SoC2) – per randomization 
• Forced Vital Capacity (mL) 
• 6-Minute Walk Test Total Distance (m) 
• DLCO corrected for HB (mmol/min/kPa) 
• UCSD – SOBQ Total Score 
• SF-36 Total Score 
• SGRQ Total Score 
• Serum galectin-3 at baseline 
 
Medical History (split by prior / ongoing) and Prior / Concomitant Medications will be 
described by frequency tables for the Safety Set.  
 
The number of subjects randomized at each country and site will be summarized by 
treatment group for the ITT. 
 
All summaries (other than those in the PP Set) will be repeated for the SoC1 /Combination 
and SoC2 / Monotherapy populations and supportive listings will be provided.  


 
 
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6.3 
Prior and Concomitant Medication (excluding pirfenidone and nintedanib) 
Data relating to medications other than pirfenidone or nintedanib will be presented 
according to data collected in the ‘Prior and Concomitant Medications’ page of the eCRF and 
will be coded using the most recent upversioned World Health Organization (WHO) Drug 
Dictionary as specified in the Data Management Plan (DMP).  
 
Each medication will be assessed for whether it was prior medication, concomitant 
medication or medication taken post-treatment.  
 
For partial/missing dates, the following approach will be taken:  
• Prior medication: If the stop month/year (if day is missing) or year (if day and month 
are missing) of the medication is prior to the respective month/year or year of the 
first dose of study drug then the medication will be classed as prior.  
• Medications taken post-treatment: If the start month/year (if day is missing) or year 
(if day and month are missing) of the medication is after the respective month/year 
or year of the date of discontinuation of study drug then the medication will be 
classed as taken during follow-up. 
• Otherwise, the medication will be concomitant. 
 
Subject incidence of prior and concomitant medication (excluding pirfenidone and 
nintedanib usage (separate summaries)) will be summarized for the Safety Analysis Set by 
Anatomic Therapeutic Class (ATC) 1, ATC 3 and preferred name as well as overall. Summaries 
will be presented by ATC 1, ATC 3 and preferred name, sorted by decreasing frequency over 
all subjects and then alphabetically. Subjects will be counted only once for each ATC code or 
preferred name, if they have multiple records of the same ATC codes or preferred name in 
the database.  
 
Summaries will be repeated for both the SoC1 / Combination and SoC2 / Monotherapy 
Populations and a listing will be provided. Medications taken post-treatment will be listed 
only.  
 
6.4 
Previous use of Pirfenidone and Nintedanib 
Previous use of pirfenidone and nintedanib will be recorded in the ‘Pirfenidone/Nintedanib 
Usage’ page of the CRF and will be summarized separately to other previous medications. 
Duration of treatment (up to date of randomization, for those on pirfenidone or nintedanib 
at baseline), time since end of treatment (where applicable) and reasons for discontinuation 
will be summarized.  
 


 
 
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Summaries will be repeated for both the SoC1 / Combination and SoC2 / Monotherapy 
populations, and a supportive listing will be provided. 
 
6.5 
Prior and Concomitant Procedures 
Data related to concurrent and post-treatment surgery or procedures in the ‘Surgery and 
Procedure’ eCRF will be coded using most recent up-versioned MedDRA coding as specified 
in the DMP.  
 
The same definitions of concomitant and post-treatment will be applied as for medications 
(see Section 6.3).  
 
Subject incidence of concurrent and follow-up surgery or procedures will be summarized 
separately, presented overall and by System Organ Class (SOC) and preferred term (PT). 
Within each separate summary, subjects will be counted only once for each SOC or PT if they 
have multiple records of the same SOC or PT term in the database.  
7. STATISTICAL METHODS AND PRINCIPLES 
 
This section describes the statistical analyses, presentation of the results, and the study 
endpoints that will be collected and/or derived during the study at the time points specified 
in the Schedule of Events (see Appendix 2 (Section 11.2)). 
 
7.1 
General Methods and Principles 
7.1.1 Analysis of Subgroups 
Key subgroups for the study are:- 
• Baseline FVC (%PRED): <80%, >=80% 
• GAP index: I, II or higher 
• Baseline GAL-3 level: < median, >= median* 
• Baseline MMP7: < median, >= median 
• Gender (Female, Male) 
• SoC treatment at baseline per eCRF (pirfenidone, nintedanib) for SoC1 / 
Combination Population only. Any SoC1 subject per the randomization who did 
not receive pirfenidone/nintedanib per the eCRF will be omitted from these 
subgroup analyses** 
 
* Median baseline GAL-3 levels will be estimated per SoC population separately. 
** Only to be used for FVC (primary endpoint) and treatment compliance. 
 
Other subgroups may be analyzed on inspection of the data. 


 
 
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7.1.2 Methods for Handling Missing Values 
In general, missing data will not be imputed. Exceptions are detailed in the subsequent 
sections. 
 
7.1.3 Multiplicity  
No adjustments for multiplicity are to be made in this study.  
 
7.1.4 Pooling of Sites 
No pooling of sites will be performed in this study. 
 
7.2 
Efficacy 
All efficacy data described below will be summarized by visit including the change from 
baseline (when applicable).  
7.2.1 Primary Efficacy Endpoint Analysis 
The primary efficacy endpoint is the annual rate of decline in Forced Vital Capacity (FVC; 
expressed in mL over 52 weeks). Spirometry data provided by an external vendor showing 
the FVC (L) will be multiplied by 1000 to convert to mL. The analyses will be based on all FVC 
values obtained. Any FVC values post Day 453 will be omitted from the analyses. 
The primary efficacy endpoint will be analyzed according to the estimand framework. 
Strategies for handling FVC data affected by the inter-current events (ICEs) of death, 
treatment discontinuation, and initiation of additional IPF therapy (pirfenidone or 
nintedanib) will be employed. Full details regarding use and imputation of FVC data in 
relation to ICEs are given in the next section. 
7.2.2  Main Estimand and Analysis 
The primary analysis will test for superiority of GB0139 3mg compared to Placebo (Plc) for 
the annual rate of decline in FVC in mL over 52 weeks in subjects not receiving pirfenidone 
or nintedanib at baseline in the mITT Set. The main estimand for the primary efficacy 
endpoint is as follows: 
• Population: Primary Population, mITT set.  
• Variable of interest: Change from baseline in FVC in mL over 52 weeks 
• Intercurrent events: 
o Death: FVC attributed the lowest value recorded in the trial when a patient 
dies 


 
 
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o Treatment Discontinuation: Analysis will include any FVC measurements after 
randomised treatment discontinuation 
o Initiation of additional IPF therapy (nintedanib or pirfenidone): Analysis will 
include any FVC measurements after initiation of additional IPF therapy 
• Summary measure: Comparison of slopes assessed through the treatment by time 
interaction.  
The null hypothesis is: 
H0: There is no difference in the annual rate of decline in FVC in mL between 
GB0139 3mg and Plc 
The alternative hypothesis is: 
Ha : There is a difference in the annual rate of decline in FVC in mL between 
GB0139 3mg and Plc 
A restricted maximum likelihood (REML) approach will be used, with a random coefficient 
regression (random slopes and intercepts) model fitted to test the hypotheses. The decrease 
in FVC is assumed to be linear within each subject over 52 weeks [5].  
Baseline FVC and time will be fitted as continuous covariates. The treatment group and the 
interaction term for time by treatment group will be added as fixed effects. Random subject 
intercept and time effects will be fitted and will be assumed to be normally distributed with 
arbitrary covariance matrix. The within-subject errors will be assumed to be independent 
and normally distributed with mean zero and a common variance. The Kenward-Roger 
approximation will be used to estimate denominators degrees of freedom. 
The statistical model will be as follows: 
Y itk = (α + ai  + τk ) + βf FVCbi + (γ + β3 T3 + gi ) t +  εit 
where: 
Y itk is the change from baseline measured for ith patient at time t (actual time) in 
treatment group k  
t is the time since randomization in years 
T3 =1 if the subject is in the GB0139 3mg group, otherwise T3 =0 
β3  is the effect of treatment on the slope compared to Placebo 
α and γ are elements of the intercept and slope respectively  
ai and gi  are random specific components of the intercept and slope respectively for the 
ith patient, assumed to be normally distributed with mean 0 and arbitrary covariance 
matrix 


