A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study of the Efficacy and the Safety and Tolerability of BMS-986278 in Participants With Pulmonary Fibrosis
Phase: PHASE2
Conditions: Pulmonary Fibrosis
Sponsor: Bristol-Myers Squibb

Official Title of Study: 
A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study of the Efficacy 
and the Safety and Tolerability of BMS-986278 in Participants with Pulmonary Fibrosis 
 
NCT Number: NCT04308681 
Document Date (Date in which document was last revised): 22 September 2022 

Page:
1
Protocol Number:
IM027040
Date:
07-Jan-2020
Revised Date:
22-Sep-2022
Clinical Protocol IM027040
A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study of the Efficacy 
and the Safety and Tolerability of BMS-986278 in Participants with Pulmonary Fibrosis
Short Title: 
Phase 2 Study of the Efficacy and Safety of BMS-986278 in Pulmonary Fibrosis
Protocol Amendment 05
Incorporates Administrative Letter 05, 06, and 07
Study Director
Clinical Trial Physician/ 
Medical Monitor
Clinical Scientist
3401 Princeton Pike, 
Lawrenceville, 
NJ 08648
3401 Princeton Pike, 
Lawrenceville, 
NJ 08648
3401 Princeton Pike, 
Lawrenceville, 
NJ 08648
Telephone:
Mobile: 
Telephone: 
Mobile: 
Telephone:
Mobile: 
24-hr Emergency Telephone Number
USA: 
International: 
Japan: 
Bristol-Myers Squibb Company
3401 Princeton Pike
Lawrenceville, NJ 08648
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
1-2-1 Otemachi, Chiyoda-ku,
Tokyo 100-0004, Japan
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IM027040
BMS-986278
LPA1 Antagonist
Protocol Amendment No.: 05
Date: 22-Sep-2022
2
REGULATORY AGENCY IDENTIFIER NUMBER(S)
IND: 139,558
EudraCT: 2019-003992-21
Ex-US: Non-IND
This document is the confidential and proprietary information of Bristol-Myers Squibb Company and its global 
affiliates (BMS). By reviewing this document, you agree to keep it confidential and to use and disclose it solely 
for the purpose of assessing whether your organization will participate in and/or the performance of the 
proposed BMS sponsored study. Any permitted disclosures will be made only on a confidential "need to know" 
basis within your organization or to your independent ethics committee(s). Any other use, copying, disclosure 
or dissemination of this information is strictly prohibited unless expressly authorized in writing by BMS. Any 
supplemental information (eg, amendments) that may be added to this document is also confidential and 
proprietary to BMS and must be kept in confidence in the same manner as the contents of this document. Any 
person who receives this document without due authorization from BMS is requested to return it to BMS or 
promptly destroy it. All other rights reserved. References to BMS in this protocol may apply to partners to 
which BMS has transferred obligations, eg, a Contract Research Organization.
© 2020 Bristol-Myers Squibb Company
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Protocol Amendment No.: 05
Date: 22-Sep-2022
3
DOCUMENT HISTORY
Document
Date of Issue
Approver(s)
Summary of Change
im027040-
protamend05
22-Sep-2022
, 
Head of Clinical Development 
Immunology and Fibrosis
Updated BMS Japan address.
Added clarifying sentence in 
Section 5.1 and 7.3.1
Updated header and footnote c in
Table 7.
Added clarifying text in 
Section 10.4.4. 
im027040-
admlet07
13-Jun-2022
Clinical Scientist Team Lead
BMS Immunology & Fibrosis 
Clinical Development
Incorporated into 
im027040-protamend05.
im027040-
admlet06
02-May-2022
Clinical Scientist Team Lead
BMS Immunology & Fibrosis 
Clinical Development
Incorporated into 
im027040-protamend05.
im027040-
admlet05
22-Feb-2022
Clinical Scientist Team Lead
BMS Immunology & Fibrosis 
Clinical Development
Incorporated into 
im027040-protamend05.
im027040-
admlet04-cn-
specific
22-Dec-2021
 
Medical Monitor
Clarified 2 separate consistency 
errors in im027040-protamend01-cn 
(China-specific).
im027040-
protamend04
21 Dec 2021
Head of Immunology & Fibrosis 
Clinical Development
Bristol-Myers Squibb
Revised the PET tracer substudy to 
allow incorporation of participants 
with PF-ILD
Clarified phrasing in inclusion and 
exclusion criteria
Added 2 secondary endpoints 
evaluating the effect of BMS-
986278 treatment
im027040-
protamend01-cn
China-specific
01 Nov 2021
Head of Immunology & Fibrosis 
Clinical Development
Bristol-Myers Squibb
Removed biomarker assessments, 
Additional Research, and intensive 
PK substudy for all participants 
enrolled in mainland China.
Clarified objectives and endpoints 
for mainland China.
im027040-
admlet03
13 Apr 2021
Clinical Trial Physician
Incorporated into 
im027040-protamend04
 
 
 
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Protocol Amendment No.: 05
Date: 22-Sep-2022
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Document
Date of Issue
Approver(s)
Summary of Change
im027040-
revprot03a-tw-
specific
15 Mar 2021
  
Clinical Program Lead - Fibrosis
Removed eCOA measures from 
main study and optional treatment 
extension
Clarified language around dosing 
time and day collection prior to PK 
visits
im027040-
admlet02
04 Mar 2021
Clinical Trial Physician
Incorporated into im027040-
protamend04
im027040-
revprot03
14 Jan 2021
Clinical Program Lead - Fibrosis
Updated sections throughout 
protocol to allow participants with 
PF-ILD to remain on stable 
background therapies.
Clarified restriction on concomitant 
use of anti-fibrotics during the main 
study.
Updated screening period from 28 to 
42 days.
Updated several inclusion and 
exclusion criteria.
Added COVID-19-related risk 
assessment.
Added language for collecting AEs 
and SAEs related to COVID-19.
Added serum collections for 
possible assessments of SARS-CoV-
2 serologic status and related 
exploratory objective and endpoint.
Added clinical laboratory sampling 
on Day 1 of the OTE.
Updated study treatment 
discontinuation criteria.    
Added requirement to record date 
and time of last study treatment 
administration prior to PK study 
visits.
Modified language referring to 
number of participants enrolled per 
treatment arm in the PK substudy.
Revised language throughout 
protocol to provide sites more 
flexibility regarding order and 
timing of study procedures.
 
 
 
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Protocol Amendment No.: 05
Date: 22-Sep-2022
5
Document
Date of Issue
Approver(s)
Summary of Change
Clarified definitions for orthostatic 
hypotension and orthostatic 
tachycardia.
Clarified the Hepatitis B virus DNA 
serology testing.
Added AE intensity definitions.
Updated definitions for Full 
Analysis Set and Safety populations.
Clarified requirement for review of 
dosing diaries.
Added section for OTE rationale.
Revised language on nintedanib 
nonclinical toxicology.
Updated contact information for 
Clinical Trial Physician/Medical 
Monitor.
Added Clinical Scientist name and 
contact info to title page.
im027040-
amend02-site-
specific
22 Sep 2020
Study Director
Incorporated into 
im027040-revprot03
im027040-
admlet01
17 Sep 2020
Clinical Trial Physician
Incorporated into 
im027040-revprot03
im027040-
revprot02a-uk-
specific
11 Sep 2020
  
Clinical Program Lead - Fibrosis
Incorporated into 
im027040-revprot03
im027040-
revprot02
25 Jun 2020
Clinical Program Lead - Fibrosis
Changed Medical Monitor
Added an optional treatment 
extension for IPF and PF-ILD 
participants who complete the main 
study
Extended intensive PK substudy 
participation to the PF-ILD cohort 
 
 
 
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Protocol Amendment No.: 05
Date: 22-Sep-2022
6
Document
Date of Issue
Approver(s)
Summary of Change
and adjusted the number of 
participants to be included 
Clarified the posttreatment HRCT 
requirement for the main study
Added spirometry measurements to 
Week 20 in the main study
Removed the FEF25-75 test from 
spirometry parameters
Added a sparse PK sample
collection at the Week 4 visit in the 
main study
Modified the secondary and 
exploratory endpoints
Added a statistical analysis for the 
PF-ILD cohort once the cohort 
completes the main study
Incorporated changes requested by 
 Ethics 
Committee:
o Added “end of study” definition
o Excluded participants with total 
bilirubin greater than 1.5 x ULN 
and specified the range 
permitted for those with 
Gilbert’s syndrome
o Excluded participants with 
history of allergy to BMS-
986278 or history of significant 
drug allergy 
o Clarified additional ECG 
assessments to be performed as 
clinically indicated
o Added a caption title to create 
Table 10
im027040-
amend01-site-
specific
12 Mar 2020
Clinical Development Team Lead 
- Fibrosis
Not applicable. PET-Tracer substudy 
will be conducted at selected US sites.
im027040-
revprot01
24 Feb 2020
Clinical Development 
Therapeutic Area Head, Fibrosis
Bristol-Myers Squibb
 
Head of IMD Regulatory & 
Pharmaceutical Sciences
Bristol-Myers Squibb
Added Medical Monitor
Added eligibility check 
Added pregnancy testing for women 
< 55 years of age 
Removed Study 
Acknowledgement/Disclosure page
Clarified drug dispensing frequency 
and treatment compliance check
Clarified when vital signs and 
orthostatic BP and HR will be 
measured
 
 
 
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Protocol Amendment No.: 05
Date: 22-Sep-2022
7
Document
Date of Issue
Approver(s)
Summary of Change
Removed approximate blood 
volumes to be collected throughout 
the study
Clarified when to withhold study 
treatment 
Clarified “progression” definition 
for PF-ILD inclusion criteria 
Lowered age limit for PF-ILD 
cohort 
Broadened language about 
excluding significant lung disease 
from both cohorts
Permitted stable DMARD use for 
PF-ILD participants
Added HBcAb and pregnancy test, 
and removed cannabinoids from 
Laboratory Assessments
Original Protocol
07 Jan 2020
Clinical Development 
Therapeutic Area Head, Fibrosis
Bristol-Myers Squibb
 
Head of IMD Regulatory & 
Pharmaceutical Sciences
Bristol-Myers Squibb
Not applicable
 
 
 
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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 05
The primary purpose of this protocol amendment is to implement the following changes:

Add clarification that the optional treatment extension (OTE) for the IPF and PF-ILD 
cohorts will be unblinded after the respective database locks occur at the end of Week 26 
of the main study for each cohort.

Clarify that select efficacy (eg, FVC) and safety data from the OTE portion of the IPF 
cohort will also be reviewed by the sponsor at the time of the IPF cohort main study 
database lock.

Implement protocol changes from administrative letters 5, 6, and 7. 

Edits made to ensure clarity and alignment between sections and with previous protocol 
versions.
All changes applied to the body were applied to the synopsis, as necessary, although not all 
synopsis changes are included in the table below.
Generally, only major additions and deletions are provided in this summary of changes, and all 
minor grammatical, formatting, rephrasing, stylistic changes, or clarifications, as well as 
reorganizational changes are not included.  
SUMMARY OF KEY CHANGES OF PROTOCOL AMENDMENT 05
Section Number & Title
Description of Change
Brief Rationale
Cover Page
Updated BMS Study Director as 
described in im027040-admlet07 and 
updated BMS Japan address
To update the Study Director 
following a change in personnel 
and to change BMS address in 
Japan
2 Schedule of Activities, Table 2
Updated footnote c as described in 
im027040-admlet06 
To rectify an inconsistency in the 
previous protocol version
5.1 Overall Design
Added clarifying sentence
To clarify that the OTE phase for 
IPF and PF-ILD cohorts will be 
unblinded after database lock at 
Week 26
Protocol Amendment No.: 05
Date: 22-Sep-2022
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SUMMARY OF KEY CHANGES OF PROTOCOL AMENDMENT 05
Section Number & Title
Description of Change
Brief Rationale
7.3.1 Maintaining the Blind
Added clarifying sentence
Add clarification that the optional 
treatment extension (OTE) 
components of the study for the 
IPF and PF-ILD cohorts will be 
unblinded after the respective 
database locks occur at the end of 
Week 26 of the main study for 
each cohort. As such, when the 
IPF OTE becomes unblinded upon 
DBL for the IPF main study, the 
PF-ILD cohort will remain 
blinded until database lock at 
Week 26 for PF-ILD main study.
9.5 Pharmacokinetics
Corrected inconsistency between the 
previous protocol version and the 
participant’s document as described 
in im027040-admlet05
To clarify that participants in the 
main study should also record 
date and time of morning and 
evening doses on the day prior to 
Week 12 study visit in addition to 
those of Weeks 4 and 26
9.5.2 Intensive PK Substudy, 
Table 7
Updated header and footnote c
To rectify an inconsistency in the 
previous protocol version
10.4.4 Other Analyses
Added clarifying text
Add clarification that the optional 
treatment extension (OTE) 
components of the study for the 
IPF and PF-ILD cohorts will be 
unblinded after the respective 
database locks occur at the end of 
Week 26 of the main study for 
each cohort.
APPENDIX 8: Site-specific 
Protocol for Qualified PET-tracer 
Sites in US
Section 1.3, Table 1
Section 4.1, Figure 1
Updated screening period
To change screening period of the 
PET-tracer substudy
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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
DOCUMENT HISTORY .............................................................................................. 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 05 ............................. 
SUMMARY OF KEY CHANGES OF PROTOCOL AMENDMENT 05 .................. 
TABLE OF CONTENTS .............................................................................................. 
1 PROTOCOL SUMMARY ......................................................................................... 
1.1 Synopsis ............................................................................................................ 
1.2 Schema .............................................................................................................. 
2 SCHEDULE OF ACTIVITIES (SOA) ...................................................................... 
3 INTRODUCTION ..................................................................................................... 
3.1 Idiopathic Pulmonary Fibrosis .......................................................................... 
3.1.1 Non-IPF, Progressive Fibrotic ILD (PF-ILD) ........................................ 
3.2 Lysophosphatidic Acid Receptor Pathway ....................................................... 
3.3 Study Rationale ................................................................................................. 
3.4 Background ....................................................................................................... 
3.4.1 Nonclinical Pharmacology ...................................................................... 
3.4.2 Nonclinical Pharmacokinetics ................................................................. 
3.4.3 Nonclinical Toxicology ............................................................................ 
3.4.3.1 Genotoxicity, Phototoxicity, Safety Pharmacology ........................ 
3.4.3.2 Repeat-dose Toxicity ....................................................................... 
3.4.3.3 Embryo-fetal Development Studies ................................................. 
3.4.3.4 Nonclinical Combination Toxicology ............................................. 
3.4.4 Clinical Experience .................................................................................. 
3.4.4.1 Efficacy of Previous LPA1 Antagonist (BMS-986020) ................... 
3.4.4.2 First-in-Human Study (Study IM027009) ....................................... 
3.4.4.3 BMS-986278 in Combination with Rifampin (Study IM027017) .... 
3.4.4.4 BMS-986278 in Combination with Pirfenidone (Study IM027041)
............................................................................................................... 
3.5 Benefit/Risk Assessment .................................................................................. 
3.5.1 COVID-19-related Benefit/Risk Assessment ............................................ 
4 OBJECTIVES AND ENDPOINTS ........................................................................... 
Objectives ............................................................................................................... 
Endpoint(s) .............................................................................................................. 
5 STUDY DESIGN....................................................................................................... 
5.1 Overall Design .................................................................................................. 
5.1.1 Screening Period ...................................................................................... 
5.1.2 Treatment Period ..................................................................................... 
5.1.2.1 Blood Pressure Monitoring............................................................. 
5.1.3 Main Study Posttreatment Follow-up Period .......................................... 
5.1.4 Optional Treatment Extension ................................................................. 
5.1.5 Data Monitoring Committee and Other External Committees ................ 
5.2 Number of Participants ..................................................................................... 
5.3 End of Study Definitions .................................................................................. 
5.4 Scientific Rationale for Study Design............................................................... 
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5.4.1 Rationale for Optional Treatment Extension (OTE) ................................ 
5.5 Justification for Dose ........................................................................................ 
6 STUDY POPULATION ............................................................................................ 
6.1 Inclusion Criteria .............................................................................................. 
6.2 Exclusion Criteria ............................................................................................. 
6.3 Lifestyle Restrictions ........................................................................................ 
6.3.1 Meals and Dietary Restrictions ............................................................... 
6.3.2 Activity ..................................................................................................... 
6.4 Screen Failures .................................................................................................. 
6.4.1 Retesting During Screening ..................................................................... 
7 TREATMENT ........................................................................................................... 
7.1 Treatments Administered .................................................................................. 
7.2 Method of Treatment Assignment .................................................................... 
7.3 Blinding............................................................................................................. 
7.3.1 Maintaining the Blind .............................................................................. 
7.3.2 Circumstances for Unblinding ................................................................. 
7.4 Dosage Modification ......................................................................................... 
7.5 Investigational Product Handling/Storage/Accountability ............................... 
7.5.1 Retained Samples for Bioavailability/Bioequivalence ............................. 
7.6 Treatment Compliance ...................................................................................... 
7.7 Concomitant Therapy........................................................................................ 
7.7.1 Prohibited and/or Restricted Treatments................................................. 
7.8 Treatment After the End of the Study ............................................................... 
8 DISCONTINUATION CRITERIA ........................................................................... 
8.1 Discontinuation from Study Treatment ............................................................ 
8.1.1 Posttreatment Follow-up ......................................................................... 
8.2 Discontinuation from the Study ........................................................................ 
8.2.1 Individual Discontinuation Criteria ........................................................ 
8.3 Lost to Follow-Up ............................................................................................. 
9 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
9.1 Efficacy Assessments ........................................................................................ 
9.1.1 Forced Vital Capacity .............................................................................. 
9.1.2 Diffusing Capacity of Carbon Monoxide ................................................. 
9.1.3 High-resolution Computed Tomography ................................................. 
9.1.4 Clinical Outcome Assessments ................................................................ 
9.1.4.1 Living with Pulmonary Fibrosis Questionnaire ............................. 
9.1.4.2 St. George’s Respiratory Questionnaire ......................................... 
9.1.4.3 University of California San Diego Shortness of Breath 
Questionnaire ........................................................................................ 
9.1.4.4 Cough Severity Visual Analog Scale ............................................... 
9.1.4.5 Patient Global Impression of Lung Fibrosis Symptom Severity and 
Patient Global Impression of Lung Fibrosis Symptom Severity Change
............................................................................................................... 
9.1.4.6 6-Minute Walk Test ......................................................................... 
9.2 Adverse Events ................................................................................................. 
9.2.1 Time Period and Frequency for Collecting AE and SAE Information .... 
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9.2.2 Method of Detecting AEs and SAEs ......................................................... 
9.2.3 Follow-up of AEs and SAEs ..................................................................... 
9.2.4 Regulatory Reporting Requirements for SAEs ......................................... 
9.2.5 AEs of Special Interest ............................................................................. 
9.2.6 Pregnancy ................................................................................................ 
9.2.7 Laboratory Test Result Abnormalities ..................................................... 
9.2.8 Potential Drug Induced Liver Injury (DILI) ............................................ 
9.2.9 Other Safety Considerations .................................................................... 
9.3 Overdose ........................................................................................................... 
9.4 Safety ................................................................................................................ 
9.4.1 Physical Examinations and Physical Measurements ............................... 
9.4.2 Vital Signs ................................................................................................ 
9.4.3 Electrocardiograms ................................................................................. 
9.4.4 Clinical Safety Laboratory Assessments .................................................. 
9.5 Pharmacokinetics .............................................................................................. 
9.5.1 Sparse PK Sampling (All Participants not Participating in PK Substudy)
..................................................................................................................... 
9.5.2 Intensive PK Substudy .............................................................................. 
9.5.3 Sparse PK Sampling for Optional Treatment Extension ......................... 
9.6 Biomarkers ........................................................................................................ 
9.6.1 Additional Research Collection ............................................................... 
9.7 Health Economics OR Medical Resource Utilization and Health Economics . 
10 STATISTICAL CONSIDERATIONS .................................................................... 
10.1 Sample Size Determination ............................................................................. 
10.2 Populations for Analyses ................................................................................ 
10.3 Endpoints ........................................................................................................ 
10.3.1 Primary Endpoints ................................................................................. 
10.3.2 Secondary Endpoints ............................................................................. 
10.3.3 Exploratory Endpoints ........................................................................... 
10.4 Statistical Analyses ......................................................................................... 
10.4.1 Efficacy Analyses ................................................................................... 
10.4.1.1 Primary Efficacy Endpoint ........................................................... 
10.4.1.2 Secondary Efficacy Endpoints ...................................................... 
10.4.2 Pharmacokinetic Analyses ..................................................................... 
10.4.3 Safety Analyses....................................................................................... 
10.4.4 Other Analyses ....................................................................................... 
10.4.5 Interim Analyses ..................................................................................... 
11 REFERENCES ........................................................................................................ 
APPENDIX 1 ABBREVIATIONS AND TRADEMARKS ........................................ 
APPENDIX 2 STUDY GOVERNANCE CONSIDERATIONS ................................. 
APPENDIX 3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, 
FOLLOW-UP AND REPORTING ........................................................................ 
APPENDIX 4 WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION ..................................................................... 
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APPENDIX 5 POTENT INHIBITORS OF ORGANIC ANION TRANSPORT 
PROTEINS ............................................................................................................. 
APPENDIX 6 STRONG INHIBITORS OR INDUCERS OF CYP3A4 ...................... 
APPENDIX 7 STRONG INHIBITORS OR INDUCERS OF CYP2C8 ...................... 
APPENDIX 8 SITE-SPECIFIC PROTOCOL FOR QUALIFIED PET-TRACER 
SITES IN US........................................................................................................... 
APPENDIX 9 PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
................................................................................................................................. 
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1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study of 
the Efficacy and the Safety and Tolerability of BMS-986278 in Participants with Pulmonary 
Fibrosis
Short Title:
Phase 2 Study of the Efficacy and Safety of BMS-986278 in Pulmonary Fibrosis
Study Phase:
Phase 2
Rationale:
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung disease that is 
characterized by worsening dyspnea, cough, and progressive loss of lung function due to scar 
formation in the lung. The diagnosis of IPF is based on integration of clinical, radiologic, and when 
available, pathologic data to exclude known causes of usual interstitial pneumonia (UIP) (eg 
connective tissue disease or environmental exposure). BMS-986278, a lysophosphatidic acid 
receptor 1 (LPA1) antagonist, is being developed for the treatment of patients with IPF. 
Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that regulates numerous aspects of 
cellular function and has been recognized as a mediator of wound healing and tissue fibrosis. LPA 
signals through a family of G protein-coupled receptors designated LPA1-6. LPA1 antagonism 
inhibits the production of profibrotic matrix proteins, such as collagen.
Beyond IPF, some patients with other forms of chronic fibrotic interstitial lung disease (ILD) 
develop a progressive phenotype characterized by worsening respiratory symptoms, lung function, 
progressive fibrosis on imaging and early mortality. There is a high unmet need for effective and 
tolerable treatments for patients with non-IPF, fibrotic ILD that exhibit disease progression. 
Because of the clinical and pathophysiological similarities among these diseases, it has been 
suggested that such disorders have a common pathobiologic mechanism regardless of the cause 
– with resultant progressive lung fibrosis – and thus could have a response to similar treatment as
IPF. Indeed, in the recently published INBUILD trial, patients with non-IPF, progressive fibrotic
ILD (PF-ILD) with diverse etiologies were treated with nintedanib or placebo. Those treated with
nintedanib had slower progression of lung fibrosis than those who received placebo, as
demonstrated by a lower annual rate of decline in forced vital capacity (FVC) over the 52-week
study period. The absolute treatment effects in the PF-ILD cohort were similar in magnitude to
those observed in the pivotal INPULSIS trials that led to approval of nintedanib for treatment of
IPF and based on data from the INBUILD trial, a number of health authorities have also approved
nintedanib for patients with PF-ILD.
This study is the first evaluation of BMS-986278 in participants with pulmonary fibrosis. This 
study is designed to provide an initial evaluation of the efficacy of BMS-986278 in participants 
with IPF, further demonstrate the safety of BMS-986278, and provide information on 
Protocol Amendment No.: 05
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IM027040
BMS-986278
LPA1 Antagonist
pharmacokinetics (PK) of BMS-986278 in participants with IPF. In addition, a secondary cohort 
consisting of PF-ILD participants will be enrolled, with the same schedule of activities and 
endpoints, in order to assess safety, tolerability, and efficacy of BMS-986278 in PF-ILD. The 
2 cohorts (and subsets within the cohorts) will be analyzed separately. 
Study Populations:
Eligible participants will be males and females 40 years of age and older with a diagnosis of IPF 
(primary cohort) or males and females 21 years of age and older with a diagnosis of PF-ILD 
(secondary cohort). Females must not be of childbearing potential, defined as being 
postmenopausal or surgically sterilized.
The primary cohort includes participants with IPF. Background standard of care (SOC) with either 
pirfenidone or nintedanib therapy is allowed. Randomization will be stratified by country 
(non-Japan versus Japan), and by concomitant use of approved IPF therapy (pirfenidone versus 
nintedanib versus none).
A separate population of participants with PF-ILD, will be enrolled in a secondary cohort. 
Although there is no global standard of care (SOC) for PF-ILD, participants in the PF-ILD cohort 
will be allowed to remain on stable background therapies commonly used as part of their usual 
care, including nintedanib, pirfenidone, and/or select immunosuppressive medications. 
Randomization within the PF-ILD cohort will be stratified by UIP pattern of lung injury (present 
versus absent) and by category of background therapy (ILD-targeted immunosuppression [ie, 
azathioprine, mycophenolate mofetil, mycophenolic acid, and/or tacrolimus] alone versus anti-
fibrotics [nintedanib, pirfenidone] with or without ILD-targeted immunosuppression versus no 
ILD-targeted immunosuppression or anti-fibrotics).  
In order to augment knowledge about safety, tolerability, and efficacy of BMS-986278 in lung 
fibrosis patients, an optional treatment extension (OTE) will be offered to those participants that 
complete the 26-week main study. 
Objectives and Endpoints:
Objective
Endpoint(s)
Primary

To evaluate the rate of change in percent predicted 
forced vital capacity (ppFVC) from baseline to 
Week 26 in IPF participants randomized to 
receive BMS-986278 at 30 mg or 60 mg twice 
daily (BID) compared to those randomized to 
receive placebo.

Rate of change in ppFVC (%) from baseline to 
Week 26 in IPF participants
Secondary

To evaluate the safety and tolerability of 
BMS-986278 through 26 weeks of treatment by 
comparing results observed in participants with 
IPF and PF-ILD randomized to receive 
BMS-986278 at 30 mg or 60 mg BID with those 

Adverse events (AEs)

Serious AEs (SAEs)

AEs leading to early discontinuation of study 
treatment

Treatment-emergent deaths
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BMS-986278
LPA1 Antagonist
Objective
Endpoint(s)
who receive placebo. The IPF and PF-ILD cohorts 
will be analyzed separately.

Clinical laboratory findings

Electrocardiograms (ECGs)

Vital signs

Physical exam findings

To evaluate the rate of change in ppFVC from 
baseline to Week 26 in PF-ILD participants 
randomized to receive BMS-986278 at 30 mg or 
60 mg twice daily (BID) compared to those 
randomized to receive placebo.

Rate of change in ppFVC (%) from baseline to 
Week 26 in PF-ILD participants

To evaluate the effect of treatment with 
BMS-986278 on clinical assessments of lung 
fibrosis in IPF and PF-ILD participants 
randomized to receive BMS-986278 at 30 mg or 
60 mg BID compared with participants 
randomized to receive placebo through Week 26. 
The IPF and PF-ILD cohorts will be analyzed 
separately.

Proportion of participants with ≥10% absolute 
decline in ppFVC (%) at Weeks 4, 8, 12, 16, 20,
and 26

Proportion of participants with > 0% change in 
ppFVC at Weeks 4, 8, 12, 16, 20, and 26

Time to first acute exacerbation

Time to first ≥10% absolute decline in ppFVC (%)

Absolute change in FVC (mL) from baseline to 
Week 26

Absolute change in ppFVC (%) from baseline to 
Week 26

Absolute change in single-breath diffusing capacity
of carbon monoxide (DLCO SB) (mL/min/mmHg) 
(corrected for hemoglobin) from baseline to 
Week 26

Absolute change in percent predicted single-breath 
diffusing capacity of carbon monoxide (ppDLCO 
SB) (%) (corrected for hemoglobin) from baseline
to Week 26  

Change in walking endurance/distance from 
baseline at Week 26 as measured using the 
6-minute walk test (6MWT)

Proportion of participants with acute exacerbations 
of lung fibrosis defined as an acute, clinically 
significant, respiratory deterioration characterized 
by evidence of new widespread alveolar 
abnormality, as follows: 
1.
Acute worsening or development of dyspnea 
(< 1 month duration)
2.
Imaging with new bilateral ground-glass 
opacity and/or consolidation superimposed on 
a background pattern of lung fibrosis
3.
Respiratory deterioration not fully explained 
by cardiac failure or fluid overload

To characterize the pharmacokinetics (PK) of 
BMS-986278 in IPF participants. 

Cmax, Tmax, and AUC(0-8) on Day 1 and Week 4 
and Ctrough on Week 4 and Week 12 of intensive 
PK substudy
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IM027040
BMS-986278
LPA1 Antagonist
Overall Design:
This is a Phase 2 randomized, double-blind, placebo-controlled clinical study investigating the 
efficacy and the safety and tolerability of BMS-986278 in participants with pulmonary fibrosis. In 
the primary cohort, a total of approximately 240 participants with IPF will be randomized to 
receive 30 mg or 60 mg BMS-986278 twice daily (BID) or placebo BID at a ratio of 1:1:1 for 
26 weeks in the main study. Stable SOC background therapy for IPF with either nintedanib or 
pirfenidone will be allowed. 
In the secondary cohort, a population of participants with PF-ILD, will be randomized and 
analyzed separately from the IPF cohort. In the PF-ILD cohort, a total of approximately 
120 participants with PF-ILD will be randomized to receive 30 mg or 60 mg
BMS-986278 BID or placebo BID at a ratio of 1:1:1 for 26 weeks. Participants with PF-ILD will 
be allowed to remain on stable background therapies commonly used as part of their usual care, 
including nintedanib, pirfenidone, and/or select immunosuppressive medications. 
IPF and PF-ILD participants receiving 30 mg or 60 mg (or placebo) BMS-986278 BID in the main 
study who meet low blood pressure (BP) criteria may be dose reduced to 10 mg BMS-986278 BID 
(or placebo for 10 mg BID) (refer to Section 5.1.2.1). 
A study schematic is provided in Section 2, and in Figure 1 for the IPF cohort and Figure 2 for the 
PF-ILD cohort. Following a screening period of up to 42 days, eligible participants with IPF or 
PF-ILD will be randomized to receive 1 of 2 dose levels of BMS-986278 (30 mg or 60 mg BID) 
or placebo for 26 weeks. In the IPF cohort, randomization will be stratified by country (non-Japan 
versus Japan) and according to concomitant use of approved IPF therapy (pirfenidone versus 
nintedanib versus none). In the PF-ILD cohort, randomization will be stratified by UIP lung injury 
pattern (present versus absent) and by category of background therapy (ILD-targeted 
immunosuppression [ie, azathioprine, mycophenolate mofetil, mycophenolic acid, and/or 
tacrolimus] alone versus anti-fibrotics [nintedanib, pirfenidone] with or without ILD-targeted 
immunosuppression versus no ILD-targeted immunosuppression or anti-fibrotics). 
All participants randomized in the main study will undergo safety, functional, quality-of-life, 
laboratory, PK, and biomarker assessments according to the Schedule of Activities (Table 1).  
A 26-week OTE will be offered to IPF and PF-ILD participants that complete the 26-week main 
study. All participants will receive active treatment in the OTE. Participants who received 30 mg 
placebo tablets in the main study will be randomized to receive 30 mg or 60 mg BMS-986278 
BID, and participants who received 30 mg or 60 mg BMS-986278 BID in the main study will 
continue with the assigned doses. Participants receiving 30 mg or 60 mg BMS-986278 BID in the 
OTE will remain blinded to study treatment until the database lock for analyses of the 26-week 
main study in IPF and PF-ILD cohorts, respectively. At the time of main study database lock in 
each cohort, the OTE will be unblinded for that cohort. Participants who dose reduced and received 
10 mg BMS-986278 BID or placebo for 10 mg BMS-986278 BID in the main study will receive 
10 mg BMS-986278 BID unblinded in the OTE. Participants receiving 30 mg or 60 mg 
BMS-986278 BID in the OTE who meet low BP criteria may be dose reduced to 10 mg 
BMS-986278 BID (refer to Section 5.1.2.1). See study schematic in Section 2 and in Figure 3.  
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IM027040
BMS-986278
LPA1 Antagonist
All participants in the OTE will undergo safety, functional, quality-of-life, laboratory, PK, and 
biomarker assessments according to the Schedule of Activities (Table 2).
Blood Pressure Monitoring:
At all study visits, including the screening visit, participants will be carefully monitored for 
symptoms associated with low BP, assessed for orthostatic intolerance, orthostatic hypotension, 
orthostatic tachycardia, and asymptomatic parameters of low BP. Vital signs (including orthostatic 
assessments) will be performed as listed in the Schedule of Activities (Section 2). Refer to 
Section 5.1.2.1 for details on BP monitoring. 
PK Assessments:
Participants will have PK samples collected as shown in Table 6. In addition, an intensive PK 
substudy will be conducted in approximately 10 participants per treatment arm in both the IPF and 
PF-ILD cohorts, for which additional PK samples will be collected and additional 
electrocardiogram (ECG), BP, and heart rate assessments will be performed, as shown in Table 7.
Positron Emission Tomography (PET) Tracer Substudy:
Participants in either cohort at selected sites will participate in a PET-Tracer substudy to evaluate 
the distribution of a radiolabeled analog of BMS-986278, [18F]BMS-986327 in each dose group. 
The substudy is described in APPENDIX 8.
Clinical Outcome Assessments (COAs):
Patient experience data will be collected using the following COA measures in the main study:

Living with Pulmonary Fibrosis Questionnaire (L-PF)

St. George’s Respiratory Questionnaire (SGRQ)

University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ)

Cough severity visual analog scale (VAS)

Patient global impression of lung fibrosis symptom severity (PGI-S) and patient global 
impression of lung fibrosis symptom severity change (PGI-C) 

