A Phase 2a Evaluation of PLN-74809 on αvβ6 Receptor Occupancy Using PET Imaging in Participants With IPF
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Sponsor: Pliant Therapeutics, Inc.

PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
Page 1
 
CLINICAL TRIAL PROTOCOL 
PLN-74809-IPF-201 
Study Title: 
A Phase 2a evaluation of PLN-
v
6 receptor occupancy using 
PET imaging in participants with IPF 
Study Number: 
PLN-74809-IPF-201 
Study Phase: 
2a 
Product Name: 
PLN-74809-000 
IND Number: 
139,998 
Indication: 
Treatment of idiopathic pulmonary fibrosis (IPF) 
Sponsor: 
Pliant Therapeutics Inc. 
260 Littlefield Avenue, South San Francisco, CA 94080, USA 
Medical Monitor: 
 
 
 
 
  
 
GCP Statement: 
This trial will be conducted in compliance with this protocol, Good Clinical 
Practices and applicable regulatory requirements. 
 
Version 
Date 
Original Protocol (v1.0): 
29 April 2019 
Protocol Amendment 1 (v2.0): 
14 May 2019 
Protocol Amendment 2 (v3.0): 
20 November 2019 
Protocol Amendment 3 (v4.0): 
16 March 2020 
Protocol Amendment 4 (v5.0): 
25 January 2021 
Protocol Amendment 5 (v6.0): 
26 October 2021 
 
 
 
Confidentiality Statement 
This document is the property of Pliant Therapeutics. The confidential information in this document 
may not be used, published or disclosed without the prior written consent of Pliant Therapeutics 
except to the extent required under applicable laws or regulations. 
 
 
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PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
Page 3
Blood samples for PLN-74809 pharmacokinetics (PK) will be obtained 
before and at 0.5, 1, 2, 3 and 4 hours postdose on Day 1 (prior to 
administration of the PET ligand) and at 24 hours postdose (Day 2). 
Biomarker blood samples will be collected as per the Schedule of 
Assessments. 
Forced vital capacity (FVC) and diffuse capacity for carbon monoxide 
(DLco) will be performed on all participants at Screening for 
inclusion/exclusion purposes; a historical FVC and DLco within 1 month of 
screening may be used. For those participants whose travel to the study center 
would prohibit study participation, housing accommodation may be provided 
by the Sponsor. Except for the previously described periods, participants will 
be allowed to return to their homes between study visits. 
Duration of Participant 
Participation/Study 
Duration: 
Screening for all participants will be up to 35 days prior to dosing (dosing 
will be on Day 1). The Baseline Visit (including PET) will be performed on 
Day -7 to allow a washout of the PET ligand between PET procedures. 
Screening and Baseline visit may occur on the same day, if appropriate. 
Participants will receive PLN-74809 on Day 1 and will attend a Follow-Up 
Visit 7 days (±2 days) after administration of the single dose. For participants 
consenting to receive 2 different single doses of PLN-74809, at least 14 days 
will be added to the study duration due to the required washout period.  
Study Population: 
Inclusion Criteria 
Each participant must meet the following criteria to be enrolled in this study: 
1. Participants aged 40 or older 
2. Confident diagnosis of IPF, within 8 years prior to Screening, according 
to the Fleischner Guidelines criteria; specifically either high-resolution 
computed tomography (HRCT) imaging showing a pattern of typical or 
probable usual interstitial pneumonia (UIP) or a histopathology specimen 
demonstrating a UIP pattern in the correct clinical context 
 
 and confirmed by multidisciplinary conference review at study site  
3. 
permitted if within 1 month of screening 
4. Diffusing capacity for carbon monoxide (DLco) (hemoglobin-adjusted) 
month of screening 
5. Participants currently receiving treatment for IPF with nintedanib or 
pirfenidone are allowed, provided these drugs have been given at a stable 
dose for at least 3 months before the Screening Visit and are expected to 
remain unchanged during the study. 
6. Female participants of non-childbearing potential must be either 
surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, 
and/or bilateral oophorectomy at least 26 weeks before the Screening 
Visit) or post-menopausal, defined as spontaneous amenorrhea for at least 
2 years.  
7. Female participants must have a negative pregnancy test at Baseline. 
8. Female participants of childbearing potential (i.e., ovulating, pre-
menopausal, and not surgically sterile) and all male participants with 
sexual partners of childbearing potential must agree to use highly 
effective methods of birth control during their participation in the study 
and for 30 and 90 days, respectively, after the last administration of study 
drug. Highly effective methods of birth control are defined as those with 
99% or greater efficacy 
 
 
 
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PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
Page 4
9. Participants must agree to abstain from egg or sperm donation through 30 
or 90 days, respectively, after administration of the last dose of study 
drug.  
10. Able to understand the purpose of the study and its procedures and to sign 
a written informed consent form 
Exclusion Criteria 
1. Hypersensitivity to PLN-74809 or to any of the excipients to PLN-74809 
2. Not a suitable candidate or unlikely to comply with study requirements, in 
the opinion of the Investigator 
3. Currently receiving or planning to initiate treatment for IPF (fibrosis) 
during the study with pharmacological agents not approved for that 
indication by the Food and Drug Administration (FDA) 
4. Forced expiratory volume during the first seconds of the forced breath 
(FEV1)/FVC ratio <0.7  
5. Suspicion of an interstitial lung disease (ILD) different from IPF 
according to the Investigator 
6. Clinical evidence of active infection, including but not limited to 
bronchitis, pneumonia, sinusitis that can affect FVC measurement or IPF 
progression 
7. Any other condition that prevents the correct assessment of spirometry 
performance (e.g., a broken rib or chest pain of other origin that prevent 
adequate forced breathing) 
8. Known acute IPF exacerbation or suspicion by the Principal Investigator 
(PI) of such, within 6 months of Screening 
9. Smoking of any kind (not limited to tobacco) within 3 months prior to 
Screening, as documented in the medical history, or unwilling to avoid 
smoking throughout the study 
10. Any ongoing known malignancy, except for localized cancers (e.g., basal 
cell carcinoma) 
11.
 
 
 
 
  
  
 
 
  
14. Any medical condition that, in the opinion of the Investigator, may make 
the candidate not suitable for the study 
15. History of anaphylaxis to intravenous (IV) drugs 
16. Any of the following liver function test criteria above specified limits: 
total bilirubin >1.5× the upper limit of normal (ULN); aspartate 
aminotransferase (AST) or alanine aminotransferase (ALT) >3× ULN; 
alkaline phosphatase >2.5× ULN 
17. Hemoglobin <10.0 g/dL at Screening 
18. Pregnant or lactating females 
19. Medical or surgical condition known to affect drug absorption 
 
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PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
Page 8
 
Document History 
Document 
Date 
Protocol Amendment 5 (v6.0) 
26 October 2021 
Protocol Amendment 4 (v5.0) 
25 January 2021 
Protocol Amendment 3 (v4.0) 
16 March 2020 
Protocol Amendment 2 (v3.0) 
20 November 2019 
Protocol Amendment 1 (v2.0) 
14 May 2019 
Original Protocol (v1.0) 
29 April 2019 
 
Protocol Amendment 5 (v6.0): 26 October 2021 
This protocol amendment will introduce the flexibility for participants to receive up to four 
doses of PLN-74809 (on different occasions) to account for the potential R01 Knottin tracer 
synthesis failure. Participants will undergo no more than 3 PET imaging scans (Baseline and 
up to 2 scans post PLN-74809). 
Updates to inclusion/exclusion criteria include: 
- 
Increase of diagnosis of IPF within 8 years prior to Screening.  
- 
 
 
Minor editorial and grammatical corrections were incorporated. 
 
