Conditions: Idiopathic Pulmonary Fibrosis Fibrosis Idiopathic Interstitial Pneumonias Pathologic Processes Lung Diseases, Interstitial Lung Diseases Respiratory Tract Diseases
Keywords: Idiopathic Pulmonary Fibrosis (IPF) Pulmonary Fibrosis CC-90001 Safety Efficacy IPF idiopathic pulmonary fibrosis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 138
Healthy volunteers: no

Brief summary:
This is a Phase 2, multicenter, multinational, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, pharmacokinetics (PK), quality of life and exploratory pharmacodynamics (PD) of two treatment doses of CC-90001, 200 mg and 400 mg, compared with placebo, when delivered once daily per os (PO) in subjects with idiopathic pulmonary fibrosis (IPF). This study is designed to assess response to treatment by using measures of lung function, disease progression, fibrosis on radiography, and patient-reported outcomes. It will also assess dose response.

Detailed description:
Approximately 165 adult male and female subjects with a confirmed diagnosis of Idiopathic pulmonary fibrosis (IPF) (according to the most recent IPF guideline for diagnosis and management) will be randomized 1:1:1 (55 subjects per arm) to treatment with oral CC-90001or matching placebo for an initial 24 weeks.

The randomization will be stratified based on the concurrent administration of SOC (Yes/No). Subjects completing the 24-week Double-blind Treatment Phase will continue onto the 80-week Active Treatment Extension Phase. At Week 24, all subjects originally randomized to receive placebo will be re-randomized 1:1 to blinded CC-90001 (200 mg or 400 mg PO QD). During the 80-week Active Treatment Extension Phase, all subjects not on concurrent SOC therapy will have the opportunity, if deemed appropriate by the Investigator, to receive allowed standard of care (SOC).

The exploratory Progressive Pulmonary Fibrosis (PPF) sub study will evaluate the efficacy, safety, PK, quality of life and exploratory PD of one PO treatment dose regimen of CC-90001, compared with placebo, for an initial 24 weeks of treatment, in subjects with PPF and long-term safety in the 80-week Active Treatment Extension Phase when all PPF subjects will receive CC-90001. Approximately 45 non-SOC subjects will be randomized in this sub study.

All subjects who complete the study treatment phases and those subjects who discontinue investigational product (IP) prior to the completion of the study will participate in the 4-week Post-treatment Observational Follow-up Phase.

The study will be conducted in compliance with the International Council Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements.

An external DMC, comprised of independent physician experts and a statistician who are not affiliated with the Sponsor and for whom there is no identified conflict of interest will be responsible for safeguarding study participants' interests and for monitoring the overall conduct of the study.

Arms:
arm 1: 55 subjects will be randomized to CC-90001 400mg arm 2: 55 subjects will be randomized to CC-90001 200mg arm 3: 55 subjects will be randomized to placebo arm 4: 30 subjects will be randomized to CC-90001 400mg arm 5: 15 subjects will be randomized to placebo

Interventions: intervention 1: CC-90001 intervention 2: Placebo
Intervention descriptions: intervention 1: CC-90001 is a potent, selective inhibitor of JNK. intervention 2: Placebo

Protocol document:
Prot_SAP_001.pdf: 
Protocol for 
 
Official Title of Study 
A PHASE 2, 24-WEEK, RANDOMIZED, 
DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER STUDY, WITH AN 80-WEEK ACTIVE 
TREATMENT EXTENSION, TO EVALUATE THE 
EFFICACY AND SAFETY OF CC-90001 IN SUBJECTS 
WITH IDIOPATHIC PULMONARY FIBROSIS 
NCT03142191 
August 28, 2019 