6-minute walk test (6MWT)
In the OTE, patient experience data will continue to be collected with the L-PF, PGI-S, PGI-C, 
and 6MWT.
Posttreatment Follow-up: 
At the end of treatment in the 26-week main study, participants that do not continue in the OTE 
will undergo a posttreatment follow-up visit which should occur 28 days (± 7 days) after the 
Week 26 visit.
At the end of treatment in the main study, participants that elect to continue in the OTE will 
receive active treatment within 1 to 15 days from the Week 26 visit. Study visits and procedures 
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IM027040
BMS-986278
LPA1 Antagonist
during the OTE are described in the study design schematic (Figure 3) and the Schedule of 
Activities (Table 2). 
Participants in the OTE that discontinue study treatment with BMS-986278 before Week 26 will 
complete the remaining study visits according to the Schedule of Activities (Table 2), including 
the post OTE treatment follow-up visit.
Number of Participants: 
In the primary study population, a total of approximately 240 IPF participants will be randomized 
to receive 30 mg or 60 mg BMS-986278 BID or placebo BID at a ratio of 1:1:1.
In the secondary cohort, a total of approximately 120 PF-ILD participants will be randomized to 
receive 30 mg or 60 mg BMS-986278 BID or placebo BID at a ratio of 1:1:1.
Randomization and Duration:
In the primary cohort, eligible participants with IPF will be randomized to receive 1 of 2 dose 
levels of BMS-986278 (30 mg or 60 mg BID) or placebo at a ratio of 1:1:1 for 26 weeks in the 
main study. Randomization will be stratified by country (non-Japan versus Japan) and according 
to concomitant use of approved IPF therapy (pirfenidone vs nintedanib vs none). 
In the PF-ILD cohort, eligible participants will be randomized to receive 1 of 2 dose levels of 
BMS-986278 (30 mg or 60 mg BID) or placebo at a ratio of 1:1:1 for 26 weeks in the main study. 
Randomization will be stratified by UIP lung injury pattern (present versus absent) and by category 
of background therapy (ILD-targeted immunosuppression [ie, azathioprine, mycophenolate 
mofetil, mycophenolic acid, and/or tacrolimus] alone versus anti-fibrotics [nintedanib, 
pirfenidone] with or without ILD-targeted immunosuppression versus no ILD-targeted 
immunosuppression or anti-fibrotics). 
For those participants that do not elect to continue in the OTE, the clinical study will last 
approximately 36 weeks including a 6-week screening period and a 4-week follow-up period.
For those participants that elect to continue in the OTE, the clinical study will last up to 
approximately 64 weeks (including the main study and the OTE). The main study will last up to 
approximately 32 weeks (including the 6-week screening period and a 26-week treatment period), 
and the OTE will last up to approximately 32 weeks (including a 1- to 15-day off-treatment period, 
a 26-week treatment period, and a 4-week post OTE treatment follow-up period).  
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IM027040
BMS-986278
LPA1 Antagonist
Study Treatment for the Main Study:
Study Treatment for Study IM027040
Study Treatment 
Potency
IP/Non-IP
BMS-986278 oral tablet
10 mg
IP
BMS-986278 oral tablet
30 mg
IP
Placebo to match 10 mg oral tablets
NA
IP
Placebo to match 30 mg oral tablets
NA
IP
IP = investigational product; NA = not applicable; non-IP = noninvestigational product 
In the OTE, participants will receive one of 3 active doses of BMS-986278 oral tablets: 30 mg 
BID, 60 mg BID, or 10 mg BID.
1.2
Schema
Following a screening period of up to 42 days, eligible participants with IPF or PF-ILD will be 
randomized in a 1:1:1 ratio to receive 1 of 2 dose levels of BMS-986278 (30 mg or 60 mg BID) 
or placebo for 26 weeks. Participants will then have the option to either end study treatment or 
continue in the OTE. Participants that opt to end study treatment will undergo a 4-week 
posttreatment follow-up. See page below for IPF and PF-ILD cohort study designs.
Study Design of IPF Cohort (Main Study):
Randomization
*BMS-986278 30 mg twice daily (n = 80)
*BMS-986278 60 mg twice daily (n = 80)
*Placebo twice daily (n = 80)
Treatment
(Day 1 to Week 26)
Posttreatment
follow-up 
or enter OTE
Posttreatment
follow-up
or enter OTE
Posttreatment
follow-up
or enter OTE
Posttreatment 
follow-up 
(28 [± 7] days)
or enter OTE
Screening
(Day -42 to 
Day -1)
End of treatment
IPF
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Clinical Protocol
IM027040
BMS-986278
LPA1 Antagonist
Study Design of PF-ILD Cohort (Main Study):
BID = twice daily; BP = blood pressure; IPF = idiopathic pulmonary fibrosis; OTE = optional treatment extension; 
PF-ILD =  non-IPF, progressive fibrotic interstitial lung disease
* Participants receiving 30 mg or 60 mg (or placebo) BMS-986278 BID in the main study who meet low BP criteria 
may be dose reduced to 10 mg BMS-986278 BID (or placebo for 10 mg BID)
At the end of treatment in the 26-week main study, participants in the IPF and PF-ILD cohorts will 
have the opportunity to participate in the OTE. See below for the OTE study design.
Randomization
*BMS-986278 30 mg twice daily (n = 40)
*BMS-986278 60 mg twice daily (n = 40)
*Placebo twice daily (n = 40)
Posttreatment
follow-up
or enter OTE
Posttreatment
follow-up
or enter OTE
Posttreatment
follow-up
or enter OTE
End of treatment
PF-ILD
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Clinical Protocol
IM027040
BMS-986278
LPA1 Antagonist
Study Design of OTE (for each of the separate IPF and PF-ILD Cohorts):
BID = twice daily;  IPF = idiopathic pulmonary fibrosis; OTE = optional treatment extension; PF-ILD =  non-IPF, 
progressive fibrotic interstitial lung disease
* Participants that were dose-reduced in the main study
† Participants on 10 mg BMS-986278 BID are unblinded in the OTE
± Participants receiving 30 mg or 60 mg BMS-986278 BID in the OTE who meet low BP criteria may be dose reduced 
to 10 mg BMS-986278 BID
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IM027040
BMS-986278
LPA1 Antagonist
Data Monitoring Committee:
Study results will be monitored by an Independent Data Monitoring Committee (DMC); the scope 
of responsibility of the DMC will be outlined in the DMC Charter. Safety results will be reviewed 
by the DMC after approximately 30 randomized participants with either IPF or PF-ILD have 
completed at least 4 weeks after the first dose and at subsequent points outlined in the DMC 
Charter. Based on their reviews, the DMC will make recommendations to the sponsor on whether 
the study should be allowed to continue or be modified or terminated. Additional DMC meetings 
may also be scheduled to review the study data during the treatment period, as described in the 
DMC Charter. 
Based on their overall benefit/risk evaluation, the DMC recommendations may include proceeding 
with the study without modification, proceeding with the study with modification, or study 
suspension. The scope, conduct, membership, processes, and accountabilities of the DMC are 
specified in the DMC Charter.
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IM027040
BMS-986278
LPA1 Antagonist
2
SCHEDULE OF ACTIVITIES (SOA)
All schedules of activities will be the same for the primary study cohort of IPF participants and for 
those in the PF-ILD secondary cohort.  
Refer to Table 1 for the main study SOA and Table 2 for the OTE SOA.
In the event assessments are planned for the same scheme time, the order of the assessments should 
be arranged in such a way that PK and biomarker blood sampling will be done after the ECG and 
vital signs recordings have been conducted, with PK and biomarker blood sampling being 
performed as close to the planned time as possible. Clinical laboratory blood samples may be taken 
thereafter.
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IM027040
BMS-986278
LPA1 Antagonist
Table 1:
Schedule of Activities for Study IM027040 (Main Study)
Screening 
(Day -42 to 
Day -1)
Treatment (Day 1 to Week 26)a
Post-
treatment 
follow-upc
(28 ± 7 
days after 
Week 26)
Notes
Day 
1
Day 
2b
Day 8
Day 29 Day 57 Day 85 Day 113 Day 141 Day 183
Week 1 
(± 3 
days)
Week 4 
(± 3 
days)
Week 8 
(± 5 
days)
Week 
12 
(± 5 
days)
Week 16 
(± 5 
days)
Week 20 
(± 5 
days)
Week 26
(+ 5 days) 
Informed 
consent
X
Eligibility 
check
X
X
Predose on Day 1.
Medical and 
medication 
history
X
Including but not limited to oxygen 
use, hospitalizations, smoking 
history.
Demographics
X
Hepatitis and 
HIV screening
X
See Section 9.4.4 and Table 5 for 
further details.
Test for drugs 
of abuse 
X
See Section 9.4.4 and Table 5 for 
further details.
Pregnancy test 
X
Urine pregnancy test prior to Day 1 
dosing in women < 55 years of age.
Pregnancy testing to be performed 
any time pregnancy is suspected 
during the study.
Blood sample 
for FSH
X
Postmenopausal women (< 55 years 
of age only) to confirm menopausal 
state (see APPENDIX 4).
Randomization
X
Randomization within 3 days prior to 
Day 1 is permitted. 
Update medical 
and medication 
history
X
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IM027040
BMS-986278
LPA1 Antagonist
Table 1:
Schedule of Activities for Study IM027040 (Main Study)
Screening 
(Day -42 to 
Day -1)
Treatment (Day 1 to Week 26)a
Post-
treatment 
follow-upc
(28 ± 7 
days after 
Week 26)
Notes
Day 
1
Day 
2b
Day 8
Day 29 Day 57 Day 85 Day 113 Day 141 Day 183
Week 1 
(± 3 
days)
Week 4 
(± 3 
days)
Week 8 
(± 5 
days)
Week 
12 
(± 5 
days)
Week 16 
(± 5 
days)
Week 20 
(± 5 
days)
Week 26
(+ 5 days) 
Height and 
weight 
measurement
X
X
X
X
Height measured at screening only.
Laboratory/Safety Assessments
12-lead ECG
X
X
X
X
X
All ECGs must be performed prior to 
bronchodilator administration OR at 
least 20 hours after bronchodilator 
administration. ECG on Day 1, 
Weeks 4 and 12 to be collected 
before morning dosing.
See Section 9.4.3 for further details.
Serial ECG for 
participants 
enrolled in 
intensive PK 
substudy 
See notes. 
Intensive PK substudy only. 
According to schedule in 
Table 7. 
Clinical 
laboratory 
samples
X
X
X
X
X
X
X
X
X
X
Hematology, chemistry, and 
urinalysis. 
Physical 
examination
X
X
X
X
X
X
Vital signs for 
all participants
X
Xd
X
X
X
X
X
X
X
X
X
Predose vital signs include body 
temperature, respiration rate, and 
orthostatic BP and HR. 
Refer to Section 9.4.2 for further 
details on vital signs. 
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Clinical Protocol
IM027040
BMS-986278
LPA1 Antagonist
Table 1:
Schedule of Activities for Study IM027040 (Main Study)
Screening 
(Day -42 to 
Day -1)
Treatment (Day 1 to Week 26)a
Post-
treatment 
follow-upc
(28 ± 7 
days after 
Week 26)
Notes
Day 
1
Day 
2b
Day 8
Day 29 Day 57 Day 85 Day 113 Day 141 Day 183
Week 1 
(± 3 
days)
Week 4 
(± 3 
days)
Week 8 
(± 5 
days)
Week 
12 
(± 5 
days)
Week 16 
(± 5 
days)
Week 20 
(± 5 
days)
Week 26
(+ 5 days) 
During post-Day 1 visits, additional 
BP monitoring is required (similar to 
Day 2 visit) if either asymptomatic or 
symptomatic low BP criteria are met, 
as specified in Section 5.1.2.1.
Orthostatic 
evaluations 
See notes.
At every visit, including screening, 
symptoms that could indicate the 
presence of orthostatic intolerance, 
orthostatic hypotension, and 
orthostatic tachycardia will be 
gathered. 
Refer to section 9.4.2 and section 
5.1.2.1 further details on orthostatic 
evaluations. 
Serial BP and 
HR for 
participants 
enrolled in 
intensive PK 
substudy 
See notes. 
Intensive PK substudy only. 
According to schedule in 
Table 7. 
Pharmacokinetic and Biomarker Assessments
Blood samples 
for sparse PK 
profiling
See notes.
According to schedule in 
Table 6.
Blood samples 
for intensive 
PK profiling 
See notes.
Intensive PK substudy only. 
According to schedule in 
Table 7.
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IM027040
BMS-986278
LPA1 Antagonist
Table 1:
Schedule of Activities for Study IM027040 (Main Study)
Screening 
(Day -42 to 
Day -1)
Treatment (Day 1 to Week 26)a
Post-
treatment 
follow-upc
(28 ± 7 
days after 
Week 26)
Notes
Day 
1
Day 
2b
Day 8
Day 29 Day 57 Day 85 Day 113 Day 141 Day 183
Week 1 
(± 3 
days)
Week 4 
(± 3 
days)
Week 8 
(± 5 
days)
Week 
12 
(± 5 
days)
Week 16 
(± 5 
days)
Week 20 
(± 5 
days)
Week 26
(+ 5 days) 
Blood samples 
for biomarkers
See notes.
See Section 9.6 and Table 9 for 
further details.
Efficacy-related Assessments
HRCT
X
X
Screening HRCT must be read by 
central reader before randomization.
See Section 9.1.3 and Section 6.4.1
for further details.
Spirometrye
X
X
X
X
X
X
X
X
See Section 9.1.1 for further details. 
DLCO SB
X
X
X
X
See Section 9.1.2 for further details.
Clinical Outcome Assessments (COAs)
L-PF
X
X
X
If possible, eCOAs should be 
administered using the electronic 
device prior to other study related 
procedures (except for the Day 1 
visit where COAs should be 
administered after vital signs and 
ECG).
SGRQ
X
X
X
UCSD SOBQ
X
X
X
Cough VAS
X
X
X
PGI-S
X
X
X
PGI-C
X
X
6MWT
X
X
X
If possible, to be administered after 
eCOAs.
Separate instructions on the 6MWT 
will be provided.  
See Section 9.1.4.6 for further 
details.
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Table 1:
Schedule of Activities for Study IM027040 (Main Study)
Screening 
(Day -42 to 
Day -1)
Treatment (Day 1 to Week 26)a
Post-
treatment 
follow-upc
(28 ± 7 
days after 
Week 26)
Notes
Day 
1
Day 
2b
Day 8
Day 29 Day 57 Day 85 Day 113 Day 141 Day 183
Week 1 
(± 3 
days)
Week 4 
(± 3 
days)
Week 8 
(± 5 
days)
Week 
12 
(± 5 
days)
Week 16 
(± 5 
days)
Week 20 
(± 5 
days)
Week 26
(+ 5 days) 
O2 Titration 
Test
X
An oxygen titration test is required 
for all participants at screening. 
Study Treatment/Concomitant Medication
Dispense study 
treatment
Participants will receive study treatment twice daily for a total of 
26 weeks (from Day 1 to Day 182 of Week 25). At every study 
visit, morning administration of study treatment will occur at the 
clinical research site. Fed/fasted status and time of meal (if fed) 
at every visit must be recorded on the case report form. A 
sufficient study treatment supply will be dispensed to each 
participant at every scheduled study visit, except for the Day 8 
visit. New study treatment supplies will be provided to those 
participants whose dose is reduced (see Section 7).
Any leftover study treatment should 
be returned to the site for the drug 
accountability. Treatment 
compliance should be performed at 
each study visit between Day 29 
(Week 4) and Week 26. Treatment 
compliance will also be performed at 
the time of dose reduction or dose 
discontinuation (if applicable).
Concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
Collected throughout the study.
Adverse Events
Adverse events
See notes.
Collected from first dose and 
throughout the study.
Serious adverse 
events
See notes.
Serious adverse events to be 
recorded starting from the time of 
informed consent until 30 days from 
last visit.
6MWT = 6-Minute Walk Test; BP = blood pressure; DLCO SB = single-breath diffusing capacity of carbon monoxide; ECG = electrocardiogram; FSH = follicle-
stimulating hormone; HIV = human immunodeficiency virus; HR = heart rate; HRCT = high-resolution computed tomography; L-PF = Living with Pulmonary 
Fibrosis Questionnaire; O2 = oxygen; OTE = optional treatment extension; PGI-C = patient global impression of lung fibrosis symptom severity change; PGI-S = 
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patient global impression of lung fibrosis symptom severity; SGRQ = St. George’s Respiratory Questionnaire; UCSD SOBQ = University of California San Diego 
Shortness of Breath Questionnaire; VAS = visual analog scale
a Visit windows may be extended to accommodate participants’ schedules on a case-by-case after consultation with the Medical Monitor.
b Participants will only attend the Day 2 visit if required due to defined low BP criteria being met on Day 1. If dose reduction is decided on or after the Day 8 
visit, the participant is required to follow the Day 2 BP monitoring instructions at the site (see Section 5.1.2.1). 
c Only participants that choose not to enter the OTE will attend the posttreatment follow-up visit in the main study. 
d In addition to the predose measurements, orthostatic BP and HR will be performed at 1.5, 2, and 4 hours post dose on Day 1 for all participants. Refer to BP 
monitoring in Section 5.1.2.1. 
e Measurements must be performed more than 6 hours after administration of short-acting β-agonists or anticholinergics, at least 12 hours after administration of 
a long-acting bronchodilator, and at least 24 hours after administration of longer-acting agents.
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Table 2:
Schedule of Activities for Study IM027040 (Optional Treatment Extension) 
Treatment (Day 1 to Week 26)a
Post OTE
treatment 
follow-up
(28 ± 7 days 
after OTE 
Week 26)
Notes
OTE 
Day 1
OTE 
Day 2b
OTE 
Day 8
OTE 
Day 29
OTE 
Day 113
OTE 
Day 183
Week 1 
(± 3 days)
Week 4 
(± 3 days)
Week 16 
(± 5 days)
Week 26
(+ 5 days) 
Informed consent
X
Informed consent for the OTE can be obtained prior 
to the OTE Day 1 visit.
Randomization / 
Treatment 
Assignment
X
When entering the OTE, participants that were 
assigned to placebo and had not had dose reduction 
will be randomized to 30 mg or 60 mg 
BMS-986278 BID.
Weight 
measurement
X
X
Laboratory/Safety Assessments
12-lead ECG
X
X
All ECGs must be performed prior to 
bronchodilator administration OR at least 20 hours 
after bronchodilator administration. ECG at Week 4 
to be collected before morning dosing.
See Section 9.4.3 for further details.
Clinical 
laboratory 
samples
X
X
X
X
X
X
Hematology, chemistry, and urinalysis. 
A clinical laboratory sample will be collected at the 
OTE Day 1 visit. Collection of Day 1 clinical 
laboratory samples is not required if the Week 26 
clinical laboratory sampling in the main study is 
completed within 3 days prior to the OTE Day 1 
visit.
Physical 
examination
X
X
X
X
Vital signs 
Xc
X
X
X
X
X
X
Predose vital signs include body temperature, 
respiration rate, and orthostatic BP and HR. Refer 
to Section 9.4.2 for further details on vital signs. 
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Table 2:
Schedule of Activities for Study IM027040 (Optional Treatment Extension) 
Treatment (Day 1 to Week 26)a
Post OTE
treatment 
follow-up
(28 ± 7 days 
after OTE 
Week 26)
Notes
OTE 
Day 1
OTE 
Day 2b
OTE 
Day 8
OTE 
Day 29
OTE 
Day 113
OTE 
Day 183
Week 1 
(± 3 days)
Week 4 
(± 3 days)
Week 16 
(± 5 days)
Week 26
(+ 5 days) 
During post-Day 1 visits, additional BP monitoring 
is required (similar to Day 2 visit) if either 
asymptomatic or symptomatic low BP criteria are 
met, as specified in section 5.1.2.1.
Orthostatic 
evaluations 
See notes.
At every visit, symptoms that could indicate the 
presence of orthostatic intolerance, orthostatic 
hypotension, and orthostatic tachycardia will be 
gathered. 
Refer to section 9.4.2 and section 5.1.2.1 further 
details on orthostatic evaluations. 
Pharmacokinetic and Biomarker Assessments
Blood samples for 
sparse PK 
profiling
See notes.
According to schedule in Table 8.
Blood samples for 
biomarkers
X
See Section 9.6 for further details.
Efficacy-related Assessments
HRCT
X
See Section 9.1.3 for further details.
Spirometryd
X
X
X
See Section 9.1.1 for further details. 
DLCO SB
X
X
X
See Section 9.1.2 for further details.
Clinical Outcome Assessments (COAs)
L-PF
X
X
PGI-S
X
X
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Table 2:
Schedule of Activities for Study IM027040 (Optional Treatment Extension) 
Treatment (Day 1 to Week 26)a
Post OTE
treatment 
follow-up
(28 ± 7 days 
after OTE 
Week 26)
Notes
OTE 
Day 1
OTE 
Day 2b
OTE 
Day 8
OTE 
Day 29
OTE 
Day 113
OTE 
Day 183
Week 1 
(± 3 days)
Week 4 
(± 3 days)
Week 16 
(± 5 days)
Week 26
(+ 5 days) 
PGI-C
X
X
If possible, eCOAs should be administered using 
the electronic device prior to other study related 
procedures.
6MWT
X
If possible, to be administered after eCOAs.
Separate instructions on the 6MWT will be 
provided. 
See Section 9.1.4.6 for further details.
Study Treatment/Concomitant Medication
Dispense study 
treatment
Participants will receive study treatment twice daily for 
a total of 26 weeks (from OTE Day 1 to OTE Day 182 
of Week 25). At every study visit, morning 
administration of study treatment will occur at the 
clinical research site. Fed/fasted status and time of meal 
(if fed) at every visit must be recorded on the case 
report form. A sufficient study treatment supply will be 
dispensed to each participant during the study. New 
study treatment supplies will be provided to those 
participants whose dose is reduced (see Section 7).
Any leftover study treatment should be returned to 
the site for the drug accountability. Treatment 
compliance should be performed at each study visit 
between Day 29 (Week 4) and Week 26. Treatment 
compliance will also be performed at the time of 
dose reduction or dose discontinuation (if 
applicable).
Concomitant 
medications
X
X
X
X
X
X
X
Collected throughout the study.
Adverse Events
Adverse events
See notes.
Collected throughout the study.
Serious adverse 
events
See notes.
Serious adverse events will continue to be recorded 
throughout the entire study until 30 days from last 
visit.
6MWT = 6-Minute Walk Test; BID = twice daily; BP = blood pressure; DLCO SB = single-breath diffusing capacity of carbon monoxide; 
ECG = electrocardiogram; HR = heart rate; HRCT = high-resolution computed tomography; L-PF = Living with Pulmonary Fibrosis Questionnaire; OTE = optional 
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treatment extension; PGI-C = patient global impression of lung fibrosis symptom severity change; PGI-S = patient global impression of lung fibrosis symptom 
severity 
a Visit windows may be extended to accommodate participants’ schedules on a case-by-case after consultation with the Medical Monitor.
b Participants will only attend the Day 2 visit if required due to defined low BP criteria being met on Day 1. If dose reduction is decided on or after the Day 8 visit, 
the participant is required to follow the Day 2 BP monitoring instructions at the site (see Section 5.1.2.1). 
c In addition to the predose measurements, orthostatic BP and HR will be performed at 1.5, 2, and 4 hours post dose on OTE Day 1 for all participants. Refer to 
BP monitoring in Section 5.1.2.1. 
d Measurements must be performed more than 6 hours after administration of short-acting β-agonists or anticholinergics, at least 12 hours after administration of 
a long-acting bronchodilator, and at least 24 hours after administration of longer-acting agents.
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3
INTRODUCTION
3.1
Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung disease of unknown 
cause that is characterized by worsening dyspnea, cough, and progressive loss of lung function 
due to scar formation in the lung.1 IPF belongs to a family of lung disorders known as interstitial 
lung diseases (ILDs) and is characterized by the pathological and radiographic pattern known as 
usual interstitial pneumonia (UIP). A diagnosis of IPF is diagnosis of exclusion, as it is reserved 
to those individuals with the UIP pattern of lung injury without any identifiable cause such as 
connective tissue disease or environmental exposure. It is a progressive disease in which scarring 
and lack of elasticity in the lung continues to increase until the majority of patients die from 
respiratory failure. Non-drug treatments include supplemental oxygen, pulmonary rehabilitation, 
and lung transplant.
To date, 2 drugs have been approved for treatment of IPF in several countries globally: pirfenidone, 
a small-molecule inhibitor of fibrosis (precise mechanism of action is unknown), and nintedanib, 
a triple tyrosine kinase inhibitor, that blocks signaling from vascular endothelial growth factor, 
fibroblast growth factor-, and platelet-derived growth factor receptors. In separate Phase 3 trials in 
IPF patients, both pirfenidone and nintedanib slowed the rate of decline in forced vital capacity 
(FVC). In addition, nintedanib significantly improved respiratory related quality of life. Both drugs 
have significant gastrointestinal side effects, many patients progress despite treatment and as such, 
there remains a significant unmet need based on the benefits and risks of the approved treatments.
3.1.1
Non-IPF, Progressive Fibrotic ILD (PF-ILD)
Beyond IPF, some patients with other chronic forms of fibrotic ILD develop a progressive 
phenotype characterized by worsening respiratory symptoms, lung function, progressive fibrosis 
on imaging and early mortality. There is a high unmet need for effective and tolerable treatments 
for patients with PF-ILD that exhibit disease progression.2, 3, 4 Because of the clinical and 
pathophysiological similarities among these diseases, it has been suggested that such disorders 
have a common pathobiologic mechanism regardless of the cause – with resultant progressive lung 
fibrosis – and thus could have a response to similar treatment as IPF.2, 3, 4 Indeed, in the recently 
published INBUILD trial, patients with PF-ILD with diverse etiologies were treated with 
nintedanib vs placebo. Those treated with nintedanib had slower progression of lung fibrosis than 
those who received placebo, as demonstrated by a lower annual rate of decline in FVC over the 
52-week study period. The absolute treatment effects in this PF-ILD cohort were similar in 
magnitude to those observed in the pivotal INPULSIS trials that led to approval of nintedanib for 
treatment of IPF and based on data from the INBUILD trial, a number of health authorities have 
also approved nintedanib for patients with PF-ILD.5
3.2
Lysophosphatidic Acid Receptor Pathway
Aberrant wound healing responses to lung injury are widely assumed to contribute to the 
pathogenesis of fibrotic lung diseases, such as IPF. Lysophosphatidic acid (LPA), by virtue of its 
ability to mediate many basic cellular functions in several cell types associated with wound healing 
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(survival/apoptosis, proliferation, migration, and contraction), can regulate the transition from 
normal scar formation to aberrant wound repair (fibrosis), which is characterized by excessive 
deposition of extracellular matrix. LPA mediates its physiological effects by binding to and 
activating a family of G protein-coupled receptors (LPA1-6).
Several lines of published evidence support targeting the LPA/lysophosphatidic acid receptor 
subtype 1 (LPA1) receptor pathway in fibrotic diseases and for the treatment of IPF.6, 7 Increased 
LPA concentrations have been reported in the alveolar space of both IPF patients and the 
corresponding bleomycin (BLEO) mouse lung model, in which genetic deletion6, 8 or 
pharmacological inhibition9 of LPA1 attenuated the development of the modeled disease, 
suggesting a direct involvement of LPA and LPA1 in disease pathogenesis. Increased epithelial 
cell apoptosis in response to lung injury has also been implicated in the development of IPF and 
linked to LPA. LPA signaling through LPA1 has been reported to promote epithelial cell apoptosis 
induced by BLEO injury in mice.8 The number of apoptotic cells present in the alveolar and 
bronchial epithelia of LPA1-deficient mice was significantly reduced compared with wild-type 
mice after BLEO challenge.8
Consistent with these in vivo rodent results, increases in LPA levels and LPA signaling through 
LPA1 have been observed in individuals with fibrotic diseases. LPA levels are elevated in the 
bronchoalveolar lavage (BAL) of patients with IPF.6 Increased concentrations of autotaxin, the 
enzyme largely responsible for extracellular LPA production, have been found to be elevated in 
both murine and human fibrotic lungs.10 Together these data suggest that antagonizing the LPA1
receptor may be beneficial in treating patients with IPF. Furthermore, a previous Phase 2 study 
demonstrated improvements in the rate of decline in lung function (as measured by FVC) in IPF 
patients treated with the LPA1 antagonist BMS-986020 compared to placebo.11
BMS-986278 is a potent full antagonist at LPA1 that has been shown to potently inhibit 
LPA-stimulated activation of multiple signal transduction pathways. BMS-986278 is being 
developed as a potential treatment for IPF (see the Investigator’s Brochure for additional details).
3.3
Study Rationale
A clinical need exists for more effective treatment of pulmonary fibrosis. Nonclinical studies 
support the development of BMS-986278 as a potential treatment for IPF by its antagonistic effect 
on LPA1. The overall objective of the clinical development program is to demonstrate that 
BMS-986278 is effective and safe for the treatment of IPF.
A separate cohort of PF-ILD, will also be enrolled to evaluate whether BMS-986278 is safe and 
efficacious for the treatment in PF-ILD.
In order to augment knowledge about safety, tolerability, and efficacy of BMS-986278, an optional 
treatment extension (OTE) will be offered to those participants that complete the 26-week main 
study. 
The proof of concept for antifibrotic activity with an LPA1 antagonist was demonstrated in a 
randomized, double-blind, placebo-controlled Phase 2 study with BMS-986020, another selective, 
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small-molecule LPA1 antagonist (Study IM136003) discussed below in Section 3.4.4.1. The 
present study is designed to provide an initial evaluation of the efficacy of BMS-986278, further 
demonstrate the safety and the tolerability of BMS-986278 and provide information on the 
pharmacokinetics of BMS-986278 in participants with IPF and in those with PF-ILD. In this study, 
it is anticipated that the average rate of decline in percent predicted forced vital capacity (ppFVC) 
between baseline and Week 26 will be smaller among participants taking 1 of the 2 different doses 
of BMS-986278 than among those taking placebo.
3.4
Background
Details on the nonclinical pharmacology, pharmacokinetics (PK), and toxicology of BMS-986278 
are in the Investigator’s Brochure.
3.4.1
Nonclinical Pharmacology
See the Investigator’s Brochure for additional details on nonclinical pharmacology studies.
BMS-986278 is a potent full antagonist of LPA1 (Kb = 6.9 nM). BMS-986278 potently inhibited 
LPA-stimulated activation of multiple signal transduction pathways mediated by G protein-
coupled receptors Gq, Gi, and G12, as well as -arrestin recruitment in heterologous cells and 
endogenous cells expressing human LPA1 (hLPA1), exhibiting 3.9 to 25 nM affinity in all assays. 
BMS-986278 also acts as a potent but partial inhibitor of LPA3 (Kb = 2.1 nM, maximal inhibition 
(Imax) = 36%); however, was inactive at other LPA receptor isoforms tested, including LPA2, 
LPA4, and LPA5. BMS-986278 is also a potent inhibitor of the mouse and rat LPA1 receptor 
(Kb = 4 nM), indicating the suitability of these animal species for preclinical efficacy testing. 
LPA1 signaling has been shown in preclinical studies to contribute to the development of lung 
fibrosis, in part, through the stimulation of Gq-mediated Ca2+ flux and fibroblast proliferation. 
BMS-986278 was a potent inhibitor of LPA-stimulated proliferation of human lung fibroblasts 
with IC50 of 25 nM.
In vivo, BMS-986278 demonstrated antifibrotic efficacy in both the murine subcutaneous 
bleomycin systemic model as well as in the intratracheal BLEO rat model of lung fibrosis.
BMS-986278 administered orally at 10 mg/kg (twice daily [BID] for 14 days, administered 
starting on Day 7 after BLEO treatment) decreased BLEO-induced fibrosis, as measured by 
quantitative histological analysis, by 55% (P < 0.01; plasma trough concentration 244 nM; 
calculated occupancy 87%) in the rat model and by 58% (P < 0.01; plasma trough concentration 
239 nM; calculated occupancy 95%) in the mouse model.
Taken together these data suggest that antagonizing the LPA1 receptor with BMS-986278 may be 
beneficial in treating patients with IPF and with PF-ILD in general.
3.4.2
Nonclinical Pharmacokinetics
See the Investigator’s Brochure for additional details on nonclinical PK studies.
The nonclinical PK of BMS-986278 following a single intravenous (IV) or oral dose were 
characterized in mice, rats, dogs, and monkeys. After IV administration, the apparent elimination 
half-life (T-HALF) of BMS-986278 was 2.5, 4.5, 5.7 and 11 hours in mice, rats, dogs, and 
monkeys, respectively. Total plasma clearance was low in monkeys and moderate in other 
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preclinical species (37, 15, 29, and 2 mL/min/kg in mice, rats, dogs, and monkeys, respectively). 
The steady-state volume of distribution (Vss), ranging from 1.6 L/kg to 5.5 L/kg in mice, rats, 
dogs, and monkeys, indicated extensive extravascular distribution of BMS-986278. The absolute 
oral bioavailability was 70%, > 100%, 35%, and 79% in mice, rats, dogs, and monkeys, 
respectively.
BMS-986278 showed significant metabolic turnover in hepatocytes across species (mouse, rat, 
dog, monkey, and human). Direct glucuronidation of the carboxylic acid moiety to form an 
acylglucuronide (BMT-332415) was predominant in dog and monkey hepatocytes, and major in 
hepatocytes of other species. N-demethylation (BMT-323719) was another major metabolic 
pathway in human, monkey, and rodent hepatocytes. Oxidation, dealkylation, and epimerization 
were minor in human hepatocytes.
3.4.3
Nonclinical Toxicology
See the Investigator’s Brochure for additional details on nonclinical toxicology studies.
3.4.3.1
Genotoxicity, Phototoxicity, Safety Pharmacology
Briefly, BMS-986278 is neither genotoxic nor phototoxic. Moreover, the compound has displayed 
no safety pharmacology concerns based on off-target, central nervous system, respiratory, or 
electrocardiogram (ECG) assessments. In telemeterized monkeys (Good Laboratory Practice 
[GLP] study), a single 20 mg/kg dose (highest dose tested), produced transient and minimal 
decreases in systolic blood pressure (SBP) and mean arterial blood pressure (BP) (7 to 9 mmHg) 
from approximately 4.5 to 8 hours post dose, a transient increase in heart rate (HR) (6 beats per 
minute [bpm]) from 2 to 2.5 hours post dose, and a minimal decrease in HR (-14 bpm) from 4.5 to 
6.5 hours post dose. These effects were not replicated in a subsequent telemeterized monkey study 
(non-GLP) at higher doses, 50 and 100 mg/kg. There were no effects noted in any of the 
cardiovascular parameters (hemodynamics, ECG, rate, rhythm, or waveform morphology). Based 
on these studies, the monkey may not be predictive of the BP changes observed in humans.
3.4.3.2
Repeat-dose Toxicity
In the 1-month oral rat toxicity study, BMS-986278 was well tolerated up to the highest dose tested 
(300 mg/kg/day) with no BMS-986278-related adverse findings. Therefore, the no-observed 
adverse effect level (NOAEL) was considered to be 300 mg/kg/day.
In the 6-month oral toxicity study in rats with a 3-month recovery period, BMS-986278 was well 
tolerated up to the highest dose tested, 300 mg/kg/day (area under the plasma concentration-time 
curve from time 0 to 24 hours post dose [AUC(0-24h)] = 2,400 µg•h/mL in males and AUC[0-24h] 
= 3,120 µg•h/mL in females). The only adverse finding was increased incidence/severity (minimal 
to moderate) of degenerative joint disease at the femorotibial joint (common age-related 
spontaneous background change in rats, characterized by articular cartilage fibrillation, clefting, 
erosion and/or chondrocyte loss/cloning, synovial inflammation, capsular fibrosis without bone 
changes) in males at > 100 mg/kg/day (≥ AUC[0-24h] = 615 µg•h/mL). Therefore, the NOAEL 
was considered to be 30 mg/kg/day (AUC[0-24h] = 45.2 µg•h/mL; males and AUC[0-24h] = 
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106 µg•h/mL females). Similar findings were not observed in sexually mature monkeys dosed for 
9 months up to 150 mg/kg/day (see below).
In the 1-month oral toxicity study in sexually immature monkeys, BMS-986278 was well tolerated 
up to the highest dose tested (100 mg/kg/day). At 100 mg/kg/day the only noteworthy 
BMS-986278-related finding was moderate physeal dysplasia, segmented at the caudal aspect of 
the distal femur in 1 of 5 monkeys assessed with no associated changes in bone biomarkers. The 
bone change was considered adverse because, in sexually immature monkeys with a continuously 
growing growth plate, it could potentially result in malalignment of the adjacent articular surfaces 
before attainment of full sexual maturity. The bone finding is consistent with the role of LPA1 in 
development of the growth plate and chondrocyte proliferation and positioning to promote 
cartilage formation. No bone findings were evident in recovery monkeys. Based on the bone 
findings at 100 mg/kg/day, the NOAEL in sexually immature monkeys was considered to be 
50 mg/kg/day (mean sex-combined AUC(0-24h) = 251 µg•h/mL).
In the 9-month oral toxicity study in sexually mature monkeys with a 3-month recovery period, 
doses tested were 0 (vehicle), 20, 50, or 150 mg/kg/day. BMS-986278 was well tolerated by 
monkeys up to the highest dose tested with no adverse BMS-986278-related findings. Moderate 
physeal dysplasia noted in 1/5 females in sexually immature monkeys at 100 mg/kg/day in the 
1-month toxicity study did not recapitulate in sexually mature monkeys (with closed growth 
plates). Therefore, the NOAEL was considered 150 mg/kg/day (mean sex-combined 
AUC[0-24h] = 1,140•µg·h/mL).
3.4.3.3
Embryo-fetal Development Studies
Embryo-fetal development studies in rat and rabbit indicated that BMS-986278 is a selective 
developmental toxicant. In pregnant rats, BMS-986278 was administered orally at 0, 15, 45, and 
75 mg/kg/day during the period of organogenesis (Gestation Day [GD] 6 to 16). Fetal external, 
visceral, and skeletal malformations, predominantly localized to the craniofacial and thoracic/rib 
regions were noted starting at the lowest dose tested (15 mg/kg/day; mean AUC[0-24h] = 
16 µg•h/mL). The malformations occurred in the absence of any apparent maternal toxicity. In 
rabbits, BMS-986278 was administered orally at 0, 20, 75, and 200 mg/kg/day during the period 
of organogenesis (GD 7 to 19). BMS-986278-related effects on maternal survival, body weight 
(including body weight loss), food consumption (inappetence), and fetal viability (increased 
postimplantation loss) were observed at 200 mg/kg/day. An increased incidence of fetal skeletal 
malformations (ribs, sternebrae, cranium/skull) was noted at ≥ 75 mg/kg/day (absence of maternal 
toxicity at 75 mg/kg/day). In light of these findings, the developmental NOAEL was considered 
to be 20 mg/kg/day (mean AUC[0-24h] = 32.1 µg•h/mL).
In an oral study of fertility and early embryonic development, BMS-986278 was well tolerated by 
male and female rats, with no effects noted on fertility or early embryonic development up to doses 
of 300 mg/kg/day. Therefore, 300 mg/kg/day (BMS-986278 AUC[0-24h] = 1,870 μg•h/mL male 
and 1,390 μg•h/mL female) was considered the reproductive NOAEL.
Overall, based on data available to date, the nonclinical safety assessments support continued 
development of BMS-986278. Evidence for teratogenicity in rats and rabbits highlights the need 
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for special precautions when enrolling women of childbearing potential (WOCBP) in clinical 
studies.
3.4.3.4
Nonclinical Combination Toxicology
The objective of the clinical development program is to demonstrate that BMS-986278 is safe and 
effective for the treatment of IPF when used alone or concomitantly with approved IPF treatments. 
To date, 2 drugs have been approved for treatment of IPF in several countries globally: pirfenidone, 
a small-molecule inhibitor of fibrosis (precise mechanism of action unknown) and nintedanib (a 
multiple tyrosine kinase inhibitor).
BMS conducted a definitive 3-month combination toxicity study in rats with BMS-986278 and 
pirfenidone or nintedanib to determine the potential toxicokinetic and toxicological interactions 
between the compounds and to support the Phase 2 clinical study. To support the definitive 
3-month combination toxicity study dose selection and study design, 2 preceding 7-day dose 
range-finding studies for BMS-986278 were conducted. Pirfenidone and nintedanib doses were 
equivalent to the area under the plasma concentration-time curve (AUC) at the maximum 
recommended human dose (MRHD); pirfenidone 500 mg/kg/day and nintedanib 20 mg/kg/day.
The two 7-day range-finding studies in rats suggested that BMS-986278 exacerbated 
pirfenidone-induced clinical signs (decreased activity, ataxia, eyelids partially closed, abnormal 
posture/gait, piloerection, increased/labored breathing, and/or cold to touch). Female animals were 
more sensitive to the combination effect than the males, resulting in some moribundity at 
BMS-986278 doses ≥ 15 mg/kg/day in both range-finding studies. The clinical signs/moribundity 
were partially attributed to observed higher pirfenidone exposures on Day 1. As previously 
described, rats generally developed tolerability to pirfenidone within 2 to 3 days. Systemic 
exposure to BMS-986278 was generally lower (2) when coadministered with pirfenidone. 
Based on range-finding studies, doses in the 3-month study for BMS-986278 doses were decreased 
to 15/7.5 mg/kg/day (male/female) and pirfenidone dosing was initiated a week prior to 
BMS-986278 to enable development of tolerance.
Nintedanib and BMS-986278, in combination, was well tolerated in two range-finding studies. In 
one range-finding study, the observed decrease in nintedanib exposure was attributed to the 
vehicle. BMS-986278 doses selected for the definitive 3-month combination toxicology study in 
rat were 30/15 mg/kg/day (male/female) and dosing was initiated concurrently. No PK or 
toxicological interaction were noted between BMS-986278 and nintedanib.
In a definitive 3-month combination toxicology study, BMS-986278 doses in the pirfenidone 
combination part of the study were 15 mg/kg/day in males and 7.5 mg/kg/day females (1 to 3
projected high/low human efficacious AUC) and that of pirfenidone was 500 mg/kg/day 
(1MRHD). There were no unique clinical pathology or anatomic pathology findings when 
BMS-986278 was administered in combination with pirfenidone at doses providing clinically 
relevant exposures. All findings were consistent with those reported previously for each drug 
alone.12, 13, 14 There was a slight increase in alanine aminotransferase (ALT) levels in animals 
receiving the combination (1.41 to 1.45×). When administered in combination with pirfenidone, 
BMS-986278 systemic exposures (maximum concentration [Cmax] and AUC[0-24h]) were 0.2 to 
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0.5those when administered alone, indicating a possible toxicokinetic interaction in rat. Although 
initiation of pirfenidone dosing 1 week ahead of BMS-986278 enabled development of tolerance 
to the central nervous system-related signs caused by pirfenidone, clinical signs were observed 
sporadically in a small number of rats after BMS-986278 administration was initiated on Day 8 in 
a small number of rats. Additionally, 4 rats were euthanized or found dead on or after Day 45 (3 in 
the combination group compared to 1 in the pirfenidone alone group). However, when accounting 
for the different group sizes, there was a similar incidence [5% to 8%] in the combination and 
pirfenidone-only treatment groups. Nevertheless, the clinical signs and mortality suggested a 
possible toxicologic interaction between BMS-986278 and pirfenidone.
BMS-986278 doses in the nintedanib combination part of the study were 30 mg/kg/day in males 
and 15 mg/kg/day females and that of nintedanib was 20 mg/kg/day. There was no toxicokinetic 
or toxicologic interaction between BMS-986278 and nintedanib when coadministered at doses 
providing clinically relevant exposures. All findings were consistent with those reported 
previously for each drug alone.
3.4.4
Clinical Experience
3.4.4.1
Efficacy of Previous LPA1 Antagonist (BMS-986020)
The proof of concept for antifibrotic activity with an LPA1 antagonist was demonstrated in a 
randomized, double-blind, placebo-controlled Phase 2 study with BMS-986020, another selective, 
small-molecule LPA1 antagonist (Study IM136003). Study IM136003 was a 26-week study 
comparing BMS-986020 600 mg (n=96) to placebo (n=47) in 143 patients with IPF. Study drug 
was administered either once daily (QD) or BID. The primary endpoint was the rate of change in 
absolute FVC from baseline to study end, measured at 26 weeks.
For the higher-dose regimen of BMS-986020 600 mg twice daily, the primary treatment 
comparison, active treatment versus placebo, showed a significant difference in the primary 
endpoint, change in FVC (liters) from baseline to Week 26. The estimate (95% CI) of the slope of 
decline in FVC was -0.042 liters (-0.106, 0.022) in the BID group, compared with -0.134 liters 
(-0.201-0.068) in the placebo group and the difference in estimates of rate of change in FVC from 
baseline to 26 weeks was 0.093 liters per 26 weeks (0.000, 0.185) (P=0.049). There was no 
statistically significant difference in slope of FVC decline between BMS-986020 600 mg QD and 
placebo. The estimate (95% CI) of the slope of decline (liters per 26 weeks) in FVC at Week 26 
was -0.073 liters (-0.138,-0.007) in the QD group, compared with -0.134 liters (-0.201,-0.068) in 
the placebo group and the difference in estimates of rate of change in FVC from baseline to 
26 weeks was 0.062 liters per 26 weeks (-0.032, 0.155) (P=0.194).
In Study IM136003, there were 3 drug-associated events of cholecystitis leading to 
cholecystectomy, and the decision was made to discontinue development of BMS-986020 due to 
these events. Nonclinical and clinical studies to date with BMS-986278 do not show 
physiologically significant hepatobiliary effects.
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3.4.4.2
First-in-Human Study (Study IM027009)
The first-in-human (FIH) study for BMS-986278, Study IM027009, was a double-blind, 
placebo-controlled, randomized single-ascending-dose and multiple-ascending-dose study. 
The primary objective of the study was to evaluate the safety and tolerability of single and multiple 
ascending oral doses of BMS-986278 in healthy participants. Secondary objectives included:

To evaluate the plasma PK of single and multiple ascending oral doses of BMS-986278 in 
healthy participants.