  
 
 
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PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
Page 9
 
SYNOPSIS .................................................................................................................................2 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ....................................................8 
TABLE OF CONTENTS ...........................................................................................................9 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..........................................12 
1 
INTRODUCTION .................................................................................................14 
1.1 
Summary of Clinical Development .................................................................15 
1.1.1 
Completed Phase 1 Studies ..................................................................15 
1.1.1.1 
Overview of Treatment Emergent Adverse Events (TEAEs) 
for completed Phase 1 Studies ....................................................16 
1.1.2 
Ongoing Phase 1 Studies .....................................................................17 
1.1.3 
Ongoing Phase 2 Studies .....................................................................17 
2 
STUDY OBJECTIVES ..........................................................................................19 
3 
INVESTIGATIONAL PLAN ................................................................................20 
3.1 
Overall Study Design and Plan ........................................................................20 
3.2 
Rationale for Study Design and Control Group ...............................................20 
3.3 
Dose Rationale .................................................................................................21 
3.4 
Study Duration and Dates ................................................................................22 
4 
STUDY POPULATION ........................................................................................23 
4.1 
Inclusion Criteria .............................................................................................23 
4.2 
Exclusion Criteria ............................................................................................24 
5 
STUDY TREATMENTS .......................................................................................26 
5.1 
Description of Treatments................................................................................26 
5.1.1 
Study Drug ...........................................................................................26 
5.1.2 
Placebo or Control ...............................................................................26 
5.1.3 
R01 Knottin PET tracer ........................................................................26 
5.2 
Treatments Administered .................................................................................26 
5.3 
Selection and Timing of Dose for Each Participant .........................................26 
5.4 
Method of Assigning Participants to Treatment Groups .................................27 
5.5 
For Participants Receiving an Additional Single Dose....................................27 
5.6 
Blinding............................................................................................................27 
5.7 
Concomitant Therapy.......................................................................................27 
5.8 
Restrictions ......................................................................................................28 
5.8.1 
Prior Therapy .......................................................................................28 
5.8.2 
Fluid and Food Intake ..........................................................................28 
5.8.3 
Participant Activity Restrictions ..........................................................28 
5.8.4 
Contraception .......................................................................................29 
5.8.5 
Diet and Other Restrictions ..................................................................29 
 
 
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PLN-74809 
 
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Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
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5.9 
Treatment Compliance .....................................................................................29 
5.10 
Packaging and Labeling ...................................................................................29 
5.11 
Storage and Accountability ..............................................................................30 
6 
STUDY PROCEDURES .......................................................................................31 
6.1 
Informed Consent.............................................................................................31 
6.2 
Medical History ...............................................................................................31 
6.3 
Demographic Information ................................................................................31 
6.4 
Physical Examination.......................................................................................31 
6.5 
Vital Signs ........................................................................................................31 
6.6 
 
6.7 
Clinical Laboratory Tests .................................................................................32 
6.8 
Pharmacokinetic Assessments .........................................................................32 
6.9 
Pharmacodynamic Assessments ......................................................................32 
6.9.1 
PET Imaging ........................................................................................32 
6.9.2 
HRCT ...................................................................................................33 
6.9.3 
 
6.9.4 
Spirometry Testing for FVC Measurement .........................................33 
6.9.5 
 
6.10 
Adverse Events Assessments ...........................................................................33 
6.10.1 
Timing ..................................................................................................33 
6.10.2 
Definition of an Adverse Event ...........................................................33 
6.10.3 
Severity of an Adverse Event ..............................................................34 
6.10.4 
Causal Relationship of an Adverse Event ............................................35 
6.10.5 
Outcome ...............................................................................................36 
6.10.6 
Pregnancy .............................................................................................36 
6.10.7 
Clinical Laboratory Adverse Events ....................................................36 
6.10.8 
Serious Adverse Events .......................................................................37 
6.10.8.1 
Definition of Serious Adverse Events.........................................37 
6.10.8.2 
Reporting Serious Adverse Events .............................................37 
6.11 
Removal of Participants from the Study or Discontinuation of Study Drug ...38 
6.12 
Appropriateness of Measurements ...................................................................38 
7 
STUDY ACTIVITIES ...........................................................................................39 
8 
QUALITY CONTROL AND ASSURANCE .......................................................40 
9 
PLANNED STATISTICAL METHODS ..............................................................41 
9.1 
General Considerations ....................................................................................41 
9.2 
Determination of Sample Size .........................................................................41 
9.3 
Analysis Populations ........................................................................................41 
9.4 
Pharmacokinetic Analysis ................................................................................41 
9.5 
Pharmacodynamic Analysis .............................................................................42 
 
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PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
Page 12
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ABNM 
American Board of Nuclear Medicine 
ADL 
Activities of Daily Living 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATS 
American Thoracic Society 
AUC(0-4) 
area under the drug concentration-time curve from time zero to 4 hours after 
dosing 
AUC(0-24) 
area under the drug concentration-time curve from time zero to 24 hours after 
dosing 
AUClast 
area under the drug concentration-time curve from time zero to the time of the 
last measurable concentration 
BALF 
bronchoalveolar lavage fluid 
 
 
Cmax 
maximum observed drug concentration 
Cavg 
average drug concentration 
COL1A1 
collagen type 1 1 (human) 
CRO 
contract research organization 
CT 
computerized tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLco 
diffusing capacity for carbon monoxide 
 
 
 
 
eCRF 
electronic case report form 
EoS 
End of Study (visit) 
ET 
Early Termination (visit) 
FDA 
Food and Drug Administration 
FEV1 
forced expiratory volume during the first seconds of the forced breath 
FIH 
first-in-human 
FP-R01-MG-F2 
R01 cystine knot peptide 
FVC 
forced vital capacity 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
HRCT 
high-resolution computerized tomography 
IC50 
50% inhibitory concentration 
ICF 
informed consent form 
ICH 
International Council for Harmonisation  
 
 
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PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
Page 13
ILD 
interstitial lung disease 
IPF 
idiopathic pulmonary fibrosis 
IRB 
Institutional Review Board 
IV 
intravenous 
IWRS 
interactive web response system 
MAD 
multiple ascending dose 
MATE1 
multidrug and toxin extrusion transporter 
MedDRA 
Medical Dictionary for Regulatory Activities 
mRNA 
messenger ribonucleic acid 
 
 
PD 
pharmacodynamics(s) 
PET 
positron emission tomography 
PI 
Principal Investigator 
PK 
pharmacokinetic(s) 
PLN 
Pliant 
R01 Knottin 
[18F]FP-R01-MG-
v
6 receptor 
SAD 
single ascending dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
 
 
 
SOC 
system organ class 
SOP 
standard operating procedure 
SpO2 
peripheral capillary oxygen saturation 
SUV 
standardized uptake value 
Tmax 
time to maximum observed drug concentration 
TEAE 
treatment-emergent adverse event 
 
 
 
 
UIP 
usual interstitial pneumonia 
ULN 
upper limit of normal 
US 
United States 
WHO 
World Health Organization  
 