 
 
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FVCbi  is the baseline FVC (mL) for the ith patient 
τk  is the intercept coefficient of the effect of treatment k (k=1, 2) 
βf  is the effect of 1ml increase in the baseline FVC  
εit  is the random error for ith patient at time t assumed to be independent and normally 
distributed with mean 0 and variance σ2 
 
This approach adopts a missing at random (MAR) assumption (i.e., the probability of an 
observation being missing depends only on observed measurements). Subjects with missing 
data at a particular time point still contribute to the analysis at that time point based on 
their other observed data used in the model (i.e., treatment, baseline FVC, and the FVC at 
baseline). Data that remain unobserved due to ICEs will be handled as described above. 
Other missing data will be imputed within the regression model under the MAR assumption.  
The linearity assumption for the rate of change in FVC from baseline to week 52 will be 
explored graphically. Graphical displays will be provided of the mean (± SEM) observed FVC 
and mean change from baseline for each treatment group by visit. 
The assumptions of the analysis will be checked by inspection of graphical displays of the 
residuals. 
A cumulative distribution plot of the percentage of subjects by change from baseline in FVC 
in mL at week 52 will be presented. 
 
The primary analysis detailed above will be repeated for the Primary Population, PP Analysis 
Set and for SoC1 / Combination and SoC2 / Monotherapy Populations (only for the mITT  
Analysis Set). 
 
7.2.2.1 Primary Endpoint Supporting Analyses 
 
Supporting analyses will be carried out in the SoC1 / Combination and SoC2 / Monotherapy 
Populations. The estimands for these analyses differ from the primary estimand of Section 
7.2.1 only in the population and the variable of interest.  
 
In all supporting analyses, the variable of interest, in addition to the change from baseline in 
FVC over 52 weeks, is the change from baseline in FVC in mL over 26 weeks. Any FVC values 
post Day 232 will be omitted from these analyses. The estimated rate of decline in FVC in mL 
will be produced based on 26 weeks of data. This analysis will also be repeated for the 
Primary Population.  
 
Separate analyses will be performed for each of the SoC1/ Combination and SoC2 / 
Monotherapy Populations in the mITT Set.  


 
 
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All statistical analyses and graphical summaries will be as described in Section 7.2.1. 
 
7.2.2.2 Subgroup Analysis 
 
The primary analysis detailed in Section 7.2.1 will also be repeated by subgroup (separately 
for each subgroup factor of interest) for the Primary Population (52 week and 26 week 
endpoint) and the SoC1 / Combination Population (52 week and 26 week endpoint) in the 
mITT Set. The time by treatment group interaction will be replaced with a time by treatment 
group by subgroup interaction and fixed effect for the subgroup factor will also be added. 
The effect on slope between treatments will be assessed within each level of the subgroup. 
 
7.2.2.3 Supplementary Analysis 
 
Supplementary analyses of the primary efficacy endpoint in the Primary Population will be 
performed as follows: 
 
 
 
Handling of intercurrent events 
Supple-
mentary 
Analysis 
Analysis Set 
Death 
Treatment 
discontinuation 
Initiation of 
additional IPF 
therapy 
1 
mITT Set, 
Primary 
Population 
FVC attributed 
lowest value 
recorded in 
the trial when 
a patient dies 
Analysis will exclude 
all available FVC 
measurements after 
randomized 
treatment 
discontinuation 
 
Analysis will 
exclude all 
available FVC 
measurements 
after initiation of 
additional IPF 
therapy 
2 
mITT Set, 
Primary 
Population 
FVC attributed 
0 when a 
patient dies 
Analysis will include 
all available FVC 
measurements after 
randomized 
treatment 
discontinuation 
 
Analysis will 
include all 
available FVC 
measurements 
after initiation of 
additional IPF 
therapy 
 
 
 


 
 
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7.2.2.4 Primary Estimand Sensitivity Analysis 
 
A Mixed Model with Repeated Measures (MMRM) will be fitted to the change from baseline 
in FVC across all visits with data imputed at Week 52 per the primary estimand (i.e. Week 52 
will be attributed the lowest value recorded in the trial when a patient dies). Treatment, 
visit, baseline FVC, and treatment-by-visit interaction will be fitted as fixed effects. A 
restricted maximum likelihood (REML) approach will be used, and an unstructured 
covariance structure shared across treatment groups will be used to model the within-
subject errors. If the model fails to converge, a heterogeneous Toeplitz structure 
(TYPE=TOEPH option in PROC MIXED rather than TYPE=UN) will be used. The Kenward-
Roger’s correction to degrees of freedom will be applied. 
 
If there are concerns regarding the amount of missing data for the primary estimand, a 
sensitivity analysis to test the robustness of the MAR assumption used in the main estimand 
analysis will be performed to assess the results with missing Week 52 FVC data. A multiple 
imputation approach will be used. Full details of the methods to be followed are given in 
Section 11.4 and 11.5.  
 
7.2.3 Key Secondary Efficacy Endpoints Analysis 
For all key secondary endpoints, analyses will be performed in the Primary Population and in 
the SoC1 / Combination and SoC2 / Monotherapy Populations. As described previously, for 
the SoC1 / Combination and SoC2 / Monotherapy Populations, endpoints that refer to 52 
weeks will in addition consider the 26 week timepoint (where applicable). Subgroup analyses 
will only be performed for the Primary Population and the SoC1 / Combination Population.  
 
Initial analyses and subgroup analyses will be performed in only the mITT Analysis Set . 
Kaplan-Meier plots (where applicable) will only be produced for the mITT Set.  
 
7.2.3.1             Proportion of subjects with an absolute decline from baseline in % Predicted 
FVC of ≤10% at Week 52 
 
Spirometry data provided by an external central vendor (Clario/ERT) showing the calculated 
% Predicted FVC will be used to derive whether the subject showed an absolute decline 
≤10% from baseline in predicted %FVC at Week 52. 
 
The superiority of GB0139 3mg compared to Placebo will be tested for the proportion of 
subjects with an absolute decline ≤10% from baseline in predicted %FVC at week 52. 
 


 
 
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The null hypothesis is: 
H0: There is no difference in the proportion of subjects with an absolute decline ≤10% 
from baseline in predicted %FVC between GB0139 3mg and Plc. 
 
The alternative hypothesis is: 
Ha: There is a difference in the proportion of subjects with an absolute decline ≤10% 
from baseline in predicted %FVC between GB0139 3mg and Plc. 
 
A logistic regression model will be fitted with treatment and baseline FVC (mL) included in 
the model. The Wald test will be used to test for differences between treatments. Odds 
ratios together with 90% and 95% confidence intervals will be used to quantify the effect of 
treatment, comparing GB0139 3mg to Placebo as the reference. 
 
Subjects lost to follow-up prior to Week 52 are imputed to have absolute decline >10% from 
baseline in predicted %FVC at Week 52. 
 
The analysis will be repeated by subgroup (separately for each subgroup factor of interest, 
Section 7.1.1) by adding a fixed effect for the subgroup factor and adding a treatment by 
subgroup interaction term. The odds ratio between treatments will be assessed within each 
level of the subgroup. 
 
Graphical displays will be provided of the mean (± SEM) observed predicted %FVC and mean 
change from baseline for each treatment group by visit. 
 