To evaluate the effect of a high-fat meal and of a modified gastric pH on the plasma PK of a 
single dose of BM-986278 in healthy participants.

To compare the plasma PK of multiple ascending oral doses of BMS-986278 in Japanese and 
non-Japanese healthy participants.
Following both single and repeat administrations of BMS-986278, plasma concentrations of the 
parent compound peaked rapidly each day approximately 1.5 hours after dosing. A similar second 
peak, presumably due to enterohepatic recycling, was observed each day approximately 4.5 hours 
after dosing, followed by a log-linear decline. BMS-986278 area under the plasma concentration-
time curve from time 0 extrapolated to infinite time (AUC[INF]) and Cmax increased 
proportionally with dose with both single and repeat administrations; oral clearance was 
independent of dose. Steady-state plasma concentrations of the compound were reached at 
approximately 6 days after the first administration of the compound. There was minimal plasma 
accumulation of BMS-986278 and its metabolites.
BMS-986278 was generally well tolerated at single doses up to 150 mg and at multiple doses of 
up to 125 mg BID for 14 days. No deaths or serious treatment-emergent adverse events (TEAEs) 
were reported, and no participant discontinued dosing due to TEAEs. There were no clinically 
significant laboratory findings. The maximum tolerated single dose was determined to be 150 mg. 
Dose-limiting toxicity was not observed up to 125 mg BID for 14 days.
BMS-986278 was associated with reversible, generally dose-dependent reductions in BP that 
generally reached a maximum 4 to 8 hours after dosing, returned to baseline within 24 hours, and 
were not associated with meaningful changes in HR. Orthostasis was infrequently observed in both 
placebo and active dose groups, with no clear association with BMS-986278. BP reductions were 
mostly asymptomatic.
3.4.4.3
BMS-986278 in Combination with Rifampin (Study IM027017)
Study IM027017 was an open-label, 2-period drug-drug interaction study in a planned total of 
15 participants (healthy male and female [non-childbearing potential] participants). The primary 
objective of the study was to assess the effect of rifampin, a potent inhibitor of organic anion 
transport protein (OATP)1B1 and OATP1B3, on the single-dose PK of BMS-986278 in healthy 
participants. In Period 1 BMS-986278 was administered alone and in Period 2 BMS-986278 was 
administered immediately following a single oral dose of 600 mg rifampin.
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BMS-986278 was generally well tolerated both alone and when coadministered with rifampin. 
Only 4 TEAEs were reported in the study. No deaths, serious adverse events (SAEs), or treatment-
related TEAEs were reported and no participant discontinued treatment due to a TEAE. As in 
Study IM027009, asymptomatic BP reductions were observed, but the mean changes in SBP- and 
diastolic blood pressure (DBP)-time profiles were similar between the 2 treatments, indicating that 
elevated exposures to BMS-986278, when coadministered with rifampin, did not result in larger 
BP reductions.
3.4.4.4
BMS-986278 in Combination with Pirfenidone (Study IM027041)
Study IM027041 was an open-label, three-period, randomized crossover study in 22 healthy, male 
and female participants (in order to achieve 18 participants who complete the study) who are not 
users of nicotine; female participants must not be of childbearing potential. The primary objective 
of the study was to characterize the PK of BMS-986278 after administration of a single dose of 
BMS-986278 alone or in combination with pirfenidone.
 
 
 
 
 
 
 
3.5
Benefit/Risk Assessment
The known benefit of participation in this study is limited to a baseline assessment of health being 
provided for all participants in this study. The overall risk for participation is considered low based 
on safety and tolerability data from the FIH study with BMS-986278. Transient, mostly 
asymptomatic decreases in BP were reported in the IM027009 study, but in all cases BP returned 
to baseline with no intervention. Vital signs assessments will be in place to monitor the potential 
occurrence of BP reductions, and participants will be monitored closely at the study site for the 
first 4 hours following the first dose of study treatment. Participants may undergo 
BMS-986278 dose reduction if BP reduction criteria (described in Section 5.1.2.1) are observed.
In nonclinical studies, physeal dysplasia of the bone was observed, but the risk for similar bone 
effects in this study is considered low. Moreover, bone growth plates are expected to be closed in 
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the participant population eligible for the study (40 years and above for the IPF cohort and 21 years 
and above for the PF-ILD cohort). BMS-986278 was not genotoxic in the Ames assay, but 
BMS-986278 has demonstrated reproductive and developmental toxicities in rats and rabbits, thus 
WOCBP will not be included in the study.
More detailed information about the known and expected benefits and risks and reasonably 
anticipated adverse events (AEs) of BMS-986278 may be found in the Investigator’s Brochure.
3.5.1
COVID-19-related Benefit/Risk Assessment
The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is a risk that needs to be 
considered by the site investigator, particularly as lung fibrosis patients are at increased risk for 
respiratory infections in general. Similar to other infections, participants with recent acute 
infection with SARS-CoV-2 are excluded. Evaluation and management of SARS-CoV-2 infection 
arising during the course of the trial are left to the discretion and expertise of the site investigator.   
Importantly, as BMS-986278 is not immunosuppressive in nature, there is no known additional 
risk for SARS-CoV-2 infection associated with administration of the investigational medicinal 
product (IMP) in this clinical trial. 

In the event participants are unable or not permitted to attend an onsite visit due to the
COVID-19 pandemic, the study site should contact the Study Director or Medical Monitor and
each instance will be addressed on a case by case basis.
4
OBJECTIVES AND ENDPOINTS
Table 3:
Objectives and Endpoints
Objectives
Endpoint(s)

Primary

To evaluate the rate of change in ppFVC
from baseline to Week 26 in IPF participants
randomized to receive BMS-986278 at
30 mg or 60 mg BID compared to those
randomized to receive placebo.

Rate of change in ppFVC (%) from baseline to
Week 26 in IPF participants

Secondary

To evaluate the safety and tolerability of
BMS-986278 through 26 weeks of treatment
by comparing results observed in participants
with IPF and PF-ILD randomized to receive
BMS-986278 at 30 mg or 60 mg BID with
those who receive placebo. The IPF and
PF-ILD cohorts will be analyzed separately.

AEs

SAEs

AEs leading to early discontinuation of study
treatment

Treatment-emergent deaths

Clinical laboratory findings and ECGs

Vital signs

Physical exam findings

To evaluate the rate of change in ppFVC
from baseline to Week 26 in PF-ILD
participants randomized to receive

Rate of change in ppFVC (%) from baseline to
Week 26 in PF-ILD participants
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Table 3:
Objectives and Endpoints
Objectives
Endpoint(s)
BMS-986278 at 30 mg or 60 mg BID 
compared to those randomized to receive 
placebo.

To evaluate the effect of treatment with
BMS-986278 on clinical assessments of lung
fibrosis in participants with IPF and PF-ILD
randomized to receive BMS-986278 at
30 mg or 60 mg BID compared with
participants randomized to receive placebo
through Week 26. The IPF and PF-ILD
cohorts will be analyzed separately.

Proportion of participants with ≥10% absolute
decline in ppFVC (%) at Weeks 4, 8, 12, 16,
20, and 26

Proportion of participants with > 0% change in
ppFVC at Weeks 4, 8, 12, 16, 20, and 26

Time to first acute exacerbation

Time to first ≥10% absolute decline in
ppFVC (%)

Absolute change in FVC (mL) from baseline to
Week 26

Absolute change in ppFVC (%) from baseline
to Week 26

Absolute change in DLCO SB
(mL/min/mmHg) (corrected for hemoglobin)
from baseline to Week 26

Absolute change in ppDLCO SB (%)
(corrected for hemoglobin) from baseline to
Week 26

Change in walking endurance/distance from
baseline at Week 26 as measured using the
6MWT

Proportion of participants with acute
exacerbations of lung fibrosis defined as an
acute, clinically significant, respiratory
deterioration characterized by evidence of new
widespread alveolar abnormality, as follows:15
1. Acute worsening or development of
dyspnea (< 1 month duration)
2. Imaging with new bilateral ground-glass
opacity and/or consolidation
superimposed on a background pattern of
lung fibrosis
3. Respiratory deterioration not fully
explained by cardiac failure or fluid
overload

To characterize the PK of BMS-986278 in
IPF participants.

Cmax, Tmax, and AUC(0-8) on Day 1 and
Week 4 and Ctrough on Week 4 and Week 12
of intensive PK substudy
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Table 3:
Objectives and Endpoints
Objectives
Endpoint(s)
Exploratory

To characterize the PK of BMS-986278 in 
PF-ILD participants, if applicable

Cmax, Tmax, and AUC(0-8) on Day 1 and 
Week 4 and Ctrough on Week 4 and Week 12 
of intensive PK substudy

To characterize PK of the inactive metabolite 
BMT-323719.

Exposure parameters, including but not limited 
to AUC(0-8), Ctrough, Cmax, and Tmax of 
intensive PK study

To explore potential interactions between 
nintedanib or pirfenidone and BMS-986278 
using population pharmacokinetics.

Plasma concentrations of nintedanib and 
pirfenidone in participants who receive 
nintedanib or pirfenidone alone and 
co-administered with BMS-986278

To evaluate the effect of treatment on the 
rate of change in lung fibrosis in IPF and 
PF-ILD as measured by HRCT through 26 
weeks of treatment in participants 
randomized to BMS-986278 at 30 mg or
60 mg BID compared with participants 
randomized to receive placebo. The IPF and 
PF-ILD cohorts will be analyzed separately.

Change in quantitative lung fibrosis using the 
Quantitative HRCT Fibrosis Score from 
baseline to Week 26

To assess the effect of treatment in 
participants with IPF and PF-ILD 
randomized to BMS-986278 at 30 mg or 
60 mg BID to that of placebo on assessments 
of disease outcomes through 26 weeks of 
treatment. The IPF and PF-ILD cohorts will 
be analyzed separately.

Composite endpoint of time to first all-cause 
hospitalization or overall survival

Pulmonary fibrosis progression-free survival: 
Progression of pulmonary fibrosis is defined as 
≥ 10% decline in ppFVC relative to baseline, 
≥50 m decline in 6MWT relative to baseline, 
lung transplantation, or death

To assess changes in COAs during treatment 
in participants with IPF and PF-ILD 
randomized to BMS-986278 at 30 mg or 
60 mg BID compared with participants 
randomized to placebo. The IPF and PF-ILD 
cohorts will be analyzed separately.

Change in HRQoL from baseline at each 
assessment timepoint during treatment as 
measured by the L-PF

Change in HRQoL from baseline at each 
assessment timepoint during treatment as 
measured by the SGRQ

Change in dyspnea from baseline at each 
assessment timepoint during treatment as 
measured by the UCSD SOBQ

Change in cough severity from baseline at each 
assessment timepoint during treatment as 
measured using a VAS

Change in walking endurance/distance from 
baseline at each assessment timepoint during 
treatment as measured using the 6MWT
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Table 3:
Objectives and Endpoints
Objectives
Endpoint(s)

To assess the effect of treatment in 
participants with IPF and PF-ILD 
randomized with BMS-986278 at 30 mg or 
60 mg BID to that of placebo on additional 
categorical clinical assessments of disease 
through 26 weeks of treatment. The IPF and 
PF-ILD cohorts will be analyzed separately.

Proportion of participants with > 5% decline in 
FVC (mL) relative to baseline 

Proportion of participants with > 10% decline 
in FVC (mL) relative to baseline

Proportion of participants with > 5% absolute 
decline in ppFVC (%)

Proportion of participants with > 5% decline in 
ppFVC (%) relative to baseline

Proportion of participants with > 10% decline 
in ppFVC (%) relative to baseline

Time to first > 5% absolute decline in 
ppFVC (%)

Time to first > 5% decline in ppFVC relative to 
baseline (%)

Time to first > 10% decline in ppFVC relative 
to baseline (%)

Time to first > 5% decline in FVC (mL) 
relative to baseline

Time to first > 10% decline in FVC (mL)  
relative to baseline

To assess the effect of BMS-986278 on 
blood-based biomarkers.

Change from baseline of blood-based 
biomarkers of lung fibrosis and inflammation; 
including gene expression profiles

To assess the effects of IPF-related genes on 
drug response.

To assess the effect of genetic variations in 
genes associated with drug absorption, 
distribution, metabolism, excretion, and 
transport on the PK of BMS-986278.

Presence or absence of single nucleotide 
variants in genes associated with lung fibrosis

Presence or absence of single nucleotide 
polymorphism variants in genes encoding 
organic anion transporting polypeptides, 
cytochrome P450 (CYP)2C8, and breast cancer 
resistance protein

To assess the impact of SARS-CoV-2 
serologic status on participants with IPF or 
PF-ILD receiving BMS-986278.

Exploratory measurements of SARS-CoV-2 
serology (anti-SARS-CoV-2 total or IgG) from 
serum samples collected at baseline and end of 
the main study.
Exploratory - Optional Treatment Extension

To further evaluate the safety and tolerability 
of BMS-986278 in participants with IPF or 
PF-ILD that participate in the optional 
treatment extension (OTE).

AEs

SAEs

Treatment-emergent deaths

Clinical laboratory findings, PK
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Table 3:
Objectives and Endpoints
Objectives
Endpoint(s)

To further evaluate the efficacy of
BMS-986278 in participants with IPF or 
PF-ILD that participate in the OTE.

FVC trajectory (eg, rate of change of 
ppFVC [%] and FVC [mL] from Week 26 in 
the main study to Week 26 in the OTE and 
from baseline in the main study to Week 26 in 
the OTE) 

DLCO trajectory (eg, rate of change of 
ppDLCO SB [%] and DLCO SB 
[mL/min/mmHg] from Week 26 in the main 
study to Week 26 in the OTE and from 
baseline in the main study to Week 26 in the 
OTE)

Changes in quantitative lung fibrosis using the 
Quantitative HRCT Fibrosis Score 

Changes in HRQoL as measured by the L-PF

Changes in walking endurance/distance as 
measured using the 6MWT

Blood-based biomarkers of lung fibrosis and 
inflammation; including gene expression 
profiles

To assess the impact of SARS-CoV-2 
serologic status on participants with IPF or 
PF-ILD receiving BMS-986278.

Exploratory measurements of SARS-CoV-2 
serology (anti-SARS-CoV-2 total or IgG) from 
serum samples collected at the end of the OTE.
5
STUDY DESIGN
5.1
Overall Design
This is a Phase 2 randomized, double-blind, placebo-controlled clinical study investigating the 
efficacy and the safety and tolerability of BMS-986278 in participants with pulmonary fibrosis. In 
the primary cohort, a total of approximately 240 participants with IPF will be randomized to 
receive 30 mg or 60 mg BMS-986278 BID or placebo BID at a ratio of 1:1:1 for 26 weeks in the 
main study. Stable standard of care (SOC) background therapy for IPF with either nintedanib or 
pirfenidone will be allowed. 
In a secondary cohort, a total of approximately 120 participants with PF-ILD will be randomized 
to receive 30 mg or 60 mg BMS-986278 BID or placebo BID at a ratio of 1:1:1 for 26 weeks. 
Participants with PF-ILD will be allowed to remain on stable background therapies commonly 
used as part of their usual care, including nintedanib, pirfenidone, and/or select 
immunosuppressive medications (ie, azathioprine, mycophenolate mofetil, mycophenolic acid, 
and/or tacrolimus). 
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IPF and PF-ILD participants receiving 30 mg or 60 mg (or placebo) BMS-986278 BID in the main 
study who meet low BP criteria may be dose reduced to 10 mg BMS-986278 BID (or placebo for 
10 mg BID) (refer to Section 5.1.2.1). 
An optional treatment extension (OTE) that will last 26 weeks will be offered to IPF and PF-ILD 
participants that complete the 26-week main study. All participants will receive active treatment 
in the OTE. Participants who received 30 mg placebo tablets in the main study will be randomized 
to receive 30 mg or 60 mg BMS-986278 BID, and participants who received 30 mg or 60 mg 
BMS-986278 BID in the main study will continue with the assigned doses. Participants receiving 
30 mg or 60 mg BMS-986278 BID in the OTE will remain blinded to study treatment until the 
database lock for analyses of the 26-week main study in IPF and PF-ILD cohorts, respectively. At 
the time of main study database lock in each cohort, the OTE will be unblinded for that cohort. 
Participants who dose reduced and received 10 mg BMS-986278 BID or placebo for 10 mg 
BMS-986278 BID in the main study will receive 10 mg BMS-986278 BID unblinded in the OTE. 
Participants receiving 30 mg or 60 mg BMS-986278 BID in the OTE who meet low BP criteria 
may be dose reduced to 10 mg BMS-986278 BID (refer to Section 5.1.2.1).
The study includes: 

A screening period of up to 42 days

A 26-week, double-blind treatment period, during which participants will receive 1 of the 
following 3 treatments: 30 mg BMS-986278 oral tablets BID, 60 mg BMS-986278 oral tablets 
BID, or matching placebo tablets

A 4-week posttreatment follow-up period for those participants that do not elect to continue in 
the OTE

A 26-week OTE phase in which IPF and PF-ILD participants that choose to participate will 
receive one of 3 doses of BMS-986278 (30 mg BID, 60 mg BID, or 10 mg BID)

A 4-week post OTE treatment follow-up period

The study design schematics for the main study are presented in Figure 1 for the IPF cohort
and Figure 2 for the PF-ILD cohort. Refer to Table 1 for the Schedule of Activities for the 
main study.