 
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PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
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1 
INTRODUCTION 
Pliant Therapeutics Inc is developing PLN-74809-000 (hereafter referred to as PLN-74809) 
for the treatment of idiopathic pulmonary fibrosis (IPF), the most common interstitial lung 
disease. IPF is a condition that is usually observed in the elderly and that is characterized by 
dyspnea and progressive loss of lung function leading to death, with median survival of 
3.8 years after diagnosis based on 2014 data in the United States. The hallmark honeycomb 
appearance of IPF on high-resolution computerized tomography (HRCT) is the result of 
extensive fibrosis 
. 
Although not completely understood, IPF appears to be a response to alveolar epithelial 
injury with the resultant fibrosis mediated by growth factors 
 
 and propagated by myofibroblasts. As has also been indicated to be the case 
v integrins is central to the control of 
v 6 
v 1 in 
PLN-74809. 
PLN-
v 6 
v 1 integrins (50% 
inhibitory concentration [IC50] 5.7 nM and 3.4 nM, respectively). PLN-74809 reduced 
collagen synthesis in mice with bleomycin-induced lung injury, a commonly used 
experimental model for IPF 
. In ex vivo human IPF lung tissue 
(precision cut lung slices), treatment with PLN-74809 significantly decreased collagen 
type 1 1 (COL1A1) messenger ribonucleic acid (mRNA) expression levels after a 3-day 
incubation period, providing an indication of antifibrotic activity in IPF. Mice completely 
def
v 6 function live a normal lifespan 
 suggesting that even 
full inhibition of such integrins is well tolerated. 
Integrins 
v 6 and 
v 1 mediate the release of activated transforming growth factor beta 
(TGF- )1, leading to binding of TGF- 1 to its receptor (TGF R)I/II and induction of 
SMAD2 and SMAD3 phosphorylation 
 
. Measurement of SMAD phosphorylation in lung lysates and in 
cells from bronchoalveolar lavage fluid (BALF) has, therefore, been proposed to serve as a 
pharmacodyn
v 6 integrin engagement 
 
PLN-74809 treatment of mice exposed to bleomycin via oropharyngeal aspiration to induce 
lung injury and fibrosis was shown to inhibit phosphorylation of SMAD3 in lung tissue and 
in cells isolated from BALF, confirming PLN-74809-mediated inhibition of the release of 
activated TGF- 1 in the mouse lung. PLN-75068 (a tool compound with similar 
potency/integrin selectivity to PLN-74809) was also shown to inhibit the phosphorylation of 
SMAD2 in BALF cells isolated from the lungs of healthy cynomolgus monkeys. In both 
mouse and non-human primate studies, t
v 6
v 1 integrin 
inhibitors correlated with reduced SMAD phosphorylation levels, demonstrating a clear 
pharmacokinetic (PK)/PD relationship. 
The present positron-emission tomography (PET) study described here is designed to address 
a relevant clinical question in participants with IPF. The dose- and exposure-response 
interaction of PLN-74809 with
v
6 integrin will be investigated by performing PET imaging 
 
 
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  p 
 
 
   
 
 
 
   
 
 
 
     

PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
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with a competitive v 6-binding probe at or near the maximum observed drug concentration 
(Cmax) of PLN-74809. Evaluation of PLN-74809 receptor occupancy of 
v 6 will be analyzed 
v 6-specific PET probe ([18F]FP-R01-MG-F2; R01), also known as the 
Knottin tracer. Previous work conducted in collaboration with Stanford Medical Center 
demonstrated the 
v 6 
protein expression in the lung 
 The R01 cystine knot peptide (FP-R01-
MG-F2) is a 36-amino acid peptide which has been shown to bind selectively and 
specifically to 
v
6, in vivo and in vitro, with nanomolar affinity 
 The 
18F radiotracer decays in the body with a short half-life of ~110 minutes (refer to the 
Radiology Manual for details about the Knottin tracer). Pliant has previously conducted 
studies in tissue and purified proteins demonstrating the ability of PLN-74809 to block the 
binding of a fluorescently tagged R01 peptide to
v
6.  
The present study will characterize the effect of PLN-
v 6 receptor occupancy 
using PET imaging in participants with IPF. This study will also characterize the safety, 
tolerability, PK, and PD of PLN-74809 in participants with IPF.  
1.1 
Summary of Clinical Development 
 
 
 
  
1.1.1 
Completed Phase 1 Studies 
 
 
 
 
 
  
 
 
 
 
 
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PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
Page 16
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
1.1.1.1 
Overview of Treatment Emergent Adverse Events (TEAEs) for completed 
Phase 1 Studies 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
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PLN-74809 
 
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Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
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PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
Page 19
2 
STUDY OBJECTIVES 
The primary objective of this study is: 
 
v 6 receptor occupancy by PLN-74809 in the lungs, as assessed by 
v 6 PET tracer uptake patterns following a single dose. 
The secondary objective is: 
 Assessment of the safety and tolerability of PLN-74809 in IPF participants 
The exploratory objective is:  
 
 
 
 
 
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PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
Page 22
 
 
 
 
3.4 
Study Duration and Dates 
Screening for all participants will be performed up to 35 days prior to dosing (dosing will be 
on Day 1). The Baseline Visit (including PET) will be performed on Day -7 to allow for 
washout of the PET ligand between PET procedures. Screening & Baseline visit may occur 
on the same day, if appropriate. 
Participants will receive PLN-74809 on Day 1 and will attend a Follow-Up Visit 7 days 
(±2 days) after administration of the single dose.  The study duration will be approximately 
43 days for participants testing 1 dose of PLN-74809. 
For participants consenting to receive up to four single doses of PLN-74809, at least 14 days 
will be added to the study duration due to the required washout period. Refer to Section 5.5 
for further information. 
 
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PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
Page 23
4 
STUDY POPULATION  
4.1 
Inclusion Criteria 
Each participant must meet the following criteria to be enrolled in this study: 
1. Participants aged 40 or older. 
2. Confident diagnosis of IPF, within 8 years prior to Screening, according to the Fleischner 
Guidelines criteria; specifically either HRCT imaging showing a pattern of typical or 
probable usual interstitial pneumonia (UIP) or a histopathology specimen demonstrating 
a UIP pattern in the correct clinical context (
 and confirmed by 
multidisciplinary conference review at study site. 
3. 
 45%; historical FVC for entry in the study is permitted if 
within 1 month of screening. 
4. Diffusing capacity for carbon monoxide (DLco) (hemoglobin-
DLco for entry in the study is permitted if within 1 month of screening.  
5. Participants currently receiving treatment for IPF with nintedanib or pirfenidone are 
allowed, provided these drugs have been given at a stable dose for at least 3 months 
before the Screening Visit and are expected to remain unchanged during the study. 
6. Female participants of nonchildbearing potential must be either surgically sterile 
(hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at 
least 26 weeks before the Screening Visit) or postmenopausal, defined as spontaneous 
amenorrhea for at least 2 years. 
7. Female participants must have a negative pregnancy test at Baseline. 
8. Female participants of childbearing potential (i.e., ovulating or premenopausal and not 
surgically sterile) and all male participants with sexual partners of childbearing potential 
must agree to use highly effective methods of birth control during their participation in 
the study and for 30 and 90 days, respectively, after the last administration of study drug. 
Hormonal contraceptives are not allowed. Highly effective methods of birth control are 
defined as those with 99% or greater efficacy 
 
9. Participants must agree to abstain from sperm or egg donation through 90 or 30 days, 
respectively, after administration of the last dose of study drug.  
10. Able to understand the purpose of the study and its procedures and to sign a written 
informed consent form. 
 
 
 
 
 
 
 
 
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Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
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4.2 
Exclusion Criteria 
Participants who meet any of the following criteria will be excluded from the study. 
1. Hypersensitivity to PLN-74809 or to any of the excipients to PLN-74809. 
2. Not a suitable candidate or unlikely to comply with study requirements, in the opinion of 
the Investigator. 
3. Currently receiving or planning to initiate treatment for IPF (fibrosis) during the study 
with pharmacological agents not approved for that indication by the Food and Drug 
Administration (FDA). 
4. Forced expiratory volume during the first seconds of the forced breath (FEV1)/FVC ratio 
<0.7. 
5. Suspicion of an interstitial lung disease (ILD) different from IPF according to the 
Investigator. 
6. Clinical evidence of active infection, including but not limited to bronchitis, pneumonia, 
sinusitis that can affect FVC measurement or IPF progression.  
7. Any other condition that prevents the correct assessment of spirometry performance (e.g., 
a broken rib or chest pain of other origin that prevent adequate forced breathing). 
8. Known acute IPF exacerbation or suspicion by the Investigator of such within 6 months 
of Screening. 
9. Smoking of any kind (not limited to tobacco) within 3 months prior to Screening, as 
documented in the medical history, or unwilling to avoid smoking throughout the study. 
10. Any ongoing known malignancy, except for localized cancers (e.g., basal cell 
carcinoma). 
 