7.2.3.2 
Change from baseline in St. George’s Respiratory Questionnaire total score at Week 
52. 
 
Data from an external central vendor (Clario/ERT) with the SGRQ results will be used. The 
details of scoring are provided in Section 11.6. 
 
A Mixed Model with Repeated Measures (MMRM) will be fitted to the change from baseline 
in the SGRQ Total Score across all visits (Weeks 12, 26 and 52 - see Section 11.2). Treatment, 
visit, baseline SGRQ Total Score, and treatment-by-visit interaction will be fitted as fixed 
effects. A restricted maximum likelihood (REML) approach will be used, and an unstructured 
covariance structure shared across treatment groups will be used to model the within-
subject errors. If the model fails to converge, a heterogeneous Toeplitz structure 
(TYPE=TOEPH option in PROC MIXED rather than TYPE=UN) will be used. The Kenward-
Roger’s correction to degrees of freedom will be applied. 
 
Domain scores will be summarized by treatment group and visit only. 


 
 
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The analysis will be repeated by subgroup (separately for each subgroup factor of interest). 
A fixed effect for the subgroup factor will be added and all interaction terms between 
treatment, visit and the subgroup factor will be included. The comparisons between 
treatments at each visit will be assessed within each level of the subgroup. 
 
7.2.3.3 
Time to first hospitalization (respiratory related, including acute exacerbation of 
IPF) 
 
The time to first hospitalization (respiratory related, including acute exacerbation of IPF) will 
be derived from the ‘Exacerbation’ and ‘Adverse Events’ eCRF. 
 
If the subject was hospitalized and the AE linking to the hospitalization indicates that the 
PI/treating physician classed the AE as the result of an exacerbation of IPF then the 
hospitalization will be defined as being respiratory related, including acute exacerbation of 
IPF.  
 
Other respiratory related causes will be defined as all AEs in the ‘Respiratory, Thoracic and 
Mediastinal Disorders’ System Organ Class (SOC), plus those AEs in the ‘Infections and 
Infestations’ SOC with preferred terms containing the character strings ‘resp’, ‘bronch’, 
‘covid-19’ or ‘pneumo’, or the specific PTs as follows: 
 
• Influenza 
• Legionella infection 
• Viral infection 
 
If a subject was hospitalized (respiratory related, including acute exacerbation of IPF) prior to 
or on Day 379 (Week 52 plus 2 weeks) then the (date of first such hospitalization – date of 
randomization +1)/7 will be derived as the time to first hospitalization (respiratory related, 
including acute exacerbation of IPF) in weeks. 
 
If a subject does not require hospitalization (respiratory related, including acute 
exacerbation of IPF) prior to or on Day 379, they will be censored in the analysis. The 
following censoring rules will be applied:- 
• If lost to follow-up (LTFU), a subject will be censored at the earliest of date of last 
contact and Day 379 
• If a subject discontinued (and not lost to follow-up), they will be censored at the earlier 
of the date of study discontinuation and Day 379. 
• Otherwise, censor at the earliest of last contact date or Day 379. 
 


 
 
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The superiority of GB0139 3mg compared to Placebo will be tested for the time to first 
hospitalization (respiratory related, including acute exacerbation of IPF). 
 
The null hypothesis is: 
H0 : There is no difference in the time to first hospitalization between GB0139 3mg and 
Plc 
 
The alternative hypothesis is: 
Ha: There is a difference in the time to first hospitalization between GB0139 3mg and 
Plc 
 
A Cox proportional hazards model will be fitted with treatment and baseline FVC (mL) 
included in the model. The Wald test will be used to test for differences between 
treatments. Hazard ratios together with 90% and 95% confidence intervals will be used to 
quantify the effect of treatment, comparing GB0139 3mg to Placebo as the reference. 
Breslow’s method for handling ties will be used.  
 
The analysis will be repeated by subgroup (separately for each subgroup factor of interest) 
by adding a fixed effect for the subgroup factor and adding a treatment by subgroup 
interaction term. The hazard ratio between treatments will be assessed within each level of 
the subgroup. 
If there are fewer than 15 events (respiratory related, including acute exacerbation of IPF) 
then a formal statistical analysis will not be performed, and only frequencies of 
hospitalizations by treatment group will be provided. If an overall analysis is performed, then 
the subgroup analyses will automatically be performed, regardless of the number of events 
in the subgroup levels.  
Kaplan-Meier plots by treatment group will also be presented. 
 
7.2.3.4 
Time to death (from all causes) 
 
If a patient dies on or prior to Day 379, the date of death will be obtained from the 
‘Disposition Study Completion’ eCRF. The time to death in weeks will be derived as (date of 
death – date of randomization +1)/7 .  
 
If a patient does not die on or prior to Day 379, the same censoring rules will apply as in Section 
7.2.3.3. 
 
The superiority of GB0139 3mg compared to Placebo for time to death from all causes from 
date of randomization will be tested, regardless of the number of events. 


 
 
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The null hypothesis is: 
H0: There is no difference in time to death for all causes between GB0139 3mg and 
Plc. 
The alternative hypothesis is: 
Ha: There is a difference in time to death for all causes between GB0139 3mg and Plc. 
The same model will be used as described in Section 7.2.3.3. 
 
7.2.4 Other Secondary Endpoint Analysis 
Unless otherwise stated, all other secondary endpoints will be statistically analyzed only for 
the Primary Population. For the SoC1 / Combination and SoC2 / Monotherapy Populations, 
only descriptive summaries will be provided. All analyses will use the mITT set, unless 
otherwise specified.  
No subgroup analyses will be performed for these endpoints.  
 
7.2.4.1 
Proportion of subjects with an absolute decline from baseline in % Predicted FVC of 
≤ 5% at Week 52 
 
The same data source and analyses (logistic regression) as detailed in Section 7.2.3.1 will be 
used.  
7.2.4.2 
Change from baseline in 6-minute walk test (6MWT) distance over 52 weeks 
 
Data from an external vendor with the 6MWT results will be used. To compare the change 
from baseline in the distance covered in the 6MWT at Week 52, an Analysis of Covariance 
(ANCOVA) will be fitted with treatment and baseline 6MWT distance included in the model. 
The least squares means per treatment and difference in least square means between 
treatments and 90% and 95% CI will be presented.  
Data collected at early withdrawal visit will be summarized descriptively only.  
7.2.4.3 
Change from baseline in diffusion capacity of the lung for carbon monoxide (DLCO), 
corrected for HB, at 52 weeks 
 
Data from an external vendor with the DLCO result (mmol/min/kPa) will be used. The same 
analyses (ANCOVA) as detailed in Section 7.2.4.2 will be used but using the baseline DLCO 
rather than baseline 6MWT in the ANCOVA model. 
Data collected at early withdrawal visit will be summarized descriptively only. 


 
 
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7.2.4.4 
Change form baseline at week 52 in dyspnea assessment by University of California 
San Diego - Shortness of Breath Questionnaire (UCSD - SOBQ) 
 
Data from an external vendor with the UCSD – SOBQ scores will be used. The UCSD – SOBQ 
comprises of 24 items scored 0-5 where (0 = "not at all" to 5 = "maximal or unable to do 
because of breathlessness"). The item scores will be summed (treating any missing as 5) to 
derive a total score between 0 and 120. The UCSD – SOBQ items are provided in Section 
11.7. The same MMRM analysis as detailed in Section 7.2.3.2 will be used for the change 
from baseline at week 52 in UCSD – SOBQ Total Score, using the baseline UCSD – SOBQ Total 
Score rather than the baseline SGRQ Total Score. 
 
7.2.4.5 
Change from baseline at Week 52 for HRQoL as assessed by Short Form Survey (SF-
36)  
 
Data from an external vendor with the SF-36 scores will be used. The change from baseline 
in SF-36 total score will be analyzed using an MMRM the same as detailed in Section 7.2.3.2 
using the corresponding baseline SF-36 total score rather than the baseline SGRQ total 
score.  
 