The study design schematic for the OTE is presented in Figure 3. Refer to Table 2 for the 
Schedule of Activities for the OTE. 
5.1.1
Screening Period
Eligibility will be based on specified inclusion and exclusion criteria (Section 6), including 
medical history, disease activity, and safety assessments. Eligibility criteria for this study have 
been carefully considered to ensure the safety of the participants and that the results of the study 
can be analyzed properly. It is imperative that participants fully meet all eligibility criteria.
The investigator will maintain a screening log to record details of all participants screened and to 
confirm eligibility or record reasons for screening failure, as applicable. Certain procedures 
conducted as part of the participant’s routine clinical management and obtained before signing of 
informed consent may be utilized for screening purposes provided the procedure meets the 
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protocol-defined criteria and has been performed within the timeframe defined in the Schedule of 
Activities (Section 2).
5.1.2
Treatment Period
In the primary cohort of IPF participants, eligible participants will be randomized to receive 1 of 
2 dose levels of BMS-986278 (30 mg or 60 mg BID) or placebo for 26 weeks. Randomization will 
be stratified by country (non-Japan versus Japan), and concomitant use of approved IPF therapy 
(pirfenidone versus nintedanib versus none). 
In the secondary cohort of PF-ILD participants, eligible participants will be randomized to receive 
1 of 2 dose levels of BMS-986278 (30 mg or 60 mg BID) or placebo for 26 weeks. Randomization 
will be stratified by UIP pattern (present vs absent) of lung injury and by category of background 
therapy 
(ILD-targeted 
immunosuppression 
[ie, 
azathioprine, 
mycophenolate 
mofetil, 
mycophenolic acid, and/or tacrolimus] alone versus anti-fibrotics [nintedanib, pirfenidone] with 
or without ILD-targeted immunosuppression versus no ILD-targeted immunosuppression or 
anti-fibrotics).
All participants randomized will undergo functional, quality-of-life, PK and biomarker 
assessments according to the Schedule of Activities (Table 1).
In addition, physical examinations, vital sign measurements (including orthostatic assessments), 
12-lead ECGs, and clinical laboratory evaluations will be performed at selected times throughout 
the dosing interval. Participants will be closely monitored for AEs throughout the study. 
For all study participants, blood samples will be collected for up to 4 hours after study treatment 
administration for PK analysis on Day 1. Predose blood samples will be collected at Week 12 and 
Week 26. Additional samples will be collected from IPF and PF-ILD participants in the intensive 
PK substudy (see Section 9.5.2). 
After completing the 26-week main study, participants will have the opportunity to continue study 
treatment in the OTE for another 26 weeks. Refer to the assessments in the Schedule of Activities 
(Table 2) and Sections 7.1 and 7.2 for treatments administered and treatment assignments, 
respectively.
5.1.2.1
Blood Pressure Monitoring 
Symptoms that could indicate the presence of orthostatic intolerance, orthostatic hypotension, and 
orthostatic tachycardia (defined below, per the ACC/AHA/HRS guideline16) will be gathered at 
all study visits, including the screening visit. 
Orthostatic intolerance: defined as a syndrome consisting of a constellation of symptoms that 
include frequent, recurrent, or persistent lightheadedness, palpitations, tremulousness, generalized 
weakness, blurred vision, exercise intolerance, and fatigue upon standing. These symptoms can 
occur with or without orthostatic tachycardia, orthostatic hypotension, or syncope. Individuals 
with orthostatic intolerance have at least 1 of these symptoms associated with reduced ability to 
maintain upright posture. 
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Orthostatic hypotension: defined as a drop in SBP of ≥ 20 mmHg or DBP of ≥ 10 mmHg with 
assumption of an upright posture from either supine or seated to upright position. 
Orthostatic tachycardia: defined as a sustained increase in HR of ≥ 30 bpm within approximately 
10 minutes of moving from a recumbent to a quiet (nonexertional) standing position; defined as 
the difference in HR from either supine or seated to upright position. 
Day 1 blood pressure monitoring:
On Day 1, participants will remain at the site for at least 4 hours post dose. Orthostatic BP and HR 
will be performed predose and 1.5, 2, and 4 hours post dose. 
During orthostatic assessments, participants will be queried for any of the following symptoms 
suggestive of orthostatic intolerance: lightheadedness, palpitations, tremulousness, generalized 
weakness, blurred vision, exercise intolerance, and fatigue upon standing.
Participants will take the Day 1 evening dose at home and will return to the study site on Day 8 if
neither asymptomatic nor symptomatic low BP criteria are met. 
Participants will not receive the Day 1 evening dose if either asymptomatic or symptomatic low 
BP criteria are met.
Asymptomatic low BP criteria:
a) Seated SBP < 85 mmHg (confirmed by retest within 15 minutes)
b) Seated DBP < 55 mmHg (confirmed by retest within 15 minutes)
c) Orthostatic hypotension (confirmed by retest within 15 minutes)
Symptomatic low BP criteria:
a) The participant is experiencing symptoms that, in the opinion of the investigator, could be 
associated with low BP (eg, confusion, lightheadedness, dizziness, palpitations, falls, 
tremulousness, generalized weakness, blurred vision, exercise intolerance [if different from 
baseline], fatigue upon standing [if different from baseline], angina, transient ischemic 
attack, pre-syncope, or syncope) AND at least one of the following BP thresholds: 
i.
Seated SBP < 100 mmHg (confirmed by retest within 15 minutes) or seated DPB 
< 60 mmHg (confirmed by retest within 15 minutes) 
ii.
Decrease of seated SBP of ≥ 20 mmHg (confirmed by retest within 15 minutes) 
from previous visit or decrease of seated DBP of ≥ 10 mmHg (confirmed by retest 
within 15 minutes) from previous visit
iii.
Orthostatic hypotension (confirmed by retest within 15 minutes)
iv.
Orthostatic tachycardia (confirmed by retest within 15 minutes)
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If either asymptomatic or symptomatic low BP criteria are met, participants will not receive the 
Day 1 evening dose and will remain at the site until BP resolution criteria are met:
a) Participants provide 2 consecutive seated BP measurements (at least 30 minutes apart) 
showing SBP > 85 mmHg and DBP > 55 mmHg
b) Participants do not demonstrate orthostatic hypotension 
c) Potential symptoms of decreased BP (as described above) have not been present for at least 
30 minutes
Participants will return to the site on Day 2 prior to receipt of the morning dose. 
Day 2 blood pressure monitoring (for participants that were unable to receive evening dose 
on Day 1 due to having met either asymptomatic or symptomatic low BP criteria):
At the Day 2 visit, participants will receive a reduced dose of BMS-986278 (10 mg BID) while 
those randomized to placebo will be administered placebo for 10 mg BMS-986278 BID. Dose 
reduction should be appropriately noted in the case report form.
On Day 2, participants will remain at the site for at least 4 hours post dose. Orthostatic BP and HR 
will be performed predose and 1.5, 2, and 4 hours post dose. Participants will be carefully 
monitored for symptoms associated with low BP.
Participants will remain on reduced dose (10 mg BMS-986278 BID or matching placebo for 
10 mg BMS-986278 BID) and will take the Day 2 evening dose at home and return to the study 
site on Day 8 if neither asymptomatic nor symptomatic low BP criteria are met.
If either asymptomatic or symptomatic low BP criteria, as described for Day 1, are met on Day 2, 
participants will be discontinued from study treatment (but continue in the study). 
Blood pressure monitoring at post-Day 1 study visits:
At every post-Day 1 study visit, vital signs, including orthostatic assessments, will be performed. 
Participants will take the evening dose at home and will return for their next scheduled study visit, 
as indicated in the Schedule of Activities (Section 2), if neither asymptomatic nor symptomatic
low BP criteria are met during any post-Day 1 study visit.
If either asymptomatic or symptomatic low BP criteria, as described for Day 1, are met on any 
post-Day 1 visit (predose), participants will remain at the site for at least 4 hours. Orthostatic BP 
and HR will be performed 1.5, 2, and 4 hours after the low BP criteria at predose are detected. 
Participants will not receive the evening dose and will remain at the site until BP resolution criteria 
are met:
a) The participant provides 2 consecutive seated BP measurements (at least 30 minutes apart) 
showing SBP > 85 mmHg and DBP > 55 mmHg
b) The participant does not demonstrate orthostatic hypotension 
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c) Potential symptoms of decreased BP (as described under Day 1) have not been present for 
at least 30 minutes
If a decision is made to reduce to 10 mg BMS-986278 BID (or placebo for 10 mg BMS-986278 
BID), the participant will return to the site the following day prior to receipt of the morning dose 
and will follow the Day 2 BP monitoring instructions. Dose reduction should be appropriately 
noted in the case report form.
Identifiable causes of low BP at any study visit, unrelated to study treatment, will be managed as 
clinically indicated. The management of initial low BP without an identifiable cause will include 
BP monitoring consistent with that described for Day 1 and Day 2.
At every post-Day 1 study visit, if any predose BP and/or HR measurements meet asymptomatic
or symptomatic low BP criteria, participants will not receive study treatment during that visit.
Blood pressure monitoring criteria described above will apply to the OTE.
5.1.3
Main Study Posttreatment Follow-up Period
Participants in the main study that do not enter the OTE will undergo a posttreatment follow-up 
visit 28 days (± 7 days) after the Week 26 visit. During the follow-up period, participants will not 
receive either active treatment or placebo.
Participants in the main study that discontinue study treatment with BMS-986278 or matching 
placebo before Week 26 will complete the remaining study visits according to the Schedule of 
Activities (Table 1), including the posttreatment follow-up visit. 
5.1.4
Optional Treatment Extension 
At the end of the main study treatment period, participants will have the opportunity to participate 
in an additional 26-week OTE.
Participants that elect to enter the OTE will receive active treatment within 1 to 15 days from 
completing the Week 26 visit in the main study. Study visits and procedures during the OTE are 
described in the study design schematic (Figure 3)
and the Schedule of Activities 
(Table 2).
Participants in the OTE that discontinue study treatment with BMS-986278 before Week 26 will 
complete the remaining study visits according to the Schedule of Activities (Table 2), including 
the post OTE treatment follow-up visit.
During the OTE, BP monitoring should follow the requirements in Section 5.1.2.1 for every study 
visit, including OTE Day 1.
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Figure 1:
Study Design Schematic of the IPF Cohort (Main Study)
BID = twice daily; BP = blood pressure; IPF = idiopathic pulmonary fibrosis; OTE = optional treatment extension 
* Participants receiving 30 mg or 60 mg (or placebo) BMS-986278 BID in the main study who meet low BP criteria may be dose reduced to 10 mg BMS-986278 
BID (or placebo for 10 mg BID)
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Figure 2:
Study Design Schematic of the PF-ILD Cohort (Main Study)
BID = twice daily; BP = blood pressure; OTE = optional treatment extension; PF-ILD =  non-IPF, progressive fibrotic interstitial lung disease
* Participants receiving 30 mg or 60 mg (or placebo) BMS-986278 BID in the main study who meet low BP criteria may be dose reduced to 10 mg BMS-986278 
BID (or placebo for 10 mg BID)
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Figure 3:
Study Design Schematic for the OTE (for each of the separate IPF and PF-ILD Cohorts)
BID = twice daily; IPF = idiopathic pulmonary fibrosis; OTE = optional treatment extension; PF-ILD =  non-IPF, progressive fibrotic interstitial lung disease
* Participants that were dose reduced in the main study
† Participants on 10 mg BMS-986278 BID are unblinded in the OTE 
± Participants receiving 30 mg or 60 mg BMS-986278 BID in the OTE who meet low BP criteria may be dose reduced to 10 mg BMS-986278 BID
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5.1.5
Data Monitoring Committee and Other External Committees
Study results will be monitored by an Independent Data Monitoring Committee (DMC); the scope 
of responsibility of the DMC will be outlined in the DMC Charter. Safety results will be reviewed 
by the DMC after approximately 30 randomized participants from either the IPF or PF-ILD cohort 
have completed at least 4 weeks after the first dose and at subsequent points outlined in the DMC 
Charter. Based on their reviews, the DMC will make recommendations to the sponsor on whether 
the study should be allowed to continue or be modified or terminated. Additional DMC meetings 
may also be scheduled to review the study data during the treatment period, as described in the 
DMC Charter. 
Based on their overall benefit/risk evaluation, the DMC recommendations may include proceeding 
with the study without modification, proceeding with the study with modification, or study 
suspension. The scope, conduct, membership, processes, and accountabilities of the DMC are 
specified in the DMC Charter. 
5.2
Number of Participants
This study will randomize approximately 360 participants in total.
Approximately 240 participants with IPF will be randomized to receive 30 mg BMS-986278 BID, 
60 mg BMS-986278 BID, or placebo BID at a ratio of 1:1:1 for 26 weeks in the main study.
In addition, a secondary cohort of approximately 120 PF-ILD participants will be randomized to 
receive 30 mg or 60 mg BMS-986278 BID or placebo BID at a ratio of 1:1:1 for 26 weeks in the 
main study.
Following the 26-week main study, participants from both IPF and PF-ILD cohorts will have the 
opportunity to participate in an additional 26-week OTE. All participants in the OTE will receive 
an active dose of BMS-986278 (30 mg BID, 60 mg BID, or 10 mg BID).
5.3
End of Study Definitions
The start of the study is defined as the visit for first participant screening. 
The last day of the main study will occur when the last participant has completed the follow-up 
visit (28 ± 7 days after the Week 26 visit). Primary study completion is defined as the final date 
on which data for the primary endpoint of the 26-week main study was or is expected to be 
collected. Participants will be considered to have completed the main study if they complete 
26 weeks of evaluation.
The last participant visit of the OTE is defined as the last visit or scheduled procedure shown in 
the Schedule of Activities (Table 2) for the last participant, whichever occurs last. This last 
participant visit will be the last visit for the entire study. 
End of study is defined as the date of the last visit of the last participant.
5.4
Scientific Rationale for Study Design
Several lines of published evidence support targeting the LPA/LPA1 receptor pathway in fibrotic 
diseases and for the treatment of IPF.6, 7 Increased LPA concentrations have been reported in the 
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alveolar space of both IPF patients and the corresponding BLEO mouse lung model, in which 
genetic deletion6, 8 or pharmacological inhibition9 of LPA1 attenuated the development of the 
modeled disease, suggesting a direct involvement of LPA and LPA1 in disease pathogenesis. 
Increased epithelial cell apoptosis in response to lung injury has also been implicated in the 
development of IPF and linked to LPA. LPA signaling through LPA1 has been reported to promote 
epithelial cell apoptosis induced by BLEO injury in mice.8 The number of apoptotic cells present 
in the alveolar and bronchial epithelia of LPA1-deficient mice was significantly reduced compared 
with wild-type mice after BLEO challenge.8
Consistent with these in vivo rodent results, increases in LPA levels and LPA signaling through 
LPA1 have been observed in individuals with fibrotic diseases. LPA levels are elevated in the 
bronchoalveolar lavage (BAL) of patients with IPF6 and were also found to be higher in patients 
with systemic sclerosis versus normal healthy volunteers.17 Increased concentrations of autotaxin, 
the enzyme largely responsible for extracellular LPA production, were elevated in both murine 
and human fibrotic lungs.10 Together these data suggest that antagonizing the LPA1 receptor may 
be beneficial in treating patients with IPF. Furthermore, the proof of concept for antifibrotic 
activity with an LPA1 antagonist was demonstrated in a randomized, double-blind, placebo-
controlled Phase 2 study with BMS-986020, another selective, small-molecule LPA1 antagonist 
(Study IM136003) discussed above in Section 3.4.4.1.11
BMS-986278 is a potent full antagonist at LPA1 that has been shown to potently inhibit 
LPA-stimulated activation of multiple signal transduction pathways. BMS-986278 is being 
developed as a potential treatment for IPF (see the Investigator’s Brochure for additional details).
Beyond IPF, some patients with other chronic forms of fibrotic ILD develop a progressive 
phenotype characterized by worsening respiratory symptoms, lung function, progressive fibrosis 
on imaging and early mortality. There is a high unmet need for effective and tolerable treatments 
for patients with non-IPF, fibrotic ILD that exhibit disease progression.2, 3, 4 Because of the clinical 
and pathophysiological similarities among these diseases, it has been suggested that such disorders 
have a common pathobiologic mechanism regardless of the cause – with resultant progressive lung 
fibrosis – and thus could have a response to similar treatment as IPF.2, 3, 4 Indeed, in the recently 
published INBUILD trial, patients with PF-ILD with diverse etiologies were treated with 
nintedanib vs placebo. Those treated with nintedanib had slower progression of lung fibrosis than 
those who received placebo, as demonstrated by a lower annual rate of decline in FVC over the 
52-week study period. The absolute treatment effects in this PF-ILD cohort were similar in 
magnitude to those observed in the pivotal INPULSIS trials that led to approval of nintedanib for 
treatment of IPF and based on data from the INBUILD trial, a number of health authorities have 
also approved nintedanib for patients with PF-ILD.5 In this study, it is anticipated that the average 
rate of decline in ppFVC between baseline and Week 26 will be smaller among participants taking 
2 different doses of BMS-986278 than among those taking placebo. It is also anticipated that the 
rate of decline in ppFVC between baseline and Week 26 will be smaller among participants taking 
each individual dose than among those taking placebo.
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This study is the first evaluation of BMS-986278 in participants with pulmonary fibrosis. This 
study is designed to provide an initial evaluation of the efficacy of BMS-986278 in participants 
with IPF, further demonstrate the safety of BMS-986278, and provide information on the PK of 
BMS-986278 in participants with IPF. In addition, a secondary cohort consisting of PF-ILD 
participants will be enrolled in order to assess safety, tolerability, and efficacy of BMS-986278 in 
PF-ILD. The PF-ILD cohort will be analyzed separately from the IPF cohort, but with the same 
schedule of activities and endpoints.
In order to augment knowledge about the safety, tolerability, and efficacy of BMS-986278, an 
OTE will be offered to all participants that complete the 26-week main study.
5.4.1
Rationale for Optional Treatment Extension (OTE)
An optional treatment extension of an additional 26 weeks of IP is being offered to participants 
who complete the 26-week main study. Decisions about whether to continue in the OTE are left to 
the discretion of the clinical investigator and the willingness of the participant. Many factors will 
be taken into consideration by the investigator and participant, including a clinical assessment of 
disease status (ie, whether the enrolled participant is benefiting from ongoing treatment) along 
with assessments of tolerability and safety considerations.
A chief focus of the OTE is to augment knowledge regarding safety and tolerability of 
BMS-986278 in participants with IPF and PF-ILD. As such, vigilant safety and tolerability 
monitoring are the primary focus of the frequent visits during the OTE.
Finally, during the OTE, management decisions regarding concomitant background antifibrotic or 
immunosuppressive medications are left to the discretion of the clinical investigator and 
participant preference. There are no known contraindications to the combination of BMS-986278 
with antifibrotic (eg, pirfenidone, nintedanib) medications or any of the immunosuppressive 
medications other than cyclosporine. (Cyclosporine use is contraindicated in the main study and 
OTE because it is a potent inhibitor of OATPs [APPENDIX 5].)
5.5
Justification for Dose
The expected therapeutic dose range for BMS-986278 is 26 mg to 100 mg based on in vitro and 
animal models.6, 7, 8, 9, 18, 19 In the FIH study (Study IM027009), single BMS-986278 doses of up 
to 150 mg and daily doses of up to 125 mg BID for 14 days were generally well tolerated, and the 
events of decrease in BP observed in the study were generally asymptomatic and are monitorable. 
The doses selected for this study (30 mg BID and 60 mg BID) were informed by the safety and 
tolerability of BMS-986278 observed in the FIH study of BMS-986278 (Study IM027009), as well 
as the results of a prior exposure-response analysis for BMS-986020, another LPA1 antagonist 
that was studied in a Phase 2 study in patients with IPF (Study IM036003). 30 mg BID and 60 mg 
BID were selected such that both dose levels are likely to achieve a profile of halting disease 
progression based on ppFVC, thus enabling the achievement of a compelling efficacy as well as 
safety profile. Both doses are expected to be safe and well tolerated based on the overall clinical 
experience in healthy volunteers at doses as high as 125 mg BID in Study IM027009. Studying at 
least a 2× difference in exposure is expected to allow delineation of any potential differences in 
safety profile, as well as any potential differences in BP response. Data on a lower dose level (ie, 
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10 mg BID) may be collected in case one of the 2 dose levels is not well tolerated (eg, due to 
significant BP lowering following the first few hours after dosing), allowing further delineation of 
exposure-efficacy and exposure-safety relationships.
6
STUDY POPULATION
The section below outlines the inclusion and exclusion criteria for the IPF and PF-ILD cohorts. 
These criteria specify which concomitant therapies (eg, antifibrotic or immunosuppressive 
therapies) are permitted for IPF and PF-ILD during the main study. Decisions about whether a 
patient with IPF or PF-ILD will choose to consider participation in this clinical study are left to 
the discretion of the clinical investigator, as well as the patient himself/herself, after due 
consideration of the inclusion criteria, study design, and numerous other variables. Factoring in 
the background therapies permitted during the 26-week main study may impact such consideration. 
Potential decisions to modify or discontinue background therapies to enable potential enrollment 
in this clinical study are not recommended, determined, or mandated by the study sponsor; rather, 
any such decision is left strictly to the discretion of the clinical investigator and the willingness of 
the potential patient.
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria:
6.1
Inclusion Criteria
1) Signed Written Informed Consent
a) Not applicable per Revised Protocol 03. Willing to participate in the study and sign the 
informed consent form (ICF) by participants or their legal authorized representative.
b) Willing and able to complete all study-specific procedures and visits.
c) Willing to participate in the study and sign the informed consent form (ICF) by participants.
2) Type of Participant and Target Disease Characteristics:
a) For the IPF cohort:
i)
Not applicable per Protocol Amendment 04; refer to Inclusion Criterion 2)a)v. 
Diagnosis of IPF within 7 years of screening (including screening period). 
ii) Centrally read chest high-resolution computed tomography (HRCT) obtained at 
screening:
(1) HRCT interpretation as consistent with UIP or probable UIP.
(2) If the HRCT interpretation on central reading is inconsistent with UIP, there must 
be verification that surgical lung biopsy histopathology is consistent with UIP. UIP 
pattern identification via cryobiopsy will be considered on a case-by-case basis.
iii) If not currently on pirfenidone or nintedanib, participants must be naïve to either 
medication or have not received either of these medications within 4 weeks prior to 
Day 1. See Section 7.7.1 for OTE guidance.
iv) If on pirfenidone or nintedanib, participants must have been receiving a stable dose for 
at least 3 months prior to screening and during the screening period. Pirfenidone or 
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nintedanib concomitant treatment should be used as per usual prescribing information 
approved by local regulatory agencies but patients on stable reduced dose can be 
included. See Section 7.7.1 for OTE guidance.
v) Diagnosis of IPF within 7 years of screening.
b) For the PF-ILD cohort:
i)
Not applicable per Revised Protocol 03. Diagnosis of ILD within 7 years of screening 
(including screening period). 
ii) Evidence of progressive ILD within the 24 months before screening, defined as either: 
(1) a decline in the relative ppFVC of ≥ 10%, or
(2) a decline in the relative ppFVC of ≥ 5% to < 10% along with an increased extent 
of fibrosis on pre-screening thoracic computed tomography compared with prior 
imaging, or 
(3) symptoms associated with progression of ILD along with an increased extent of 
fibrosis on pre-screening thoracic computed tomography compared with prior 
imaging.
iii) Centrally read HRCT obtained at screening demonstrating evidence of > 10% 
parenchymal fibrosis within the whole lung. 
iv) If not currently on pirfenidone or nintedanib, participants must be naïve to either 
medication or have not received either of these medications within 4 weeks prior to 
Day 1. See Section 7.7.1 for OTE guidance.
v) If on pirfenidone or nintedanib, participants must have been receiving a stable dose for 
at least 3 months prior to screening and during the screening period. Pirfenidone or 
nintedanib concomitant treatment should be used as per usual prescribing information 
approved by local regulatory agencies but participants on stable reduced dose can be 
included. See Section 7.7.1 for OTE guidance.
vi) Mycophenolate mofetil, mycophenolic acid, azathioprine or and/or tacrolimus are 
permitted only if the participant is on a stable dose at least 6 months prior to screening.  
These immunosuppressive medications cannot be initiated during the course of the 
main study. 
3) Target Disease Characteristics
a) ppFVC ≥ 40%
b) Forced expiratory volume in 1 second (FEV1)/FVC ≥0.7, based on prebronchodilator 
spirometry.
c) ppDLCO SB (percent predicted single-breath carbon monoxide diffusing capacity, 
corrected for hemoglobin) ≥25%.
4) Age and Reproductive Status
a) Female Participants:
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i)
Women not of childbearing potential ≥ 40 years of age for the IPF cohort and ≥21 years 
of age for the PF-ILD cohort.
ii) Women participants must have documented proof that they are not of childbearing 
potential (refer to APPENDIX 4).
iii) A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and is not a WOCBP.
b) Male Participants:
i)
Male ≥40 years of age for the IPF cohort and ≥ 21 years of age for the PF-ILD cohort. 
ii) Azoospermic males are not exempt from contraceptive requirements and will be 
required to always use a latex or other synthetic condom during any sexual activity (eg, 
vaginal, anal, oral) with WOCBP even if the participant has undergone a successful 
vasectomy or if the partner is pregnant.
iii) Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception (APPENDIX 4) for the duration of treatment with 
BMS-986278 and for at least 3 days after treatment completion. 
iv) Male participants must refrain from sperm donation during the duration of treatment 
with BMS-986278 and for at least 3 days after dosing has been completed.
v) Male participants will be required to always use a latex or other synthetic condom 
during any sexual activity (eg, vaginal, anal, oral) with WOCBP; even if the 
participants have undergone a successful vasectomy or if their partner is already 
pregnant or breastfeeding. Males should continue to use a condom during the duration 
of treatment with BMS-986278 and for at least 3 days after dosing has been completed.
vi) Male participants with a pregnant or breastfeeding partner must agree to remain 
abstinent from sexual activity or use a male condom during any sexual activity 
(eg, vaginal, anal, oral) even if the participants have undergone a successful vasectomy, 
during the treatment and for at least 3 days after the end of treatment.
vii)Female partners of males participating in the study should be advised to use highly 
effective methods of contraception until the end of relevant systemic exposure, defined 
as 3 days after the end of treatment in the male participant.
viii) Breastfeeding partners should be advised to consult their health care providers about 
using appropriate highly effective contraception during the time the participant is 
required to use condoms.
Investigators shall counsel male participants who are sexually active with WOCBP on the 
importance of pregnancy prevention, the implications of an unexpected pregnancy and the 
potential of fetal toxicity occurring due to transmission of study drug, present in seminal 
fluid, to a developing fetus, even if the participant has undergone a successful vasectomy 
or if the partner is pregnant.
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6.2
Exclusion Criteria
An individual who meets any of the following criteria will be excluded from participation in this 
study:
1) Medical Conditions
a) Women who are of childbearing potential
b) Women who are breastfeeding
c) For the IPF cohort:  
i)
ILD associated with known primary causes.
ii) Diagnosis of any systemic autoimmune disease (also known as “connective tissue 
disease”) (including but not limited to scleroderma, polymyositis/dermatomyositis, 
systemic lupus erythematosus, and rheumatoid arthritis).
d) For the PF-ILD cohort:
i)
A diagnosis of IPF, along with UIP pattern on central reading of HRCT, surgical lung 
biopsy, or cryobiopsy.  
ii) Not applicable per Revised Protocol 03. A diagnosis of sarcoidosis or any systemic 
autoimmune disease (also known as “connective tissue disease”) other than rheumatoid 
arthritis (including but not limited to scleroderma, polymyositis/dermatomyositis, 
systemic lupus erythematosus) as confirmed by the principal investigator. (Rheumatoid 
arthritis-ILD is the lone systemic autoimmune disease eligible for the PF-ILD cohort. 
Furthermore, participants that are considered as having “interstitial pneumonia with 
autoimmune features” are eligible for the PF-ILD cohort.)
iii) Not applicable per Revised Protocol 03. Use of either pirfenidone and nintedanib 
within 4 weeks of Day 1. Neither pirfenidone nor nintedanib are allowed during this 
study for the PF-ILD cohort. See Section 7.7.1 for guidance in the OTE.
iv) A diagnosis of sarcoidosis or any systemic autoimmune disease (also known as 
“connective tissue disease”) other than rheumatoid arthritis (including but not limited 
to scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, and 
systemic vasculitis) as confirmed by the principal investigator. (Rheumatoid arthritis-
ILD is eligible for the PF-ILD cohort. Furthermore, participants that are considered as 
having “interstitial pneumonia with autoimmune features” are eligible for the PF-ILD 
cohort.)
e) Clinically significant (in the opinion of the investigator) non-parenchymal lung disease, 
(eg, asthma, chronic obstructive pulmonary disease, cavitary or pleural diseases) at 
screening. 
f)
Known significant pulmonary arterial hypertension (PAH) (ie, previous clinical or 
echocardiographic evidence of significant right heart failure, history of right heart 
catheterization showing a cardiac index < 2 L/min/m2, or PAH requiring combination of 
PAH-specific therapies or any PAH parenteral therapy).
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g) Emphysema ≥ 50% on HRCT assessed by a central reader, or the extent of emphysema is 
greater than the extent of fibrosis according to reported results from the most recent HRCT.
h) Acute IPF/ILD exacerbation within 6 weeks before or during screening, defined as an 
acute, clinically significant, respiratory deterioration characterized by evidence of new 
widespread alveolar abnormality, as follows:15
1. Acute worsening or development of dyspnea (< 1 month duration).
2. Imaging with new bilateral ground-glass opacity and/or consolidation superimposed on 
a background pattern consistent with fibrotic lung disease.
3. Respiratory deterioration not fully explained by cardiac failure or fluid overload.
i)
Not applicable per Revised Protocol 03. Clinically significant respiratory tract infection 
(in the opinion of the investigator) (eg, active tuberculosis, infectious pneumonia) within 
4 weeks prior to screening or during screening. 
j)
Significant cardiac disease (eg, hospitalization for congestive heart failure; myocardial 
infarction, unstable angina, coronary angioplasty or coronary artery bypass graft within 
6 months of screening) or uncontrolled atrial or ventricular cardiac arrhythmias.
k) Known presence of significant left-ventricular dysfunction (ie, echocardiography with 
ejection fraction of < 40%).
l)
History, within the last 2 years, of alcohol or frequent nonprescription drug abuse (in the 
opinion of the investigator), significant mental illness, or physical dependence on any 
opioid.
m) Positive urine test during screening for illegal drugs of abuse (with the exception of 
marijuana), unless these drugs are prescribed by the treating physician (prescription must 
be documented by the investigator or the designee in source documents).
n) Participants who have: 1) current malignancy or 2) a previous malignancy up to 5 years 
prior to screening are excluded except for those with a documented history of cured 
nonmetastatic squamous cell skin carcinoma, basal cell skin carcinoma, or cervical 
carcinoma in situ. Participants who have a biopsy that is suspicious for malignancy, and in 
whom the possibility of malignancy cannot be reasonably excluded following additional
clinical, laboratory or other diagnostic evaluations, are also excluded.
o) History of stroke or transient ischemic attack within 6 months prior to screening.
p) Not applicable per Protocol Amendment 04; refer to Exclusion Criterion 1)y. History 
of lung reduction surgery or transplant, or is awaiting lung transplant, or plans to undergo 
lung reduction surgery or transplant during the study.
q) Positive for hepatitis C antibody (unless documented hepatitis C virus RNA negative), 
positive hepatitis B surface antigen (HBsAg) or positive hepatitis B core antibody (HBcAb)
(unless documented hepatitis B virus DNA negative), human immunodeficiency virus 
(HIV)-1 antibody, or HIV-2 antibody.
r)
Cigarette smoking (including e-cigarettes) within 3 months before screening or unwilling 
to avoid smoking throughout the study.
s) Inability to tolerate oral medication.
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t)
Inability to be venipunctured and/or tolerate venous access.
u) Not applicable per Revised Protocol 03. Any other sound medical, psychiatric, and/or 
social reason as determined by the investigator.
v) Positive pregnancy test prior to Day 1 study treatment administration. 
w) Clinically significant respiratory tract infection (in the opinion of the investigator) (eg, 
active tuberculosis, infectious pneumonia) within 4 weeks prior to screening or during 
screening.  Additionally, in the case of prior SARS-CoV-2 infection, symptoms must have 
completely resolved and based on investigator assessment in consultation with the medical 
monitor or study director, there are no sequelae that would place the participant at a higher 
risk of receiving investigational treatment. 
x) Any other sound medical, psychiatric, and/or social reason as determined by the 
investigator. Additionally, in the case of prior SARS-CoV-2 infection, symptoms must 
have completely resolved and based on investigator assessment in consultation with the 
medical monitor or study director, there are no sequelae that would place the participant at 
a higher risk of receiving investigational treatment. 
y) History of lung reduction surgery or lung transplantation, or is on an active transplant list, 
or plans to undergo lung reduction surgery or lung transplantation during the study.
2) Prior Therapy
a) Use of systemic corticosteroids equivalent to prednisone > 15 mg/day within 2 weeks of 
Day 1. See Section 7.7.1 for guidance in the OTE.
b) Not applicable per Revised Protocol 03. Use of azathioprine, cyclophosphamide, 
cyclosporine, methotrexate, leflunomide, mycophenolate mofetil, mycophenolic acid, 
and/or tacrolimus within 4 weeks of Day 1. Additionally, use of rituximab or other specific 
B-cell depleting therapies within 6 months of Day 1. Disease modifying anti-rheumatic 
drugs (DMARDs), including but not limited to hydroxychloroquine, sulfasalazine, anti-
TNF alpha antagonists, interleukin antagonists, abatacept, tofacitinib, and baricitinib, will 
be permitted as long as these agents have been in place and stable for at least 6 months 
prior to screening (refer to Section 7.7). See Section 7.7.1 for guidance in the OTE. 
c) Use of potent inhibitors of OATPs, defined as inhibitors expected to increase exposures of 
OATP substrates by more than 2× within 4 weeks of Day 1 (see APPENDIX 5).
d) Use of potent inhibitors or inducers of cytochrome P450 CYP3A4 or CYP2C8 (see 
APPENDIX 6 and APPENDIX 7, respectively) within 4 weeks of Day 1.
e) Received experimental IPF or other experimental ILD therapy within 4 weeks before 
screening.
f)
Not applicable per Protocol Amendment 04; refer to Exclusion Criterion 2)i. Long-
acting phosphodiesterase 5 inhibitors (eg, tadalafil, vardenafil).  Daily use of short-acting 
phosphodiesterase 5 inhibitors (eg, sildenafil) taken as needed for erectile dysfunction is 
allowed during the study, but is not allowed within 7 days pre or post Day 1.  Short-acting 
phosphodiesterase 5 inhibitors taken daily for treatment of pulmonary arterial hypertension 
are not allowed during the study.  
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g) Simultaneous use of pirfenidone and nintedanib at screening.
h) Use of, cyclophosphamide, cyclosporine, methotrexate, and/or leflunomide within 4 weeks 
of Day 1. Additionally, use of rituximab or other specific B-cell depleting therapies within 
6 months of Day 1. Mycophenolate mofetil, mycophenolic acid, azathioprine or and/or 
tacrolimus are permitted only if the participant is on a stable dose at least 6 months prior 
to screening. These immunosuppressive medications cannot be initiated during the course 
of the main study. Disease modifying anti-rheumatic drugs (DMARDs), including but not 
limited to hydroxychloroquine, sulfasalazine, anti-TNF alpha antagonists, interleukin 
antagonists, abatacept, tofacitinib, and baricitinib, will be permitted as long as these agents 
have been in place and stable for at least 6 months prior to screening (refer to Section 7.7). 
See Section 7.7.1 for guidance in the OTE.
i)
Long-acting phosphodiesterase 5 inhibitors (eg, tadalafil, vardenafil) and chronic use of 
short-acting 
phosphodiesterase 
5 
inhibitors 
(eg, 
sildenafil). 
Short-acting 
phosphodiesterase 5 inhibitors taken as needed for erectile dysfunction is allowed during 
the study, but is not allowed within 7 days pre or post Day 1.
3) Physical and Laboratory Test Findings
a) Participants with a seated SBP of < 100 mmHg (confirmed by retest within 15 minutes) or 
seated DBP of < 60 mmHg (confirmed by retest within 15 minutes) at screening or prior 
to Day 1 study treatment will be excluded from participation in this study.
b) Not applicable per Revised Protocol 03. Participants with orthostatic intolerance, 
orthostatic hypotension or orthostatic tachycardia (as defined in Section 5.1.2.1) at 
screening or prior to Day 1 study treatment will be excluded from participation in this 
study.
c) Not applicable per Protocol Amendment 04; refer to Exclusion Criterion 3)i.
Uncontrolled hypertension, defined as SBP > 160 mmHg or DBP > 100mmHg at screening 
or prior to the first dose of study treatment. BP may be rechecked no more than twice as 
clinically indicated.
d) ALT or aspartate aminotransferase (AST) ≥2× the upper limit of normal (ULN) at 
screening. 
e) Estimated glomerular filtration rate < 30 mL/min at screening.
f)
Any of the following on ECG prior to study treatment administration, confirmed by repeat:
i)
Not applicable per Revised Protocol 03. PR 210 msec
ii) Not applicable per Revised Protocol 03. QRS 120 msec
iii) QT 500 msec
iv) QTcF 450 msec
g) Not applicable per Protocol Amendment 04; refer to Exclusion Criterion 3)j. Baseline 
total bilirubin > 1.5× ULN unless the participant has Gilbert’s syndrome. Participants with 
Gilbert’s syndrome must have total bilirubin between ≥1.5× ULN and ≤ 5× ULN, with 
direct bilirubin ≤ ULN and no clinical or laboratory evidence of hemolysis. 
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h) Participants with orthostatic intolerance, orthostatic hypotension (confirmed by retest 
within 15 minutes) or orthostatic tachycardia (confirmed by retest within 15 minutes) (refer 
to Section 5.1.2.1 for definitions) at screening or prior to Day 1 study treatment will be 
excluded from participation in this study. 
i)
Uncontrolled hypertension, defined as seated SBP > 180 mmHg or seated DBP 
> 100 mmHg at screening or prior to the first dose of study treatment. BP may be rechecked 
no more than twice as clinically indicated.
j)
Screening total bilirubin > 1.5× ULN unless the participant has Gilbert’s syndrome. 
Participants with Gilbert’s syndrome must have total bilirubin between ≥1.5× ULN and 
≤5× ULN, with direct bilirubin ≤ ULN and no clinical or laboratory evidence of hemolysis. 
k) Screening WBC < 2.5× 103, Hemoglobin < 9 g/dL, platelets < 75× 109/L
4) Other Exclusion Criteria
a) Prisoners or participants who are involuntarily incarcerated. 
b) Participants who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness.
c) Participants who lack capacity to consent for themselves.
5) Allergies and Adverse Drug Reaction
a) History of allergy to BMS-986278 or related compounds.
b) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
participants and that the results of the study can be used. It is imperative that participants fully 
meet all eligibility criteria.
6.3
Lifestyle Restrictions
Participants should not consume ≥7 units/week of alcohol during the study. One drink “unit” or 
1 standard drink is equivalent to 12 ounces of beer, 4 ounces of wine, or 1 ounce of hard liquor.
6.3.1
Meals and Dietary Restrictions
No restrictions are required, except for items specified in APPENDIX 6. However, fed/fasted 
status and time of morning meal (if fed) must be recorded at every visit, including intensive PK 
sample days. 
6.3.2
Activity
No restrictions are required.
6.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but who 
are not subsequently entered in the study/included in the analysis population. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure participants, 
to meet the Consolidated Standards of Reporting Trials publishing requirements, as applicable, 
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and to respond to queries from regulatory authorities. Minimal information includes date of 
consent, demography, screen failure details, eligibility criteria, and any serious AEs.
6.4.1
Retesting During Screening
The most current result prior to randomization is the value by which study inclusion will be 
assessed, as it represents the participant’s most current, clinical state.
Screening laboratory parameters and/or assessments that are included in Table 1 may be repeated 
in an effort to find all possible well-qualified participants. Consultation with the Medical Monitor 
may be needed to identify whether repeat testing of any particular parameter is clinically relevant.
Participants may be rescreened once according to the discretion of the investigator. Additional 
rescreening may be allowed after consultation with the Medical Monitor. For participants who are 
rescreened, HRCT does not need to be repeated if obtained within 10 weeks of randomization.
Participants who are included in the intensive PK substudy and/or PET-Tracer substudy will be 
consented for the substudies in addition to being consented to the main study.
7
TREATMENT
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, 
procedure(s), or medical device intended to be administered to a study participant according to the 
study protocol.
Study treatment includes investigational [medicinal] product (IP/IMP) as shown in Table 4.
An IP, also known as IMP in some regions, is defined as a pharmaceutical form of an active 
substance or placebo being tested or used as a reference in a clinical study, including products 
already with a marketing authorization but used or assembled (formulated or packaged) differently 
than the authorized form, or used for an unauthorized indication, or when used to gain further 
information about the authorized form.
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the SOC for a given diagnosis, may be considered as noninvestigational 
products.
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Table 4:
Study Treatments for Study IM027040
Product Description/
Class and Dosage 
Form
Potency
IP/Non-IP
Blinded or 
Unblinded
Packaging/
Appearance
Storage Conditions
(per label)
BMS-986278/oral 
tablets
10 mga
IP
Blinded
Film-coated 
oral tablet
Refer to the label on 
container 
Store in a tightly 
closed container
BMS-986278/oral 
tablets
30 mgb
IP
Blinded
Film-coated 
oral tablet
Refer to the label on 
container 
Store in a tightly 
closed container
Placebo oral tablets for 
10 mg BMS-986278
NA
IP
Blinded
Film-coated 
oral tablet
Refer to the label on 
container 
Store in a tightly 
closed container
Placebo oral tablets for 
30 mg BMS-986278
NA
IP
Blinded
Film-coated 
oral tablet
Refer to the label on 
container 
Store in a tightly 
closed container
BID = twice daily; IP = investigational product; NA = not applicable; non-IP = noninvestigational product; 
OTE = optional treatment extension
a Participants receiving 10 mg BMS-986278 BID in the OTE will be unblinded
b Participants receiving 30 mg or 60 mg BMS-986278 BID in the OTE will remain blinded until database lock for 
analyses of the 26-week main study
7.1
Treatments Administered
A double-blind design will be employed in the main study. Each participant will take 2 identical 
oral tablets in a blinded fashion every day in the morning and evening, as following:  

Placebo: 2 × placebo for 30 mg BMS-986278 tablets

30 mg dose: 1 × 30 mg BMS-986278 tablet and 1 × placebo for 30 mg tablet

60 mg dose: 2 × 30 mg BMS-986278 tablets
If participants receive reduced dose on Day 2 or beyond, they will take 1 tablet 
(10 mg BMS-986278 BID or matching placebo for 10 mg BMS-986278 BID) in a blinded fashion 
every day in the morning and evening for the rest of treatment.
Tablets should be taken orally (swallowed whole) with a full glass (240 mL) of water in the 
morning and in the evening approximately 12 hours after the morning dose every day for 26 weeks. 
On the days of study visits, participants will not self-administer morning doses; doses will be 
administered at the site. Doses at any dose reduction visit will also be administered at the site. 
Participants will be issued study medication kits/containers on Day 1, and at Weeks 4, 8, 12, 16 
and 20 (as shown in Table 1), and at any dose reduction study visit, containing sufficient treatment 
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to last until the next protocol-scheduled study visit. Participants should bring their study 
medication kits/containers with them to each study visit. If a participant has leftover treatment at 
the time of the next protocol-scheduled study visit, they should return it at the visit prior to 
receiving their next medication kit/container. If a participant has an unscheduled visit (except for 
dose reduction visits), study medication kits/containers do not need to be brought back to the site 
until the next protocol-scheduled visit. Starting at the Week 4 visit, any remaining study treatment 
will be returned to the site with every protocol-scheduled visit.
If a participant meets dose reduction criteria post-Day 1, the site must destroy the treatments 
previously assigned to the participant once IMP reconciliation has been performed, and contact 
IRT for new study medication kits/container on the dose reduction visit.
After completing the 26-week main study, participants that elect to continue in the OTE will take 
1 or 2 identical oral tablets every day in the morning and evening, as follows:   

30 mg dose: 1 × 30 mg BMS-986278 tablet and 1 × placebo for 30 mg tablet

60 mg dose: 2 × 30 mg BMS-986278 tablets

10 mg dose: 1 × 10 mg BMS-986278 tablet
Treatment administration in the OTE will follow the same directions as the main study (described 
above). Participants will be issued sufficient study medication kits/containers on Day 1, Week 4, 
Week 16, and at any dose reduction study visit (as shown in Table 2). Refer to the main study 
above for additional details on study medication kits/container instructions. 
7.2
Method of Treatment Assignment
Blinded treatment assignments will be managed using interactive response technology (IRT). Each 
cohort will be randomized to treatments independently in the IRT.  
Before the study is initiated, users at each investigative site will receive log-in information and 
directions on how to access the IRT system. At the time of the screening visit, immediately after 
informed consent is obtained and before any study-related procedures are performed, the 
investigative site will access the IRT system for assignment of a participant number for all 
participants, including participants not subsequently randomized or treated. The participant 
number is assigned sequentially by the system and will be unique across all sites. The participant 
number will not be used for any other participant. If a participant is rescreened, they will be given 
a new participant number.
Prior to the dosing on Day 1, participants who meet all criteria for enrollment at screening and 
Day 1 will be centrally randomized in a 1:1:1 ratio to BMS-986278 30 mg BID, BMS-986278 
60 mg BID, or placebo, determined by a computer-generated randomization schedule using the 
IRT. The randomization lists will be generated by the IRT vendor using a permuted block design 
within each combination of stratum level. For the IPF cohort, randomization will be stratified by 
country (non-Japan versus Japan). Participants will be further stratified according to concomitant 
use of approved IPF therapy (pirfenidone vs nintedanib vs none). For the PF-ILD cohort, 
randomization will be stratified by UIP pattern (present vs absent) of lung injury on either 
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centrally-read HRCT, surgical lung biopsy, or cryobiopsy. Approximately 75 of 120 participants 
(62.5%) are expected to have UIP pattern of lung injury. Stratification for the PF-ILD cohort will 
also be based on category of background therapy (immunosuppression alone [ie, azathioprine, 
mycophenolate mofetil, mycophenolic acid, and/or tacrolimus] versus anti-fibrotic [nintedanib, 
pirfenidone] versus none).
After randomization, a medication kit/container number will be assigned to the participant 
corresponding to the treatment assignment. At subsequent visits, when new treatment containers 
need to be provided, the investigative site will access the IRT to obtain the container number 
assigned to the participant.
All participants in the OTE will receive active treatment with BMS-986278. Participants that 
receive 30 mg BMS-986278 in the main study will continue on 30 mg BMS-986278 in the OTE 
and remain blinded to dose. Participants that receive 60 mg BMS-986278 in the main study will 
continue on 60 mg BMS-986278 in the OTE and remain blinded to dose. Participants that receive 
2 placebo tablets for 30 mg BMS-986278 in the main study will be randomized at a ratio of 1:1 to
receive either 30 mg BMS-986278 or 60 mg BMS-986278 and will be blinded to dose in the OTE.   
Participants that receive 10 mg BMS-986278 or placebo for 10 mg BMS-986278 in the main study 
will be assigned to receive 10 mg BMS-986278 and will be unblinded in the OTE.
Refer to Figure 3 for the OTE study design.
7.3
Blinding
7.3.1
Maintaining the Blind
BMS-986278 30 mg and placebo for 30 mg are identical in appearance. BMS-986278 10 mg and 
placebo for 10 mg are also identical in appearance. Investigative site staff, sponsor and designee 
personnel, participants and their families will remain blinded to treatment assignments until the 
time of the respective database lock for IPF and PF-ILD cohorts at Week 26 of main study, at 
which time the OTE phase will be unblinded for that cohort.
During the OTE, participants that complete the main study at reduced dose (10 mg BMS-986278 
or placebo for 10 mg BMS-986278) will be unblinded to treatment. 
7.3.2
Circumstances for Unblinding
Blinding of study treatment assignment is critical to the integrity of this clinical study. However, 
in the event of a medical emergency in an individual participant or pregnancy of the partner of a 
male participant in which knowledge of the IP is critical to the participant’s management, the blind 
for that participant may be broken by the investigator. The participant’s safety takes priority over 
any other considerations in determining if a treatment assignment should be unblinded.
Before breaking the blind of an individual participant’s treatment, the investigator should 
determine if the unblinded information is necessary (ie, that it will alter the participant's immediate 
management). In many cases, particularly when the emergency is clearly not related to the IP, or 
the problem may be properly managed by assuming that the participant is receiving the IP. It is 
highly desirable that the decision to unblind treatment assignment be discussed with the medical 
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monitor, but the investigator always has ultimate authority for the decision to unblind. The actual 
task of unblinding can be delegated by the investigator to a designee assigned the task on the 
Delegation of Authority. The Principal Investigator or appointed designee should only call in for 
emergency unblinding after the decision to unblind the participant has been documented.
In case of an emergency unblinding, the investigator(s) has unrestricted access to randomization 
information via the IRT system and is capable of breaking the blind through the IRT system 
without prior approval from the sponsor. Following the unblinding the investigator shall notify the 
medical monitor.
In cases of accidental unblinding, contact the medical monitor and ensure every attempt is made 
to minimize additional disclosure and the impact of unblinding.
Any request to unblind a participant for nonemergency purposes should be discussed with the 
medical monitor.
A scientist in the NonClinical Disposition and Bioanalysis department of BMS (and/or a designee 
in the external bioanalytical laboratory) will be unblinded to the randomized treatment assignments 
in order to minimize unnecessary bioanalytical analysis of samples. Any results shared by the 
NonClinical Disposition and Bioanalysis group with the Sponsor’s study team will be blinded to 
ensure integrity of the study.
7.4
Dosage Modification 
Day 1 study visit:
On Day 1, participants will not self-administer morning the dose; the dose will be administered at 
the site. Participants will remain at the site for at least 4 hours post dose. Orthostatic BP and HR 
will be performed predose and 1.5, 2, and 4 hours post dose. 
Participants will not receive the Day 1 evening dose if any of the defined low BP criteria are met 
(refer to Day 1 BP monitoring in Section 5.1.2.1 for details).
If either asymptomatic or symptomatic low BP criteria are met, participants will not receive the 
Day 1 evening dose and will remain at the site until:
a) The participant provides 2 consecutive seated BP measurements (at least 30 minutes apart) 
showing SBP > 85 mmHg and DBP > 55 mmHg
b) The participant does not demonstrate orthostatic hypotension 
c) Potential symptoms of decreased BP (as described above) have not been present for at least 
30 minutes
Participants will return to the site on Day 2 prior to receipt of the morning dose. 
Day 2 study visit:
On Day 2, participants will be issued new kits/containers. Participants will not self-administer the 
morning dose; the dose will be administered at the site.
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At the Day 2 visit, participants will receive a reduced dose. Those randomized to 30 mg or 60 mg 
BMS-986278 will have their medication kits/containers replaced with 10 mg BMS-986278. Those 
randomized to placebo will have their medication kits/containers replaced with the placebo for 
10 mg BMS-986278. These participants will continue on 10 mg BMS-986278 BID or matching 
placebo for 10 mg BMS-986278 BID. All instances of dose reduction are communicated by the 
site or vendor to the central study team.
On Day 2, participants will remain at the site for at least 4 hours post dose. Orthostatic BP and HR 
will be performed predose and 1.5, 2, and 4 hours post dose. Participants will be carefully 
monitored for symptoms associated with low BP. 
If either asymptomatic or symptomatic low BP criteria are met (refer to Day 1 BP monitoring in 
Section 5.1.2.1 for details), participants will be discontinued from study treatment (but continue in 
the study). All other participants will remain on reduced dose (10 mg BMS-986278 BID or 
matching placebo for 10 mg BMS-986278 BID). 
Post-Day 1 study visits:
At every post-Day 1 study visit, participants will not self-administer morning doses; doses will be 
administered at the site. Vital signs, including orthostatic assessments, will be performed at every 
post-Day 1 study visit. 
If either asymptomatic or symptomatic low BP criteria are met (refer to Day 1 BP monitoring in 
Section 5.1.2.1 for details), participants will remain at the site for at least 4 hours post dose. 
Orthostatic BP and HR will be performed 1.5, 2, and 4 hours after the low BP criteria at predose 
are detected. Participants will be carefully monitored for symptoms associated with low BP. If a 
decision is made to reduce to 10 mg BMS-986278 BID (or placebo for 10 mg BMS-986278 BID), 
the participant will return to the site the following day prior to receipt of the morning dose. Dose 
reduction should be appropriately noted in the case report form.
Dose modification criteria described above will apply to the OTE.
Dosage modifications for other reasons are otherwise not permitted.
7.5
Investigational Product Handling/Storage/Accountability
The IP should be stored in a secure area according to local regulations. It is the responsibility of 
the investigator, or designee where permitted, to ensure that IP is only dispensed to study 
participants. The IP must be dispensed only from official study sites by authorized personnel 
according to local regulations.
The product storage manager should ensure that the IP is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by BMS. If concerns 
regarding the quality or appearance of the IP arise, the IP should not be dispensed, and BMS must 
be contacted immediately.
Study intervention not supplied by BMS will be stored in accordance with the package insert.
IP documentation (whether supplied by BMS or not) must be maintained that includes all processes 
required to ensure drug is accurately administered. This includes documentation of drug storage, 
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administration and, as applicable, storage temperatures, reconstitution, and use of required 
processes (eg, required diluents, administration sets).

Further guidance and information for final disposition of unused study treatment are provided 
in APPENDIX 2.
7.5.1
Retained Samples for Bioavailability/Bioequivalence
Not applicable.
7.6
Treatment Compliance
At each protocol-scheduled visit from Day 29 (Week 4) to Week 26 (as shown in Table 1 for the 
main study and Table 2 for the OTE) and at the time of dose reduction or dose discontinuation (if 
applicable), treatment compliance will be evaluated for each participant by comparing the number 
of tablets taken by the participant with the number of tablets planned. Percentage compliance will 
be calculated as follows:
% compliance = (number of tablets taken ÷ number of tablets planned) × 100
If the estimated treatment compliance falls below 90%, the participant must be retrained at the site 
on study treatment administration. 
Participant Study Medication diaries will be used by participants to record study treatment 
administration. Dosing diaries that have been completed should be reviewed at each study visit.
7.7
Concomitant Therapy
For the PF-ILD cohort, mycophenolate mofetil, mycophenolic acid, azathioprine or and/or 
tacrolimus are permitted only if the participant is on a stable dose at least 6 months prior to 
screening. These immunosuppressive medications cannot be initiated during the course of the main 
study. 
Although pirfenidone or nintedanib are allowed during the main study for both cohorts, they are 
not allowed in combination with one another during the main study. 
Stable DMARDs used to manage synovitis in rheumatoid arthritis patients will be permitted, as 
long as these agents have been in place and stable for at least 6 months prior to screening. 
DMARDs include, but are not limited to, hydroxychloroquine, sulfasalazine, anti-TNF alpha 
antagonists, interleukin antagonists, abatacept, tofacitinib, and baricitinib. 
During the OTE, modifications and initiation of DMARD use are allowed per clinician discretion 
or patient preference.
7.7.1
Prohibited and/or Restricted Treatments
Prohibited and/or restricted medications during the study are as described in the study exclusion 
criteria in Section 6.2. Medications taken within 4 weeks prior to study treatment administration 
must be recorded on the electronic case report form (eCRF).
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Once a participant completes the 26-week main study, modifications to background treatment of 
lung fibrosis are allowed per clinician discretion or patient preference for those in either cohort 
during the OTE. As such, during the OTE, anti-fibrotic therapy (eg, pirfenidone or nintedanib) 
may be started or used in combination, and no restrictions are placed with regards to concomitant 
use of immunosuppressive medications or corticosteroids. However, all other concomitant 
medications specified in Section 6.2 #2) will continue to be restricted in the OTE. 
No concomitant prescribed medications are to be administered during study unless they are:
1) Prescribed for treatment of a clinical condition AND 
2) Not prohibited in the exclusion criteria or elsewhere in the protocol. 
All concomitant therapies (prescription, over the counter, or herbal) must be recorded on the eCRF.
7.8
Treatment After the End of the Study
Upon completion of either the main study or the OTE, treatment for IPF or PF-ILD will be at the 
discretion of the clinical provider. 
BMS reserves the right to terminate access to BMS-supplied study treatment if any of the following 
occur: a) the study is terminated due to safety concerns; b) the development of BMS-986278 is 
terminated for other reasons, including but not limited to lack of efficacy and/or not meeting the 
study objectives; c) the participant can obtain medication from a government sponsored or private 
health program. In all cases BMS will follow local regulations.
8
DISCONTINUATION CRITERIA
8.1
Discontinuation from Study Treatment
Participants MUST discontinue the IP for any of the following reasons:

Participant’s request to stop study treatment. Participants who request to discontinue study 
treatment will remain in the study and must continue to be followed for protocol-specified 
follow-up procedures. The only exception to this is when a participant specifically withdraws 
consent for any further contact with him/her or persons previously authorized by participant to 
provide this information.