 
 
  
  
 
 
  
14. Any medical condition that, in the opinion of the Investigator, may make the candidate 
not suitable for the study. 
15. History of anaphylaxis to intravenous (IV) drugs. 
16. Any of the following liver function test criteria above specified limits: total bilirubin 
>1.5× the upper limit of normal (ULN); aspartate aminotransferase (AST) or alanine 
aminotransferase (ALT) >3× ULN; alkaline phosphatase >2.5× ULN. 
 
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Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
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17. Hemoglobin <10.0 g/dL at Screening. 
18. Pregnant or lactating females. 
19. Medical or surgical condition known to affect drug absorption. 
20. Participation in a clinical trial with an investigational agent in the 30 days prior to 
Screening apart from PLN-74809. 
 
 
 
  
 
 
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Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
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5.4 
Method of Assigning Participants to Treatment Groups 
 
 
 
 
5.5 
For Participants Receiving an Additional Single Dose 
 
 
 
 
 
 
 
  
5.6 
Blinding 
This is an open-label study. 
5.7 
Concomitant Therapy 
Treatment with current standard of care (nintedanib or pirfenidone) for IPF is allowed 
provided these drugs have been given at a stable dose for at least 3 months before initiation 
of Screening and are expected to remain unchanged during the study. 
Treatment for IPF (fibrosis) with any other non-FDA-approved agent is not permitted during 
the study. Treatments to address IPF disease symptoms, (cough, gastroesophageal reflux 
disease, etc) are allowed. 
 
 
 
 
  
 
  
 
 
 
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PLN-74809 
 
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Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
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Treatment with another investigational drug, investigational device, or approved therapy for 
investigational use within 30 days or 5 half-lives (whichever is longer) before anticipated 
dosing is prohibited apart from PLN-74809. 
Other medications to provide reasonable patient care of IPF or other comorbidities are 
allowed during the study; however, these should only be used if necessary because, at this 
stage of development, no formal drug-drug interaction studies with PLN-74809 have been 
performed.  
During screening, all medications, including over-the-counter medications and herbal 
supplements, taken during the 30 days prior to Screening will be recorded and reviewed by 
the Principal Investigator (PI) in consultation with the Medical Monitor to determine whether 
the participant is suitable for inclusion. For other concomitant medications that are needed 
during the study conduct, the PI should consult with the Medical Monitor as soon as feasible. 
If used, all concomitant medications, including both prescription and nonprescription drugs, 
should first be discussed with the PI and Medical Monitor before administration. This 
requirement does not apply in the case of urgent, necessary treatment of adverse events 
(AEs). In all cases, all medications, including over-the-counter medications and herbal 
supplements, that are taken by participants during the course of the study will be recorded 
using the generic name of the medication. In addition, for participants who are receiving 
nintedanib or pirfenidone, the time of drug administration should be collected on each day on 
which samples are obtained for assessing PLN-74809 PK. 
5.8 
Restrictions 
5.8.1 
Prior Therapy 
Previous use of IPF standard-of-care treatment (pirfenidone or nintedanib) is allowed for 
participation in this study. Prohibited medications (see Section 5.7, Concomitant Therapy) 
should be stopped at least 5 half-lives before dosing on Day 1. 
5.8.2 
Fluid and Food Intake  
 
 
   
 
  
5.8.3 
Participant Activity Restrictions 
Smoking of any kind is not permitted within 3 months of Screening or during the study. 
 
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5.8.4 
Contraception 
Female participants of childbearing potential (i.e., ovulating or premenopausal and not 
surgically sterile) and all male participants with sexual partners of childbearing potential 
must use highly effective methods of birth control during their participation in the study and 
for 90 days after the last administration of study drug.  Highly effective methods of birth 
control are defined as those with 99% or greater efficacy 
 
Acceptable methods of contraception for female and male participants enrolled in the study 
include the following:  
 
preferred lifestyle 
 Implanted contraceptives 
 Oral hormonal contraceptives if using for 1 year or more 
 Dual method of contraception: 
o Condom in conjunction with use of an intrauterine device 
o Condom in conjunction with use of a diaphragm 
o Oral hormonal contraceptives with less than 1 year of use in conjunction with 
condom 
 Sexual partner with surgical sterilization (e.g., vasectomy, tubal ligation, 
hysterectomy and/or bilateral oophorectomy).  
Females who are using hormonal contraceptives should have started use at least 12 weeks 
before Screening. 
Participants must agree to abstain from egg or sperm donation and to continue condom use 
through 30 or 90 days, respectively, after administration of the last dose of study drug. 
5.8.5 
Diet and Other Restrictions 
There are no specific dietary restrictions.  
Smoking and vaping are not permitted during the study. Use of recreational drugs and/or 
abuse of alcohol consumption are not permitted during the study.  
5.9 
Treatment Compliance 
Dosing will be performed in the presence of site staff. Site staff will ensure the full dose 
amount is taken. Participants who are receiving nintedanib or pirfenidone will be provided 
with a dosing log in which they will collect dosing information on the day before and the day 
of study drug dosing.  
5.10 
Packaging and Labeling 
 
 
 
 
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5.11 
Storage and Accountability 
 
 
 
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6 
STUDY PROCEDURES 
6.1 
Informed Consent 
An informed consent form (ICF) describing the study and all anticipated risks of 
participation will be prepared and submitted to the institutional review board (IRB) for 
approval. Written and dated informed consent will be obtained from each study participant 
prior to any study-related procedures being performed. 
6.2 
Medical History 
Medical history will be reviewed and recorded at Screening. 
6.3 
Demographic Information 
Date of birth, sex, ethnicity, and race will be recorded at Screening. Body weight and height 
will be measured with the participant in light clothing. Weight will be recorded in kilograms 
and height will be recorded in centimeters.  
6.4 
Physical Examination 
Complete and directed physical examinations will be performed at the time points specified 
in the Schedule of Events (Appendix 1). Complete physical examinations include general 
appearance, head, ears, eyes, nose, throat, dentition, thyroid, chest (heart, lungs), abdomen, 
skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes. Directed 
physical examination includes head, ears, eyes, nose, throat, heart, lungs, abdomen, skin, 
musculoskeletal, and lymph nodes and any pertinent system based on any prior findings. 
Physical examinations may be performed at various unscheduled time points if deemed 
necessary by an Investigator. 
6.5 
Vital Signs 
Blood pressure and heart rate will be recorded after participants have rested for at least 
3 minutes in a supine position. Ear temperature will be measured and peripheral capillary 
oxygen saturation (SpO2) will be measured using a finger pulse oximeter. 
6.6 
  
 
 
 
 