In addition, the actual and change from baseline in individual component scores as follows 
will be summarized by treatment group and visit:  
 
• Physical component scale (PCS) and mental component scale (MCS). 
• Physical functioning (PF), role physical (RF), bodily pain (BP), general health (GH), 
vitality (VT), social functioning (SF), role emotional (RE) and mental health (MH). 
The details of scoring are provided in Section 11.8. 
7.2.4.6 
Percentage of subjects with Adverse Events (AE) or Serious Adverse Events (SAE) 
over 52 weeks 
 
Only TEAEs with a start date prior to Day 379 will be considered for inclusion in the analysis. 
Summaries of the percentage of subjects with AE or SAEs will be presented for each 
population by SOC and PT. No formal analyses will be performed.   
7.2.4.7 
Time to first hospitalization (IPF related, including acute exacerbation of IPF) 
 
The time to first hospitalization (IPF related, including acute exacerbation of IPF) will be 
derived from the ‘Exacerbation’ and ‘Adverse Events’ eCRF. 
 


 
 
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If the subject was hospitalized and the AE linking to the hospitalization indicates that the 
PI/treating physician classed the AE as the result of an exacerbation of IPF then the 
hospitalization will be defined as being IPF related, including acute exacerbation of IPF.  
 
The time to first hospitalization (IPF related, including acute exacerbation of IPF) in weeks will 
be derived as (date of first such hospitalization – date of randomization +1)/7.  
 
If a patient does not require hospitalization (IPF related, including acute exacerbation of IPF) 
on or prior to Day 379, the same censoring rules will apply as in Section 7.2.3.3. 
 
If there are fewer than 15 hospitalizations (IPF related, including acute exacerbation of IPF) 
then statistical analysis will not be performed, and only frequencies of hospitalizations by 
treatment group will be provided. Otherwise, the same analysis (Cox proportional hazards 
modelling) as detailed in Section 7.2.3.3 will be performed. 
7.2.4.8 
Time to first hospitalization (all cause) 
 
If the subject was hospitalized, then the hospitalization will be defined as all cause. The time 
to first hospitalization (all cause) in weeks will be derived as (date of first hospitalization – date 
of randomization +1)/7.  
 
If a patient does not require hospitalization on or prior to Day 379, the same censoring rules 
will apply as in Section 7.2.3.3. 
 
If there are fewer than 15 hospitalizations (all cause) then statistical analysis will not be 
performed, and only frequencies of hospitalizations by treatment group will be provided. 
Otherwise, the same analysis (Cox proportional hazards modelling) as detailed in Section 
7.2.3.3 will be performed. 
7.2.4.9 
Time to respiratory-related death 
 
Respiratory related causes will be defined as in Section 7.2.3.3. The time to death due to 
respiratory related causes, in weeks, will be derived as (date of respiratory-related death – 
date of randomization +1)/7. 
 
If a patient does not die due to respiratory related causes on or prior to Day 379, the same 
censoring rules will apply as in Section 7.2.3.3. 
 
Cox proportional hazards modelling, as detailed in Section 7.2.3.3, will be performed. 
 


 
 
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7.2.4.10 Change in FVC expressed in mL over 52 weeks for subjects who have never been 
treated with pirfenidone or nintedanib  
 
The same data source and analyses (random coefficients regression model) as detailed in 
Section 7.2.1 will be used. Statistical analysis will be performed for the Primary Population 
and descriptive analyses only for the SoC2 / Monotherapy Population.  
7.2.5 Exploratory Endpoints 
Unless otherwise stated, exploratory endpoints will be summarized in the Primary 
Population only, using the mITT analysis set.  
 
7.2.5.1 Biomarkers 
 
Biomarker results will be provided by the central laboratory in standard units. The results, 
change from baseline and percentage change from baseline (for post baseline assessments) 
will be summarized by visit. 
 
Correlation analyses assessing the relationship between Biomarker results and 
efficacy/safety endpoints may be performed.   
 
7.2.5.2 Time to initiation of pirfenidone or nintedanib treatment for SoC2 subjects 
recruited to the original study design 
 
Only the SoC2 / Monotherapy Population will be used, with only subjects recruited to the 
original study design (pre-Protocol V6.0).  
The time to initiation of pirfenidone or nintedanib treatment will be derived from the 
‘Pirfenidone/Nintedanib Usage’ eCRF. The time to initiation of pirfenidone or nintedanib 
treatment in weeks will be derived as (date of first initiation of pirfenidone or nintedanib 
treatment – date of randomization +1)/7. 
 
Time to initiation will be summarized descriptively by treatment. 
 
7.2.5.3 Time to termination of pirfenidone or nintedanib treatment 
 
Summaries of time to termination of pirfenidone or nintedanib treatment will be conducted 
only for the SoC1 / Combination Population.  
The time to termination of pirfenidone or nintedanib treatment will be derived from the 
‘Pirfenidone/Nintedanib Usage’ eCRF. The time to termination of pirfenidone or nintedanib 
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treatment – date of randomization +1)/7. 
 
Time to termination of pirfenidone or nintedanib treatment in the SoC1 / Combination 
Population will be summarized descriptively. 
 
7.2.5.4 Pharmacogenetics 
 
Pharmacogenetic results will be provided by the central laboratory. The results will be 
summarized by treatment group. 
 
The primary and key secondary endpoint subgroup analyses may be repeated including a 
post-hoc classification of pharmacogenetic results as a subgroup.   
  
Additional analyses assessing the relationship between Pharmacogenetic results versus 
safety endpoints may also be performed. 
7.3 
Safety 
 
Safety evaluations will be performed on the Safety Set, unless otherwise specified.  Missing 
assessments will not be imputed unless stated otherwise. All analyses will be conducted on 
the Primary Population. Key safety will also be summarized for the SoC1 / Combination and 
SoC2 / Monotherapy Populations, as detailed in the individual sections. 
 
7.3.1 Exposure and Treatment Compliance 
Details of exposure and treatment compliance will be summarized for the mITT  Analysis Set, 
as well as for the Safety Analysis Set. In addition, for the Primary Population only, exposure 
and compliance will be summarized in the PP Analysis Set.  
 
Date of first dose of study treatment will be derived as the earliest date of drug dispense 
from the ‘Treatment Compliance’ eCRF forms. 
 
Extent of exposure to GB0139 (mg) or Placebo will be calculated based on information from 
the ‘Treatment Compliance’ eCRF forms. The number of capsules used will be derived as the 
number of GB0139 capsules dispensed minus the number of unused GB0139 capsules 
returned during the study. The number of GB0139 capsules used and the dose of GB0139 in 
the capsules known to have been dispensed will be used to derive the extent of exposure 
(mg) to GB0139.   
 


 
 
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The duration of exposure to GB0139 in days will be calculated as the date of last dose 
recorded in the ‘Disposition Study Completion’ eCRF minus the date of first dispensing of 
GB0139 + 1.   
 
The duration of exposure to GB0139 will be summarized both as a continuous variable and 
categorically, with categories 0-13 weeks, >13 weeks – 26 weeks, >26 weeks=39 weeks, >39 
weeks – 52 weeks, > 52 weeks.   
  
The extent of exposure (mg) will be summarized as a continuous variable by treatment 
group.  
 
The extent (mg) and duration of exposure (days) between each dispensing and returning of 
study drug will be presented in the listings but will not be summarized.   
 
The duration of exposure to nintedanib or pirfenidone during treatment with study drug will 
be derived based on the start and stop dates of nintedanib and pirfenidone from the 
‘Pirfenidone/Nintedanib Usage’ eCRF and the first and last date of study drug. 
 
The expected treatment exposure (capsules) will be derived using the treatment duration 
with study drug multiplied by 2 (the planned daily number of capsules).  
 