For participants that were unable to receive the evening dose on Day 1 due to having met either 
asymptomatic or symptomatic low BP criteria and received a reduced dose of 
BMS-986278 10 mg BID (or placebo for 10 mg BMS-986278 BID) on Day 2, if either 
asymptomatic or symptomatic low BP criteria are met on Day 2 (refer to Day 1 BP monitoring 
in Section 5.1.2.1 for details), they will be discontinued from further treatment (but continue 
in the study). This also applies to the Day 1 and Day 2 visits in the OTE.

For participants receiving 10 mg BMS-986278 BID (or placebo for 10 mg BMS-986278 BID) 
after Day 2, if either asymptomatic or symptomatic low BP criteria are met (refer to Day 1 BP 
monitoring in Section 5.1.2.1 for details), they will be discontinued from further treatment (but 
continue in the study). This also applies to the OTE.  

For participants receiving 30 mg or 60 mg BMS-986278 (or placebo) after Day 1, if either 
asymptomatic or symptomatic low BP criteria are met (refer to Day 1 BP monitoring in 
Section 5.1.2.1 for details), a decision to reduce to 10 mg BMS-986278 BID (or placebo for 
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10 mg BMS-986278 BID) or discontinue study treatment (but continue in the study) will be 
discussed with the Medical Monitor/Study Director. This also applies to the OTE. 

Any clinical AE, laboratory abnormality or intercurrent illness which, in the opinion of the 
investigator, indicates that continued participation in the study is not in the best interest of the 
participant. 

This may include progression of the participant’s lung fibrosis. Decisions about 
discontinuing the IP due to progression of disease are left to the discretion of the clinical 
investigator. Similarly, following discontinuation from study treatment during either the
main study or the OTE, decisions regarding potential initiation of antifibrotic or 
immunosuppressive medications not allowed during the 26-week main study are left to the 
discretion of the investigator.

Termination of the study and/or program by BMS.

Noncompliance of the participant with protocol-mandated procedures based on the judgment 
and agreement of both the investigator and Sponsor. 

The participant becomes pregnant (study treatment must be discontinued immediately). In the 
case of pregnancy, refer to Section 9.2.6.

QTcF > 500 msec and/or changes in QTcF > 60 msec compared to baseline (confirmed on 
repeat ECG). Sites will inform the medical monitor of ECG values meeting discontinuation 
criteria.

For participants with normal Day 1 (Randomization) liver enzymes, total bilirubin, and 
international normalized ratio (INR), if there is new elevation of ALT or AST > 3× ULN, 
repeat testing should be performed within 48 to 72 hours. If elevation persists, then standard 
drug induced liver injury (DILI) discontinuation criteria (see Section 9.2.8) will be applied and 
study treatment will be discontinued if any of the following occur:

ALT or AST > 8× ULN

ALT or AST > 5× ULN for more than 2 weeks

ALT or AST > 3× ULN and (total bilirubin > 2× ULN or INR > 1.5)

ALT or AST > 3× ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%)
Note: If participant lives remotely to study site, a local laboratory may be used for repeat 
testing, and results should be promptly communicated to the site. Participants meeting the 
criteria above may have potential DILI (see Section 9.2.8 for additional details). 
For participants with elevated AST, ALT, or total bilirubin at Day 1 (Randomization), if 
there is a new elevation of ALT or AST > 2× baseline, or total bilirubin > 1.5× Day 1 total 
bilirubin (and to more than ULN), repeat testing should be performed within 48 to 72 hours. 
If elevation persists, then study treatment will be discontinued if any of the following occur:

ALT or AST levels increase to > 5× Day 1 (Randomization) measurement.

ALT or AST levels increase > 2× Day 1 (Randomization) measurements AND the increase 
is accompanied by a concomitant increase in total bilirubin to > 2× Day 1 bilirubin or the 
INR concomitantly increases by > 0.3.
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
Appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, 
rash, and/or eosinophilia (> 5%).
Note: If participant lives in a remote location, a local laboratory may be used for repeat 
testing, and results should be promptly communicated to the site. Participants meeting the 
criteria above may have potential DILI (see Section 9.2.8 for additional details).

Loss of ability to freely provide consent through imprisonment or involuntary incarceration for 
treatment of either a psychiatric or physical illness (eg, infectious disease). (Note: Under 
specific circumstances and only in countries where local regulations permit, a participant who 
has been imprisoned may be permitted to continue as a participant. Strict conditions apply, and 
BMS approval is required.)

Discretion of investigator.
Refer to the Schedule of Activities (Section 2) for data to be collected at the time of treatment 
discontinuation and follow-up and for any further evaluations that can be completed.
In the case of pregnancy, the investigator must immediately, within 24 hours of awareness of the 
pregnancy, notify the Medical Monitor/designee of this event. In most cases, the study treatment 
will be permanently discontinued in an appropriate manner (eg, dose tapering if necessary for 
participant safety). Refer to Section 9.2.6. 
All participants who discontinue study treatment should comply with protocol-specified follow-up 
procedures as outlined in the Schedule of Activities (Section 2). The only exception to this 
requirement is when a participant withdraws consent for all study procedures including 
posttreatment study follow-up or loses the ability to consent freely (ie, is imprisoned or 
involuntarily incarcerated for the treatment of either a psychiatric or physical illness).
If study treatment is discontinued prior to the participant’s completion of the study, the reason for 
the discontinuation must be documented in the source documents and entered on the appropriate 
eCRF page.
8.1.1
Posttreatment Follow-up
Posttreatment follow-up is of critical importance and is essential to preserving participant safety 
and the integrity of the study. Participants who discontinue study treatment must continue to be 
followed according to the protocol.
8.2
Discontinuation from the Study
Participants who request to discontinue study treatment will remain in the study and must continue 
to be followed for protocol-specified follow-up procedures. See the Schedule of Activities 
(Section 2) for details on the data to be collected at the time of treatment discontinuation and 
follow-up. The only exception to this is when a participant specifically withdraws consent for any 
further contact with him/her or persons previously authorized by participant to provide this 
information. 
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
Participants should notify the investigator of the decision to withdraw consent from future 
follow-up in writing, whenever possible.

The withdrawal of consent should be explained in detail in the medical records by the 
investigator, as to whether the withdrawal is from further treatment with study intervention 
only or also from study procedures and/or post-treatment study follow-up, and entered on the 
appropriate eCRF page.

In the event that vital status (whether the participant is alive or dead) is being measured, 
publicly available information should be used to determine vital status only as appropriately 
directed in accordance with local law.

If the participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 

Assessments for the end of treatment/end of study visit must be performed, provided that the 
participant has not withdrawn consent for these activities. 

All required eCRF pages must be completed, including the date of and explanation for the 
withdrawal. 

As indicated, appropriate follow-up and/or alternate medical care must be arranged for the 
participant. 
If a participant discontinues prematurely from the intensive PK substudy and/or the PET-Tracer 
substudy, they may still continue in the main study. If, however, a participant withdraws consent 
from the main study, they should also discontinue from the substudy.
8.2.1
Individual Discontinuation Criteria

A participant may withdraw completely from the study at any time at his/her own request, or 
may be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. This is expected to be uncommon. Stopping study 
intervention is not considered withdrawal from the study.

At the time of discontinuing from the study, if possible, an early termination visit should be 
conducted, as shown in the Schedule of Activities. See the Schedule of Activities for data to 
be collected at the time of study discontinuation and follow-up and for any further evaluations 
that need to be completed.

The participant will be permanently discontinued both from the study treatment and from the 
study at that time.

If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent.
8.3
Lost to Follow-Up

All reasonable efforts must be made to locate participants to determine and report their ongoing 
status. This includes follow-up with persons authorized by the participant.

Lost to follow-up is defined by the inability to reach the participant after a minimum of 
3 documented phone calls, faxes, or emails as well as lack of response by participant to one 
registered mail letter. All attempts should be documented in the participant’s medical records.
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
If it is determined that the participant has died, the site will use permissible local methods to 
obtain date and cause of death.

If investigator’s use of third-party representative to assist in the follow-up portion of the study 
has been included in the participant’s informed consent, then the investigator may use a 
sponsor retained third-party representative to assist site staff with obtaining participant’s 
contact information or other public vital status data necessary to complete the follow-up 
portion of the study. 

The site staff and representative will consult publicly available sources, such as public health 
registries and databases, in order to obtain updated contact information.

If after all attempts, the participant remains lost to follow-up, then the last known alive date as 
determined by the investigator should be reported and documented in the participant’s medical 
records.
9
STUDY ASSESSMENTS AND PROCEDURES
Study procedures and timing are summarized in the Schedule of Activities in Table 1 for the main 
study and in Table 2 for the OTE. 
Every effort must be made to ensure that the same evaluator(s) completes the assessment for each 
participant. If the evaluator(s) is unable to complete the evaluation, then a qualified individual with 
overlapping experience may perform the assessment. It is preferable that assessments be performed 
at approximately the same time of day throughout the duration of the study. Day 1 (Randomization) 
assessments must be performed per protocol (SOC assessments may not be used for baseline). 
Procedures not specified in the protocol that are part of standard care may be performed if they do 
not interfere with study procedures; any data arising from such procedures are not to be reported 
in the eCRF.
9.1
Efficacy Assessments
9.1.1
Forced Vital Capacity
Forced vital capacity (FVC) is the maximum amount of air a person can expel from the lungs after 
a maximum inhalation. Measurements are used to help diagnose lung disease and determine its 
severity and progression.
Pulmonary function, which includes FVC assessment, will be assessed through spirometry 
performed at the study center. Spirometry measures the volume of air that can be exhaled. For this 
assessment, the participant should be seated in a chair and asked to breath comfortably. A clip will 
be placed over the participant’s nose. The participant should seal their lips tightly over the 
spirometer tube, inhale as deeply as possible and exhale into the spirometer tube as forcefully as 
possible. The assessment should be performed according to the manual provided by the central 
vendor. 
The site-based spirometry will be provided to the site by a central vendor and will meet the criteria 
for acceptability and repeatability as defined in the ATS/ERS guidelines (Miller, et al.).20
All spirometry evaluations will be reviewed by a central reader.
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Timing of Spirometry:
The spirometry test is to be performed prior to the morning dose, preferably at approximately the 
same time (± 1 h) at every visit in which spirometry is performed. The spirometry test is permitted 
to be completed up to 3 days prior to the scheduled study visit.
Timing of Spirometry Versus Bronchodilator Use:
All spirometry evaluations should be performed prebronchodilator. Prebronchodilator spirometry 
is defined as spirometry testing performed for a participant who has: withheld their short-acting 
β-agonist (eg, albuterol) or anticholinergic (eg, ipratropium bromide) for > 6 h prior to the 
spirometry assessment AND withheld their long-acting bronchodilator (eg, salmeterol, formoterol) 
for > 12 h and other longer-acting agents (eg, indacaterol, tiotropium) for > 24 h prior to the 
spirometry assessment. If the participant is taking bronchodilators, the participant may use the 
bronchodilator after the spirometry but prior to HRCT.
Spirometry Parameters and Calculation of Predicted Values:
The following parameters will be measured as part of the spirometry assessment:

FEV1 (mL) and percent predicted forced expiratory volume in 1 second (ppFEV1)

FVC (mL) and ppFVC

FEV1/FVC ratio
The 2012 Global Lung Function Initiative Equations' will be used to estimate ppFVC (Quanjer, 
et al.).21
Additional details on the FVC assessment and ppFVC calculation are in the Study Manual.
9.1.2
Diffusing Capacity of Carbon Monoxide 
Diffusing capacity of carbon monoxide (DLCO) is a measurement of the extent to which oxygen 
passes from the alveoli into the blood. This test involves measuring the partial pressure difference 
between inspired and expired carbon monoxide. It relies on the strong affinity and large absorption 
capacity of red blood cells for carbon monoxide and thus demonstrates gas uptake by the capillaries 
that are less dependent on cardiac output.
The single-breath diffusing capacity test is the most common way to determine DLCO, and is the 
test employed in the current study. The test is performed by having the participant blow out all of 
the air that they can, leaving only the residual lung volume of gas. The participant then inhales a 
test gas mixture rapidly and completely, reaching the total lung capacity as nearly as possible. This 
test gas mixture contains a small amount of carbon monoxide (usually 0.3%) and a tracer gas 
(helium or methane) that is freely distributed throughout the alveolar space but which doesn't cross 
the alveolar-capillary membrane. The test gas is held in the lung for about 10 seconds during which 
time the carbon monoxide (but not the tracer gas) continuously moves from the alveoli into the 
blood. The participant then exhales into the analyzer tube. By analyzing the concentrations of 
carbon monoxide and inert gas in the inspired gas and in the exhaled gas, it is possible to calculate 
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single-breath diffusing capacity of carbon monoxide (DLCO SB). The DLCO test is permitted to 
be completed up to 3 days prior to the scheduled study visit. 
9.1.3
High-resolution Computed Tomography 
High-resolution computed tomography (HRCT) has become the most common and sensitive 
imaging method for diagnosing ILD, as it offers the most detailed images of the lungs.22 IPF is a 
specific form of chronic, progressive fibrotic interstitial pneumonia of unknown cause, limited to 
the lungs and associated with the histopathologic and/or radiologic pattern of UIP.23 The hallmark 
pathologic feature of UIP is a heterogeneous, variegated appearance with alternating areas of 
healthy lung, interstitial inflammation, fibrosis, and honeycomb change, while fibrosis 
predominates over inflammation. The characteristic HRCT manifestations of IPF consist of 
symmetric bilateral reticulation, architectural distortion, and honeycombing involving mainly the 
subpleural lung regions and lower lobes. As IPF progresses, honeycombing becomes more 
prominent.24
Although identification of UIP on surgical lung biopsy has been considered the gold standard for 
diagnosis,25 typical clinical and HRCT features may suffice for a confident diagnosis and eliminate 
the need for surgical lung biopsy.23, 26 Considering that some centers perform cryobiopsy and data 
suggest this technique compares favorably with histologic accuracy of surgical lung biopsy, UIP 
pattern identification via cryobiopsy will be considered on a case-by-case basis in this protocol.27
Accordingly, HRCT assessment has been adopted as an important diagnostic criterion in the 2018 
ATS/ERS/JRS/ALAT Clinical Practice Guidelines.28 Extent of reticulation and honeycombing on 
HRCT findings is considered an important independent predictor of mortality in patients with 
IPF.29 HRCT has been applied in multiple clinical studies of lung fibrosis for drug development, 
serving as an inclusion criterion,30, 31 a predictive marker of positive treatment response,32, 33, 34
and efficacy readout.35, 36
For the PF-ILD cohort, > 10% extent of fibrosis on screening thoracic HRCT is required.  
Participants will be stratified by UIP pattern (present vs absent) vs other fibrotic pattern. The target 
enrollment for UIP pattern (present vs absent) is expected at 75 out of 120 participants (62.5%). 
For the PF-ILD cohort, stratification will also be by category of background therapy 
(immunosuppression alone [ie, azathioprine, mycophenolate mofetil, mycophenolic acid, and/or 
tacrolimus] versus anti-fibrotic [nintedanib, pirfenidone] versus none).
A computer-assisted diagnosis (CAD) score to quantify lung fibrosis as the percentage 
involvement of reticulation patterns based on texture measures from HRCT has been developed 
and validated37, 38 as a measure of quantitative lung fibrosis (QLF) and a potential surrogate 
imaging marker. Computer-assisted diagnosis scores of QLF have been successfully applied as 
outcome measurements to test treatment efficacy in an ILD trial.35 Compared with visual 
assessments, CAD scores have been shown to improve objectivity, sensitivity, and repeatability 
when measuring quantitative changes in lung features.39, 40, 41
In this study, full-chest HRCT will be performed at qualified imaging centers per guidelines 
outlined in the Study Imaging Manual. HRCT will be performed on all study participants during 
the screening period and at Week 26. To ensure comparability, the same scan, equipment, method,
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and technique used during the baseline HRCT scan should be used for the follow-up HRCT scan 
(Week 26). For all participants, screening HRCT scans will be performed at total lung capacity 
and residual volume, with no contrast agent administration, reconstructed every 1 to 1.5 mm, using 
a low-dose protocol. At Week 26, HRCT will be performed at total lung capacity. Residual volume 
HRCT is optional at Week 26. For efficacy assessments, HRCT images of both during the 
screening period and follow-up scans (Week 26) will be analyzed by a centralized blinded reader. 
The HRCT analysis will focus on visual and CAD scores for regional lung fibrosis evaluation. 
Changes in the lung fibrosis scores from the screening period HRCT will be used to evaluate the 
treatment responses. The correlation of HRCT data to other efficacy readouts and biomarker data 
will be performed if applicable. Sites should be trained prior to scanning the first study participant. 
Detailed imaging procedures of HRCT will be defined in the Study Imaging Manual, and detailed 
image analysis procedures of HRCT will be defined in the Study Imaging Review Charter.
In addition to the screening and Week 26 scans in the main study, participants that enter the OTE 
will have HRCT performed at Week 26 of the OTE.  
9.1.4
Clinical Outcome Assessments 
The evaluation of clinical outcome assessments (COAs) is an increasingly important aspect of 
clinical efficacy in studies of treatments for IPF and other fibrotic ILDs that may present a 
progressing phenotype. Such data provide an understanding of the impact of treatment from the 
participant’s perspective and offer insights into patient experience that may not be captured 
through physician reporting. 
Participants will be asked to complete COA measures, including the Living with Pulmonary 
Fibrosis Questionnaire (L-PF), St. George’s Respiratory Questionnaire (SGRQ), University of 
California San Diego Shortness of Breath Questionnaire (UCSD SOBQ), a visual analog scale 
(VAS) measuring cough severity, patient global impression of lung fibrosis symptom severity 
(PGI-S), and perform the 6-Minute Walk Test (6MWT) at the Day 1, Week 12, and Week 26 visits. 
Additionally, all participants will be asked to perform an oxygen titration walk at screening and 
complete the patient global impression of lung fibrosis symptom severity change (PGI-C) at the 
Week 12 and Week 26 visits. COA measures other than the 6MWT (including oxygen titration 
walk) will be administered electronically, and the responses entered by trial participants into 
source records cannot be overridden by site staff or investigators. If possible, eCOAs should be 
administered using the electronic device prior to other study related procedures (except for the 
Day 1 visit where COAs should be administered after vital signs and ECG). Table 1 provides 
information regarding the timing of COAs during the study.  
The same COA measures will be administered in both study cohorts. Patients with IPF and those 
with PF-ILD experience worsened respiratory symptoms and fatigue, though the impact of 
symptoms on functioning and well-being may be more pronounced for the latter individuals.42, 43, 
44, 45 There have been few specific studies of the quality of life of patients with PF-ILD, and 
additional research is needed to assess the performance characteristics of existing COA measures 
in this population.42
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Participants in the OTE will be asked to complete the L-PF, PGI-S, and PGI-C at the Day 1 and 
Week 26 visits, and also perform the 6MWT at the Week 26 visit. Refer to Table 2.
9.1.4.1
Living with Pulmonary Fibrosis Questionnaire 
The Living with Pulmonary Fibrosis Questionnaire (L-PF) is a multidimensional measure of the 
health-related quality of life (HRQoL) of patients living with pulmonary fibrosis (PF). The L-PF 
was adapted from the Living with Idiopathic Pulmonary Fibrosis Questionnaire (L-IPF),46 which 
was in turn adapted from A Tool to Assess Quality of Life in IPF (ATAQ-IPF)47 based on input 
received though the Food and Drug Administration (FDA) Drug Development Tool (DDT) 
Qualification Process (DDT COA #000027). There are no material differences in the item content 
of the L-PF and L-IPF. The 2 measures differ only in regard to PF as being "idiopathic". 
The conceptual framework for the L-PF includes 4 domains: shortness of breath, cough, energy, 
and global. Items are divided between modules targeting symptoms (eg, coughing and dyspnea), 
measured using as 24-hour recall, and their impacts (eg, frustration, embarrassment, perceived 
inconvenience, diminished quality of life), measured using a 1-week recall. Additional items 
included in the symptoms module assess supplemental oxygen use. Validation of the psychometric 
properties of the L-PF is ongoing, though the instrument has been used in trials of treatments for 
patients with PF-ILD.5, 48
9.1.4.2
St. George’s Respiratory Questionnaire 
The St. George’s Respiratory Questionnaire (SGRQ) is a 50-item questionnaire developed to 
measure symptoms and health impairments in patients with airway obstruction.49, 50 The 
questionnaire includes 8 items assessing the frequency and severity of symptoms, while the 
remaining items assess activity limitations due to breathlessness, including reduced social 
functioning and psychological disturbances resulting from airway disease. The SGRQ is scored 
from 0 to 100 with higher scores indicating greater health impairment. In patients with IPF, 
clinically meaningful score changes have been estimated to range from 5 to 8 points.51 The 
questionnaire is widely used in studies of respiratory disease to assess disease symptoms, activities, 
and impacts and has been validated in IPF.51
9.1.4.3
University of California San Diego Shortness of Breath Questionnaire 
The University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) 
includes 21 items assessing the severity of shortness of breath experienced during activities of 
daily living.52, 53, 54, 55, 56 Three additional items assess limitations due to shortness of breath, fear 
of harm from overexertion, and fear of shortness of breath. Respondents who do not routinely 
perform an activity are requested to estimate the degree of shortness of breath anticipated. The 
SOBQ is scored by summing responses across all 24 items to generate a total score ranging from 
0 to 120 with higher scores indicating greater symptom severity. In patients with IPF, clinically 
meaningful score changes have been estimated to range from 5 to 11 points.55 The SOBQ has been 
widely used in IPF trials, and evidence exists for its content validity in IPF.56
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9.1.4.4
Cough Severity Visual Analog Scale 
A 100 mm visual analog scale (VAS) similar to that utilized in the INPULSIS-1 trial will be used 
to assess cough severity in the planned study. Participants will be asked to assess their cough by 
making a mark on a 100 mm line with 0 mm representing “no cough” and 100 mm representing 
“the worst imaginable cough.” 
9.1.4.5
Patient Global Impression of Lung Fibrosis Symptom Severity and 
Patient Global Impression of Lung Fibrosis Symptom Severity Change
Single items measuring patient global impression of lung fibrosis symptom severity (PGI-S) and 
patient global impression of lung fibrosis symptom severity change (PGI-C) will be administered 
in the study. The PGI-S will assess perceptions of the overall severity of lung fibrosis symptoms 
during the preceding 7 days with response options ranging from "none" to "very severe." The PGI-
C will assess perceptions of the overall change in symptom severity since before treatment with 
response options ranging from "much worse" to "much improved." Data collected via the PGI-S 
and PGI-C will be used as anchors in assessing the psychometric properties of other COA measures 
and deriving and interpreting thresholds for meaningful change.
9.1.4.6
6-Minute Walk Test 
The 6-Minute Walk Test (6MWT) is a submaximal exercise test used to assess aerobic capacity 
and endurance. Before starting the test, the participant should be informed that the objective is to 
walk as far as possible during 6 minutes. The test should be conducted on a hard, flat surface, such 
as located in a hallway. If the participant becomes breathless or exhausted, then he or she may 
slow down, stop, or rest as necessary. The participant may lean against a wall while resting but 
should resume walking as soon as able to do so. He or she should be informed of the time remaining 
after each minute elapses and 15 seconds prior to the test's conclusion. At the end of 6 minutes, 
the participant should be told to stop, and the distance traveled should be measured and recorded 
in the eCRF. In patients with IPF, the threshold for clinically meaningful change in 6MWT 
outcomes has been estimated to range from 24 to 45 meters.57, 58
If possible, the 6MWT should be administered after eCOAs. Additional details on the 6MWT 
assessment and related oxygen titration walk are provided in the Guidance Manual for Conducting 
a 6MWT.
9.2
Adverse Events
The definitions of an AE or SAE can be found in APPENDIX 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant's legally authorized representative). 
The investigator and any designees are responsible for detecting, documenting, and reporting 
events that meet the definition of an AE or SAE and remain responsible for following up AEs that 
are serious, considered related to the study treatment or the study, or that caused the participant to 
discontinue before completing the study. 
Refer to APPENDIX 3 for SAE reporting.
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9.2.1
Time Period and Frequency for Collecting AE and SAE Information
The collection of nonserious AE information should begin at initiation of study treatment until 
discharge, at the timepoints specified in the Schedule of Activities (Section 2). The Reference 
Safety Information in Appendix 1 of the Investigator’s Brochure should be used to determine the 
expectedness of SAEs for expedited reporting. 
All SAEs must be collected from the time of signing the consent, including those thought to be 
associated with protocol-specified procedures, and within 30 days of discontinuation of the study 
treatment or participant’s participation in the study if the last scheduled visit occurs at a later time. 
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study treatment or protocol-specified procedure (eg, a follow-up skin biopsy).

Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the appropriate section of the eCRF module.

All SAEs will be recorded and reported to sponsor or designee within 24 hours, as indicated in
APPENDIX 3. 

The investigator will submit any updated SAE data to the sponsor or designee within 24 hours 
of updated information being available.
Investigators are not obligated to actively seek AEs or SAEs in former study participants. 
However, if the investigator learns of any SAE, including a death, at any time after a participant 
has been discharged from the study, and he/she considers the event reasonably related to the study 
treatment or study participation, the investigator must promptly notify the sponsor.
The method of evaluating and assessing causality of AEs and SAEs and the procedures for 
completing and reporting/transmitting SAE reports are provided in APPENDIX 3.
9.2.2
Method of Detecting AEs and SAEs
AEs can be spontaneously reported or elicited during open-ended questioning, examination, or 
evaluation of a participant.  Care should be taken not to introduce bias when collecting AEs and/or 
SAEs. Inquiry about specific AEs should be guided by clinical judgement in the context of known 
AEs, when appropriate for the program or protocol.
9.2.3
Follow-up of AEs and SAEs

Nonserious AEs should be followed to resolution or stabilization or reported as SAEs if they 
become serious (see APPENDIX 3).

Follow-up is also required for nonserious AEs that cause interruption or discontinuation of 
study treatment and for those present at the end of study treatment as appropriate.

All identified nonserious AEs must be recorded and described on the nonserious AE page of 
the eCRF. Completion of supplemental eCRFs may be requested for AEs and/or laboratory 
abnormalities that are reported/identified during the course of the study.
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All SAEs will be followed until resolution, until the condition stabilizes, until the event is 
otherwise explained, or until the participant is lost to follow-up (as defined in Section 8.3).
Further information on follow-up procedures is given in APPENDIX 3.
9.2.4
Regulatory Reporting Requirements for SAEs

Prompt notification by the investigator to the sponsor of SAEs is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
product under clinical investigation are met.

An investigator who receives an investigator safety report describing SAEs or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will file it along with 
the Investigator’s Brochure and will notify the IRB/IEC, if appropriate according to local 
requirements.
The Sponsor or designee will be reporting AEs to regulatory authorities and ethics committees 
according to local applicable laws and regulations. A SUSAR (Suspected, Unexpected Serious 
Adverse Reaction) is a subset of SAEs and will be reported to the appropriate regulatory authorities 
and investigators following local and global guidelines and requirements.
9.2.5
AEs of Special Interest
AEs of special interest (AESIs) are AEs for a particular product or class of products that a Sponsor 
may wish to monitor carefully. AESIs may be serious or nonserious. Such events may require 
further investigation to better characterize and understand them. In the BMS-986278 clinical 
development program, certain asymptomatic and symptomatic BP-related AEs are defined as 
AESIs; however, there has been no definitive assessment on the causal relationship between these 
events and treatment with BMS-986278. Additional information about asymptomatic and 
symptomatic BP-related AEs will be collected on the case report form in order to better 
characterize and understand them.
Symptomatic Decreased Blood Pressure AESI
Includes events associated with the following symptoms: confusion, lightheadedness, dizziness, 
palpitations, falls, tremulousness, generalized weakness, blurred vision, exercise intolerance (if 
different from baseline), fatigue upon standing (if different from baseline), angina, transient 
ischemic attack, pre-syncope, or syncope. 
Clinical Evaluation of Hypotension AESI
Includes any of the events meeting any of the asymptomatic or symptomatic low BP criteria.
Asymptomatic low BP criteria:

Seated SBP < 85 mmHg (confirmed by retest within 15 minutes)

Seated DBP < 55 mmHg (confirmed by retest within 15 minutes)

Orthostatic hypotension (defined as a drop in SBP of ≥ 20 mmHg or DBP of ≥ 10 mmHg with 
assumption of an upright posture from either supine or seated to upright position16) (confirmed 
by retest within 15 minutes) 
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Symptomatic low BP criteria:
a) The participant is experiencing symptoms that, in the opinion of the investigator, could be 
associated with low BP (eg, confusion, lightheadedness, dizziness, palpitations, falls, 
tremulousness, generalized weakness, blurred vision, exercise intolerance [if different from 
baseline], fatigue upon standing [if different from baseline], angina, transient ischemic 
attack, pre-syncope, or syncope) AND at least one of the following BP thresholds: 
i. Seated SBP < 100 mmHg (confirmed by retest within 15 minutes) or seated DPB 
< 60 mmHg (confirmed by retest within 15 minutes) 
ii. Decrease of seated SBP of ≥ 20 mmHg (confirmed by retest within 15 minutes) from 
previous visit or decrease of seated DBP of ≥ 10 mmHg (confirmed by retest within 15 
minutes) from previous visit
iii. Orthostatic hypotension (defined as a drop in SBP of ≥ 20 mmHg or DBP of ≥ 10 mmHg 
with assumption of an upright posture from either supine or seated to upright position16) 
(confirmed by retest within 15 minutes)
iv. Orthostatic tachycardia (defined as a sustained increase in HR of ≥ 30 bpm within 
approximately 10 minutes of moving from a recumbent to a quiet [nonexertional] 
standing position; defined as the difference in HR from either supine or seated to upright 
position16) (confirmed by retest within 15 minutes)
9.2.6
Pregnancy
If, following initiation of the study treatment, it is subsequently discovered that a participant is 
pregnant or may have been pregnant at the time of study exposure, including during at least 
5 half-lives after product administration, the investigator must immediately notify the BMS 
Medical Monitor/designee of this event and complete and forward a Pregnancy Surveillance Form 
to the BMS designee within 24 hours of awareness of the event and in accordance with SAE 
reporting procedures described in APPENDIX 3.
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
participant.
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
the Sponsor or designee. In order for the Sponsor or designee to collect any pregnancy surveillance 
information from the female partner, the female partner must sign an ICF for disclosure of this 
information. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
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9.2.7
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the AE eCRF page or 
SAE eCRF, as appropriate. Paper forms are only intended as a back-up option when the electronic 
system is not functioning.

Any laboratory test result that is clinically significant or meets the definition of an AE or SAE 

Any laboratory test result abnormality that required the participant to have study treatment 
discontinued or interrupted