 
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6.7 
Clinical Laboratory Tests 
Participants will be in a seated or supine position during blood collection. Clinical laboratory 
tests will include hematology, clinical chemistry, and urinalysis. Safety laboratory tests 
(hematology and clinical chemistry) will be collected from fasting (at least 2 hours) 
participants where appropriate.  
Urine pregnancy tests will be performed on all women at Baseline prior to the dose of study 
drug and, if positive, will be confirmed by a blood pregnancy test.  
A detailed list of laboratory tests is provided in Appendix 2. 
6.8 
Pharmacokinetic Assessments 
Plasma samples for PK analysis will be obtained before and at 0.5, 1, 2, 3, and 4 hours after 
dosing on Day 1 (prior to receiving the R01 Knottin tracer) and at 24 hours after dosing (Day 
2). A collection window of ±5 minutes will be allowed for samples up to 1-hour post-dose 
and a collection window of ±10 minutes will be allowed for samples that are collected at 2 
hours post-dose and after. Samples will be obtained and stored as detailed in the study PK 
Manual. 
The actual collection time of each sample must be recorded in the source data and on the 
eCRF. If the participant discontinues the study early, a plasma sample for PK should be taken 
at the Early Termination (ET) Visit if possible. 
Aliquots of these PK samples may be used to measure nintedanib and or pirfenidone 
concentrations in participants receiving these drugs.  
6.9 
Pharmacodynamic Assessments 
6.9.1 
PET Imaging 
All PET imaging will be performed at prespecified times according to the Schedule of Events 
(see Appendix 1), using the R01 Knottin tracer as synthetized by the Radiology Department 
at Stanford Medical Center, and following predefined instructions as detailed in the study 
Radiology Manual.  
PET imaging that is performed following administration of PLN-74809 on Day 1 will be 
conducted as much as possible to coincide with PLN-74809 Tmax (at least 4 hours post-dose 
v 6 receptor 
occupancy. 
Blood samples for radiotracer PK will be obtained at the following time points: 1, 3, 5, 10, 
30, and 60 minutes after completion of radiotracer injection for PET-computed tomography 
(CT) to obtain blood time activity measurements. Each collection time point has a +4-minute 
window. During some PET-CT scans, sample collection may not be possible or may be 
obviated due to staffing availability or scientific considerations. Refer to the Radiology 
Manual for details, including definitive information regarding the allowed sample collection 
windows. 
 
 
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6.9.2 
HRCT 
An HRCT will be performed at Screening only if a scan meeting the quality necessary for 
diagnosis purposes is not already available. If an HRCT is performed at Screening, a second 
one is not needed during PET-CT. An HRCT during PET-CT may be performed if the entry 
HRCT is not adequate for the assessment of HRCT-PET relationship. 
6.9.3 
 
 
 
 
 
 
 
 
6.9.4 
Spirometry Testing for FVC Measurement 
Spirometry will be performed according to American Thoracic Society (ATS) guidelines and 
using the Chest Clinic equipment at Stanford Medical Center. FVC will be assessed for all 
participants at Screening for inclusion criteria purposes.  
6.9.5 
 
 
 
 
 
 
6.10 
Adverse Events Assessments 
6.10.1 
Timing 
In this study, AEs will be collected from the time the participant signs the ICF until the last 
study visit. 
6.10.2 
Definition of an Adverse Event  
An AE is any event, side effect, or other untoward medical occurrence that occurs in 
conjunction with the use of a study drug in humans, whether or not considered to have a 
causal relationship to this treatment. An AE can, therefore, be any unfavorable and 
unintended sign (that could include a clinically significant abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a study drug, whether or not 
considered related to the study drug. Events meeting the definition of an AE include:  
 
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 Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition. 
 New conditions detected or diagnosed after study drug administration even though it may 
have been present prior to the start of the study. 
 Signs, symptoms, or the clinical sequelae of a suspected interaction.  
 Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug or 
a concomitant medication (overdose per se will not be reported as an AE/serious adverse 
event [SAE]). Events that do not meet the definition of an AE include: 
- 
Medical or surgical procedure (e.g., endoscopy, appendectomy); the condition that 
leads to the procedure is an AE.  
- 
Situations where an untoward medical occurrence did not occur (e.g., social and/or 
convenience admission to a hospital).  
- 
Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.  
 If there is evidence of an AE through report or observation, the Investigator or designee 
will evaluate further and record the following information:  
- 
Time of onset and resolution 
- 
Severity 
- 
Causality/relation to study treatment 
- 
Action taken regarding study drug 
- 
Outcome 
6.10.3 
Severity of an Adverse Event 
Grading the severity of AEs will use the Common Terminology Criteria for Adverse Events 
(CTCAE) grading system (Version 5.0), as described below. The clinical significance of the 
AE is determined by the Investigator. The Investigator is encouraged to consult with the 
Medical Monitor.  
 
 
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Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental ADL*. 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADL**. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE. 
A semi-
 
*Instrumental Activities of Daily Living (ADL) refer to preparing meals, shopping for groceries or clothes, 
using the telephone, managing money, etc. 
**Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, or taking 
medications and not bedridden. 
Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Published: November 27, 2017. 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_8.5x1
1.pdf 
 
6.10.4 
Causal Relationship of an Adverse Event 
The Investigator will assess the relationship between study drug and the occurrence of each 
e relationship of each AE to study drug will be 
recorded in the source documents and the eCRF. Alternative causes, such as medical history, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study drug should be considered and investigated, if appropriate. The relationship or 
association of the AE to a study drug (PLN-74809 or placebo) should be assessed using 
clinical judgment and the following considerations: 
No: 
Evidence exists that the adverse event has an etiology other than the study 
drug. For SAEs, an alternative causality must be provided (e.g., 
preexisting condition, underlying disease, intercurrent illness, or 
concomitant medication). 
Yes: 
A temporal relationship exists between the AE onset and administration 
clinical state or concomitant therapies. Furthermore, the AE appears with 
some degree of certainty to be related, based on the known therapeutic 
and pharmacologic actions or AE profile of the study drug. In case of 
cessation or reduction of the dose, the AE abates or resolves and 
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The relationship to study procedures (such as venipuncture) should be assessed using the 
following considerations: 
No: 
Evidence exists that the AE has an etiology other than the study 
procedure 
Yes: 
The AE occurred as a result of protocol-mandated procedures. 
6.10.5 
Outcome  
The outcome of an AE will be recorded on the AE eCRF as follows:  
 Recovered / Resolved 
 Recovering / Resolving 
 Recovered / Resolved with Sequelae 
 Not Recovered / Not Resolving 
 Fatal 
 Unknown 
 
6.10.6 
Pregnancy 
A pregnancy is not an AE. If a female participant or the female partner of a male study 
participant becomes pregnant while enrolled in the study following administration of study 
drug or within 90 days after last dose, the Sponsor must be notified within 24 hours of the 
Investigator learning of the pregnancy.  The participant or the female partner of a male study 
participant will be followed through the outcome of the pregnancy. The Investigator is 
required to provide all the relevant information to the Sponsor using the Pregnancy 
Information Form to do so. 
6.10.7 
Clinical Laboratory Adverse Events 
Abnormal laboratory findings (e.g., clinical chemistry, hematology, urinalysis) or other 
abnormal assessments 
 per se are not reported as AEs. However, those 
abnormal findings that are deemed clinically significant or that are associated with signs 
and/or symptoms must be recorded as AEs if they meet the definition of an AE (or recorded 
as an SAE if they meet the criteria of being serious), as described in Section 6.10.2. 
Clinically significant abnormal laboratory or other abnormal findings that are detected after 
consent or that are present at Baseline and worsen after consent are included as AEs (and 
SAEs if serious). 
The Investigator should exercise his/her medical and scientific judgment in deciding whether 
an abnormal laboratory finding or other abnormal assessment is clinically significant. 
Usually, the abnormality should be associated with a clinically evident sign or symptom, or 
 