Treatment compliance based on dispensing data will be derived as 100 x treatment exposure 
(capsules) / expected treatment exposure for duration of study treatment through study 
treatment discontinuation (capsules).  
 
The treatment exposure to study drug (capsules), treatment duration with study drug (days) 
and treatment compliance (continuous and grouped as < 80%, 80% to 120%, > 120%) will be 
summarized.  
 
The treatment exposure to study drug (capsules), treatment duration with study drug (days) 
and treatment compliance between each dispensing and returning of study drug will be 
presented in the listings but will not be summarized. 
 
Summaries will be repeated in the SoC1 / Combination and SoC2 /Monotherapy Populations. 
In the SoC1 / Combination Population treatment compliance will be repeated by baseline 
SoC treatment at baseline (Nintedanib vs Pirfenidone vs Pirfenidone and Nintedanib). 
 
7.3.2 Adverse Events 
Adverse events (AEs) from the ‘Adverse Events’ eCRF will be coded for summarization using 
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coding information is available for a specific AE, the AE will be presented as an “Uncoded” in 
summary tables. 
 
A Treatment Emergent AE (TEAE) is defined as any protocol defined AE (collected as a unique 
record from the AE eCRF page) with an onset between the date of first dispensing of study 
drug (from the ‘Treatment Compliance’ eCRF forms) and date of last dose recorded + 14 
days inclusive (date of last dose from the ‘Disposition Study Completion’ eCRF). If the date of 
onset is the same as the date of first dispensing of study drug, then the recorded start of 
event relative to first dose from the eCRF (before/after) will be used to classify the AE as 
either a TEAE (after) or a non-TEAE (before).  
 
Missing and/or incomplete dates/times for AEs will not be imputed. For partial/missing 
dates:   
• If the start or stop month/year (if day is missing) or year (if day and month are 
missing) of the AE is prior to the respective month/year or year of the first dose of 
study drug, then the AE will be classed as a Non-TEAE.   
• If the start month/year (if day is missing) or year (if day and month are missing) of 
the AE is after the respective month/year or year of the last dose of study drug + 30 
days, then the AE will be classed as a Non-TEAE.   
• Otherwise, the AE will be classed as a TEAE. 
 
For TEAE summaries presenting the incidence frequency and percentage, the number of 
actual unique TEAEs (meeting each criteria) will also be presented. For incidence summaries, 
a subject with multiple TEAEs will contribute only once to the count for a given summary and 
the maximum severity and relationship will always be used. The number of unique TEAEs will 
always be presented as per the severity and relationship for the unique TEAEs. Missing 
relationship will be considered related to study drug and missing severity will be considered 
severe.  
 
The number and percentage of subjects reporting at least one of the following will be 
summarized:  
• TEAE  
• TEAE by maximum severity (overall and within related TEAEs)  
• TEAE by maximum relationship to study drug (overall and within serious TEAEs)  
• Serious TEAE  
• TEAE leading to treatment discontinuation  
• TEAE leading to death 
• All deaths (Note: time to death is limited to a follow-up period of Day 379) 
 


 
 
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Further summaries by SOC and PT will be produced for all TEAEs, TEAEs by SoC, PT and 
maximum severity, treatment related TEAEs, serious TEAEs, TEAEs leading to treatment 
discontinuation and TEAEs leading to death. These will be presented by SOC and PT, sorted 
by decreasing frequency overall and then alphabetically. An additional summary all AEs post 
follow-up (i.e. post treatment end date + 14) will be produced by SOC and PT. 
 
Additional summaries of all TEAEs and of serious TEAEs by PT only, sorted by decreasing 
frequency overall, will be presented.  
 
Summaries of COVID related (per eCRF) TEAEs and serious COVID related TEAEs will also be 
produced. In addition, summaries of TEAEs and Serious TEAEs related to IPF exacerbations 
(i.e. those events marked on the eCRF as related to IPF exacerbation) will be provided.  
  
Serious TEAEs and TEAEs leading to discontinuation of study drug will be presented 
separately for the SoC1 / Combination and SoC2 / Monotherapy Populations.   
  
Additionally, the incidence of by time period (0 - 13 weeks, >13 weeks – 26 weeks, >26 
weeks - 39 weeks, >39 weeks – 52 weeks, ≥ 52 weeks) will be presented. The presentation 
will include all TEAEs, serious TEAEs, TEAEs leading to treatment discontinuation, and TEAEs 
leading to death. The denominator for each period will be the number of subjects on 
treatment at the beginning of that time period. This summary will be repeated for the SoC1 / 
Combination and SoC2 / Monotherapy Populations.  
 
Each TEAE event rate (per 100 patient years) will also be summarised by preferred term 
within each system organ class. For each preferred term, the event rate will be presented 
and will be defined as the number of patients with that AE divided by the sum of the 
duration from the start of treatment to 14 days after the last treatment dose (for patients 
without the event) and the time to the AE (for patients with the event) in each group 
multiplied by 100. This will also be repeated for serious TEAEs. 
 
Risk differences for proportion of subjects with the following TEAEs (with associated 95% 
confidence intervals) comparing GB0139 groups to Placebo will be estimated:- 
• TEAE  
• TEAE by maximum severity (overall and within related TEAEs)  
• TEAE by maximum relationship to study drug (overall and within serious TEAEs)  
• Serious TEAE  
• TEAE leading to treatment discontinuation  
• TEAE leading to death  
Separate subject listings will be provided for AEs leading to death (including a flag for TEAEs), 
Serious TEAEs and TEAEs leading to treatment discontinuation. A listing of all deaths will also 
be produced. 


 
 
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7.3.3 Major Adverse Cardiovascular Events (MACE) 
 
Cardiac events of interest will be defined as the following preferred terms:  
 
• Torsade de Pointes 
• Ventricular tachycardia 
• Ventricular fibrillation  
• Ventricular flutter 
• Syncope 
• Seizures 
• Sudden death 
• Sudden cardiac death 
A summary table of these 8 terms by PT only will be provided, with all terms included in the 
table even when the number of events is zero.  
 
MACE will be summarized for the Primary, SoC1 / Combination and SoC2 / Monotherapy 
Populations. A supporting listing will be provided, with a flag for treatment emergent MACE.  
 
7.3.4 Laboratory Data 
 
Système International (SI) units provided by a central laboratory will be used for presenting 
all laboratory values.   
 
Values below the lower limit of quantification (LLOQ) will be replaced by the value of the 
LLOQ.  
 
The hematology and clinical chemistry parameters to be summarized are as follows:  
• Hematology: Hematocrit, Hemoglobin, Leukocytes with differential count, Platelet 
(count)  
• Clinical chemistry:  Albumin, Alkaline phosphatase (ALP), Aspartate aminotransferase 
(AST), Alanine aminotransferase (ALT), Bilirubin (total), Calcium, Creatinine, Glucose, 
Potassium, Sodium  
The values provided by the central laboratory in standard units as well as the flags for 
Low/Normal/High (L/N/H) values relative to the normal range or Normal/Abnormal 
classifications will be used for summaries.  
 


 
 
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For the continuous parameters, the results and the change from baseline (for post baseline 
assessments) will be summarized by treatment and visit. This summary will be repeated in 
the SoC1 / Combination and SoC2 / Monotherapy Populations.   
 
For any categorical parameters (including incidence of abnormalities), the results will be 
summarized by treatment and visit based on the number of subjects with non-missing data 
at the visit as the denominator.  
 
Separate subject listings of abnormalities across all populations, sorted by SoC, will be 
presented showing all data within the abnormal parameter over the study for the respective 
subject. 
 
All laboratory results will be listed, including all unscheduled visits.   
 
Serum pregnancy results (at screening) and urinary pregnancy results (post-screening) will 
be listed per subject and visit. 
 
7.3.5 Vital Signs (including Pulse Oximetry) 
 
Vital signs (including Pulse Oximetry) data from the ‘Vital Signs – Complete’, ‘Vital Signs – 
Brief’ and ‘Pulse Oximetry’ eCRFs will be used.   
 