Any laboratory test result abnormality that required the participant to receive specific 
corrective therapy
It is expected that wherever possible, the clinical rather than laboratory term would be used by the 
reporting investigator (eg, anemia versus low hemoglobin value).
9.2.8
Potential Drug Induced Liver Injury (DILI)
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. All occurrences of potential DILIs, meeting 
the defined criteria, must be reported as SAEs (see Section 9.2 and APPENDIX 3 for reporting 
details). 
Potential DILI is defined as:
1) Treatment-emergent ALT or AST > 3× ULN (> 2× baseline AND > 3× ULN for participants 
with baseline elevation),
AND
2) Total bilirubin > 2× ULN (> 2× baseline AND > 2× ULN for participants with baseline
elevation) or clinical jaundice, without initial findings of cholestasis (elevated serum
alkaline phosphatase),
AND
3) No other immediately apparent possible causes of elevated liver
enzymes and 
hyperbilirubinemia, including, but not limited to, viral hepatitis, preexisting chronic or acute 
liver disease, or the administration of other drug(s) known to be hepatotoxic.
9.2.9
Other Safety Considerations
Any significant worsening of conditions noted during interim or final physical examinations, ECG, 
x-ray filming, or any other potential safety assessment required or not required by protocol should 
also be recorded as a nonserious AE or an SAE, as appropriate, and reported accordingly.
To collect information around the impact of COVID-19 on this study, COVID-19–related 
AEs/SAEs, changes in study visit schedules, missing study visits, study drug modification/ 
discontinuation, study discontinuation, etc, will be captured in the CRF.
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9.3
Overdose
For this study, any dose of BMS-986278 greater than 180 mg within a 24-hour time period 
(± 4 hours) will be considered an overdose. Overdoses that meet the regulatory definition of SAE 
will be reported as an SAE (see APPENDIX 3).
In the event of an overdose the investigator should:
1) Contact the medical monitor immediately.
2) Closely monitor the participant for AEs/SAEs and laboratory abnormalities until [study 
treatment] can no longer be detected systemically (at least 3 days).
3) Obtain a plasma sample for PK analysis within 3 days from the date of the last dose of study 
treatment if requested by the medical monitor (determined on a case-by-case basis).
4) Document the quantity of the excess dose as well as the duration of the overdosing in the eCRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
9.4
Safety
Planned timepoints for all safety assessments are listed in the Schedule of Activities (Section 2). 
All urgent safety concerns must be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue treatment.
The safety of BMS-986278 will be assessed by evaluation of the incidence of all AEs and SAEs, 
physical examinations, vital signs, laboratory data, ECG monitoring, and biomarkers.
9.4.1
Physical Examinations and Physical Measurements
Schedules for physical examinations are provided in Schedule of Activities (Section 2). Physical 
examinations may be performed by a Doctor of Medicine (MD) or equivalent, or someone who is 
authorized to perform the examinations by training and has been delegated this task by the 
principal investigator. 
Physical examinations will be performed at the timepoints indicated in the Schedule of Activities 
for the main study (Table 1) and for the OTE (Table 2).
Every effort should be made to ensure the same evaluator will complete the examination for each 
participant at all visits throughout the study. Documentation of who performed the examination is 
to be recorded in source notes.
Schedules for physical measurements are provided in Schedule of Activities (Section 2).
9.4.2
Vital Signs
Predose vital signs will be collected at the timepoints provided in Schedule of Activities 
for the main study (Table 1) and for the OTE (Table 2), and will include body temperature, 
respiration rate, and orthostatic BP and HR. 
During visits when orthostatic BP and HR are required (refer to Section 5.1.2.1), body temperature 
and respiration rate will only be required predose. 
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During orthostatic assessments, participants will be monitored for orthostatic intolerance, 
orthostatic hypotension, and orthostatic tachycardia, as defined in Section 5.1.2.1. 
Additional serial BP and HR measurements will be collected as part of the intensive PK substudy 
in the main study, as shown in Table 7.
BP monitoring on Days 1 and 2 and for all subsequent study visits is described in Section 5.1.2.1.
Details for BP measurements and orthostatic assessments will be provided.
Participants who are discontinued from study treatment do not require BP monitoring and 
orthostatic assessments, as described in Section 5.1.2.1. Vital signs will be collected per the 
Schedule of Activities (Section 2).  
9.4.3
Electrocardiograms
ECGs will be performed before study treatment administration (except at Week 26) at the 
timepoints specified in Table 1 for the main study and in Table 2 for the OTE. All ECGs must be 
performed prior to bronchodilator administration OR at least 20 hours after bronchodilator 
administration. Additional ECG collections post dose will be conducted as part of the intensive 
PK substudy in the main study (see Table 7). Additional ECG assessments must be conducted any 
time during the main study and the OTE if clinically indicated.
9.4.4
Clinical Safety Laboratory Assessments
Investigators must document their review of each laboratory safety report. A central laboratory 
will perform the analyses and will provide reference ranges for these tests. Local laboratory testing 
may be permitted for repeats or as per Medical Monitor approval when central laboratory testing 
cannot be performed.
Hematology, serum chemistry and urinalysis assessments are listed in Table 5.
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Table 5:
Laboratory Assessments
Hematology
Complete blood count (including differential)
Prothrombin time
Partial thromboplastin time
International normalized ratio
White blood cell (absolute) 
Hemoglobin
Hematocrit
Mean corpuscular volume
Mean corpuscular hemoglobin concentration
Red cell distribution width 
Platelet count
Chemistry
Aspartate aminotransferase
Alanine aminotransferase
Total bilirubin
Direct bilirubin
Alkaline phosphatase
Lactate dehydrogenase
Creatinine
Blood urea nitrogen 
Uric acid 
Glucose 
Estimated glomerular filtration rate (screening 
only)
Total protein
Albumin
Sodium
Potassium
Chloride
Calcium
Phosphorus
Magnesium
Creatine kinase
Urinalysis
pH
Specific gravity
Protein
Glucose
Ketones 
Leukocyte esterase
Nitrite
Creatinine
Microscopic examination (only to follow-up 
abnormal findings)
Serology (screening only)
Hepatitis C antibody or RNA
Hepatitis B surface antigen and core antibody. Hepatitis B virus (HBV) DNA test can be 
performed directly in participants with suspected positive Hepatitis B surface antigen and core 
antibody in participating countries with high HBV prevalence.
Human immunodeficiency virus (HIV)-1 antibody
HIV-2 antibody
Hepatitis C RNA will be performed in hepatitis C antibody-positive participants. Hepatitis B 
surface antigen (HBsAg)-positive participants or hepatitis B core antibody (HBcAb)-positive 
participants will be tested for hepatitis B virus (HBV) DNA. 
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Table 5:
Laboratory Assessments
Other Analyses
Test for drugs of abuse (screening): Amphetamines, Barbiturates, Benzodiazepines, 
Phencyclidine, Cocaine, Opiates, Ethanol (per local regulations).
Follicle-stimulating hormone (FSH) (screening only for postmenopausal women < 55 years of 
age). 
Urine pregnancy test prior to Day 1 dosing and if pregnancy is suspected at any time throughout 
the study (women < 55 years of age); performed locally.
9.5
Pharmacokinetics
The PK of BMS-986278 and inactive major metabolite BMT-323719 will be derived from plasma 
concentration vs time data. 
The plasma samples will be analyzed for BMS-986278 by a validated assay and BMT-323719 by 
a qualified assay. PK samples collected from participants who received placebo will not be 
analyzed.
In addition, plasma samples will be archived for potential analysis of other metabolite(s) if the 
need arises and to the extent possible.
Detailed instructions for the PK blood collection, labeling, processing, storage, and shipping will 
be provided to the site in the procedure manual. Participants will receive a document to record the 
date and exact clock time of the morning and evening doses of study treatment taken on the day 
prior to the Week 4, Week 12, and Week 26 study visits for the main study, and on the day prior 
to the Week 4 and Week 26 study visits for the OTE. In the main study, if the participant is taking 
nintedanib or pirfenidone, he/she will also be asked to record the last dosing date and exact clock 
time of nintedanib or pirfenidone taken prior to sample collection.
9.5.1
Sparse PK Sampling (All Participants not Participating in PK Substudy)
All participants will have PK samples collected before the first administration of study treatment
on Day 1. PK samples will also be collected at approximately 1.5 and 4 hours after the first 
administration of study treatment on Day 1, before the morning administration of study treatment
at Week 4 and Week 12, and up to 5 days after the last study treatment administration at the 
Week 26 visit (see Table 6). Fed/fasted status and time of morning meal (if fed) must be recorded 
at each visit.
In addition to assessing concentrations of BMS-986278 and the BMT-323719 metabolite, 
additional PK samples will be collected predose on Day 1 and at Week 12 and will be used to 
analyze for concentrations of pirfenidone or nintedanib by validated assays in participants that 
receive these medications.
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Table 6:
Sparse PK Sampling Schedule for IPF and PF-ILD Cohorts
Study Day of Sample 
Collection
Event
Time Relative to 
BMS-986278 
Dose 
(hr:min)a
BMS-986278 and 
BMT-323719 
Metabolite PK 
Plasma Sampleb
Concomitant 
Medication PK 
Plasma 
Samplesc
Day 1
Predosea
0:00
X
X
1:30
X
4:00
X
Day 29 Week 4 (± 3 days)
Predosea
0:00
X
Day 85 Week 12 (± 5 days)
Predosea
0:00
X
X
Day 183 Week 26 (+ 5 days) 
Day after last 
dose
X
Early treatment discontinuation
(if applicable)d
Day of treatment 
discontinuation
X
IPF = idiopathic pulmonary fibrosis; PF-ILD = progressive fibrotic interstitial lung disease; PK = pharmacokinetic
a Actual PK sampling times will be recorded. Samples should be collected as close as possible to the scheduled time.
b One PK sample will be collected at each timepoint and analyzed for BMS-986278 and BMT-323719. The date and 
time of the morning and evening doses of study medication taken prior to the study visit must be recorded at the 
Week 4, Week 12, and Week 26 study visits.
c Participants who are on pirfenidone or nintedanib therapy will have an additional plasma sample collected for that 
specific concomitant medication. The last dosing date and time of the concomitant medication taken prior to the 
concomitant PK sample collection must be recorded. 
d No further samples should be taken at subsequent visits.
9.5.2
Intensive PK Substudy
An intensive PK substudy will be conducted in approximately 10 participants per treatment arm 
in both the IPF and PF-ILD cohorts, for which serial PK samples, ECGs, and BP and HR 
measurements will be collected (see details in Table 7 and further below).  
Table 7:
PK Sampling, ECG, BP, and HR Schedule for Intensive PK 
Substudy (IPF and PF-ILD Cohorts)
Study Day of 
Sample 
Collection
Event
Time 
Relative to  
BMS-986278 
Dose 
(hr:min)a
BMS-986278 
and 
BMT-323719 
Metabolite 
PK Plasma 
Sampleb
Concomitant 
Medication 
PK Plasma 
Samplec
ECG
Blood 
Pressure 
and Heart 
Rated
Day 1
Predosea
0:00
X
X
X
X
1:30
X
X
X
2:00
X
X
4:00
X
X
6:00
X
X
X
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Table 7:
PK Sampling, ECG, BP, and HR Schedule for Intensive PK 
Substudy (IPF and PF-ILD Cohorts)
Study Day of 
Sample 
Collection
Event
Time 
Relative to  
BMS-986278 
Dose 
(hr:min)a
BMS-986278 
and 
BMT-323719 
Metabolite 
PK Plasma 
Sampleb
Concomitant 
Medication 
PK Plasma 
Samplec
ECG
Blood 
Pressure 
and Heart 
Rated
8:00
X
X
Day 29 Week 4 
(± 3 days)
Predosea
0:00
X
X
X
X
1:30
X
X
X
2:00
X
X
4:00
X
X
6:00
X
X
X
8:00
X
X
Day 85 Week 
12 (± 5 days)
Predosea
0:00
X
X
X
X
1:30
X
X
X
Day 183 Week 
26 (+ 5 days) 
Day after last 
dose
X
X
X
Early treatment 
discontinuation
(if applicable)e  
Day of 
treatment 
discontinuation
X
X
X
BP = blood pressure; ECG = electrocardiogram; HR = heart rate; IPF = idiopathic pulmonary fibrosis; PK = pharmacokinetic
a Actual PK sampling times will be recorded. Samples should be collected as close as possible to the scheduled time.
b One PK sample will be collected at each timepoint  and analyzed for BMS-986278 and BMT-323719. The date and 
time of the morning and evening doses of study medication taken prior to the study visit must be recorded at the 
Week 4, Week 12, and Week 26 study visits. 
c Participants who are on pirfenidone or nintedanib therapy will have an additional plasma sample collected for that 
specific concomitant medication. The last dosing date and time of the concomitant medication taken prior to the 
concomitant PK sample collection must be recorded.
d Refer to vendor manual.
e No further samples should be taken at subsequent visits.
Fed/fasted status and time of morning meal (if fed) must be recorded at each visit.
In addition to assessing concentrations of BMS-986278 and the BMT-323719 metabolite, 
additional PK samples will be collected predose on Day 1, Week 4, and Week 12 and will be used 
to analyze for concentrations of pirfenidone or nintedanib by validated assays in participants that 
receive these medications.
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Key PK parameters to be assessed in the intensive PK sampling study include:
Cmax
Maximum observed plasma concentration (Day 1 and Week 4)
Tmax
Time of maximum observed plasma concentration (Day 1 and Week 4)
AUC(0-8)
Area under the plasma concentration-time curve from time zero to 8 
hours post dose (Day 1 and Week 4)
Ctrough
Trough observed plasma concentration (Week 4 and Week 12)
Individual participant PK parameter values will be derived by noncompartmental methods by a 
validated PK analysis program. Actual times will be used for the analyses.
Concentration data from this study may be combined with data from the Phase 1 studies in healthy 
subjects to further characterize the PK of BMS-986278 using population PK analysis. The 
relationship between measures of exposure and endpoints for efficacy and safety may also be 
explored using model-based exposure-response analysis. Results of these analyses will be reported 
separately.
9.5.3
Sparse PK Sampling for Optional Treatment Extension
All participants in the OTE will have PK samples collected before the first administration of study 
treatment on Day 1. PK samples will also be collected at approximately 1.5 and 4 hours after the 
first administration of study treatment on Day 1, before the morning administration of study 
treatment at Week 4, and up to 5 days after the last study treatment administration at the Week 26 
visit (see Table 8). Fed/fasted status and time of morning meal (if fed) must be recorded at each 
visit.
Table 8:
PK Sampling Schedule for the OTE
Study Day of Sample Collection
Event
Time Relative to 
BMS-986278 Dose 
(hr:min)a
BMS-986278 and 
BMT-323719 Metabolite 
PK Plasma Sampleb
OTE Day 1
Predosea
0:00
X
1:30
X
4:00
X
OTE Day 29 Week 4 (± 3 days)
Predosea
0:00
X
OTE Day 183 Week 26 (+ 5 days)
Day after last dose
X
OTE Early treatment 
discontinuation (if applicable)c
Day of treatment 
discontinuation
X
OTE = optional treatment extension; PK = pharmacokinetic
a Actual PK sampling times will be recorded. Samples should be collected as close as possible to the scheduled time.
b One PK sample will be collected at each timepoint and analyzed for BMS-986278 and BMT-323719. The date and 
time of the morning and evening doses of study medication taken prior to the study visit must be recorded at the 
OTE Week 4 and OTE Week 26 study visits
c No further samples should be taken at subsequent visits.
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PK concentrations of BMS-986278 and BMT-323719 will be listed and summarized by treatment.
9.6
Biomarkers
Blood-based biomarkers of disease activity will be evaluated to support pharmacodynamic effects, 
dose selection, mechanism of action, demonstration of impact on disease, and treatment response 
prediction. Blood, plasma, and serum will be collected at the times indicated in Table 9 for the 
measurement of soluble factors and blood cell phenotypes, characterization of gene expression 
profiles, and analysis of DNA single nucleotide polymorphisms (SNPs).
Soluble factors related to IPF may include but will not be limited to the lung injury biomarkers 
MMP-7 and SP-D; fibrosis biomarkers TIMP-1, OPN, periostin, decorin, and tenascin-C; and 
inflammation biomarkers CXCL13, CCL18, YKL-40, EN-RAGE, eotaxin, and adiponectin. 
Biomarkers of tissue collagen turnover that have been associated with IPF disease progression may 
include but will not be limited to the collagen neoepitopes C3M, C6M, PRO-C3, and PRO-C6. In 
addition, plasma LPA concentrations will be measured.
Additionally, since some leukocytes play a significant role in fibrotic processes, and have been 
associated with IPF disease progression, flow cytometric analyses for changes in leukocytes 
subsets (eg, monocytes, T cells, and B cells) will be evaluated. Blood cell gene expression (mRNA) 
analyses may also be explored. In all participants, predose samples for biomarkers will include 
blood and serum, collected at baseline, Week 4, Week 12, and Week 26 of the main study, and 
also at Week 26 of the OTE.
Additionally, blood samples for DNA SNP analysis will be collected for exploratory analysis of 
genes previously associated with IPF and/or familial pulmonary fibrosis, possibly including but 
not limited to variants in surfactant proteins (SFTPA2, SFTPC), telomerase (TERT, TERC), toll 
interacting protein (TOLLIP), and mucin 5B (MUC5B). Since BMS-986278 is a weak inhibitor of 
OATP1B, DNA SNP analysis in absorption, distribution, metabolism, and excretion genes will 
also be analyzed.  Blood samples for DNA will be drawn on Day 1, as indicated in Table 1, from 
all participants. 
As indicated in Table 9, serum will be collected for possible assessments of SARS-CoV-2 
serologic status (anti-SARS-CoV-2 IgG or total antibody) at baseline, at the end of the main study, 
and at the end of the OTE. SARS-CoV-2 serology will also be performed approximately 4 weeks 
after a documented or suspected SARS-CoV-2 infection.
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Table 9:
Biomarker Sampling Schedule for All Participants 
Study Day of 
Sample 
Collectiona
Whole 
Blood for 
Genotyping
Whole 
Blood for 
Gene 
Expression 
Analysis
Whole 
Blood for 
Flow 
Cytometry
Serum 
Exploratory 
Biomarkers
Plasma 
Exploratory 
Biomarkersb
Plasma LPA 
Quantificationb
SARS-
CoV-2 
Serology 
(IgG or 
Total)c
Day 1 
(Predose)
X
X
X
X
X
X
X
Day 29 Wk 4 
(± 3 days)
X
X
X
X
X
Day 85 Wk 12 
(± 5 days)
X
X
X
Day 183 Wk 26 
(+ 5 days)
X
X
X
X
X
X
OTE Day 183 
Wk 26 
(+ 5 days)
X
X
X
X
Day of early 
treatment 
discontinuation 
(if applicable)d
X
X
X
LPA = lysophosphatidic acid; Wk = Week
a All samples are to be collected prior to the first dose of study treatment on Day 1 and before the morning dose of 
study treatment on the day of the other indicated visits. 
b Samples are aliquots of a single blood collection at each visit.
c Also to be collected approximately 4 weeks after a documented or suspected SARS-CoV-2 infection, for potential 
future assessment of anti-SARS-CoV-2 total or IgG, per national and local requirements.
d No further samples should be taken at subsequent visits.
9.6.1
Additional Research Collection
This protocol will include residual sample storage for additional research (AR).
For All US sites:
AR is required for all study participants, or academic/institutional requirements. Where one or 
more of these exceptions occurs, participation in the AR should be encouraged but will not be a 
condition of overall study participation. 

If the IRB/ethics committees and site agree to the mandatory AR retention and/or collection, 
then the study participant must agree to the mandatory AR as a requirement for inclusion in 
the study.

If optional participation is permitted and approved, then the study participants may opt out of 
the AR retention and/or collection.
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For Non-US Sites
AR is optional for all study participants, except where retention and/or collection is prohibited by 
local laws or regulations, ethics committees, or institutional requirements. 
AR is intended to expand the translational R&D capability at BMS and will support as yet 
undefined research aims that will advance our understanding of disease and options for treatment. 
It may also be used to support health authority requests for analysis, and advancement of 
pharmacodiagnostic development to better target drugs to the right patients. This may also include 
genetic/genomic exploration aimed at exploring disease pathways, progression, and response to 
treatment, etc. 
Sample Collection and Storage
All requests for access to samples or data for AR will be vetted through a diverse committee of the 
study sponsor’s senior leaders in Research and Development (or designee) to ensure the research 
supports appropriate and well-defined scientific research activities.

Residual samples from PK collections (see Table 6, Table 7, and Table 8) and biomarkers (see 
Section 9.6) will also be retained for AR purposes.
Samples kept for future research will be stored at the BMS Biorepository in 
 or 
an independent, BMS-approved storage vendor.
The manager of these samples will ensure they are properly used throughout their usable life and 
will destroy the samples at the end of the scheduled storage period, no longer than fifteen (15) 
years after the end of the study or the maximum allowed by applicable law.
Transfers of samples by research sponsor to third parties will be subject to the recipient’s 
agreement to establish similar storage procedures.
Samples will be stored in a coded fashion, and no researcher will have access to the key. The key 
is securely held by the investigator at the clinical site, so there is no direct ability for a researcher 
to connect a sample to a specific individual.
Further details of sample collection and processing will be provided to the site in the procedure 
manual.
9.7
Health Economics OR Medical Resource Utilization and Health 
Economics
Health Economics/Medical Resource Utilization and Health Economics parameters will not be 
evaluated in this study.
10
STATISTICAL CONSIDERATIONS
10.1
Sample Size Determination
In determining the sample size for the IPF cohort, both statistical considerations and clinical 
feasibility criteria were utilized. Among the considerations were:
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Sizing of published early phase trials in IPF. 

Precision to estimate the difference of the 30 mg BID and 60 mg BID doses to placebo on the 
primary efficacy measure of ppFVC.

The assumption that a 2.5% difference in ppFVC (favoring 30 mg BID or 60 mg BID vs 
placebo) would be meaningful and that the standard deviation of this difference would 6.5%.

The assumption that 80% of participants randomized will complete the 26-week treatment 
period.

PK and tolerability data will be key factors in the selection of a dose for further evaluation. 
Given the limitations on participant recruitment and resulting sample size, it is not anticipated 
that the 30 mg BID and 60 mg BID cohorts  will be differentiated relative to FVC. 
95% two-sided confidence intervals were computed for a range of sample sizes. The confidence 
level was based on an overall Type 1 error of 0.10, with 0.05 allocated to each dose comparison 
(30 mg BID and 60 mg BID) relative to placebo. The resulting confidence intervals are described 
in Table 10.
Table 10:
95% CI of the Absolute Difference in ppFVC (%) Between 
BMS-986278 (30 mg BID or 60 mg BID) Compared to Placebo 
Based on an Observed Difference of 2.5%
Sample Size per Arm
Lower Bound 95% CI
Upper Bound 95% CI
60
0.17
4.83
80
0.49
4.51
100
0.70
4.30
CI = confidence interval 
Based on these considerations, a sample size of 80 participants per arm was selected. Note that for 
all sample sizes, the lower bound of the 95% confidence interval excludes zero, consistent with a 
nominal p-value < 0.05.  For the purposes of this study, if either dose comparison achieves a 
p-value of 0.05 or less, it will be described as “statistically significant.” 
With regards to the PF-ILD cohort, statistical considerations were not utilized. A total of 
120 participants will be enrolled. A target of enrolling 75 out of 120 (62.5%) with UIP pattern is 
expected and randomization will be stratified by UIP pattern (present versus absent) and by 
category of background therapy (ILD-targeted immunosuppression [ie, azathioprine, 
mycophenolate mofetil, mycophenolic acid, and/or tacrolimus] alone versus anti-fibrotics 
[nintedanib, pirfenidone] with or without ILD-targeted immunosuppression versus no ILD-
targeted immunosuppression or anti-fibrotics). These participants will be analyzed separately and 
considered as supportive to the findings within the IPF cohort.
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10.2
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled 
All participants who sign informed consent.
Full Analysis Set (FAS)
All participants who are randomized and receive at least 1 dose of 
study treatment. Participants will be analyzed according to the 
treatment group assigned at randomization. The FAS will be the 
primary efficacy analysis population.
Pharmacokinetic
All randomized participants who receive at least 1 administration 
of BMS-986278 and have any quantifiable concentration data.
Safety
All participants who are randomized and receive at least 1 dose of 
study treatment. Participants will be analyzed according to the 
treatment group assigned; participants who receive incorrect study 
treatment  will be analyzed according to the actual treatment 
received.
10.3
Endpoints
10.3.1
Primary Endpoints
The primary endpoint is the rate of change in ppFVC (%) in IPF participants, estimated from 
measurements taken over 26 weeks of treatment. The decrease in ppFVC is assumed to be linear 
within each participant over the 26 weeks.
10.3.2
Secondary Endpoints
Secondary endpoints are as follows:
Safety Assessments:

AEs

SAEs

AEs leading to early discontinuation of study treatment

Treatment-emergent deaths

Clinical laboratory findings and ECGs

Vital signs

Physical exam findings
Efficacy Endpoints: 

PF-ILD cohort only: 

Rate of change in ppFVC (%) in PF-ILD participants will be estimated from measurements 
taken over 26 weeks of treatment. The decrease in ppFVC is assumed to be linear within 
each participant over the 26 weeks.
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IPF and PF-ILD cohorts:

Proportion of participants with a at least 10% absolute decline from baseline in ppFVC (%) 
at Weeks 4, 8, 12, 16, 20, and 26

Proportion of participants with > 0% change in ppFVC at Weeks 4, 8, 12, 16, 20, and 26

Time to first acute exacerbation

Time to first occurrence ≥ 10% absolute decline in ppFVC (%)

Absolute change in ppFVC (%) from baseline to Week 26 

Absolute change in FVC (mL) from baseline to Week 26

Absolute change in DLCO SB (mL/min/mmHg) (corrected for hemoglobin) from baseline 
to Week 26

Absolute change in ppDLCO SB (%) (corrected for hemoglobin) from baseline to Week 26

Change in walking endurance/distance from baseline at Week 26 as measured using the 
6MWT

Proportion of participants with acute exacerbations (evidence of which will be captured in 
the eCRF) of lung fibrosis defined as an acute, clinically significant, respiratory 
deterioration characterized by evidence of new widespread alveolar abnormality, as 
follows:15
1. Acute worsening or development of dyspnea (< 1 month duration)
2. Imaging with new bilateral ground-glass opacity and/or consolidation superimposed on 
a background pattern consistent with fibrotic lung disease.
3. Respiratory deterioration not fully explained by cardiac failure of fluid overload
BMS-986278 PK Parameters:

Cmax

Tmax

AUC(0-8)

Ctrough
10.3.3
Exploratory Endpoints
Exploratory endpoints in the main study and/or OTE include but are not limited to the following:
HRCT:

Change in QLF using the Quantitative HRCT Fibrosis Score from baseline to Week 26
COAs:

Change in HRQoL from baseline at each assessment timepoint during treatment as measured 
by the L-PF

Change in HRQoL from baseline at each assessment timepoint during treatment as measured 
by the SGRQ
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
Change in dyspnea from baseline at each assessment timepoint during treatment as measured 
by the UCSD SOBQ

Change in cough severity from baseline at each assessment timepoint during treatment as 
measured using a VAS

Change in walking endurance/distance from baseline at each assessment timepoint during 
treatment as measured using the 6MWT
PK:

Cmax, Tmax, and AUC(0-8) on Day 1 and Week 4 and Ctrough on Week 4 and Week 12 of 
intensive PK substudy

Plasma concentrations of nintedanib and pirfenidone in participants who receive nintedanib or 
pirfenidone alone and co-administered with BMS-986278

Plasma concentrations of the BMT-323719 metabolite (including but not limited to 
AUC(0-8), Ctrough, Cmax, and Tmax of intensive PK study)
Disease Outcomes:

Composite endpoint of time to first all-cause hospitalization or overall survival

Pulmonary fibrosis progression-free survival (pulmonary fibrosis progression is defined as any 
of the following: ≥10% decline in ppFVC relative to baseline, ≥ 50 m decline in 6MWT 
relative to baseline, lung transplantation, or death)
Clinical Assessments of Disease:

Proportion of participants with > 5% decline in FVC (mL) relative to baseline 

Proportion of participants with > 10% decline in FVC (mL) relative to baseline

Proportion of participants with > 5% absolute decline in ppFVC (%)

Proportion of participants with > 5% decline in ppFVC (%) relative to baseline

Proportion of participants with > 10% decline in ppFVC (%) relative to baseline

Time to first > 5% absolute decline in ppFVC (%)

Time to first > 5% decline in ppFVC (%) relative to baseline 

Time to first > 10% decline in ppFVC (%) relative to baseline

Time to first > 5% decline in FVC (mL) relative to baseline

Time to first > 10% decline in FVC (mL) relative to baseline
Biomarkers:

Change from baseline of blood-based biomarkers (including gene expression profiles) of lung 
fibrosis and inflammation

Presence or absence of single nucleotide variants in genes associated with lung fibrosis
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
Presence or absence of SNP variants in genes encoding organic anion transporting 
polypeptides, CYP 2C8, and breast cancer resistance protein

Exploratory measurements of SARS-CoV-2 serology (anti-SARS-CoV-2 total or IgG) from 
serum samples collected at baseline, main study completion, and end of the OTE
10.4
Statistical Analyses
The Statistical Analysis Plan (SAP) will be developed and finalized before first unblinding event 
of the study (see Section 10.4.5), and will provide detailed specifications of the analysis of all 
efficacy endpoints and safety data. This section provides a summary of planned statistical analyses.
Categorical data will be summarized using counts and percentages. Continuous data will be 
summarized using n, mean, standard deviation, median, minimum, and maximum unless otherwise 
specified.
10.4.1
Efficacy Analyses
10.4.1.1
Primary Efficacy Endpoint
The primary endpoint is the rate of change in ppFVC in IPF participants (estimated from 
measurements taken over 26 weeks of treatment). The decrease in ppFVC is assumed to be linear 
within each participant over the 26 weeks.
The primary analysis will compare the rate of change in ppFVC from baseline to Week 26 using a 
random coefficient linear mixed model using the Full Analysis Set (FAS). The model will include 
ppFVC at each visit as dependent variable, random coefficients for intercept and slope and fixed 
effect terms for treatment, time since randomization, treatment × time interaction, and baseline 
stratification factors. No imputation of missing values will be performed for the primary analysis. 
Sensitivity analysis may be performed to assess the impact of missing values as well as impact of 
dose reduction on the primary analysis. There will be no adjustment for multiple comparisons. 
Subgroup analyses will be performed for concomitant use of pirfenidone or nintedanib therapy 
(vs neither pirfenidone nor nintedanib) for IPF and for other demographic and baseline 
characteristics.  
10.4.1.2
Secondary Efficacy Endpoints
All secondary analyses will be based on the FAS population. As appropriate, continuous secondary 
endpoints will be analyzed using mixed model repeated measures (MMRM) with a random effect 
for participant and fixed effects for treatment, visit, treatment-by-visit interaction, and baseline 
stratification factors. The baseline value of the endpoint being tested will be added into the model 
as a covariate. In addition, as appropriate analysis of covariance models will be used to analyze 
continuous secondary endpoints with treatment and factors used for randomization as fixed effects. 
The baseline value will be added into the model as a covariate.
Cochran-Mantel-Haenszel tests will be used to compare dichotomous endpoints between either 
BMS-986278 dose group vs placebo. 
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The Kaplan-Meier product limit method will be used to estimate the survival curves for 
time-to-event endpoints. Treatment comparisons between each BMS-986278 dose group and 
placebo will be performed using the log-rank test stratified by baseline stratification factors. 
The PF-ILD cohort will be analyzed separately from the primary study cohort of IPF. The PF-ILD 
statistical analysis methods will be similar to IPF cohort. The details will be described in the SAP.  
10.4.2
Pharmacokinetic Analyses
The PK population will be defined as all randomized participants who receive at least 
1 administration of BMS-986278 and have any quantifiable concentration data. PK analyses will 
be based on the PK population. BMS-986278 and BMT-323719 concentration data as well as 
nintedanib and pirfenidone concentration data from participants also receiving nintedanib or 
pirfenidone will be summarized by visit and timepoint, as applicable, using descriptive statistics 
for the PK population. Descriptive statistics will also be provided for the plasma BMS-986278 PK 
parameters for each BMS-986278 dose. In addition, trough concentrations of nintedanib and 
pirfenidone will be summarized by visit. For the participants that undergo intensive PK 
assessments, geometric means and percent coefficients of variation (%CV) will be presented for 
PK parameters such as AUC(0-8), Cmax, and Ctrough. Participants in the PET-tracer substudy 
will only have their PK concentration data listed and not summarized. 
Medians and ranges will be presented for Tmax. Scatter plots for Ctrough over time will be 
presented for each active treatment to assess the attainment of steady state. Additionally, Ctrough 
will be summarized (geometric mean and %CV) by visit and active treatment. Results of these 
analyses will be reported separately.
Concentration data from both sparse and intensive PK samples will be used to further characterize 
the PK of BMS-986278 using population PK analysis, and to estimate model-based PK parameters 
such as apparent oral clearance at steady state (CLss/F) and apparent volume of distribution at 
steady state (Vss/F). Results of these analyses will be reported separately.
10.4.3
Safety Analyses
Analyses of safety data will be based on the safety set, which is defined as all participants who 
take at least 1 dose of study treatment. 
Treatment-emergent AEs and study drug-related AEs and SAEs will be summarized using counts 
and percentages of participants experiencing the event as well as the number of events by system 
organ class, preferred term, and treatment group. Physical examination findings, vital signs, 
clinical laboratory test results, and ECG test results will be summarized using descriptive statistics 
(n, mean, standard deviation, median, minimum, and maximum) for continuous variables and 
frequency distributions (counts and percentages) for categorical variables. 
The proportions of participants in each treatment group who discontinue study treatment due to 
changes in BP will be summarized using descriptive statistics.
The PF-ILD cohort will be analyzed separately from the primary study cohort of IPF.  
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10.4.4
Other Analyses
PK and biomarker exploratory analyses will be described in the SAP and finalized before database 
lock. The population pharmacokinetics analysis and pharmacodynamic analyses will be presented 
separately from the main clinical study report. Exploratory analyses of COAs will be described in 
the SAP finalized before database lock.
Exploratory PK will be summarized by dose and timepoint for the PK population. If warranted, 
analysis of PK and exposure-response relationships will be reported separately from the clinical 
study report (CSR).
Selected biomarkers will be summarized by treatment and timepoint using the FAS population. 
Summaries will be provided for raw, change from baseline, and percent change from baseline.
At the time of database lock for the IPF cohort (Week 26 of the main study), the OTE for the IPF 
cohort will continue unblinded until completion. To better assess longer-term efficacy and safety 
with BMS-986278, select efficacy (eg, FVC) and safety data from the OTE portion of the IPF 
cohort will be reviewed by the sponsor based on the locked database. The blind will be maintained 
for the PF-ILD cohort until the database lock for the PF-ILD cohort (Week 26 of the main study).
An analysis is planned for the PF-ILD cohort when 100% of participants (N = 40/arm) complete 
Week 26. This analysis will be performed and results reviewed by the independent DMC. Results 
will be descriptive and based on estimation of effect size and associated confidence intervals. 
Further details on statistical considerations, review of data, and unblinding will be included in the 
DMC Charter and SAP. At the time of the PF-ILD cohort main study database lock (Week 26 of 
the main study), the OTE for the PF-ILD cohort will continue unblinded until completion.
All safety, tolerability, and efficacy data from the OTE will be analyzed separately from the main 
study. The presentation of participants treated with BMS-986278 during the OTE will be done by 
the following groups: participants randomized to 30 mg at the start of the main study, participants 
randomized to 60 mg at the start of the main study, participants randomized to 30 mg in the OTE 
(placebo participants in the main study), participants randomized to 60 mg in the OTE (placebo 
participants in the main study), participants who received an unblinded reduced dose of 10 mg at 
the start of the OTE. 
10.4.5
Interim Analyses 
An interim analysis is planned for the IPF cohort when approximately 50% of participants (N = 
40/arm) complete Week 26. This analysis will be performed and results reviewed by the 
independent DMC. No formal test of statistical significance is planned given the limited sample 
size at Week 26. Results will be descriptive and based on estimation of effect size and associated 
confidence intervals. Thus, no adjustments to overall type I error will be made. Further details on 
statistical considerations, review of data, and unblinding will be included in the DMC Charter and 
SAP.
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Wijsenbeek M, Kreuter M, Olson A, et al. Progressive fibrosing interstitial lung diseases: 
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BMS-986278: One-month oral toxicity study in cynomolgus monkeys with a two-week 
post-dose recovery period (Study DN17119). Bristol-Myers Squibb Company; 2017. 
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BMS-986278: Nine-month oral toxicity study in rats with a 3-month post-dose recovery 
period (Study DN17159). Bristol-Myers Squibb Company; 2019. Document Control No. 
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Evaluation of BMS-986278 in a mouse systemic bleomycin model of lung fibrosis (Study 
FI00190). Bristol-Myers Squibb Company; 2017. Document Control No. 930119291.
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FI00189). Bristol-Myers Squibb Company; 2017. Document Control No. 930119296.
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Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. European 
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official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 
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pulmonary fibrosis: diagnosis and prognosis. Am J Respir Crit Care Med 2005;172(4):488-
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results from a 1-year, proof-of-principle study. Rheumatology (Oxford) 2010;49(2):271-
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fibrosis: Randomized placebo-controlled trial results. Am J Respir Crit Care Med 
2010;181(6):604-10.
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response to therapy and survival. Am J Respir Crit Care Med 1998;157(4 Pt 1):1063-72.
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subsets in scleroderma-related interstitial lung disease. Arthritis Rheum 2011;63(9):2797-
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Tashkin DP, Elashoff R, Clements PJ, et al. Cyclophosphamide versus placebo in 
scleroderma lung disease. N Engl J Med 2006;354(25):2655-66.
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Kim HJ, Brown MS, Elashoff R, et al. Quantitative texture-based assessment of one-year 
changes in fibrotic reticular patterns on HRCT in scleroderma lung disease treated with 
oral cyclophosphamide. Eur Radiol 2011;21(12):2455-65.
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Daniels CE, M.D. Gleevec idiopathic pulmonary fibrosis (IPF) study. (NCT00131274): 
2007. Updated 5 October 2005. Accessed 20 September 2019.
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Kim HJ, Li G, Gjertson D, et al. Classification of parenchymal abnormality in scleroderma 
lung using a novel approach to denoise images collected via a multicenter study. Acad 
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quantitative scoring of extent of lung fibrosis in scleroderma patients. Clin Exp Rheumatol 
2010;28(5 Suppl 62):S26-35.
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disease in fibrosing alveolitis on thin section computed tomography and chest radiography. 
Clin Radiol 1994;49(4):236-40.
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Camiciottoli G, Orlandi I, Bartolucci M, et al. Lung CT densitometry in systemic sclerosis: 
correlation with lung function, exercise testing, and quality of life. Chest 2007;131(3):672-
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Lynch DA. Quantitative CT of fibrotic interstitial lung disease. Chest 2007;131(3):643-4.
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Swigris JJ, Brown KK, Abdulqawi R, et al. Patients' perceptions and patient-reported 
outcomes in progressive-fibrosing interstitial lung diseases. Eur Respir Rev 2018;27(150).
43.
Mittoo S, Frankel S, LeSage D, et al. Patient perspectives in OMERACT provide an anchor 
for future metric development and improved approaches to healthcare delivery in 
connective tissue disease related interstitial lung disease (CTD-ILD). Curr Respir Med Rev 
2015;11(2):175-83.
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Natalini JG, Swigris JJ, Morisset J, et al. Understanding the determinants of health-related 
quality of life in rheumatoid arthritis-associated interstitial lung disease. Respir Med 
2017;127:1-6.
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Baron M, Sutton E, Hudson M, et al. The relationship of dyspnoea to function and quality 
of life in systemic sclerosis. Ann Rheum Dis 2008;67(5):644-50.
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Graney B, Johnson N, Evans CJ, et al. Living with idiopathic pulmonary fibrosis (L-IPF): 
Developing a patient-reported symptom and impact questionnaire to assess health-related 
quality of life in IPF.  C37 New insights in the epidemiology, management, and outcomes 
of cystic fibrosis, ILD, and respiratory disease: American Thoracic Society; 2017, pp. 
A5353-A.
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Swigris JJ, Wilson SR, Green KE, et al. Development of the ATAQ-IPF: a tool to assess 
quality of life in IPF. Health Qual Life Outcomes 2010;8:77.
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Flaherty KR, Brown KK, Wells AU, et al. Design of the PF-ILD trial: a double-blind, 
randomised, placebo-controlled phase III trial of nintedanib in patients with progressive 
fibrosing interstitial lung disease. BMJ Open Respir Res 2017;4(1):e000212.
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Jones PW, Quirk FH, Baveystock CM, et al. A self-complete measure of health status for 
chronic airflow limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis 
1992;145(6):1321-7.
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Jones PW, Quirk FH, Baveystock CM. The St George's Respiratory Questionnaire. Respir 
Med 1991;85 Suppl B:25-31; discussion 3-7.
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Swigris JJ, Wilson H, Esser D, et al. Psychometric properties of the St George's Respiratory 
Questionnaire in patients with idiopathic pulmonary fibrosis: insights from the INPULSIS 
trials. BMJ Open Respir Res 2018;5(1):e000278.
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52.
Archibald CJ, Guidotti TL. Degree of objectively measured impairment and perceived 
shortness of breath with activities of daily living in patients with chronic obstructive 
pulmonary disease. Canadian Journal of Rehabilitation 1987.
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Eakin EG, Sassi-Dambron DE, Ries AL, et al. Reliability and validity of dyspnea measures 
in patients with obstructive lung disease. Int J Behav Med 1995;2(2):118-34.
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Eakin EG, Resnikoff PM, Prewitt LM, et al. Validation of a new dyspnea measure: the 
UCSD Shortness of Breath Questionnaire. University of California, San Diego. Chest 
1998;113(3):619-24.
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Kupferberg DH, Kaplan RM, Slymen DJ, et al. Minimal clinically important difference for 
the UCSD Shortness of Breath Questionnaire. J Cardiopulm Rehabil 2005;25(6):370-7.
56.
Gries KS, Esser D, Wiklund I. Content validity of CASA-Q cough domains and UCSD-
SOBQ for use in patients with Idiopathic Pulmonary Fibrosis. Glob J Health Sci 
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Balke B. A Simple Field Test for the Assessment of Physical Fitness. Rep 63-6. Rep Civ 
Aeromed Res Inst US 1963:1-8.
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A. T. S. Committee on Proficiency Standards for Clinical Pulmonary Function 
Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit 
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APPENDIX 1
ABBREVIATIONS AND TRADEMARKS
Term
Definition
6MWT
6-Minute Walk Test
ACC/AHA/HRS
American College of Cardiology/American Heart Association Task Force 
on Clinical Practice Guidelines and the Heart Rhythm Society
AE
adverse event
ALT
alanine aminotransferase
AR
additional research
AST
aspartate aminotransferase
AUC
area under the concentration-time curve
AUC(0-24h)
area under the plasma concentration-time curve form time 0 to 24 hours 
post dose
AUC(INF)
area under the concentration-time curve from time zero extrapolated to 
infinite time
BAL
bronchoalveolar lavage
BID
twice daily
BLEO
bleomycin
BMS
Bristol-Myers Squibb
BP
blood pressure
CAD
computer-assisted diagnosis
CFR
Code of Federal Regulations
CLss/F
apparent oral clearance at steady state
Cmax
maximum observed concentration
COA
clinical outcome assessment
COVID-19
Coronavirus Disease 2019
CRF
Case Report Form
CSR
clinical study report
Ctrough
trough observed plasma concentration
CTAg
clinical trial agreement
%CV
percent coefficient of variation
CYP
cytochrome P450
DBP
diastolic blood pressure
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Term
Definition
DDT
Drug Development Tool
DILI
drug induced liver injury
DLCO
diffusing capacity of carbon monoxide
DLCO SB
single-breath diffusing capacity of carbon monoxide 
ppDLCO SB
percent predicted single-breath diffusing capacity of carbon monoxide
DMARD
disease modifying anti-rheumatic drug
DMC
Data Monitoring Committee
ECG
electrocardiogram
eCRF
electronic case report form
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FEV1
forced expiratory volume in 1 second
PF
pulmonary fibrosis
ppFEV1
percent predicted forced expiratory volume in 1 second
FIH
first-in-human
FSH
follicle-stimulating hormone
FVC
forced vital capacity
ppFVC
percent predicted forced vital capacity
GCP
Good Clinical Practice
GD
gestation day
GLP
Good Laboratory Practice
HBcAb
hepatitis B core antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HR
heart rate
HRT
hormone replacement therapy
HRCT
high-resolution computed tomography
HRQoL
health-related quality of life
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Term
Definition
ICF
informed consent form
ICH
International Council for Harmonisation 
IEC
Independent Ethics Committee
ILD
interstitial lung disease
I(M)P
investigational (medicinal) product
INR
international normalized ratio
IPF
idiopathic pulmonary fibrosis
IRB
Institutional Review Board
IRT
Interactive Response Technology
IV
intravenous
L-IPF
Living with Idiopathic Pulmonary Fibrosis Questionnaire
L-PF
Living with Pulmonary Fibrosis Questionnaire
LPA
lysophosphatidic acid
LPA1
lysophosphatidic acid receptor 1
MMRM
mixed model repeated measures
MRHD
maximum recommended human dose
mRNA
messenger ribonucleic acid
NA
not applicable
NOAEL
no-observed adverse effect level
O2
oxygen
OATP
organic anion transport protein
OTE
optional treatment extension
PAH
pulmonary arterial hypertension
PET
positron emission tomography
PF-ILD
non-IPF, progressive fibrotic interstitial lung disease
PGI-C
patient global impression of lung fibrosis symptom severity change
PGI-S
patient global impression of lung fibrosis symptom severity
PK
pharmacokinetics
PT
prothrombin time
QD
once daily
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Term
Definition
QLF
quantitative lung fibrosis
SAE
serious adverse event
SAP
Statistical Analysis Plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SBP
systolic blood pressure
SGRQ
St. George’s Respiratory Questionnaire
SNP
single nucleotide polymorphism
SOC
Standard of Care
TEAE
treatment-emergent adverse event
T-HALF
elimination half-life
Tmax
time of maximum observed concentration
UCSD SOBQ
University of California San Diego Shortness of Breath Questionnaire
UIP
usual interstitial pneumonia
ULN
upper limit of normal
VAS
visual analog scale
Vss/F
apparent volume of distribution at steady state
WOCBP
women of childbearing potential
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APPENDIX 2
STUDY GOVERNANCE CONSIDERATIONS
The terms “participant” and “subject” refer to a person who has consented to participate in the 
clinical research study. Typically, the term “participant” is used in the protocol and the term 
“subject” is used in the Case Report Form (CRF).
REGULATORY AND ETHICAL CONSIDERATIONS
GOOD CLINICAL PRACTICE
This study will be conducted in accordance with:

Consensus ethical principles derived from international guidelines including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences (CIOMS)
International Ethical Guidelines

Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines

Applicable laws, regulations, and requirements
The study will be conducted in compliance with the protocol. The protocol, any 
revisions/amendments, and the participant informed consent form (ICF) will receive 
approval/favorable opinion by Institutional Review Board/Independent Ethics Committee 
(IRB/IEC), and regulatory authorities according to applicable regulations prior to initiation of the 
study.
All potential serious breaches must be reported to the Sponsor or designee immediately. A 
potential serious breach is defined as a Quality Issue (eg, protocol deviation, etc) that is likely to 
affect, to a significant degree one or more of the following:  (1) the physical, safety or mental 
integrity of one or more subjects/participants; (2) the scientific value of the trial (eg, reliability and 
robustness of generated data). Items (1) or (2) can be associated with either GCP Regulation(s) or 
Trial protocol(s). 
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or where 
there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, Investigator’s Brochure, product labeling information, ICF, 
participant recruitment materials (eg, advertisements), and any other written information to be 
provided to participants. 
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The investigator, sponsor or designee should provide the IRB/IEC with reports, updates, and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
The investigator is responsible for providing oversight of the conduct of the study at the site and 
adherence to requirements of the following where applicable:

ICH guidelines, 

United States Code of Federal Regulations, Title 21, Part 50 (21CFR50)

European Union Directive 2001/20/EC; or

European Regulation 536/2014 for clinical studies (if applicable), 

European Medical Device Regulation 2017/745 for clinical device research (if applicable),

the IRB/IEC

and all other applicable local regulations.
COMPLIANCE WITH THE PROTOCOL AND PROTOCOL REVISIONS
The investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and if 
applicable, also by local health authority) except where necessary to eliminate an immediate 
hazard(s) to study participants. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining relevant approval/favorable opinion(s) the deviation or change will be submitted, as soon 
as possible to:

IRB/IEC for 

Regulatory Authority(ies), if applicable by local regulations (per national requirements)
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IRB(s)/IEC(s) and if applicable, also by local health authority, must be sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the 
participant: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review 
and approval/favorable opinion; (2) the revised form must be used to obtain consent from 
participants currently enrolled in the study if they are affected by the amendment; and (3) the new 
form must be used to obtain consent from new participants prior to enrollment.
FINANCIAL DISCLOSURE
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate health authorities. 
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Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study.
INFORMED CONSENT PROCESS
Investigators must ensure that participants are clearly and fully informed about the purpose, 
potential risks, and other critical issues regarding clinical studies in which they volunteer to 
participate. 
The Sponsor or designee will provide the investigator with an appropriate sample ICF, which will 
include all elements required by ICH GCP and applicable regulatory requirements. The sample 
ICF will adhere to the ethical principles that have their origin in the Declaration of Helsinki.
The investigator or his/her representative must:

Obtain the IRB/IEC’s written approval/favorable opinion of the written ICF and any other 
information to be provided to the participant prior to the beginning of the study, and after any 
revisions are completed for new information.