 
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be likely to result in an evident sign or symptom in the near term, to be considered clinically 
significant. A clinically significant laboratory abnormality in the absence of clinical 
symptoms may jeopardize the participant and may require intervention to prevent immediate 
consequences. For example, a markedly low serum glucose concentration may not be 
accompanied by coma or convulsions, yet be of a magnitude to require glucose 
administration to prevent such sequelae. 
6.10.8 
Serious Adverse Events 
6.10.8.1 
Definition of Serious Adverse Events 
An SAE is any untoward medical occurrence that at any dose:  
 Is life-threatening 
 Results in death 
 Requires inpatient hospitalization (i.e., admission, overnight stay) or prolongs existing 
hospitalization 
 Results in persistent or significant disability/incapacity, or 
 Is a congenital anomaly/birth defect  
An AE is considered life-threatening if, in the opinion of either the Investigator or the 
Sponsor, its occurrence places the participant at immediate risk of death. It does not include 
an AE that, had it occurred in a more severe form, might have caused death. 
Important medical events that are not one of the above may be considered to be SAEs by the 
Investigator when, based upon appropriate medical judgement, they are considered to be 
clinically significant and may jeopardize the participant or when medical or surgical 
intervention may be required to prevent one of the outcomes listed above. (Examples of such 
events include allergic bronchospasm requiring intensive treatment at an emergency room or 
at home, blood dyscrasias, convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse.) 
6.10.8.2 
Reporting Serious Adverse Events 
In order to meet the requirements for expedited reporting of SAEs meeting specific 
requirements to applicable regulatory authorities and IRBs, all SAEs must be reported to the 
Sponsor within 24 hours from the time site personnel first become aware of the event. This 
may be initially achieved by telephone or by completing an SAE report form and e-mailing it 
to the email address, as provided on the form.  
Initial notification of an SAE by telephone must be confirmed in writing 24 hours from the 
time the site investigational team first become aware of the event using the serious adverse 
event report form as described above. As further information regarding the SAE becomes 
available, such follow up information should be documented on a new SAE report form, 
marked as a follow-up report, and scanned and e-mailed to the address provided. 
 
 
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Withdrawal from the study in the event of a SAE and therapeutic measures taken shall be at 
the discretion of the Investigator. A full explanation for the discontinuation from the study 
should be made in the eCRF. 
The reporting of any SAEs to applicable regulatory authorities will be the responsibility of 
the Sponsor in compliance with applicable country regulations. All SAEs must be reported to 
the IRB by the Investigator in accordance with their regulations. 
6.11 
Removal of Participants from the Study or Discontinuation of Study 
Drug 
In accordance with the Declaration of Helsinki, participants have the right to withdraw from 
the study at any time for any reason. The Investigator or Sponsor may withdraw a participant 
from the study or discontinue study drug for any of the following reasons: 
 Noncompliance with protocol procedures, including those relating to administration of 
study drug. 
 A serious or intolerable adverse event occurs. 
 A clinically significant change in a laboratory parameter occurs. 
 The Sponsor or Investigator terminates the study. 
 The participant requests to be discontinued from the study. 
If a participant is withdrawn from the study or discontinues study drug, he or she will 
undergo ET assessments (refer to the Schedule of Evaluations in Appendix 1).  
6.12 
Appropriateness of Measurements 
All PK, PD, and safety assessments are typical of those that are usually employed in studies 
aiming to establish a PK/PD relationship. When available, appropriate standard guidelines 
will be used.  
We 
v 6 
integrin receptor can be measured utilizing PET probes in IPF patients. The evaluation of 
receptor occupancy of an investigational compound with PET imaging has been a well-
established method in the study of neurological receptors for many years. We are applying 
both approaches to evaluate the PK/PD relationship of PLN-74809 in IPF patients. 
Assessment of the primary endpoint will be made using standard methods for quantifying the 
v 6 integrin receptor in the lungs before and after 
administration of study drug. Standard mathematical and analytical tools will be used to 
determine if the presence of PLN-74809 reduces the binding of the PET tracer. Tracer uptake 
before and after treatment will be quantified to estimate changes in receptor density. 
 
 
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7 
STUDY ACTIVITIES 
The Schedule of Events with study activities is provided in Appendix 1. 
When multiple study procedures are scheduled at the same time point, the suggested order of 
procedures is as follows but may be adjusted by the site staff to allow flexibility in the study 
flow: 
 obtain vital signs, collect urine sample, and collect blood sample. When 
several assessments are required at the same time point, evaluations should be completed so 
that the PK sample is collected at the required time. 
 
 
 
 When samples 
for PK purposes are scheduled for collection around a PET procedure, the PK samples should 
be obtained as close as possible to the prescheduled timing while minimizing interference 
with the PET procedure, which has priority.  
 
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8 
QUALITY CONTROL AND ASSURANCE 
During the study, the Sponsor and/or representatives of the Sponsor may visit the site to 
conduct an audit of the study. The purpose of this visit will be to determine 
to assessing the accuracy of the study data. Prior to initiating this audit, the Investigator will 
be contacted by the Sponsor to arrange a convenient time for this visit. The Investigator and 
staff are expected to cooperate with the auditors and allow access to all participant records 
supporting the eCRFs and other study-related documents. 
At some point during the development program for the study drug, a regulatory authority 
may visit the Investigator to conduct an inspection of the study and the site. The Investigator 
and staff are expected to cooperate with the inspectors and allow access to all source 
documents supporting the eCRFs and other study related documents. The Investigator must 
immediately notify the Sponsor when contacted by any regulatory authority for purposes of 
conducting an inspection. 
 
 
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9 
PLANNED STATISTICAL METHODS 
9.1 
General Considerations 
This is an exploratory study; as such, no statistical hypotheses are being tested. In general, 
data will be summarized using statistical summary methods; graphic presentations of data 
may also be prepared. The contract research organization (CRO) will be responsible for the 
preparation of tables and listings and will assist in the preparation of figures, which may be 
done by Sponsor personnel. A statistical analysis plan (SAP), prepared and agreed before 
final database lock, will describe the analytic approach and methods in more detail. 
9.2 
Determination of Sample Size 
The sample size has been set empirically. Up to 12 participants should provide proof of 
v 6 receptor occupancy by 
PLN-74809). Pharmacodynamic, PK, and safety/tolerability evaluation of PLN-74809 will be 
assessed in the target population. 
9.3 
Analysis Populations 
Safety Population: All participants who receive one dose of study drug will be included in 
the Safety Population. 
PET Population: All participants with at least a baseline PET will be included in the PET 
Population. 
PK Concentration Population: All participants who receive one dose of study drug and 
have any measurable PLN-74809 concentration data will be included in PK Concentration 
Population.  
PK Analysis Population: All participants who have sufficient PLN-74809 concentration 
data for PK calculation will be included in the PK Analysis Population.  
 
 
 
9.4 
Pharmacokinetic Analysis 
Plasma PLN-74809 concentrations at each sampling time point will be presented in listings 
and summarized with descriptive statistics. Plasma PLN-74809-versus-time profiles (with 
plasma concentrations on both a log and linear scale) will be plotted for each participant.  
Non-compartmental analysis will be used to calculate the PK parameters Tmax, Cmax, area 
under the drug concentration-time curve from time zero to the time of the last measurable 
concentration (AUClast), AUC from time zero to 4 hours (AUC(0-4)) and from time zero to 
24 hours (AUC(0-24)) after dosing, and average drug concentration (Cavg), if applicable. 
Plasma PK parameters will be presented in listings and summarized with descriptive 
 
 
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All AEs will be listed by participant and summarized in a table. The incidence of AEs, the 
incidence of treatment-emergent AEs (TEAEs), the incidence of treatment-related AEs, and 
the severity of AEs will be summarized by system organ class (SOC), preferred term, and 
maximum severity. In cases in which a participant reports multiple occurrences of the same 
event (preferred term), the greatest severity will be included in the summary. The number 
and percentage of participants with SAEs and treatment-related SAEs and the number and 
percentage of participants who withdraw due to an AE will be tabulated. 
Clinical laboratory test parameters will be listed, using the CTCAE grading scale, for 
individual participants, with values outside the reference ranges flagged. The incidence of 
treatment-emergent laboratory abnormalities will be summarized by severity. Summary 
statistics will be calculated for each parameter. 
 