CC-90001
Protocol CC-90001-IPF-001
Celgene Corporation
Confidential and Proprietary
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CC-90001-IPF-001 Amendment 3.0 Final:  28 Aug 2019
TITLE PAGE
A PHASE 2, 24-WEEK, RANDOMIZED, 
DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER STUDY, WITH AN 80-WEEK ACTIVE
TREATMENT EXTENSION, TO EVALUATE THE 
EFFICACY AND SAFETY OF CC-90001 IN SUBJECTS 
WITH IDIOPATHIC PULMONARY FIBROSIS
PROTOCOL NUMBER:
CC-90001-IPF-001
DATE FINAL:
08 Nov 2016
DATE AMENDMENT 1.0 FINAL:
25 Aug 2017
DATE AMENDMENT 2.0 FINAL:
18 Jul 2018
DATE AMENDMENT 3.0 FINAL:
28 Aug 2019
EudraCT NUMBER:
2016-003473-17
IND NUMBER:
119667
SPONSOR NAME/ ADDRESS:
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or 
consultant for review by you, your staff, and ethics committee/institutional 
review board.  The information contained in this document is regarded as 
confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by 
law or regulations.  Persons to whom the information is disclosed must be 
informed that the information is confidential and may not be further 
disclosed by them.
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Protocol CC-90001-IPF-001
Celgene Corporation
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MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION
Contact Information: Medical Director for the Americas and Canada
Contact Information: Medical Monitor for Europe 
Contact Information: Medical Monitor for Asia Pacific
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24-hour Urgent Medical Contact
Medical Emergency Contact Center:
or 
 (alternative 
number)
Note: The Celgene back-up 24-hour global emergency contact call center should only be 
used if you are not able to reach the Medical Monitor or 24-hour 
Medical 
Emergency Contact Center for emergency calls.
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Protocol CC-90001-IPF-001
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CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
 
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.  
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SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name: _______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, International Council for
Harmonisation (ICH) Good Clinical Practices Guidelines, and local regulations 
governing the conduct of clinical studies.
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Protocol CC-90001-IPF-001
Celgene Corporation
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COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name: _______________________________________
By my signature, I agree the protocol has been written to comply with ICH Good 
Clinical Practices guidelines and agree to offer guidance throughout the study as 
needed.
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Protocol CC-90001-IPF-001
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PROTOCOL SUMMARY
Study Title
A Phase 2, 24-Week, Randomized, Double-blind, Placebo-controlled, Multicenter Study, With
an 80-Week Active Treatment Extension, to Evaluate the Efficacy and Safety of CC-90001 in 
Subjects With Idiopathic Pulmonary Fibrosis 
Indication
Idiopathic Pulmonary Fibrosis (IPF)
Objectives
Primary Objective
To evaluate the effect of CC-90001, 200 mg and 400 mg, when orally administered (PO) once 
daily (QD), compared with placebo, on percent of predicted forced vital capacity (FVC) after 
24 weeks of treatment in subjects with IPF.
Secondary Objective(s)
To evaluate the effects of CC-90001, 200 mg and 400 mg PO QD, compared to placebo, after 
24 weeks of treatment in subjects with IPF, on: 
!
FVC (milliliters [mL])
!
Six-minute Walk Test (6MWT)
!
Disease progression
!
Health-related quality of life: St. George’s Respiratory Questionnaire (SGRQ) and 
University of California San Diego-Shortness of Breath Questionnaire (UCSD-
SOBQ)
!
Dose response
!
Safety and tolerability
To examine the effect of CC-90001 PO QD, compared to placebo, in subjects with progressive 
pulmonary fibrosis (PPF), on:
!
Safety and tolerability
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Protocol CC-90001-IPF-001
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Protocol CC-90001-IPF-001
Celgene Corporation
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Study Design
This is a Phase 2, multicenter, multinational, double-blind, randomized, placebo-controlled study 
evaluating the efficacy, safety, 
 quality of life 
 