The vital sign parameters to be summarized are  
• Diastolic and systolic blood pressure (mmHg), 
• Heart rate (beats/min), 
• Body temperature (°C), 
• Respiratory rate (breaths/min), 
• Hemoglobin saturation with oxygen (%), 
• Body weight (kg), 
• BMI (kg/m2). 
 
If body temperature is recorded in °F then the following formula will be applied:- 
Temperature (°C) = 5/9 x (Temperature [°F]-32)  
 
The results and the change from baseline (for post baseline assessments) will be summarized 
by treatment and visit for each parameter, repeated for all populations.   
 


 
 
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7.3.6 ECG 
ECG data from the ‘Electrocardiogram Local’ eCRF will be used.   
 
The ECG parameters to be summarized are  
• ECG Mean Heart Rate (beats/min),  
• PR Interval (msec),  
• QRS Duration (msec), 
• QT Interval (msec), 
• QTcF (Fridericia's Correction Formula) (msec). 
The results and the change from baseline (for post baseline assessments) will be summarized 
by treatment and visit for each parameter.   
 
The overall ECG interpretation (Normal/ Abnormal – Not Clinically Significant [NCS]/ 
Abnormal – Clinically Significant [CS]) will be summarized by visit based on the number of 
subjects with non-missing data at the visit as the denominator.  
 
Each of the above summaries will be repeated for the SoC1 / Combination and SoC2 / 
Monotherapy Populations.  
 
Separate subject listings of CS abnormalities across all populations, sorted by SoC, will be 
presented showing all data within the CS abnormal parameter over the study for the 
respective subject. 
 
7.3.7 Physical Examination 
Physical Exam data from the ‘Physical Exam’ eCRF will be used.    
 
The results of the physical examination (Normal, Abnormal – NCS, Abnormal – CS) will be 
summarized by treatment and visit for each body system. These summaries will be repeated 
for all populations. 
 
Separate subject listings of CS abnormalities across all populations, sorted by SoC, will be 
presented showing all data within the CS abnormal body system over the study for the 
respective subject.   
 
7.3.8 Time to Premature Treatment Discontinuation 
The date of premature treatment discontinuation will be derived from the ‘Disposition Study 
Completion’ eCRF.   
  


 
 
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The time to premature treatment discontinuation (i.e. prior to Day 358, Week 52 – 1 week) 
in weeks will be derived as (date of treatment discontinuation – date of randomization 
+1)/7.   
  
If a subject does not prematurely discontinue treatment prior to Day 358, they will be 
censored in the analysis at Day 359.  
  
Summary tables of the time to premature treatment discontinuation by treatment group (as 
a continuous variable for those that prematurely discontinued), as well as Kaplan Meier plots 
by treatment will be produced. These summaries and plots will be repeated for all 
populations.  
 
7.3.9 COVID-19  
Cases of Covid-19 will be obtained from the ‘Covid-19’ eCRF form. Cases post first dose of 
study treatment will be summarized by treatment arm and split into the following periods:-  
• 
Overall  
• 
On treatment  
• 
Post treatment  
  
These summaries will be repeated for all populations.  
 
8. REFERENCES 
 
1. GALACTIC-1 Clinical Trial Protocol v7.0  
2. GALACTIC-1 Case Report Form v156, Nov 2021. 
3. ICH E3 Guideline Ref 
4. ICH E9 Guideline Ref 
5. Fainberg HP, Oldham JM, Molyneau PL, et al. Forced vital capacity trajectories 
inpatients with idiopathic pulmonary fibrosis: a secondary analysis of a multicentre, 
prospective, observational cohort. Lancet Digit Health 2022; published online Nov 1. 
https://doi.org/10.1016/ S2589-7500(22)00173-X 
 
The relevant study documents referenced were the current version at the time of SAP 
finalization. Should a study document above postdate the SAP sign-off then that version will 
be used. 
 


 
 
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9. CHANGES TO STATISTICAL ANALYSIS FROM PROTOCOL 
 
The following clarifications have been made compared to the statistical analysis documented 
in the protocol at the time of writing (Version 7.0, 28 January 2022): 
 
The protocol stated that two separate sensitivity analyses would be carried out for the 
primary estimand, and a tipping point analysis. The tipping point analysis described was 
looking for the tipping point between two sensitivity analyses, rather than relating to the 
primary analysis, and so was considered not to be informative and was removed. The second 
sensitivity analysis was also removed.  
 
The protocol stated that for the endpoint of time to death, if fewer than 5% of subjects 
experienced the event during the study then only frequencies per treatment group would be 
displayed and no formal statistical analysis would be performed. The threshold for deaths 
has been removed and time to death will be analyzed regardless of the number of events. 
 
In the logistic regression analyses the Wald test will be used rather than a likelihood ratio 
test. 
 
The protocol defined a subgroup of subjects recruited prior to Protocol version 6.0 vs 
subjects recruited post v6.0, which is also removed.  
 
 
10. AMENDMENT HISTORY OF SAP 
 
Not Applicable. 


 
 
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11. APPENDICES 
 
 
11.1 
Figure 3: Trial Design Schematic, Original Design 
 
 
 
 


 
 
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11.2 
Table 4: Schedule of Assessments 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
Withdrawal9 
Follow up7 
 
Screening1 
Baseline 
Treatment 
 
 
 
 
0 
4 
8 
12 
26 
40 
52 
- 
 
Day 
 
 
29 
57 
85 
183 
281 
365 
 
7 days after 
final study 
visit (+7 
days) 
Time window 
6 weeks 
0 
±3 
±3 
±3 
±7 
±7 
±7 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
HRCT sent to central review 
X 
 
 
 
 
 
 
 
 
 
Demographics (including 
height, weight) 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
ln- /exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
Physical examination, vital 
signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
HRQoL (SGRQ, SF-36) 
 
X 
 
 
X 
X 
 
X 
 
 
Dyspnoea index (UCSD-
SOBQ) 
 
X 
 
 
X 
X 
 
X 
 
 
12-lead ECG 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
Laboratory test (chemistry, 
haematology)2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis 
X 
 
 
X 
X 
X 
X 
X 
X 
 
Pregnancy test3 
X 
X 
 
X 
 
X 
 
X 
X 
 
Biomarker sample 
 
X 
X 
 
X 
X 
 
X 
 
 
Genetics sample4 
 
X 
 
 
 
 
 
 
 
 
Spirometry (FVC, FEV1) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
SpO2 
 
X 
 
 
 
 
 
X 
 
 
DLCO 
X 
 
 
 
 
 
 
X 
X 
 


 
 
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6MWT 
 
X 
 
 
 
 
 
 
XX 
 
Administer 1st study 
medication (at clinic) and 
inhaler training5 
 
X 
 
 
 
 
 
 
 
 
Dispense trial drug 
 
X 
X 
X 
X 
X 
X 
 
 
 
Compliance / drug 
accountability6 
 
 
X 
X 
X 
X 
X 
X 
X 
 
Adverse events and conc. 
Meds8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Notes:  
1. HRCT confirmation by central reading must be obtained as soon as possible following screening visit 1 and prior to visit 2  
2. See Table 2 and Table 3 in Section 10.4.9 of the protocol. 
3. In women of child bearing potential only: serum b-HCG will be required at visit 1 only, followed by urinary testing at subsequent visits.  
4. This is optional and separate consent must be obtained. The sample can be taken at other study visits.  
5. Subjects should be observed for 1 hour after the first dose to monitor for any acute adverse effects of study drug administration. 
6. Includes checking the subject’s use of the DPI device (Plastiape monodose inhaler). 
7. The follow-up will be performed via a phone call.  
8. Events occurring prior to randomization and administration of drug are considered as pre-treatment. Adverse events are also collected for up 
to the phone follow up. 
9. FVC, DLCO and 6MWT will be performed as part of the withdrawal assessments. 
 