 
 
Vital sign measurements, other laboratory tests, concomitant medications, medical history 
and changes in physical examinations at each time point will be listed by participant. 
Concomitant medications will be coded using the most current World Health Organization 
(WHO) drug dictionary available. 
9.7 
 
 
  
 
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10 
ADMINISTRATIVE CONSIDERATIONS 
10.1 
Institutional Review Board Approval 
It is the responsibility of the Investigator to assure that all aspects of the study are conducted 
in accordance with the Declaration of Helsinki as described in the International Council for 
Harmonisation (ICH) E6: Guideline for Good Clinical Practice (GCP), and/or local laws, 
whichever provides the greatest level of protection for the study participants. The protocol 
and any information supplied to the participant to obtain informed consent, including written 
ICF(s), participant recruitment procedures (e.g., advertisements), and written information to 
be provided to participants (information leaflets), must be reviewed and approved by a 
qualified IRB prior to enrollment of participants in the study. Prior to initiation of the study, 
the Sponsor must receive documentation of the IRB approval, which specifically identifies 
the study/protocol, and a list of the committee members. 
Amendments to the protocol and revisions to the informed consent must also be submitted to 
and, if required, approved by the IRB. 
The Investigator must submit progress reports to the IRB in accordance with the IRB 
requirements. Annual re-approval of the study must be obtained. Copies of progress reports 
and Annual re-approvals must be sent to the Sponsor. 
When the Sponsor provides the Investigator with a safety report, the Investigator must 
promptly forward a copy to the IRB. 
After completion or termination of the study, the Investigator must submit a final report to 
the IRB and to the Sponsor. 
The Investigator, as part of the records retention requirements for the study, must maintain 
documentation of all submissions, correspondence, and approvals to and from the IRB. 
Each clinical Investigator is responsible to conduct the study in accordance with the protocol, 
all applicable laws, regulations, and GCP according to ICH guidelines. 
10.2 
Ethical Conduct of the Study 
The study will be carried out in accordance with the current version of the Declaration of 
Helsinki, concerning medical research in humans (recommendations guiding physicians in 
biomedical research involving human participants). The study will be conducted in adherence 
to the study protocol and GCPs, as defined in Title 21 of the US Code of Federal Regulations 
Parts 50, 54 56, and 312 and Part 11, as well as ICH E6: Guideline for Good Clinical Practice 
(ICH GCP) consolidated guidelines (E6) and applicable regulatory requirements. 
10.3 
Participant Information and Consent 
Preparation of the ICF is the responsibility of the Investigator and the Sponsor or designee. It 
must include all elements required by the ICH, GCP, and applicable regulatory requirements 
 
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and must adhere to GCP and to the ethical principles that have their origin in the Declaration 
of Helsinki. 
The Sponsor or designee must review and approve the ICF before submission to the IRB.  
The ICF must include a statement that the Sponsor or designee and regulatory authorities 
have direct access to participant records. Prior to the beginning of the study, the Investigator 
information to be provided to the participants. 
Before being enrolled in the clinical study, participants must consent to participate after the 
nature, scope, and possible consequences of the study have been explained in a form 
understandable to them. 
An ICF that includes both information about the study and the consent form will be prepared 
and given to the participant. This document will contain all the elements required by the ICH 
E6 Guideline for Good Clinical Practice and any additional elements required by local 
regulations. The document must be in a language understandable to the participant and must 
specify who informed the participant. Where required by local law, the person who informs 
the participant must be a physician. 
A copy of the signed and dated consent document must be given to the participant. The 
original signed and dated consent document will be retained by the Investigator. 
The Investigator will not undertake any measures specifically required only for the clinical 
study until valid consent has been obtained. 
10.4 
Participant Confidentiality 
Participant names will not be supplied to the Sponsor. Only the participant number will be 
recorded in the eCRF, and if the participant name appears on any other document (e.g., 
laboratory report), it must be obliterated on the copy of the document to be supplied to the 
Sponsor. Study findings stored on a computer will be stored in accordance with local data 
protection laws. The participants will be informed that representatives of the Sponsor, IRB, 
or regulatory authorities may inspect their medical records to verify the information 
collected, and that all personal information made available for inspection will be handled in 
strictest confidence and in accordance with local data protection laws. 
Applicable data privacy laws and regulations must be adhered to. The Investigator and the 
Sponsor are responsible for ensuring that sensitive information is handled in accordance with 
local requirements (e.g., Health Insurance Portability and Accountability Act [HIPAA]). 
Appropriate consent and authorizations for use and disclosure and/or transfer (if applicable) 
of protected information must be obtained. 
 
 
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10.5 
Study Monitoring 
study. Monitoring visits provide the Sponsor with the opportunity to: 
 Evaluate the progress of the study. 
 Verify the accuracy and completeness of eCRFs. 
 Ensure that all protocol requirements, applicable laws and/or regulations, and 
 
 Resolve any inconsistencies in the study records. 
The Investigator must allow the Study Monitors to periodically review, at mutually 
convenient times during the study and after the study has been completed, all eCRFs and 
office, hospital, and laboratory records that support the participation of each participant in the 
study. The eCRFs and other documentation supporting the study must be kept up to date by 
the Investigator and the research staff at the investigative site. These study materials must be 
available for review by the Study Monitor and/or other qualified representatives of the 
Sponsor at each monitoring visit. 
The Study Monitor will review the various records of the study (eCRFs, participant medical 
and laboratory records, and other pertinent data). The Study Monitor will verify the eCRF 
data against original source documentation for accuracy and completeness. The Study 
Monitor will identify data discrepancies and collaborate with the Investigator and research 
staff to resolve the discrepancies in a timely manner. Protocol deviations will also be 
identified and recorded on a Protocol Deviation Log and reviewed in accordance with the 
monitoring plan.  
10.6 
Case Report Forms and Study Records 
The investigative site will use eCRFs to record all the protocol-specified data for each 
participant in this study. Entries made in the eCRF must be verifiable against source 
documents. Data reported in the eCRF that are derived from source documents should be 
consistent with the source documents or the discrepancies should be explained. 
The Investigator will be responsible for reviewing all data and eCRF entries and will sign 
and correct. 
Queries generated by Data Management will be sent to the study site for resolution.  
10.7 
Protocol Violations/Deviations 
Participants must meet eligibility requirements to be enrolled in the study. Deviations must 
be reported to the IRB in accordance with the IRB requirements. During the course of the 
study, the monitor must notify the Sponsor of participants found not to have met eligibility 
 
 
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Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
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criteria. The Medical Monitor in collaboration with the Investigator will determine if the 
participant should be withdrawn from the study. 
10.8 
Data Generation and Analysis 
Data management will be performed using eCRFs with data entry being performed by the 
research site staff into a validated clinical database. Laboratory data will be captured in a 
separate validated database.  
All data entry and verification will be performed in accordance with the standard operating 
procedures (SOP) of the CRO. 
10.9 
Retention of Data 
The Investigator must ensure that all records pertaining to the conduct of the clinical study, 
ICFs, drug accountability records, source documents, and other study documentation are 
adequately maintained for a period of 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the study drug. 
The Investigator must not destroy any records associated with the study without receiving 
approval from the Sponsor. The Investigator must notify the Sponsor in the event of 
accidental loss or destruction of any study records.  
Whenever possible, an original recording of an observation must be retained as the source 
document. However, a photocopy of a record is acceptable provided it is legible and is a 
verified copy of the original document. 
All eCRF data entered by the site (including audit trail), as well as computer hardware and 
software (for accessing the data), will be maintained or made available at the site in 
compliance with applicable record retention regulations. The CRO will retain the original 
eCRF data and audit trail. 
10.10 
Publication and Disclosure Policy 
The data generated in this clinical study are the exclusive property of the Sponsor and are 
confidential. Any publication of the results of this study must be authorized by the Sponsor. 
The Sponsor will have the opportunity to review any publications that arise from the 
Investigators before submission for publication. Any such review and approval of 
publications related to the study shall be made pursuant to the process agreed between the 
or. Authorship on any publication of 
the results from this study will be based on contributions to study design, enrolment, data 
analysis, and interpretation of results. 
 