of two oral (PO) treatment doses of CC-90001 (200 mg and 400 mg 
QD), compared with placebo, for an initial 24 weeks of treatment, in subjects with IPF.  This 
study will also assess the efficacy and long-term safety in the 80-week Active Treatment 
Extension Phase when all IPF subjects will receive CC-90001 (200 mg or 400 mg PO QD). This 
study is designed to assess response to treatment by using measures of lung function, disease 
progression, fibrosis on radiography, and patient-reported outcomes, including cough, dyspnea, 
and quality of life assessments. It will also assess dose response.
Approximately 165 adult male and female subjects with a diagnosis of IPF (Lynch, 2018) will be 
randomized 1:1:1 (55 subjects per arm) to treatment with CC-90001 (200 mg or 400 mg PO QD) 
or matching placebo for an initial 24 weeks.  Subjects receiving concurrent protocol-allowable 
standard of care (SOC) therapy are eligible to participate in the study.  Approximately 75
subjects (25 subjects per arm) receiving protocol-allowable SOC are to be enrolled in the study.  
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The randomization will be stratified based on the concurrent administration of protocol-
allowable SOC (Yes/No). Subjects not receiving concurrent protocol-allowable SOC therapy
will also be stratified by previous exposure to either pirfenidone or nintedanib (Yes/No).  
Subjects completing 24 weeks of treatment will continue onto the 80-week Active Treatment 
Extension Phase. 
Following an initial screening at Visit 1, eligible IPF subjects will be randomized to receive 
either CC-90001 200 mg or 400 mg PO QD or matching placebo beginning on Day 1 (Baseline 
[Visit 2]) of the study. At Week 24, all subjects originally randomized to receive placebo will be 
re-randomized 1:1 to blinded CC-90001 (200 mg or 400 mg PO QD) via interactive web 
response system (IWRS).  All IPF subjects originally randomized to CC-90001 (200 mg or 400 
mg PO QD) will remain on that same blinded treatment assignment during the 80-week Active
Treatment Extension Phase. During the 80-week Active Treatment Extension Phase, all subjects 
not receiving concurrent protocol-allowable SOC therapy will have the opportunity, if deemed 
appropriate by the Investigator, to receive allowed SOC
 
.
An interim analysis will be conducted when approximately 50 non-SOC IPF subjects have 
completed 24 weeks of treatment. If the safety and efficacy of CC-90001 are favorable, a 
separate exploratory substudy in subjects with progressive pulmonary fibrosis (PPF) will be 
initiated.  The PPF substudy will enroll non-SOC subjects who do not receive a confirmed IPF 
diagnosis following central reading of high resolution computed tomography (HRCT) and lung 
biopsy (if obtained).
The exploratory substudy is a Phase 2, multicenter, multinational, double-blind, randomized, 
placebo-controlled study evaluating the efficacy, safety, 
 
of one PO treatment dose regimen of CC-90001 (400 mg QD, unless review of benefit-risk 
favors 200 mg PO QD), compared with placebo, for an initial 24 weeks of treatment, in subjects 
with PPF.  This substudy will also assess the efficacy and long-term safety in the 80-week Active 
Treatment Extension Phase when all PPF subjects will receive CC-90001.  
 
  Approximately 45 non-SOC subjects qualifying for enrollment into the 
substudy will be randomized in a 2:1 ratio to receive CC-90001 or matching placebo for an 
initial 24 weeks.
All subjects who complete the study treatment phases and those subjects who discontinue 
investigational product (IP) prior to the completion of the study will participate in the 4-week 
Post-treatment Observational Follow-up Phase.
To ensure the safety of all subjects in the study, the external Data Monitoring Committee (DMC)
and Safety Management Team (SMT) will review safety data as described in the DMC charter 
and SMT plan.  Close monitoring of safety data for all subjects will be conducted throughout the 
study and will include, but not be limited to, labs, electrocardiograms (ECGs), pulmonary 
function testing and adverse events.
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The study will be conducted in compliance with the International Council for Harmonisation 
(ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good 
Clinical Practice (GCP) and applicable regulatory requirements.
Adjudication Committee
This study will employ an independent adjudication committee that will adjudicate 
 
 hospitalizations and deaths. The adjudication committee will determine whether 
death(s) is associated with respiratory failure 
 