 


 
 
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11.3 
Primary Estimand Sensitivity and Tipping Point Analyses 
A sensitivity analysis to test the robustness of the MAR assumption used in the main estimand 
analysis will be performed to assess the results with missing Week 52 FVC data. 
Non-monotone missing data or missing data at other visits before week 52 will not be imputed. 
Multiple imputation will be used to handle missing data at week 52. The imputation model will be 
similar to the statistical model of the primary analysis.  
For the imputation of week 52 data that is not available for reasons other than the occurrence of 
an ICE, the imputation model will be run on the subset of patients who prematurely discontinued 
trial drug but have been followed up for FVC measurements at week 52. FVC measurements that 
remain unobserved due to ICEs will still be handled as described in Section 7.2.1.  Table 5 below 
contrasts the MAR approach used in the main estimand analysis with the MNAR approach used in 
the sensitivity analysis. 
Table 5 – Missing Data Approaches 
Analysis 
No FVC result but alive at Week 52 
 
Handling of 
missing FVC 
result 
Underlying 
assumption 
Primary Estimand 
Analysis 
Missing data handled by 
model. 
Assumes missing at random. 
Discontinued subjects would have 
behaved similarly to subjects who did 
not discontinue who are in the same 
treatment group. 
Sensitivity analysis 
Based on the slope 
estimates for GB0139 dose 
and placebo among subjects 
who experience ICE without 
missing FVC data. 
Subjects with a missing result would 
have behaved similarly to 
discontinued subjects with a result 
who are in the same treatment 
group. 
 
The slope (SE) estimates of both treatment groups will be used in the sensitivity analysis. This 
approach is considered appropriate since the reasons for trial drug termination are expected to be 
similar between subjects with and without missing FVC data (discontinuation mainly due to AEs). 
The Sensitivity analysis corresponds to the assumption that in subjects with missing FVC data, the 
treatment effect would have persisted in the same manner as for subjects without missing FVC 
after trial drug discontinuation.  
The number of imputations will be set to 1000 in order to ensure adequate efficiency for the 
estimation of missing data. For each imputed dataset, the same statistical model as defined for 


 
 
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the primary analysis will be used for the analysis. See Section 7.2.1 for a description of the primary 
analysis model. The results will be pooled following the standard multiple imputation procedure. 
See Section 11.4 for further information on the implementation of the multiple imputation 
approach.  
If the primary analysis and sensitivity analysis reach differing conclusions a tipping point analysis 
will be done. The tipping point analysis will be performed by applying an incremental shift from 
the imputed FVC value generated under MAR assumption toward the imputed FVC value 
generated under the MNAR assumption. The value of the shift that overturns the primary analysis 
result will represent the tipping point.  
11.4 
Multiple Imputation Procedure 
The following steps provide guidance on how missing FVC data at week 52 will be implemented 
using multiple imputation to allow sensitivity analyses of the primary endpoint. Refer to Section 
11.3 for the description of the sensitivity analyses regarding handling of missing data. 
Step 1: Run Primary Analysis Model on Observed Data 
Run the primary analysis model to get the slope estimates with standard errors (SE) for each 
treatment group. Let βˆT and σˆT denote the slope and SE estimates in treatment group GB0139 
3mg and βˆP and σˆP the slope and SE estimates for placebo. 
 
Step 2: Draw 1000 mean imputation slopes for each treatment 
Let  βT and βP represent the true slopes in drug and placebo respectively with f(βT) ~ N(βˆT, σˆT2) 
and with f(βP) ~ N(βˆP, σˆP2), using the slope (SE) estimates obtained in step 1. Draw 1000 random 
slopes from the appropriate distribution (see Section 11.3) for each treatment.  
 
Step 3: Draw 1000 slopes for each subject 
From the respective SE for each treatment slope from step 1, derive an approximation for the SD 
as SE*sqrt(n) where n is the number of subjects in the model randomized to the relevant 
treatment. For each mean imputation slope obtained in step 2, draw an individual slope for each 
subject randomized to the respective treatment from a normal distribution with mean equal to 
the mean imputation slope and relevant SD as derived above. 
Step 4: Impute any monotonic missing FVC data at 52 weeks using each slope 
a) Considering that the withdrawal of a subject leading to missing data can occur at any time 
during the study, the timepoint of the last available FVC value has to be taken into account 
to impute the missing FVC value at 52 weeks: 
b) FVC week 52 imputedij = last FVC value availablei +  βˆij * (time between date of last FVC 
value available i and planned 52 week timepoint [days]) 


 
 
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where i denotes the indicator of the ith subject, j the indicator of the jth imputation 
and βˆij denotes a random slope sampled from the distribution mentioned above for the i-
th subject in the j-th imputation.  
c) Create 1000 imputed FVC datasets for subjects with monotonic missing FVC data at 52 
weeks including replicates of any FVC data collected in the study with the addition of the 
imputation specific 52 week result. 
d) Create 1000 identical FVC datasets for subjects with no monotonic missing FVC data at 52 
weeks.  
e) Combine data from b and c. 
 
Step 5: Run primary analysis model on each imputed dataset 
Run the model of the primary analysis on each imputed dataset, using a "by _IMPUTATION_ " 
statement to obtain 1000 parameter estimates (variable = estimate) and standard errors (variable 
= stderr). 
 
Step 6: Combine the results obtained in step 4 using PROC MIANALYZE 
Ods output ParameterEstimates=step5; 
Proc Mianalyze data=step5 ; 
modeleffects estimate; 
stderr stderr; 
Run;  
 


 
 
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11.5 
SAS Code 
11.5.1 Primary analysis 
 
ods output estimates=tests tests3=fixed;  
proc mixed data=adeff;  
       where paramcd=’FVC’;  
        class subjid trt01pn;  
        model cfb  = base areltm  trt01pn trt01pn*areltm /ddfm=kr s residual outp=resplot;  
        random intercept areltm /  sub = subjid type = un;  
        estimate ‘Plc Slope’ areltm 1 trt01pn*areltm 1 0/cl;  
        estimate ‘3mg Slope’ areltm 1 trt01pn*areltm 0 1/cl;  
        estimate ‘Slope 3mg v Plc’ trt01pn*areltm 1 -1/cl;  
run;  
where   
subjid = Subject ID  
trt01pn = Randomized treatment group (1=Placebo, 2= GB0139 3mg)  
base=Baseline FVC for the subject  
areltm = Years since first dose  
cfb = Change from baseline in FVC  
<mean baseline FVC> = the mean of the variable base across all records in the 
dataset FVC relating to the population of interest (i.e. all records to be included in the 
model)   
 
 
 
 
 
 


 
 
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11.6 
SGRQ Scoring 
11.6.1 Item Weights 
The following weights are applied if the subject gives a positive response as follows: 
PART 1 (one response per question) 
 
1) Over the last year, I have coughed: 
Most 80.6 
Several 63.2 
A few 29.3 
Only 28.1 
Not 0.0 
 
2) Over the last year, I have brought up phlegm (sputum): 
Most 76.8 
Several 60.0 
A few 34.0 
Only 30.2 
Not 0.0 
 
3) Over the last year, I have had shortness of breath: 
Most 87.2 
Several 71.4 
A few 43.7 
Only 35.7 
Not 0.0 
 
4) Over the last year, I have had attacks of wheezing: 
Most 86.2 
Several 71.0 
A few 45.6 
Only 36.4 
Not 0.0 
 
5) During the last year, how many severe or very bad unpleasant attacks of chest 
trouble have you had? 
More than three 86.7 
3 attacks 73.5 
2 attacks 60.3 
1 attack 44.2 
None 0.0 
 
6) How long did the worst attack of chest trouble last? 
a week or more 89.7 
3 or more days 73.5 