Provide a copy of the ICF and written information about the study in the language in which 
the participant is most proficient prior to clinical study participation. The language must be 
nontechnical and easily understood. 

Explain the nature of the study to the participant or the participant’s legally acceptable 
representative and answer all questions regarding the study.

Inform participant that his/her participation is voluntary. Participant or participant’s legally 
acceptable representative will be required to sign a statement of informed consent that meets 
the requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability 
and Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or study 
center.

Allow time necessary for participant or participant’s legally acceptable representative to 
inquire about the details of the study.

Obtain an ICF signed and personally dated by the participant or the participant's legally 
acceptable representative and by the person who conducted the informed consent discussion. 

Include a statement in participant’s medical record that written informed consent was obtained 
before participant was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF.

Re-consent participant to the most current version of the ICF(s) during his/her participation in 
the study, as applicable.
Revise the informed consent whenever important new information becomes available that is 
relevant to the participant's consent. The investigator, or a person designated by the investigator, 
should fully inform the participant or the participant’s legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
participant's willingness to continue participation in the study. This communication should be 
documented. 
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The confidentiality of records that could identify participants must be protected, respecting the 
privacy and confidentiality rules applicable to regulatory requirements, the participant’s signed 
ICF and, in the US, the participants’ signed HIPAA Authorization.
The ICF must also include a statement that BMS and foreign regulatory authorities have direct 
access to participant records. 
In situations where consent cannot be given by participants, their legally acceptable representatives 
(as per country regulation) are clearly and fully informed about the purpose, potential risks, and 
other critical issues regarding clinical studies in which the participant volunteers to participate. 
If informed consent is initially given by a participant’s legally acceptable representative or legal 
guardian and the participant subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the participant.
The rights, safety, and well-being of the study participants are the most important considerations 
and should prevail over interests of science and society.
SOURCE DOCUMENTS
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data reported on the CRF or entered in the electronic CRF (eCRF) that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must be explained. 

The investigator may need to request previous medical records or transfer records, depending 
on the study. Also, current medical records must be available.
The investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original, and attributable, whether the data are handwritten on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical records/electronic health 
records, AE tracking/reporting, protocol-required assessments, and/or drug accountability 
records).
When paper records from such systems are used in place of electronic format to perform regulated 
activities, such paper records should be certified copies. A certified copy consists of a copy of 
original information that has been verified, as indicated by a dated signature, as an exact copy 
having all of the same attributes and information as the original. 
STUDY TREATMENT RECORDS
Records for study treatments (whether supplied by BMS, its vendors, or the site) must substantiate 
study treatment integrity and traceability from receipt, preparation, administration, and through 
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destruction or return. Records must be made available for review at the request of BMS/designee 
or a Health Authority.
If
Then
Supplied by BMS (or its vendors):
Records or logs must comply with applicable 
regulations and guidelines and should include:

amount received and placed in storage 
area

amount currently in storage area

label identification number or batch 
number

amount dispensed to and returned by each 
participant, including unique participant 
identifiers

amount transferred to another area/site for 
dispensing or storage

nonstudy disposition (eg, lost, wasted) 

amount destroyed at study site, if 
applicable

amount returned to BMS

retain samples for bioavailability/
bioequivalence/biocomparability, if 
applicable 

dates and initials of person responsible for 
IP dispensing/accountability, as per the 
Delegation of Authority Form.
Sourced by site, and not supplied by BMS or 
its vendors (examples include IP sourced from 
the sites stock or commercial supply or a 
specialty pharmacy)
The 
investigator 
or 
designee 
accepts 
responsibility for documenting traceability and 
study treatment integrity in accordance with 
requirements applicable under law and the 
standard operating procures/standards of the 
sourcing pharmacy.

BMS or designee will provide forms to facilitate inventory control if the investigational site does 
not have an established system that meets these requirements.
CASE REPORT FORMS
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the eCRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
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understanding of product safety. eCRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the sponsor or designee electronic data capture (EDC) tool, eCRFs will be prepared 
for all data collection fields except for fields specific to SAEs and pregnancy, which will be 
reported on the electronic SAE form and paper Pregnancy Surveillance Form, respectively. If 
electronic SAE form is not available, a paper SAE form can be used.
The confidentiality of records that could identify participants must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on case report forms (CRFs). 
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the 
investigator or qualified physician who is a subinvestigator and who is delegated this task on the 
Delegation of Authority Form. Subinvestigators in Japan may not be delegated the CRF approval 
task. For electronic CRFs, review and approval/signature are completed electronically through the 
electronic data capture tool. The investigator must retain a copy of the CRFs including records of 
the changes and corrections.
Each individual electronically signing electronic CRFs must meet Sponsor or designee training 
requirements and must only access the BMS EDC tool using the unique user account provided by 
sponsor or designee. User accounts are not to be shared or reassigned to other individuals.
MONITORING
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site, they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable. Certain CRF pages and/or electronic files may serve as the source 
documents.
In addition, the study may be evaluated by sponsor or designee internal auditors and government 
inspectors who must be allowed access to CRFs, source documents, other study files, and study 
facilities. BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory authorities, 
and promptly forward copies of inspection reports to sponsor or designee. 
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RECORDS RETENTION
The investigator (or head of the study site in Japan) must retain all study records and source 
documents for the maximum period required by applicable regulations and guidelines, or 
institution procedures, or for the period specified by BMS or designee, whichever is longer. The 
investigator (or head of the study site in Japan) must contact BMS prior to destroying any records
associated with the study.
BMS or designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, study site, IRB). Notice 
of such transfer will be given in writing to BMS or designee. 
RETURN OF STUDY TREATMENT
For this study, study treatments (those supplied by BMS, a vendor, or sourced by the investigator) 
such as partially used study treatment containers, vials, and syringes may be destroyed on site. 
If
Then
Study treatments supplied by BMS (including 
its vendors)
Any unused study treatments supplied by BMS 
can only be destroyed after being inspected and 
reconciled by the responsible Study Monitor, 
unless study treatments containers must be 
immediately destroyed as required for safety, 
or to meet local regulations (eg, cytotoxics or 
biologics).
Partially used study interventions and/or 
empty containers may be destroyed after 
proper reconciliation and documentation. But 
unused IMP must be reconciled by site 
monitor/Clinical Research Associate prior to 
destruction.
If study treatments will be returned, the return 
will be arranged by the responsible Study 
Monitor.
Study treatments sourced by site, not supplied 
by BMS (or its vendors; eg, study treatments 
sourced from the sites stock or commercial 
supply, or a specialty pharmacy)
It 
is 
the 
investigator’s 
or 
designee’s 
responsibility to dispose of all containers 
according to the institutional guidelines and 
procedures.
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It is the investigator’s or designee’s responsibility to arrange for disposal, provided that procedures 
for proper disposal have been established according to applicable federal, state, local, and 
institutional guidelines and procedures, and provided that appropriate records of disposal are kept. 
The following minimal standards must be met:

On-site disposal practices must not expose humans to risks from the drug.

On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.

Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s standard operating procedures and a copy provided to BMS upon request.

Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal vendor 
must be documented.

Accountability and disposal records are complete, up-to-date, and available for the Monitor to 
review throughout the clinical trial period.
It is the investigator’s or designee’s responsibility to arrange for disposal of all empty containers.
If conditions for destruction cannot be met the responsible Study Monitor will make arrangements 
for return of study treatments provided by BMS (or its vendors). Destruction of non- study 
treatments sourced by the site, not supplied by BMS, is solely the responsibility of the investigator 
or designee.
STUDY AND SITE START AND CLOSURE
The Sponsor/designee reserves the right to close the study site or to terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies have 
been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the Sponsor or investigator may include, but are 
not limited to:

Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local Health Authorities, the Sponsor’s procedures, or GCP guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study intervention development
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
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regulatory requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
DISSEMINATION OF CLINICAL STUDY DATA
In order to benefit potential study participants, patients, healthcare providers and researchers, and 
to help BMS honor its commitments to study participants, BMS will make information about 
clinical research studies and a summary of their results available to the public as per regulatory 
and BMS requirements. BMS will post study information on local, national or regional databases 
in compliance with national and international standards for disclosure. BMS may also voluntarily 
disclose information to applicable databases.
CLINICAL STUDY REPORT 
A Signatory investigator must be selected to sign the clinical study report (CSR). 
For each CSR related to this protocol, the following criteria will be used to select the Signatory 
Investigator:

National coordinating investigator 

Participant recruitment (eg, among the top quartile of enrollers)

Involvement in trial design

Regional representation (eg, among top quartile of enrollers from a specified region or country)

Other criteria (as determined by the study team)
SCIENTIFIC PUBLICATIONS
The data collected during this study are confidential and proprietary to sponsor or designee. Any 
publications or abstracts arising from this study must adhere to the publication requirements set 
forth in the clinical trial agreement (CTAg) governing [study site or investigator] participation in 
the study. These requirements include, but are not limited to, submitting proposed publications to 
sponsor or designee at the earliest practicable time prior to submission or presentation and 
otherwise within the time period set forth in the CTAg.
Scientific Publications (such as abstracts, congress podium presentations and posters, and 
manuscripts) of the study results will be a collaborative effort between the study Sponsor and the 
external authors.  No public presentation or publication of any interim results may be made by any 
principal investigator, sub-investigator or any other member of the study staff without the prior 
written consent of the Sponsor.  
Authorship of publications at BMS is aligned with the criteria of the International Committee of 
Medical Journal Editors (ICMJE, www.icmje.org). Authorship selection is based upon significant 
contributions to the study (ie, ICMJE criterion #1). Authors must meet all 4 ICMJE criteria for 
authorship:
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1) Substantial intellectual contribution to the conception or design of the work; or the acquisition 
of data (ie, evaluable subjects with quality data), analysis, or interpretation of data for the work 
(eg, problem solving, advice, evaluation, insights and conclusion); AND
2) Drafting the work or revising it critically for important intellectual content; AND
3) Final approval of the version to be published; AND
4) Agreement to be accountable for all aspects of the work in ensuring that questions related to 
the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Those who make the most significant contributions, as defined above, will be considered by BMS 
for authorship of the primary publication. Sub-investigators will generally not be considered for 
authorship in the primary publication. Geographic representation will also be considered.  
Authors will be listed by order of significant contributions (highest to lowest), with the exception 
of the last author. Authors in first and last position have provided the most significant contributions 
to the work. 
For secondary analyses and related publications, author list and author order may vary from 
primary to reflect additional contributions.
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APPENDIX 3
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP AND REPORTING
ADVERSE EVENTS
Adverse Event Definition:
An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a 
pre-existing medical condition in a clinical investigation participant administered study 
treatment and that does not necessarily have a causal relationship with this treatment.  
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of study drug, whether or not 
considered related to the study drug.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, ECGs, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically significant 
in the medical and scientific judgment of the investigator. Note that abnormal lab tests or 
other safety assessments should only be reported as AEs if the final diagnosis is not 
available. Once the final diagnosis is known, the reported term should be updated to be the 
diagnosis. 

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 intervention administration even though 
it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose, as a verbatim term (as reported by the 
investigator), should not be reported as an AE/SAE unless it is an intentional overdose taken 
with possible suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae and should specify “intentional overdose” as the verbatim term. 
Events NOT Meeting the AE Definition

Medical or surgical procedure (eg, endoscopy, appendectomy); the condition that leads to 
the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
DEFINITION OF SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met.
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SERIOUS ADVERSE EVENTS
A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any 
dose:
Results in death
Is life-threatening (defined as an event in which the participant 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 inpatient hospitalization or causes prolongation of existing hospitalization (see NOTE 
below)
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies: 

A visit to the emergency room or other hospital department < 24 hours that does not result 
in admission (unless considered an important medical or life-threatening event)

Elective surgery, planned prior to signing consent

Admissions as per protocol for a planned medical/surgical procedure

Routine health assessment requiring admission for baseline/trending of health status (eg, 
routine colonoscopy)

Medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases

Admission encountered for another life circumstance that carries no bearing on health status 
and requires no medical/surgical intervention (eg, lack of housing, economic inadequacy, 
caregiver respite, family circumstances, administrative reason)

Admission for administration of anticancer therapy in the absence of any other SAEs (applies 
to oncology protocols)
Results in persistent or significant disability/incapacity
Is a congenital anomaly/birth defect
Is an important medical event (defined as a medical event(s) that may not be immediately life-
threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the participant or may require intervention [eg, medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above.) Examples 
of such events include, but are not limited to, intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization.) Potential drug induced liver injury (DILI) is also considered an important 
medical event. (See Section 9.2.8 for the definition of potential DILI.) 
Pregnancy and potential DILI must follow the same transmission timing and processes to BMS 
as used for SAEs (see Section 9.2.6 for reporting pregnancies).
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Any component of a study endpoint that is considered related to study therapy should be reported 
as SAE (eg, death is an endpoint, if death occurred due to anaphylaxis, anaphylaxis must be 
reported). 
EVALUATING AES AND SAES
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention administration,
will be considered and investigated.

The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information for marketed products in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to Sponsor. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to Sponsor.

The investigator may change his/her opinion of causality in light of follow-up information 
and send a SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study and assign it to 1 of the following categories:

Mild: An event that is easily tolerated by the participant, causing minimal discomfort and 
not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as severe 
should not be confused with an SAE. Severe is a category utilized for rating the intensity of 
an event, and both AEs and SAEs can be assessed as severe.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as described 
in the definition of an SAE, NOT when it is rated as severe.
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Follow-up of AEs and SAEs
If only limited information is initially available, follow-up reports are required. (Note: Follow-
up SAE reports must include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study treatment or if new 
information becomes available, the SAE report must be updated and submitted within 24 hours 
to BMS (or designee) using the same procedure used for transmitting the initial SAE report.
All SAEs must be followed to resolution or stabilization.
REPORTING OF SAES TO SPONSOR OR DESIGNEE

SAEs, whether related or not related to study treatment, and pregnancies must be 
reported to BMS (or designee) immediately within 24 hours of awareness of the event.

SAEs must be recorded on the SAE Report Form.
The required method for SAE data reporting is through the eCRF.
The paper SAE Report Form is only intended as a back-up option when the 
electronic data capture (EDC) system is unavailable/not functioning for 
transmission of the eCRF to BMS (or designee).
In this case, the paper form is transmitted via email or confirmed facsimile (fax) 
transmission.
When paper forms are used, the original paper forms are to remain on site.

Pregnancies must be recorded on a paper Pregnancy Surveillance Form and transmitted 
via email or confirmed facsimile (fax) transmission 
SAE Email Address: 
SAE Facsimile Number: Will be provided by local site monitor.
SAE Telephone Contact (required for SAE and pregnancy reporting): Will be provided 
by local site monitor.
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APPENDIX 4
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION
APPENDIX 4 provides general information and definitions related to Woman of Childbearing 
Potential and methods of contraception that can be applied to most clinical trials. For information 
specific to this study regarding acceptable contraception requirements for female and male 
participants, refer to Section 6.1 of the protocol. Only the contraception methods as described in 
Section 6.1 are acceptable for this study.
DEFINITIONS
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy.
Women in the following categories are not considered WOCBP

Premenarchal

Premenopausal female with 1 of the following:
Documented hysterectomy
Documented bilateral salpingectomy
Documented bilateral oophorectomy
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.

Postmenopausal female
A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 
45 years in the absence of other biological or physiological causes. In addition, females 
under the age of 55 years must have a serum FSH level > 40 mIU/mL to confirm 
menopause.
Note: Females treated with hormone replacement therapy (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. Suggested 
guidelines for the duration of the washout periods for HRT types are presented below. Investigators 
should use their judgment in checking serum FSH levels. 

1 week minimum for vaginal hormonal products (rings, creams, gels)

4 week minimum for transdermal products

8 week minimum for oral products
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Other parenteral products may require washout periods as long as 6 months. If the serum FSH 
level is > 40 mIU/mL at any time during the washout period, the woman can be considered 
postmenopausal.
End of Relevant Systemic Exposure

End of relevant systemic exposure is the timepoint where the IMP or any active major 
metabolites has decreased to a concentration that is no longer considered to be relevant for 
human teratogenicity or fetotoxicity. This should be evaluated in context of safety margins 
from the no-observed adverse effect level (NOAEL) or the time required for 5 half-lives of the 
IMP to pass.
METHODS OF CONTRACEPTION
Local laws and regulations may require use of alternative and/or additional contraception methods.
Highly Effective Contraceptive Methods That Are User Dependent
Failure rate of <1% per year when used consistently and correctly.a

Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation and/or implantation (This method of contraception can only be used 
by WOCBP participants in studies where hormonal contraception is permitted by the study 
protocol)b
Oral (birth control pills)
Intravaginal (rings)
Transdermal 

Combined (estrogen- and progestogen-containing) hormonal contraception must begin at 
least 30 days prior to initiation of study therapy.

Progestogen-only hormonal contraception associated with inhibition of ovulation (This
method of contraception can only be used by WOCBP participants in studies where 
hormonal contraception is permitted by the study protocol)b 
Oral 
Injectable 

Progestogen-only hormonal contraception must begin at least 30 days prior to initiation of 
study therapy.
Highly Effective Methods That Are User Independent 

Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation and/or implantation (This method of contraception can only be used by WOCBP 
participants in studies where hormonal contraception is permitted by the study protocol)b

Intrauterine device (IUD) 
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
Intrauterine hormone-releasing system (IUS) (This method of contraception can only be 
used by WOCBP participants in studies where hormonal contraception is permitted by the 
study protocol) b,c

Bilateral tubal occlusion

Vasectomized partner 
Male participants will be required to always use a latex or other synthetic condom during any 
sexual activity (eg, vaginal, anal, oral) with WOCBP; even if the participants have undergone 
a successful vasectomy or if their partner is already pregnant or breastfeeding.

Sexual abstinence
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 treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
study and the preferred and usual lifestyle of the participant.

Continuous abstinence must begin at least 30 days prior to initiation of study therapy.

It is not necessary to use any other method of contraception when complete abstinence is 
elected. 

WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in Section 2. 

Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participants choose to forego complete abstinence.

Periodic abstinence (including but not limited to calendar, symptothermal, postovulation 
methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea 
method (LAM) are not acceptable methods of contraception for this study.
NOTES: 
a Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for participants 
participating in clinical studies. 
b Hormonal contraception may be susceptible to interaction with the study treatment, which may reduce 
the efficacy of the contraceptive method. Hormonal contraception is permissible only when there is 
sufficient evidence that the IMP and other study medications will not alter hormonal exposures such 
that contraception would be ineffective or result in increased exposures that could be potentially 
hazardous. In this case, alternative methods of contraception should be utilized. For information 
specific to this study regarding permissibility of hormonal contraception, refer to Sections 6.1 
INCLUSION CRITERIA and 7.7.1 PROHIBITED AND/OR RESTRICTED TREATMENTS of the 
protocol.
c IUSs are acceptable methods of contraception in the absence of definitive drug interaction studies 
when hormone exposures from intrauterine devices do not alter contraception effectiveness. For 
information specific to this study regarding permissibility of hormonal contraception, refer to Sections 
6.1 INCLUSION CRITERIA and 7.7.1 PROHIBITED AND/OR RESTRICTED TREATMENTS of 
the protocol.
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Less Than Highly Effective Contraceptive Methods That Are User Dependent 
Failure rate of >1% per year when used consistently and correctly.

Male or female condom with or without spermicide.  Male and female condoms cannot be 
used simultaneously

Diaphragm with spermicide

Cervical cap with spermicide

Vaginal Sponge with spermicide

Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action (This method of contraception cannot be used by WOCBP 
participants in studies where hormonal contraception is prohibited.)
Unacceptable Methods of Contraception

Periodic abstinence (calendar, symptothermal, post-ovulation methods)

Withdrawal(coitus interruptus).

Spermicide only

Lactation amenorrhea method (LAM)
COLLECTION OF PREGNANCY INFORMATION
Guidance for collection of Pregnancy Information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 9.2.6 and APPENDIX 3.
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APPENDIX 5
POTENT INHIBITORS OF ORGANIC ANION TRANSPORT 
PROTEINS
Potent inhibitors of organic anion transport proteins (OATPs), defined as inhibitors expected to 
increase exposures of OATP substrates by more than 2× are prohibited within 4 weeks of Day 1 
and during the study.
Examples of potent inhibitors of OATPs are:
atazanavir
cobicistat
darunavir
erythromycin
grazoprevir
lopinavir
rifampin
telaprevir
voxilaprevir
boceprevir
cyclosporine
elbasvir
faldaprevir 
itraconazole
ombitasvir
ritonavir
tenofovir
clarithromycin
darolutamide
elvitegravir
gemfibrozil
ledipasvir
paritaprevir
simeprevir
tipranavir
clopidogrel
dasabuvir
emtricitabine
glecaprevir
letermovir
pibrentasvir
sofosbuvir
velpatasvir
These lists are not meant to be all inclusive. Please consult individual drug labels for further 
information. 
Please consult the Study Director/Medical Monitor for any commonly used concomitant 
medications you use for your patients, or in case of questions on other inhibitors of OATP.
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APPENDIX 6
STRONG INHIBITORS OR INDUCERS OF CYP3A4
Strong inhibitors of CYP3A4 are prohibited within 4 weeks of Day 1 and during the study. Strong 
inhibitors are drugs that increase the exposure of substrates of a given metabolic pathway ≥ 5-fold.
Some examples of strong inhibitors of CYP3A4 are:
boceprevir
conivaptan
indinavir
LCL161
nefazodone
ritonavir
telithromycin
VIEKIRA PAK2
ceritinib
danoprevir
lopinavir
nelfinavir
saquinavir
tipranavir
clarithromycin
elvitegravir
itraconazole
mibefradil
posaconazole
saquinavir
troleandomycin
cobicistat
idelalisib
ketoconazole
mifepristone
ribociclib
telaprevir
voriconazole
In addition, excessive consumption of the following foods should be avoided:

Grapefruit and grapefruit juice

Seville oranges and Seville orange juice
Strong inducers of CYP3A4 are prohibited within 4 weeks of Day 1 and during the study. A 
strong inducer is one that causes a ≥ 50% decrease in the plasma AUC values of a substrate of a 
given metabolic pathway. Some examples of strong inducers of CYP3A4 are:
apalutamide
ivosidenib
phenytoin
avasimibe
lumacaftor
rifampin
carbamazepine
mitotane
rifapentine
enzalutamide
phenobarbital
St John's Wort extract
These lists are not meant to be all inclusive. Please consult individual drug labels for further 
information. 
Please consult the Study Director/Medical Monitor for any commonly used concomitant 
medications you use for your patients, or in case of questions on other inhibitors/inducers of 
CYP3A4.
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APPENDIX 7
STRONG INHIBITORS OR INDUCERS OF CYP2C8
Strong inhibitors of CYP2C8 are prohibited within 4 weeks of Day 1 and during the study. 
Strong inhibitors are drugs that increase the exposure of substrates of a given metabolic pathway 
≥ 5-fold.
Some examples of strong inhibitors of CYP2C8 are:
Strong inducers of CYP2C8: 
There are no known strong inducers of CYP2C8.
These lists are not meant to be all inclusive. Please consult individual drug labels for further 
information. 
Please consult the Study Director/Medical Monitor for any commonly used concomitant 
medications you use for your patients, or in case of questions on other inhibitors/inducers of 
CYP2C8.
clopidogrel 
gemfibrozil
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APPENDIX 8
SITE-SPECIFIC PROTOCOL FOR QUALIFIED PET-TRACER 
SITES in US
The following site-specific protocol was previously published as a separate document 
(Site-specific Amendment Number 01, dated 12 March 2020) and has been combined into the 
main protocol due to changes in BMS protocol standards. 
Note: The substudy now includes PF-ILD participants as well as IPF participants. The text has 
been updated accordingly.
Positron Emission Tomography (PET) Tracer Substudy in 
Pulmonary Fibrosis (IPF or PF-ILD) Participants
Site-specific Amendment Number 01
Site Numbers: Qualified PET-Tracer sites
This protocol amendment is filed to IND 139,558, and also to the
PET tracer (BMS-986327) IND 142,580 
1
PROTOCOL SUMMARY
1.3
Schedule of Activities
The assessments in APPENDIX 8 Table 1 will be conducted in addition to the assessments in the 
main protocol for all participants enrolled at sites participating in the amendment.
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Table 1:
Positron Emission Tomography Imaging Procedural Outline (IM027040)
Screening Period 
(Day 42 to Day-1)
Treatment (Day 1 to Week 26)
Notes
Day 8
Day 29
Week 1
(+ 7 days)
Week 4
(± 7 days)
Informed consent for 
substudy
X
The participant must complete informed consent and be 
enrolled in the main study prior to providing consent for 
the substudy in a separate ICF that must be signed prior 
to the PET-CT scan administered during the screening 
period.
[18F]-BMS-986327 
administration
X
X
X
IV bolus injection prior to PET-CT scan.
PET-CT scan
X
X
X
The first PET-CT scan will be administered during 
screening. A second PET-CT at Week 1 must occur after 
at least 7 days of continuous dosing with main study 
treatment and approximately 3.5 hours (after a meal) or 
approximately 1.5 hours (without a meal) after the 
morning dose of main study treatment on the day of the 
visit. The third PET-CT scan will be performed at 
Week 4 (± 7 days) prior to the morning dose of main 
study treatment on the day of the visit. The PET scan 
visit may occur on a different day from the main protocol 
visit.
BMS-986278 PK 
sample
See Notes
See Section 8.5.3 of APPENDIX 8 for further details.
Vital signs
X
X
X
Vital signs (BP, pulse oxygen, HR) will be monitored per 
local site standard of care. Vital signs taken before and 
after tracer injection will be reported to the sponsor.
Adverse events for 
PET scan visits
X
X
X
Participants will be advised to report any symptoms that 
occur within 24 hours following PET scan visit. Sponsor 
will collect events that are reported to occur within 
24 hours following PET scan visit. See Section 8.2 of 
APPENDIX 8.
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BP = blood pressure; CT = computed tomography; HR = heart rate; ICF = informed consent form; IV =intravenous; PET = positron emission tomography; 
PK = pharmacokinetics 
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2
INTRODUCTION
The purpose of this site-specific amendment is to include evaluation of a positron emission 
tomography (PET) imaging tracer, [18F]BMS-986327, as part of the ongoing “Multicenter, 
Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of the Efficacy and the Safety 
and Tolerability of BMS-986278 in Participants with Pulmonary Fibrosis” (Clinical Protocol 
IM027040).
Approximately 12 to 15 pulmonary fibrosis (IPF or PF-ILD) participants (approximately equal 
distribution between main study treatment arms: 30 mg BMS-986278, 60 mg BMS-986278, and 
placebo) will have [18F]BMS-986327 PET-computed tomography (CT) imaging under this 
site-specific amendment across qualified centers. 
2.2
RATIONALE FOR [18F]BMS-986327 PET
For many therapies, the level of specific target engagement by therapeutic drugs appears to be 
related to response, though direct measurement requires specialized assays. Currently, there are no 
existing biomarkers to assess target engagement of lysophosphatidic acid receptor (LPA1)
antagonist therapies, especially at the site of disease in IPF (ie, the lung). Consequently, a 
comprehensive and quantitative approach to assess LPA1 target engagement is needed to help 
establish a relationship between the level of target engagement, dose selection, and potential 
patient benefit as a result. Human imaging studies with target-specific PET tracers have been 
utilized in IPF and other diseases to directly visualize specific organ uptake and quantify the level 
of drug target engagement.1,2
An ongoing Phase 1 trial (IM033-002) involving [18F]BMS-986327 – an 18F-labeled PET imaging 
agent engineered to specifically bind to LPA1, – is being conducted in normal healthy volunteers 
as well as participants with IPF at baseline. As [18F]BMS-986327 directly competes with 
BMS-986278 and other LPA1 antagonists for binding to LPA1, we anticipate that PET imaging 
with [18F]BMS-986327 will reflect the level of target engagement of these therapeutic molecules. 
Preclinical studies have shown the ability of [18F]BMS-986327 to demonstrate dose-dependent 
target engagement of BMS-986278 in the lungs of animal models. We hypothesize that PET 
imaging with [18F]BMS-986327 will allow for in vivo quantification of LPA1 drug target 
engagement in the lungs of study participants receiving BMS-986278 therapy. Furthermore, 
evaluation of target engagement at 2 key time points – maximum observed plasma concentration 
(Cmax) and minimum observed plasma concentration (Ctrough) – will help to elucidate the level 
of drug target interaction across the entire dosing period. We also hypothesize that target 
engagement data, together with additional pharmacokinetics (PK)/pharmacodynamics biomarkers, 
will help determine the appropriate dose(s) of LPA1 antagonist therapy to study in future clinical 
trials with this asset. 
2.3
BENEFIT/RISK ASSESSMENT
Each participant may receive up to three [18F]BMS-986327 PET-CT scans if deemed appropriate. 
Based on previous practice in similar PET studies, tracers are administered as a microdose 
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(< 100 μg). An initial dose of 222 MBq of [18F]BMS-986327 was selected based on the 
preliminary data from nonclinical radiation dosimetry studies, with the gallbladder wall as the 
dose-limiting organ.3
The estimated radiation dose of administering 222 MBq of 
[18F]BMS-986327 is approximately 7.11 mSv (male) to 9.04 mSv (female). The estimated dose 
from a low-dose CT is about 1.5 to 3 mSv. Thus, the total radiation exposure from each 
[18F]BMS-986327 PET-CT scan will be approximately 8.61 to 12.04 mSv, which is less than or 
equal to the radiation of a conventional diagnostic CT scan (~ 15 mSv). At such low radiation 
exposures, scientists disagree about the amount of health risk, and there may be no additional risk 
at all. Upon availability of human dosimetry data from the ongoing Phase 1 clinical trial, 
IM033-002, the administered dose of [18F]BMS-986327 may be adjusted, if necessary, but not to 
exceed microdose guidelines per ICH M3(R2).
Imaging objectives and endpoints are listed in APPENDIX 8 Table 2 below.
3
IMAGING OBJECTIVES AND ENDPOINTS
Table 2:
Objectives and Endpoints
Objectives
Endpoints
Primary

Not applicable

Not applicable
Secondary

Not applicable

Not applicable
Exploratory

Assess organ and tissue distribution of 
[18F]BMS-986327 before and after administration 
of LPA1 antagonist BMS-986278