 
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Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
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PLN-74809
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Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
Page 51
 
a 
In case the PET ligand cannot be successfully synthetized on the scheduled day, participants will wait at least 1 week and then be dosed again for a 
second attempt at PET synthesis and imaging.  
b 
Time 0 refers to immediately pre-dose. 
c 
Complete physical examination at Screening and directed physical examination thereafter. 
d 
A table of blood volumes is provided in Appendix 3. 
e 
Urinalysis: dipstick followed up by microscopic examination if needed. 
f 
An HRCT at Screening may not be needed if a scan that weeks the quality necessary for diagnosis purposes exists. If an HRCT is performed at 
Screening, a second one is not needed during PET. An HRCT during PET may be performed if the Screening HRCT is not adequate for the 
assessment of HRCT-PET relationship.   
g 
PET to be performed at least 4 hours post-dose and no more than 30 minutes after the 4 hour PK timepoint. 
h 
Blood samples for radiotracer PK to be taken 1, 3, 5, 10, 30, and 60 minutes after completion of radiotracer injection for PET-CT. Each collection 
time point has a +4-min window. Refer to the Radiology Manual for details of sample collection including definitive information about allowable 
windows.  
i 
Dosing to occur in connection to PET synthesis and availability. 
j 
Day 2 plasma PK sample to be collected 24 hours post-dose. 
k 
 
l 
Adverse events and concomitant medications to be collected at each visit. 
m 
For participants testing 2 different doses of PLN-74809, the Baseline PET scan will be based on the first single dose screening and not repeated. 
Additionally, if in the opinion of the Investigator, there is no clinical decline, the other Screening and Baseline procedures do not have to be repeated. 
Participants must washout of PLN-74809 for at least 14 days prior to testing the second dose level of PLN-74809.  
n 
Screening & Baseline visit may occur on the same day, duplicative assessments will not need to be repeated 
o 
Hematology and clinical chemistry may be conducted outside of study institution for EOS visit, if appropriate. 
 
 
 
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PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
Page 52
Appendix 2 
List of Laboratory Tests 
Hematology: 
- 
Hematocrit (Hct) 
- 
Hemoglobin (Hgb) 
- 
Mean corpuscular hemoglobin (MCH) 
- 
Mean corpuscular hemoglobin 
concentration (MCHC) 
- 
Mean corpuscular volume (MCV) 
- 
Platelet count 
- 
Red blood cell (RBC) count  
- 
White blood cell (WBC) count with 
differential (absolute counts only) 
- 
Basophils 
- 
Eosinophils 
- 
Lymphocytes 
- 
Monocytes 
- 
Neutrophils 
 
 
Urinalysis:  
- 
Appearance 
- 
Bilirubin 
- 
Color 
- 
Glucose 
- 
Ketones 
- 
Microscopic examination of sediment  
- 
Nitrite  
- 
Occult blood 
- 
pH 
- 
Protein 
- 
Specific gravity 
- 
Urobilinogen 
Urine pregnancy test for all female participants 
Clinical Chemistry: 
- 
Alanine aminotransferase (ALT; 
SGPT) 
- 
Albumin (ALB) 
- 
Alkaline phosphatase (ALP) 
- 
Alpha-1-acid-glucoprotein (AAG) 
- 
Aspartate aminotransferase (AST; 
SGOT) 
- 
Bilirubin (total and direct) 
- 
× ULN) 
- 
Blood urea nitrogen (BUN) 
- 
Calcium (Ca) 
- 
Chloride (Cl) 
- 
Creatinine 
- 
Creatine kinase  
- 
Gamma-glutamyl transferase (GGT) 
- 
Glucose 
- 
Lactate dehydrogenase (LDH) 
- 
Phosphorus 
- 
Potassium (K) 
- 
Sodium (Na) 
- 
Total bilirubin 
- 
Total cholesterol 
- 
Total protein 
- 
Triglycerides 
- 
Total protein 
- 
Uric acid 
 
 
 
Safety laboratory tests (hematology and clinical chemistry) will be collected from fasting (at least 4 hours) 
participants where appropriate. 
 
 
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Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
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Appendix 3 
Table of Blood Volumes 
Per participant 
Type of sample 
Blood volume 
per sample (mL) 
Number of 
samples 
Total blood 
volume (mL) 
Plasma PK 
4  
8 
32 
Hematology and clinical chemistry 
10 
5 
50 
Radiotracer PK 
3 
12 
36 
Total  
 
138.5  
PK = pharmacokinetic. 
 
 
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PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
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Appendix 4 
Exposure to Radiation 
Volumetric HRCT: The amount of radiation from one procedure is 3-8 milliSieverts (mSv) 
 
PET-CT: The amount of radiation from one Knottin PET-CT scan is 9.5 mSv (2.5 mSv from 
7.5 mCi of Knottin radiotracer and 7 mSv from 3 localizer and low dose attenuation 
correction CT scans). 
The amount of radiation from 3 Knottin PET-CT and one possible HRCT is less than the 
50 mSv annual limit for radiation workers set by the United State Nuclear Regulatory 
Commission.  
 
 
 
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PLN-74809 
 
Pliant Therapeutics Inc. 
Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
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Appendix 5 
Sponsor Signature 
Study Title: 
A Phase 2a evaluation of PLN-
v
6 receptor 
occupancy using PET imaging in participants with IPF   
Study Number: 
PLN-74809-IPF-201 
Original Protocol Final Date: 
29 April 2019 
Protocol Amendment 1 Date: 
14 May 2019 
Protocol Amendment 2 Date: 
20 November 2019 
Protocol Amendment 3 Date: 
16 March 2020 
Protocol Amendment 4 Date: 
25 January 2021 
Protocol Amendment 5 Date: 
26 October 2021 
 
 
This clinical study protocol was subject to critical review and has been approved by the 
Sponsor: 
 
 
 
Signed:
Date:  
 
 
 
 
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PLN-74809 
 
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Clinical Trial Protocol: PLN-74809-IPF-201, Version 6.0
Page 56
Appendix 6 
 
Study Title: 
A Phase 2a evaluation of PLN-
v
6 receptor 
occupancy using PET imaging in participants with IPF   
Study Number: 
PLN-74809-IPF-201 
Original Protocol Final Date: 
29 April 2019 
Protocol Amendment 1 Date:  
14 May 2019 
Protocol Amendment 2 Date:  
20 November 2019 
Protocol Amendment 3 Date: 
16 March 2020 
Protocol Amendment 4 Date: 
25 January 2021 
Protocol Amendment 5 Date: 
26 October 2021 
 I have read the protocol and appendices described above. I agree to comply with all 
applicable regulations and to conduct the study as described in the protocol. 
I agree to comply with the International Council for Harmonisation (ICH), Tripartite 
Guideline on Good Clinical Practice (ICH, GCP) and the provisions of the Helsinki 
Declaration. 
I agree to ensure that the confidential information contained in this document will not be 
used for any purpose other than the evaluation or conduct of the clinical study without the 
prior written consent of Pliant Therapeutics Inc. 
The Sponsor or its designee will have access to source documentation from which case report 
forms have been completed. 
 
 
Signed: 
 
 
Date:  
 
 
 
 
Signed: 
 
 
Date:  
 
 
 
 
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