 
 
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1 or 2 days 58.8 
less than a day 41.9 
 
7) Over the last year, in an average week, how many good days (with little chest 
trouble) have you had? 
None 93.3 
1 or 2 76.6 
3 or 4 61.5 
nearly every day 15.4 
every day 0.0 
 
8) If you have a wheeze, is it worse in the morning? 
No 0.0 
Yes 62.0 
 
PART 2 
 
9) How would you describe your chest condition? (one response) 
The most important problem I have 83 .2 
Causes me quite a lot of problems 82.5 
Causes me a few problems 34.6 
Causes no problem 0.0 
 
10) If you have ever had paid employment? (one response) 
 
My chest trouble made me stop work 88.9 
My chest trouble interferes with my work or made me change my work 77.6 
My chest trouble does not affect my work 0.0 
 
11) Questions about what activities usually make you feel breathless (all that apply). 
Sitting or lying still 90.6 
Getting washed or dressed 82.8 
Walking around the home 80.2 
Walking outside on the level 81.4 
Walking up a flight of stairs 76.1 
Walking up hills 75.1 
Playing sports or games 72.1 
 
12) More questions about your cough and breathlessness (all that apply). 
My cough hurts 81.1 
My cough makes me tired 79.1 
I get breathless when I talk 84.5 
I get breathless when I bend over 76.8 
My cough or breathing disturbs my sleep 87.9 
I get exhausted easily 84.0 
 


 
 
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13) Questions about other effects your chest trouble may have on you (all that apply). 
My cough or breathing is embarrassing in public 74.1 
My chest trouble is a nuisance to my family, friends or neighbours 79.1 
I get afraid or panic when I cannot get my breath 87.7 
I feel that I am not in control of my chest problem 90.1 
I do not expect my chest to get any better 82.3 
I have become frail or an invalid because of my chest 89.9 
Exercise is not safe for me 75.7 
Everything seems too much of an effort 84.5 
 
14) Questions about your medication (all that apply). 
My medication does not help me very much 88.2 
I get embarrassed using my medication in public 53.9 
I have unpleasant side effects from my medication 81.1 
My medication interferes with my life a lot 70.3 
 
15) Questions about how activities may be affected by your breathing (all that apply). 
I take a long time to get washed or dressed 74.2 
I cannot take a bath or shower, or I take a long time 81.0 
I walk more slowly than other people, or I stop for rests 71.7 
Jobs such as housework take a long time, or I have to stop for rests 70.6 
If I walk up one flight of stairs, I have to go slowly or stop 71.6 
If I hurry or walk fast, I have to stop or slow down 72.3 
My breathing makes it difficult to do things such as walk up hills, carry things up stairs, light 
gardening such as weeding, dance, play bowls or play golf 74.5 
My breathing makes it difficult to do things such as carry heavy loads, dig the garden or 
shovel snow, jog or walk at 5 miles per hour, play tennis or swim 71.4 
My breathing makes it difficult to do things such as very heavy manual work, run, cycle, 
swim fast or play competitive sports 63.5 
 
16) We would like to know how your chest trouble usually affects your daily life (all that apply). 
I cannot play sports or games 64.8 
I cannot go out for entertainment or recreation 79.8 
I cannot go out of the house to do the shopping 81.0 
I cannot do housework 79.1 
I cannot move far from my bed or chair 94.0 
 
17) Tick the statement which you think best describes how your chest affects you (tick one). 
It does not stop me doing anything I would like to do 0.0  
It stops me doing one or two things I would like to do 42.0 
It stops me doing most of the things I would like to do 84.2 
It stops me doing everything I would like to do 96.7 
 


 
 
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11.6.2 Scoring 
 
The weights from each question included in each component will be summed as follows:  
Symptoms Component: questions 1-8 (max score 662.5). 
Activity Component: questions 11 and 15 (max score 1209.1). 
Impacts Component: questions 9-10, 12-14 and 16-17 (max score 2117.8). 
Total Score: questions 1-17 (max score 3989.4). 
Each component score will be calculated as: 100 x Summed weights for each question in that 
component / max score  
If multiple responses are given in error then the average weight will be used for the question. 
If there are missing items (depending on expected response), the maximum weight for the missing 
item will be subtracted from the max score in the denominator. The maximum number allowable 
missing items in each component are as follows:  Symptoms Component – 2 items, Activity 
Component – 4 items, Impacts Component – 6 items.  
 
 
 


 
 
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11.7 
UCSD - SOBQ 
When I do, or if I were to do, the following tasks, I would rate my breathlessness as: 
0 None at all 
1 
2 
3 
4 Severe 
5 Maximal or unable to do because of breathlessness 
 
1. At rest 
2. Walking on a level at your own pace 
3. Walking on a level with others your age  
4. Walking up a hill  
5. Walking up stairs 
6. While eating 
7. Standing up from a chair  
8. Brushing teeth 
9. Shaving and/or brushing hair 
10. Showering/bathing 
11. Dressing 
12. Picking up and straightening 
13. Doing dishes 
14. Sweeping /vacuuming 
15. Making bed 
16. Shopping 
17. Doing laundry 
18. Washing  
19. Mowing lawn 
20. Watering lawn 
21. Sexual activities 
22. Shortness of breath  
23. Fear of "hurting myself" by overexerting 
24. Fear of shortness of breath 
 
 
 


 
 
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11.8 
SF-36 Scoring 
The SF-36 (version 2) consists of 36 items.  The 36 questions are:  
1: In general, would you say your health is  
2: Compared to one year ago, how would you rate your health in general now  
3A: Vigorous activities, such as running, lifting heavy objects, participating in strenuous sports  
3B: Moderate activities, such as moving a table, pushing a vacuum cleaner, bowling, or playing golf  
3C: Lifting or carrying groceries  
3D: Climbing several flights of stairs  
3E: Climbing one flight of stairs  
3F: Bending, kneeling, or stooping  
3G: Walking more than a mile  
3H: Walking several hundred yards  
3I: Walking one hundred yards  
3J: Bathing or dressing yourself  
4A: As a result of your physical health, cut down on the amount of time you spent on work or other 
activities  
4B: As a result of your physical health, accomplished less than you would like  
4C: As a result of your physical health, were limited in the kind of work or other activities  
4D: As a result of your physical health, had difficulty performing the work or other activities (for 
example, it took extra effort)  
5A: As a result of any emotional problems, cut down the amount of time you spent on work or other 
activities  
5B: As a result of any emotional problems, accomplished less than you would like  
5C: As a result of any emotional problems, did work or other activities less carefully than usual  
6: During the past 4 weeks, to what extent has your physical health or emotional problems interfered 
with your normal social activities with family, friends, neighbors, or groups  
7: How much bodily pain have you had during the past 4 weeks  
8: During the past 4 weeks how much did pain interfere with your normal work (including both work 
outside the home and housework)  
9A: How much of the time during the past 4 weeks: did you feel full of life 
9B: How much of the time during the past 4 weeks: have you been very nervous  


 
 
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9C: How much of the time during the past 4 weeks: have you felt so down in the dumps that nothing 
could cheer you up  
9D: How much of the time during the past 4 weeks: have you felt calm and peaceful  
9E: How much of the time during the past 4 weeks: did you have a lot of energy  
9F: How much of the time during the past 4 weeks: have you felt downhearted and depressed  
9G: How much of the time during the past 4 weeks: did you feel worn out  
9H: How much of the time during the past 4 weeks: have you been happy  
9I: How much of the time during the past 4 weeks: did you feel tired  
10: During the past 4 weeks, how much of the time has your physical health or emotional problems 
interfered with your social activities (like visiting your friends, relatives, etc.)  
11A: I seem to get sick a little easier than other people  
11B: I am as healthy as anybody I know  
11C: I expect my health to get worse  
11D: My health is excellent