Assess lung target engagement of BMS-986278

Calculated SUV and/or VT in lung and 
other key organs and tissues

Additional endpoints may be evaluated as 
data become available
LPA1 = lysophosphatidic acid receptor; PET = positron emission tomography; SUV = standardized uptake values; 
VT = tracer lung volume of distribution
4
STUDY DESIGN
4.1
OVERALL DESIGN
The [18F]BMS-986327 PET-CT will be performed at selected qualified sites, for participants 
currently participating in the main IM027040 study, and will be implemented after Health 
Authority review and Institutional Review Board/Ethics Committee approval, in compliance with 
all applicable laws, rules, and regulations.
The first PET-CT scan will be performed during the screening period after the substudy-specific 
informed consent form has been signed. The second PET-CT scan will be performed at the Week 1 
visit (after at least 7 days of continuous dosing with main study treatment) approximately 3.5 hours 
(after a meal) or approximately 1.5 hours (without a meal) after the morning dose of main study 
treatment on the day of the visit. The third PET-CT scan will be performed at the Week 4 visit 
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(± 7 days) prior to the morning dose of main study treatment on the day of the visit. See Section 8.1 
of APPENDIX 8 for further details.
The study design schematic is presented in APPENDIX 8 Figure 1 below.
Figure 1:
PET-Tracer Study Design Schematic
CT = computed tomography; PET = positron emission tomography
a Week 1 PET-CT scan should occur after at least 7 days of continuous dosing with main study treatment.
4.2
NUMBER OF PARTICIPANTS
Approximately 12 to 15 participants distributed approximately evenly across main study treatment 
arms (30 mg BMS-986278, 60 mg BMS-986278, and placebo) who are enrolled in the IPF or 
PF-ILD cohorts of the IM027040 study across multiple qualified imaging centers will participate 
in [18F]BMS-986327 PET-CT imaging assessments.
5
STUDY POPULATION
5.1
INCLUSION CRITERIA
Participants enrolled in IM027040 (IPF or PF-ILD cohort), who can be imaged at qualified sites, 
and do not meet any PET imaging exclusion criteria will be eligible to participate in this PET 
imaging study. Participants will sign a separate PET imaging informed consent form.
5.2
EXCLUSION CRITERIA
Participants with the following condition(s) may be considered for participation in the main study, 
but will not undergo the [18F]BMS-986327 PET-CT imaging:
1) Participants with issues that prevent them from lying still for PET-CT imaging procedure;
2) Participants who have received therapeutic radiopharmaceutical within 7 days prior to 
participation in this study;
3) Participants who do not have adequate venous access for tracer injection;
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4) Participation 
in 
other 
research 
studies 
involving 
clinical 
PET 
scans 
(eg, 
fluorodeoxyglucose-PET) within 24 hours prior to and after injection of [18F]BMS-986327.
6
TREATMENT
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device intended to be administered to a study participant according to the study.
An investigational product (IP), also known as investigational medicinal product (IMP) in some 
regions, is defined as a pharmaceutical form of an active substance or placebo being tested or used 
as a reference in a clinical study, including products already with a marketing authorization but 
used or assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form.
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as 
noninvestigational products (non-IP)/noninvestigational medicinal product (non-IMP).
Study drug includes IP/IMP as shown in the APPENDIX 8 Table 3 below.
Table 3:
BMS-986278 PET Imaging Precursor Materials for IM027040 
(Qualified Sites or Vendors Only)
Product 
Description
Potency
IP/ 
Non-IMP
Blinded or 
Open Label
Packaging/Appearance
Storage 
Conditions (per 
label)
BMT-382761
3 mg/mL  
(1.87 gm
/1 vial)
IP
Open Label
Glass vials closed with 
stoppers and sealed/ 
Liquid
-20°C, protected 
from light
Note: [18F]BMS-986327 will be prepared on site or at a local vendor prior to administration. 
IMP = investigational medicinal product; IP = investigational product; PET = positron emission tomography
Tracer production and radiolabeling with F-18 will be performed according to Standard Operating
Procedures and performed according to state-of-the-art Good Manufacturing Practice standards.
For details on prepared drug storage, preparation, and administration, refer to the most recent
version of the BMS-986327 Investigator Brochure.3
7
DISCONTINUATION CRITERIA
Refer to main protocol.
8
STUDY ASSESSMENTS AND PROCEDURES
Each participant will receive three [18F]BMS-986327 PET-CT scans. 
Approximately 12 to 15 IPF or PF-ILD participants will undergo a baseline [18F]BMS-986327 
PET-CT scan within the screening window.
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Two additional [18F]BMS-986327 PET-CT scans will be performed during main study treatment 
dosing to assess drug target engagement at nominal Cmax [Week 1 (Day 8; + 7 days)] and Ctrough 
[Week 4 (Day 29; ± 7 days)] time points. 
Images will be acquired per specifications provided in a separate IM027040 Image Acquisition 
Guideline document. All PET-CT images will be collected and submitted to an imaging core lab 
for central analysis.
8.1
[18F]BMS-986327 IMAGING
Images will be acquired per specifications provided in a separate IM027-040 Image Acquisition 
Guideline document.
8.2
ADVERSE EVENTS
Participants will be advised to report any symptoms that occur within 24 hours following PET scan 
visit. Sponsor will collect events that are reported to occur within 24 hours following PET scan 
visit in the study case report form.
8.5
PHARMACOKINETICS
8.5.3 PET TRACER SUBSTUDY
Plasma PK samples of BMS-986278 will be collected for analysis of target engagement at the 
times described in APPENDIX 8 Table 4 below. PK samples will be collected at 3.5 hours (after 
a meal) or 1.5 hours (without a meal) after the morning dose of main study treatment on Day 8 
(+ 7 days) and prior to the morning dose of main study treatment on Day 29 (± 7 days). 
Methodology for analysis of PK samples is described in the main protocol.
Table 4:
Pharmacokinetic Sampling Schedule for PET Tracer Substudy
Study Day of Sample 
Collection
Event
Time Relative to 
Main Study Treatment 
Morning Dose (hr:min)
BMS-986278 Plasma PK 
Sample
Day 8 (+ 7 days)
1:30 (fasted) or 3:30 (fed)
X
Day 29 
(± 7 days)
Predose
0:00
X
9
STATISTICAL CONSIDERATIONS
The small sample size is not based on statistical power considerations, but is intended to provide 
sufficient data to enable comparison of lung target engagement across treatment arms.
Methodology for exploratory biomarker analyses including [18F]BMS-986327 PET-CT will be 
described in the statistical analysis plan and imaging corelab charter. Concentration summaries 
will not be reported for PK samples collected for the PET tracer substudy.
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10
REFERENCES
1.
Maher T, Simpson J, Porter J, et al. Late Breaking Abstract - A PET imaging study to 
confirm target engagement in the lungs of patients with IPF following a single dose of a novel 
inhaled avβ6 integrin inhibitor. European Respiratory Journal. 2019;54(suppl 63):OA246.
2.
Lukey PT, Coello C, Gunn R, et al. Clinical quantification of the integrin alphavbeta6 by 
[(18)F]FB-A20FMDV2 positron emission tomography in healthy and fibrotic human lung 
(PETAL Study). Eur J Nucl Med Mon Imaging 2019.
3.
BMS-986327 LPA1 PET Tracer Investigator’s Brochure, Version 01. Bristol-Myers 
Squibb Company, 2019. Document Control No. 930137711.
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APPENDIX 9
PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
Overall Rationale for the Protocol Amendment 04, 21-Dec-2021
The primary purpose of this protocol amendment is to implement the following changes:

Revise the positron emission tomography (PET) tracer substudy to allow incorporation of 
participants with non–idiopathic pulmonary fibrosis, progressive fibrotic interstitial lung 
disease (PF-ILD)

Clarify phrasing in select inclusion and exclusion criteria

Add 2 secondary endpoints evaluating the effect of BMS-986278 treatment
In addition, clarifications were made throughout the protocol amendment to align with updated 
BMS protocol regulations, requirements, and best practices.
All changes applied to the body were applied to the synopsis, as necessary, although not all 
synopsis changes are included in the table below.
Generally, only major additions and deletions are provided in this summary of changes, and all 
minor grammatical, formatting, rephrasing, stylistic changes, or clarifications, as well as 
reorganizational changes are not included.
SUMMARY OF KEY CHANGES OF PROTOCOL AMENDMENT 04
Section Number & Title
Description of Change
Brief Rationale
2 Schedule of Activities
-Table 1
-Table 2
Added footnote “a” to both Schedule 
of Activities tables
To accommodate participant 
vacation and scheduling needs
2 Schedule of Activities
-Table 2
5.1.2.1 Blood Pressure Monitoring
7.4 Dosage Modification
9.4.2 Vital Signs
Clarified procedures for participants 
with asymptomatic or symptomatic 
low BP criteria at post-Day 1 study 
visits
To rectify an error in the previous 
protocol version
4 Objectives and Endpoints
10.3.2 Secondary Endpoints
10.3.3 Exploratory Endpoints
Clarified that characterizing the PK 
of BMS-986278 in PF-ILD 
participants is an exploratory 
objective, not a secondary objective
To provide for a potential lower 
sample size in the intensive PK 
substudy of the PF-ILD cohort
Added time point (Week 20) to 
secondary endpoint evaluating the 
effect of BMS-986278 treatment
To ensure consistency between 
endpoint analyses
Added 2 secondary efficacy 
endpoints evaluating the effect of 
BMS-986278 treatment
To align secondary endpoints with 
those listed in the product labels 
of existing anti-fibrotic 
medications
5.1.2.1 Blood Pressure Monitoring
7.4 Dosage Modification
Clarified that dose reductions should 
be reported on the case report form, 
not reported to the Medical 
Monitor/Study Director
To clarify best procedures for 
reporting a dose reduction
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SUMMARY OF KEY CHANGES OF PROTOCOL AMENDMENT 04
Section Number & Title
Description of Change
Brief Rationale
6.1 Inclusion Criteria
Inclusion criterion 2)a)i was updated 
to create new criterion 2)a)v. 
Criterion 2)a)i was no longer 
applicable to this protocol.
To clarify that screening period is 
not included in the 7-year 
diagnosis time frame
6.2 Exclusion Criteria
Exclusion criterion 1)p was updated 
to create new criterion 1)y. Criterion 
1)p is no longer applicable to this 
protocol.
To clarify that potential 
participants should only be 
excluded if on an active transplant 
list
Exclusion Criterion 2)f was updated 
to create new criterion 2)i. Criterion 
2)f is no longer applicable to this 
protocol.
To clarify exclusion criterion 
regarding long-acting and short-
acting phosphodiesterase 5 
inhibitors
Exclusion Criterion 3)c was updated 
to create new criterion 3)i. Criterion 
3)c is no longer applicable to this 
protocol.
To correct study definition of 
uncontrolled hypertension
Exclusion Criterion 3)g was updated 
to create new criterion 3)j. Criterion 
3)g is no longer applicable to this 
protocol.
To correct “baseline” total 
bilirubin to “screening” total 
bilirubin
Exclusion Criterion 3)k was added.
To add WBC, hemoglobin, and 
platelet minimums for 
participation
6.4.1 Retesting During Screening
Changed rescreening procedure so 
potential participants do not need to 
repeat HRCT scan if rescreen takes 
place within 10 weeks of 
randomization 
To reduce burden on participants 
who are admitted after rescreening
7.7.1 Prohibited and/or Restricted 
Treatment
Clarified text from administrative 
letter 03 (13-Apr-2021)
To clarify that prescribed 
medications listed in the exclusion 
criteria and Section 7.7 are still 
prohibited, even if the participant 
has a clinical condition
9.5.1 Sparse PK Sampling (All 
Participants no Participating in PK 
Substudy), Table 6
9.5.2 Intensive PK Substudy, Table 
7
9.5.3 Sparse PK Sampling for 
Optional Treatment Extension, 
Table 8
9.6 Biomarkers, Table 9
Added footnote to each table 
regarding participants who 
discontinue early
To clarify that no further PK 
samples should be taken at 
subsequent visits for participants 
who discontinue treatment early
10.2 Populations for Analysis
Corrected definition of Safety 
population
To correct wording that was 
previously unclear
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SUMMARY OF KEY CHANGES OF PROTOCOL AMENDMENT 04
Section Number & Title
Description of Change
Brief Rationale
10.4.3 Safety Analyses
Clarified planned analysis of safety 
information
To clarify that PF-ILD cohort will 
be analyzed separately from the 
primary study cohort of IPF
APPENDIX 8 Site-specific Protocol 
for Qualified PET-Tracer Sites in 
US (new appendix; previously was 
separate protocol)
Combined site-specific protocol for 
qualified PET-Tracer sites into a new 
appendix, as opposed to a separate 
amendment
To allow PF-ILD participants to 
participate in the PET Tracer 
substudy
Title Page
2 Schedule of Activities
7 Treatment
7.3.2 Circumstances for Unblinding
7.5 Investigational Product 
Handling/Storage Accountability
8.1 Discontinuation from Study 
Treatment
8.2 Discontinuation from the Study
8.2.1 Individual Discontinuation 
Criteria (new section)
9.2 Adverse Events
9.2.2 Method of Detecting 
AEs/SAEs
9.2.4 Regulatory Reporting 
Requirements for SAEs
9.2.7 Laboratory Test Result 
Abnormalities
9.2.8 Potential Drug Induced Liver 
Injury (DILI)
9.2.9 Other Safety Considerations
9.3 Overdose
9.4.4 Clinical Safety Laboratory 
Assessments
APPENDIX 2 Study Governance 
Considerations
APPENDIX 3 Adverse Events and 
Serious Adverse Events: Definitions 
and Procedures for Recording, 
Evaluating, Follow-up, and 
Reporting
APPENDIX 4 Women of 
Childbearing Potential Definitions 
and Methods of Contraception
Updated with most recent BMS 
Protocol Model Document language 
and organizational requirements
To align with up-to-date BMS 
protocol regulations, 
requirements, and best practices.
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14 Jan 2021, Revised Protocol 03,
BMS Confidential
Final Approved
OVERALL RATIONALE FOR REVISED PROTOCOL 03
The primary rationale for this revised protocol is in response to the evolving landscape of treatment 
of non-IPF ILD, as the intention is to enroll a representative population of patients with 
progressive, non-IPF ILD. Most fibrotic ILD patients with a progressive phenotype, ie, the 
PF-ILD cohort in this study, are treated with immunosuppressive therapies and an increasing 
number of these patients are being treated with anti-fibrotic therapies as well. In response to these 
changes, the protocol is being updated to allow for a number of certain stable background 
ILD-targeting therapies in the PF-ILD cohort.
In addition, clarifications were made throughout the revised protocol to maintain consistency. 
All changes applied to the body were applied to the synopsis, as necessary, although not all 
synopsis changes are included in the table below.
Generally, only major additions and deletions are provided in this summary of changes, and all 
minor grammatical, formatting, rephrasing, stylistic changes, or clarifications, as well as 
reorganizational changes are not included. 
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
Title Page
Updated Clinical Trial 
Physician/Medical Monitor 
name and contact information.
To integrate the Administrative 
Letter 01 clarification.
Added Clinical Scientist name 
and contact information.
To adhere to the BMS template 
structure.
Section 1.3 Schedule of 
Activities
Added an “X” to the OTE 
Day 1 column for clinical 
laboratory samples
(Table 2).
 
 clinical 
laboratory samples will be 
collected on Day 1 of the OTE.
Section 2.4.3.4
Nonclinical Combination 
Toxicology
Updated the paragraph 
discussing nintedanib.
To further clarify the language.
Section 2.5.1
COVID-19-related 
Benefit/Risk Assessment
Added a new section to 
describe a COVID-19-related 
risk assessment.
To provide guidance for site 
investigators on conducting this 
study in IPF and PF-ILD patients
during the pandemic.
 
 
 
7
4.0
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930149229
4.0
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Approved
1.0
v

Clinical Protocol
IM027040
BMS-986278
LPA1 Antagonist
14 Jan 2021, Revised Protocol 03,
BMS Confidential
Final Approved
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
Section 3 Objectives and 
Endpoints
Added an additional
exploratory objective and 
endpoint related to SARS-
CoV-2 serologic status to the 
main study and OTE.
To collect baseline and end of 
study serum samples from 
participants to allow for an 
optional analysis of SARS-CoV-2 
serologic status on participants 
with IPF or PF-ILD receiving 
BMS-986278.
Section 4.1 Overall 
Design 
Updated language to allow 
participants with PF-ILD to 
remain on stable background 
therapies.
The landscape of non-IPF ILD is 
evolving and the intention is to 
enroll a representative population 
of real-world of non-IPF ILD.  
Most patients with a progressive 
phenotype (ie, PF-ILD) are 
treated with immunosuppressive 
therapies. Leading therapies 
include mycophenolate mofetil 
(or mycophenolic acid), 
azathioprine and/or tacrolimus. 
Furthermore, many patients are 
now being treated with nintedanib 
or pirfenidone.  
Updated screening period 
from 28 to 42 days. This 
update also applies to other 
applicable sections throughout 
the protocol. 
To offer additional flexibility to 
participants and study sites in
order to meet enrollment 
requirements. 
Section 4.1.2 Treatment 
Period
Added language to the 
PF-ILD cohort to include
stratification by background 
therapy category. This 
language has been 
implemented throughout the 
protocol where applicable.
Now that PF-ILD participants are 
permitted to remain on stable 
background therapy, there is a 
desire for balance within the 
treatment cohorts. This can be 
achieved by stratifying by the 
broad treatment categories
indicated.
Section 4.1.2.1 Blood 
Pressure Monitoring
Clarified orthostatic 
hypotension and orthostatic 
tachycardia definitions. These 
clarifications were also made 
to Section 8.2.5, as applicable.
To align with the definitions in 
the vendor manual.
 
 
8
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930149229
4.0
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Approved
1.0
v

Clinical Protocol
IM027040
BMS-986278
LPA1 Antagonist
14 Jan 2021, Revised Protocol 03,
BMS Confidential
Final Approved
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
Clarified that findings of 
orthostatic hypotension and 
orthostatic tachycardia must 
be confirmed by retest.
To ensure uniform BP data 
collection.
Section 4.4.1 Rationale 
for Optional Treatment 
Extension (OTE)
Added a new section to 
provide context for the OTE.
To incorporate changes from the 
UK-specific revised protocol.
Section 5 Study 
Population
Added an additional 
paragraph to the inclusion and 
exclusion criteria introduction
to further clarify protocol 
entry criteria.
To incorporate changes from the 
UK-specific revised protocol.
Section 5.1 Inclusion 
Criteria
Inclusion criterion (IC) 1)a)
was updated to 1)c) to remove 
the reference to legally 
authorized representative.
To incorporate changes from the 
UK-specific revised protocol and 
the 
 site-specific 
amendment.
IC 2)b)i) was removed.
Any PF-ILD participants will 
have had to demonstrate 
progression within 24 months, 
which negates the need for the 
7-year disease duration cutoff.
IC 2)b)iv), v), and vi) were 
added.
To permit stable 
immunosuppressive and anti-
fibrotic background therapies for
PF-ILD participants.
Section 5.2 Exclusion 
Criteria
Exclusion criterion (EC) 
1)d)ii) was updated to 1)d)iv).
To further clarify existing 
terminology.
EC 1)d)iii) was removed.
Stable anti-fibrotic background 
therapies are to be permitted for 
PF-ILD participants.
EC 1)i) was updated to 1)w).
To further clarify existing 
terminology in light of the 
COVID-19 pandemic. 
EC 1)u) was updated to 1)x).
To further clarify existing 
terminology in light of the 
COVID-19 pandemic.
 
 
9
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930149229
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Approved
1.0
v

Clinical Protocol
IM027040
BMS-986278
LPA1 Antagonist
14 Jan 2021, Revised Protocol 03,
BMS Confidential
Final Approved
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
EC 2)b) was updated to 2)h).
To permit stable 
immunosuppressive background 
therapies for PF-ILD participants.
EC 3)b) was updated to 3)h).
To ensure uniform BP data 
collection.
EC 3)f)i)&ii) were removed.
To enable the enrollment of older 
adults with lung fibrosis. Slight 
widening of the QRS interval is 
very common with common 
cardiac comorbid conditions.  
Similarly, it is not uncommon to 
have some prolongation of the PR 
interval in elderly patients.   
Removing these restrictions is 
appropriate for this patient 
population and allows for better 
success in recruiting a 
representative study population of 
individuals suffering with lung 
fibrosis.
EC 4)c) was added to further 
clarify protocol entry criteria.
To incorporate changes from the 
UK-specific revised protocol and 
the 
 site-specific 
amendment.
Section 6.2 Method of 
Treatment Assignment
Added language to include 
stratification by background 
therapy category for the 
PF-ILD cohort.
Refer to rationale for 
Section 5.1.2.
Section 6.6 Treatment 
Compliance.
Added language about dosing 
diaries as part of treatment 
compliance.
To integrate the Administrative 
Letter 01 clarification. 
Section 6.7 Concomitant 
Therapy
Added new language to allow 
for stable immunosuppressive 
background therapies.
Refer to rationale for Section 5.1.
Added language regarding 
concomitant anti-fibrotic 
therapies.
To clarify that pirfenidone and 
nintedanib are not allowed in 
combination with one another 
during the main study.
 
 
10
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930149229
4.0
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Approved
1.0
v

Clinical Protocol
IM027040
BMS-986278
LPA1 Antagonist
14 Jan 2021, Revised Protocol 03,                          BMS Confidential
Final Approved
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
Section 6.7.1 Prohibited 
and/or Restricted 
Treatments
Removed sentence about 
prohibiting anti-fibrotics.
Stable anti-fibrotic background 
therapies are to be permitted for 
PF-ILD participants. 
Section 7.1
Discontinuation from 
Study Treatment
Added a subbullet to bullet #5 
to clarify that a participant can 
be discontinued from the 
study in case of disease 
progression or if it is in the 
participant’s best interest to 
start any standard of care 
treatment that is prohibited in 
the study.
To incorporate changes from the 
UK-specific revised protocol.
Section 8.1.1 Forced 
Vital Capacity
Added language to clarify 
how and when spirometry 
testing can be performed.
To integrate the Administrative 
Letter 01 clarification and to 
provide more flexibility for study 
sites.
Section 8.1.2 Diffusing 
Capacity of Carbon 
Monoxide
Added language to clarify 
when the DLCO test can be 
performed.
To provide more flexibility for 
study sites.
Removed requirement for 
DLCO calculations to be 
recorded on eCRF.
The CRF will be updated to 
capture the raw data, therefore
study sites will no longer be 
required to enter calculated 
DLCO values.
Section 8.1.3 High-
resolution Computed 
Tomography
Added language to include 
stratification by background 
therapy category for the 
PF-ILD cohort.
Refer to rationale for 
Section 5.1.2.
Section 8.1.4 Clinical 
Outcome Assessments
Revised language regarding 
timing of COAs. Language 
was also updated in the COA 
notes in the Schedule of 
Activities in Section 1.3.
To integrate the Administrative 
Letter 01 clarification, as a means 
to give study sites flexibility in 
the order of study procedures 
being performed.
 
 
 
11
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930149229
4.0
v
Approved
1.0
v

Clinical Protocol
IM027040
BMS-986278
LPA1 Antagonist
14 Jan 2021, Revised Protocol 03,
BMS Confidential
Final Approved
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
Section 8.1.4.6 6-Minute 
Walk Test
Added language regarding 
timing of 6-MWT 
administration. Language was 
also updated in the 6-MWT 
notes in the Schedule of 
Activities in Section 1.3.
To provide clarification for study 
sites.
Section 8.2.9 Other 
Safety Considerations
Added language for collecting
AEs and SAEs related to 
COVID-19.
To ensure COVID-19 events are 
captured appropriately in the 
CRF.
Section 8.4.4 Laboratory 
Assessments
Provided guidance on
Hepatitis B virus DNA 
serology testing.
To integrate the Administrative 
Letter 01 clarification.
Section 8.5
Pharmacokinetics
Added language for recording 
date and time of study 
treatment administration the 
day prior to study visits. 
Collection of the morning and 
evening study dose details from 
the day prior to PK sampling is 
required to accurately assess PK.
Section 8.5.1 Sparse PK 
Sampling (All 
Participants not 
Participating in PK 
Substudy)
Added language to footnote b 
in Table 6.
Refer to rationale for Section 9.5.
Section 8.5.2 Intensive 
PK Substudy
Added language to footnote b 
in Table 7.
Refer to rationale for Section 9.5.
Modified language describing 
the number of participants per 
treatment arm.
To allow flexibility in the number 
of participants per treatment arm.
Section 8.6 Biomarkers
Added a paragraph for the 
collection of serum for 
possible assessments of 
SARS-CoV-2 serologic status. 
A column for the serum 
collection was also added to 
Table 9.
To allow for possible 
measurements of SARS-CoV-2 
serology.
 
 
12
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930149229
4.0
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Approved
1.0
v

Clinical Protocol
IM027040
BMS-986278
LPA1 Antagonist
14 Jan 2021, Revised Protocol 03,
BMS Confidential
Final Approved
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
Section 9.2 Populations 
for Analyses
Updated Full Analysis Set
(FAS) population definition.
To clarify the intent-to-treat 
principle consistent with the ICH 
E9 guidance. The updated FAS 
definition is as complete as 
possible and as close as possible 
to the intention-to-treat ideal of 
including all randomized subjects. 
Updated Safety population 
definition.
To clarify participants will be 
analyzed according to the actual 
treatment received in case of mis-
treatment. 
Section 9.3.3 Exploratory 
Endpoints
An additional exploratory 
endpoint was added to the 
Biomarkers category.
Refer to rationale for Section 3.
APPENDIX 3
ADVERSE EVENTS 
AND SERIOUS 
ADVERSE EVENTS: 
DEFINITIONS AND 
PROCEDURES FOR 
RECORDING, 
EVALUATING, 
FOLLOW-UP AND 
REPORTING
Added definitions of mild, 
moderate, and severe AEs.
To provide definitions of AE 
intensity within the protocol.
 
 
13
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930149229
4.0
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Approved
1.0
v

Clinical Protocol 
IM027040 
BMS-986278 
LPA1 Antagonist 
25 Jun 2020, Revised Protocol 02,                            BMS Confidential 
Final Approved 
 
4 
OVERALL RATIONALE FOR REVISED PROTOCOL 02 
The primary rationale for this revised protocol is to include an “optional treatment extension” 
(OTE) for participants with either idiopathic pulmonary fibrosis (IPF) or non-IPF, progressive 
fibrotic interstitial lung disease (PF-ILD) that complete the 26-week main study. The objectives of 
the OTE are to enhance understanding of the safety, tolerability, and efficacy of BMS-986278 in 
lung fibrosis patients.  
In addition, clarifications were made throughout the revised protocol to maintain consistency.  
All changes applied to the body were applied to the synopsis, as necessary, although not all 
synopsis changes are included in the table below. 
Generally, only major additions and deletions are provided in this summary of changes, and all 
minor grammatical, formatting, rephrasing, stylistic changes, or clarifications, as well as 
reorganizational changes are not included.   
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 02 
Section Number & Title 
Description of Change 
Brief Rationale 
Title Page 
Changed Medical Monitor. 
Study Director will resume 
Medical Monitor responsibilities 
for this study. 
Section 1.1 Synopsis 
Added the OTE. 
Clarified main study vs OTE. 
Clarified that dose reduction is 
permitted for both the main 
study and OTE (also in 
Section 1.2). 
To enhance understanding of the 
safety, tolerability, and efficacy of 
BMS-986278 in lung fibrosis 
patients, an OTE was added for 
IPF and PF-ILD participants that 
complete the 26-week main study. 
Section 1.2 Schema and 
Section 4 Study Design 
Added the OTE schema 
(Figure 3) and modified the 
main study schemas (Figure 1 
and Figure 2). 
To illustrate the OTE study 
design.  
Section 1.3 Schedule of 
Activities  
Clarified the note in Table 1 
regarding posttreatment 
HRCT requirement. 
All participants are to have HRCT 
performed at Week 26 in the main 
study.  
Added spirometry 
measurements to the Week 20 
visit in Table 1.  
To provide an additional FVC 
assessment to more accurately 
estimate the slope of ppFVC. 
Permitted enrollment of  
PF-ILD participants in 
intensive PK substudy in 
Table 1.   
To collect additional PK data 
from participants in the PF-ILD 
cohort.  
3.0
Approved
930149229
3.0
v
Approved
1.0
v

Clinical Protocol 
IM027040 
BMS-986278 
LPA1 Antagonist 
25 Jun 2020, Revised Protocol 02,                            BMS Confidential 
Final Approved 
 
5 
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 02 
Section Number & Title 
Description of Change 
Brief Rationale 
Added Table 2 OTE Schedule 
of Activities.   
To list all OTE study procedures. 
Section 2.3 Study 
Rationale 
Added language for the OTE.  To describe the OTE rationale. 
Section 3 Objectives and 
Endpoints 
Added exploratory objectives 
and endpoints for the OTE. 
To continue assessing the safety, 
tolerability, and select efficacy 
measures of BMS-986278 in the 
OTE. In addition, select COAs, 
PK, and biomarkers will be 
collected. 
Adjusted the secondary and 
exploratory endpoints in 
Table 3 and in the Synopsis 
(Section 1.1).  
All secondary and exploratory 
endpoints using the expression 
“>xx% absolute decline in FVC 
(mL)” were deleted, as there are 
no known clinically relevant 
cutoffs for the decline of FVC in 
mL in the literature.  
Furthermore, the definition for 
pulmonary fibrosis progression-
free survival was modified.  
 
Clarified that participants in 
the OTE need to adhere to BP 
monitoring requirements in 
Section 4.1.2.1 Blood Pressure 
Monitoring. 
All participants in the OTE must 
continue to follow BP monitoring 
to maintain blinding, as 
participants receiving placebo in 
the main study will be exposed to 
BMS-986278 for the first time in 
the OTE.  
Section 4 Study Design  
Added the OTE study design 
schema (Figure 3) and  
Section 4.1.4 Optional 
Treatment Extension.  
Revisions made throughout 
Section 4 to include the OTE.  
To enhance understanding of the 
safety, tolerability, and efficacy of 
BMS-986278 in lung fibrosis 
patients, an OTE was added for 
IPF and PF-ILD participants that 
complete the 26-week main study.  
 
Added “end of study” 
definition to Section 4.3. 
 
3.0
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930149229
3.0
v
Approved
1.0
v

Clinical Protocol 
IM027040 
BMS-986278 
LPA1 Antagonist 
25 Jun 2020, Revised Protocol 02,                            BMS Confidential 
Final Approved 
 
6 
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 02 
Section Number & Title 
Description of Change 
Brief Rationale 
Section 5 Study 
Population 
Added a note referring to OTE 
guidance on all applicable 
inclusion criteria (Section 5.1) 
and exclusion criteria  
(Section 5.2). 
To clarify which concomitant 
therapies and prohibited/restricted 
treatments will/will not be 
permitted in the OTE. 
Added “Known” to the 
beginning of Exclusion 
Criterion 1) k). 
To clarify that only those 
participants that have a pre-
existing history of left-ventricular 
dysfunction are excluded from the 
study (ie, screening 
echocardiography to assess 
ejection fraction not required). 
Added Exclusion Criterion 
3) g). 
 
Added Exclusion Criteria 5) a) 
and b). 
 
Section 6 Treatment 
Revisions made throughout 
Section 6 to include the OTE. 
 
To include details on study 
treatment, treatment assignment, 
blinding, dose modification, and 
concomitant therapies in the OTE. 
Revised treatment compliance 
formula in Section 6.6. 
The number of tablets taken is 
collected in the eCRF. 
Section 7.1 
Discontinuation from 
Study Treatment 
Clarified discontinuation 
criteria in the OTE. 
Discontinuation criteria apply to 
the main study and the OTE.  
Section 8 Study 
Assessments and 
Procedures 
Clarified timing of spirometry 
assessment.  
Removed FEF25-75 from the 
list of spirometry parameters 
in Section 8.1.1 Forced Vital 
Capacity. 
Spirometry will be performed 
prior to morning dosing. 
The standard FEF25-75 
spirometry test was originally 
provided by the vendor, but it is 
not needed for this study.  
3.0
Approved
930149229
3.0
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Approved
1.0
v

Clinical Protocol 
IM027040 
BMS-986278 
LPA1 Antagonist 
25 Jun 2020, Revised Protocol 02,                            BMS Confidential 
Final Approved 
 
7 
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 02 
Section Number & Title 
Description of Change 
Brief Rationale 
Permitted use of cryobiopsy 
results instead of HRCT at 
screening on a case-by-case 
basis and also clarified when 
HRCT will be performed 
during the OTE in Section 
8.1.3 High-resolution 
Computed Tomography. This 
was also clarified in Section 
5.1 Inclusion Criteria, item 
2)a)ii) (2) and in Section 5.2 
Exclusion Criteria, item 1)d)i) 
To account for the possibility that 
some centers perform cryobiopsy 
and to clarify when HRCT will be 
performed during the OTE.  
Clarified the required safety 
and COA assessments for the 
OTE in Section 8.4 Safety and 
Section 8.1.4 Clinical 
Outcome Assessments. 
To clarify which assessments will 
be performed during the OTE and 
when.  
Clarified additional ECG 
assessments to be performed 
as clinically indicated in 
Section 8.4.3 
Electrocardiograms. 
 
Added a PK sample collection 
at Week 4 (Table 6) of the 
main study in Section 8.5.1 
Sparse PK Sampling. 
To obtain an additional PK trough 
sample from participants 
undergoing the sparse PK 
sampling schedule.  
Modified Section 8.5.2 
Intensive PK Substudy to 
include at least 10 participants 
per arm in both IPF and  
PF-ILD cohorts in the 
intensive PK substudy. 
To obtain intensive PK data from 
the PF-ILD cohort. 
 
Added Section 8.5.3 Sparse 
PK Sampling for OTE. 
To collect sparse PK data from 
participants in the OTE. 
Added biomarker sample 
collections during the OTE in  
Table 9 in Section 8.6 
Biomarkers. 
To explore potential changes in 
biomarkers associated with 
52 weeks of treatment with  
BMS-986278. 
3.0
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930149229
3.0
v
Approved
1.0
v

Clinical Protocol 
IM027040 
BMS-986278 
LPA1 Antagonist 
25 Jun 2020, Revised Protocol 02,                            BMS Confidential 
Final Approved 
 
8 
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 02 
Section Number & Title 
Description of Change 
Brief Rationale 
Section 9 Statistical 
Considerations 
Added a caption title to create 
Table 10. 
 
  
Modified Section 9.4.1.1 
Primary Efficacy Endpoint. 
The model was revised to include 
all factors necessary to estimate 
the rate of change. 
Modified Section 9.3.2 
Secondary Endpoints and 
Section 9.3.3 Exploratory 
Endpoints. 
All secondary and exploratory 
endpoints using the expression 
“>xx% absolute decline in FVC 
(mL)” were deleted, as there are 
no known clinically relevant 
cutoffs for the decline of FVC in 
mL in the literature.   
To include the exploratory 
endpoints for the OTE. 
Modified Section 9.4.4 Other 
Analyses. 
To perform a statistical analysis 
on the PF-ILD cohort once the 
cohort completes the main study. 
To clarify the data presentation 
for the OTE results. 
 
Modified Section 9.4.5 
Interim Analyses.  
To specify that details will be 
described in the DMC Charter and 
SAP.  
Language pertaining to DMC was 
removed and revised wording was 
added to Section 4.1.5. 
 
 
3.0
Approved
930149229
3.0
v
Approved
1.0
v

Clinical Protocol 
IM027040 
BMS-986278 
LPA1 Antagonist 
24 Feb 2020, Revised Protocol 01,                            BMS Confidential 
Final Approved 
 
3 
OVERALL RATIONALE FOR REVISED PROTOCOL 01  
The primary rationale for this revised protocol was to permit stable disease modifying  
anti-rheumatic drug (DMARD) use and the lower age allowed for the PF-ILD cohort to enhance 
recruitment potential of participants with PF-ILD, including rheumatoid arthritis-associated ILD. 
Pregnancy testing for women < 55 years of age was added,
. 
In addition, clarifications were made throughout the revised protocol to maintain consistency.  
Generally, only major additions and deletions are provided in this summary of changes, and all 
minor grammatical, formatting, rephrasing, stylistic changes, or clarifications, as well as 
reorganizational changes are not included.   
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 
Section Number & Title 
Description of Change 
Brief Rationale 
Title Page 
Added Medical Monitor. 
The Medical Monitor was 
confirmed for this study. 
Section 1.3 Schedule of 
Activities, Table 1  
Added eligibility check. 
 
Eligibility check was added to 
clarify that inclusion and 
exclusion criteria must be met at 
screening and Day 1 predose. 
Added pregnancy test. 
Pregnancy test was added 
 
 
Adjusted language to 
“Dispense Study Treatment” 
row.   
To clarify the drug dispensing 
frequency and treatment 
compliance check. 
Modified the language in 
footnote “b” 
To clarify that Day 1 orthostatic 
BP and HR measurements apply 
to all participants. 
Study Acknowledgement/ 
Disclosure 
Removed from Protocol. 
To be included as a separate 
stand-alone document with the 
Study Director/Medical Monitor 
signature. 
Section 4.1.2 Treatment 
Period 
Removed approximate blood 
volumes to be collected from 
participants. 
The estimated blood volume is 
indicated in the ICF. 
2.0
Approved
930149229
2.0
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Approved
1.0
v

Clinical Protocol 
IM027040 
BMS-986278 
LPA1 Antagonist 
24 Feb 2020, Revised Protocol 01,                            BMS Confidential 
Final Approved 
 
4 
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 
Section Number & Title 
Description of Change 
Brief Rationale 
Section 4.1.2.1 Blood 
Pressure Monitoring 
Minor adjustments made 
throughout section. 
To clarify that orthostatic BP and 
HR are required at every 
scheduled visit.  
To specify that participants will 
not receive study treatment during 
scheduled visits if their predose 
orthostatic BP and/or HR meet 
low BP criteria. 
Section 5.1 Inclusion 
Criteria 
 
Revised inclusion criterion  
2)b) for the PF-ILD cohort. 
To clarify the “progression” 
definition for PF-ILD. 
Revised inclusion criteria 
4)a) and 4)b) to lower the age 
limit for PF-ILD cohort from 
40 to 21 years of age. This 
revision was also 
incorporated into sections 1.1 
and 2.5 for consistency. 
IPF is not seen in individuals 
under 40, but as PF-ILD 
represents heterogeneous forms of 
ILD, they can be seen in younger 
adults. This adjustment was made 
to align recruitment potential of a 
broader pool of PF-ILD 
participants. 
Section 5.2 Exclusion 
Criteria 
Revised exclusion criteria 
1)e) and 1)i) to broaden 
language about excluding 
significant lung disease from 
both cohorts. 
To exclude non-ILD respiratory 
abnormalities to avoid potential 
impact on efficacy or safety 
assessments.  
Added exclusion criterion 
1)v) to exclude participants 
with a positive pregnancy 
test. 
To clarify that female participants 
with a positive pregnancy test 
prior to Day 1 dosing will be 
excluded from the study. 
Revised exclusion criterion 
2)b) to permit stable 
DMARD use for PF-ILD 
participants. 
To enhance the recruitment 
potential of rheumatoid arthritis-
ILD participants as part of the PF-
ILD cohort. 
Section 6.1 Treatments 
Administered 
Added minor clarification to 
the section.  
To ensure participants who are 
dose reduced/discontinued have 
their medication kits either 
replaced or returned to the site.   
2.0
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930149229
2.0
v
Approved
1.0
v

Clinical Protocol 
IM027040 
BMS-986278 
LPA1 Antagonist 
24 Feb 2020, Revised Protocol 01,                            BMS Confidential 
Final Approved 
 
5 
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 
Section Number & Title 
Description of Change 
Brief Rationale 
Section 6.6 Treatment 
Compliance 
Minor adjustments made to 
language in the first 
paragraph. 
To clarify when the treatment 
compliance checks will take 
place. 
Section 6.7 Concomitant 
Therapy 
Added language to allow for 
the use of stable DMARDs 
that have been in place for at 
least 6 months prior to 
screening.  
DMARDs are commonly used for 
rheumatoid arthritis. Allowing 
these agents enhances the 
recruitment of rheumatoid 
arthritis-ILD participants as part 
of the PF-ILD cohort. 
Section 8.4.2 Vital Signs 
Minor adjustments made to 
language. 
To clarify that vital signs will be 
collected predose at every visit 
and to clarify when orthostatic BP 
and HR are measured, so that 
orthostatic BP and HR are not 
measured twice at predose.  
Section 8.4.4 Laboratory 
Assessments, Table 4 
Added HBcAb to the list of 
Serology tests made minor 
adjustments to the Other 
Analyses section.  
To ensure participants are 
screened for HBcAb and to clarify 
the requirement for hepatitis C 
RNA and/or hepatitis B DNA 
testing.  
Added urine pregnancy test 
to the Other Analyses list of 
tests. 
To ensure no females have a 
positive pregnancy test prior to 
Day 1 dosing (or at any time 
throughout the study if a 
pregnancy is suspected). 
Removed cannabinoids from 
the test for drugs of abuse in 
Other Analyses section. 
Participants who use marijuana 
are allowed to participate in this 
study per local regulation. 
 
 
 
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