. Details regarding the process and actions of this committee will be 
described in a separate charter.
External Data Monitoring Committee
Although the Celgene study staff will monitor safety on an ongoing basis throughout the study, 
formal unblinded safety and efficacy assessments of the study data will be performed by an 
independent external Data Monitoring Committee (DMC). The DMC is comprised of 
independent physician experts and a statistician who are not affiliated with the Sponsor and for 
whom there is no identified conflict of interest. The scope, conduct, membership, processes, and 
accountabilities of the DMC are specified in the DMC charter.
The DMC will be also responsible for review of the interim analyses data and will make 
recommendations to a Celgene internal review committee (IRC), who will be responsible for 
final decision-making. The Celgene IRC members will not play a role in the study conduct and 
the blind will be maintained for persons responsible for the ongoing conduct and management of 
the study.  
Celgene Safety Management Team 
In addition to safety monitoring conducted by Investigators, site study personnel, and the 
Celgene study team, blinded study safety data will be reviewed by the Celgene SMT.  The SMT 
is comprised of lead representatives from multiple Celgene functions engaged in the CC-90001 
development program. 
Study Population
The study population includes adult male and female subjects, ≥40 years of age with a 
confirmed diagnosis of IPF (Lynch, 2018), percent predicted forced vital capacity (FVC) ≥45%
to ≤95%, and hemoglobin-corrected diffusion capacity of the lung for carbon monoxide (DLCO)
≥ 25% to ≤ 90% predicted at Screening.
Length of Study
The study will have a total duration of up to 116 weeks.  The study will consist of an up to
8-week Screening Phase; a 24-week Double-blind Placebo-controlled Treatment Phase; an 
80-week Active Treatment Extension Phase; and a 4-week Post-treatment Observational Follow-
up Phase. 
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
4-week Post-treatment Observational Follow-up Phase or the date of receipt of the last data point 
from the last subject that is required for primary, secondary 
 analysis, as 
prespecified in the protocol (whichever is the later date).
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Study Treatments
The IPF study subjects are provided with the following IP treatments:
!
24-Week Double-blind Placebo-controlled Treatment Phase: Baseline (Visit 2) to
Week 24
∀
CC-90001 400 mg PO QD
∀
CC-90001 200 mg PO QD
∀
Placebo PO QD
!
80-Week Active Treatment Extension Phase: Week 24 + 1 day to Week 104
∀
CC-90001 400 mg PO QD
∀
CC-90001 200 mg PO QD
The PPF substudy subjects are provided with the following IP treatments:
!
24-Week Double-blind Placebo-controlled Treatment Phase: Baseline (Visit 2) to 
Week 24
∀
CC-90001 (400 mg PO QD, unless review of benefit-risk favors 200 mg PO QD)
∀
Placebo PO QD
!
80-Week Active Treatment Extension Phase: Week 24 + 1 day to Week 104
∀
CC-90001 (400 mg PO QD, unless review of benefit-risk favors 200 mg PO QD) 
Overview of Key Efficacy Assessments
!
Pulmonary Function Tests 
∀
FVC 
∀
DLCO
∀
Arterial oxygen saturation by pulse oximetry (SpO2)
∀
6-minute Walk Test (6MWT) including Borg Scale Assessment
!
Disease Progression 
!
Patient-reported Outcomes 
∀
St. George’s Respiratory Questionnaire (SGRQ)
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∀
University of California San Diego Shortness of Breath Questionnaire (UCSD-
SOBQ)
Overview of Key Safety Assessments
!
Adverse events
!
Physical examination, vital signs, and weight
!
Clinical laboratory tests including hematology, chemistry, and urinalysis (including 
urine cytology)
!
12-lead electrocardiogram
!
Pregnancy testing and pregnancy education
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Statistical Methods
The primary objective of the study is to estimate the effect of CC-90001 in subjects with IPF 
either not receiving SOC or currently receiving SOC.
Approximately 165 subjects (55 subjects for CC-90001 200 mg with or without [±] SOC, 55
subjects for CC-90001 400 mg ± SOC, and 55 subjects for placebo ± SOC) provide 75% power 
for testing an overall difference of 2.2 percentage points or more in the Week 24 mean change 
from Baseline of percent predicted FVC value between either active treatment group ± SOC and 
the placebo group ± SOC (two-sided t-test; α = 0.1; standard deviation [SD] = 5%), assuming 
that approximately 45% of subjects will be receiving concurrent protocol-allowable SOC based 
on the projected enrollment.  The group size estimate is based on an assumed treatment 
difference of 3 in percent predicted FVC in the non-SOC cohort and 1.3 in percent predicted 
FVC in the SOC cohort at Week 24 from Baseline.  The study will also estimate the effect of 
CC-90001 in the PPF cohort.
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TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................7
1.
INTRODUCTION..................................................................................................22
1.1.
Disease Background ...............................................................................................22
1.1.1.
Idiopathic Pulmonary Fibrosis ................................................................................22
1.1.2.
Progressive Forms of Pulmonary Fibrosis Other Than IPF......................................23
1.2.
Compound Background ..........................................................................................23
1.6.
Rationale ................................................................................................................30
1.6.1.
Study Rationale and Purpose ..................................................................................30
1.6.2.
Rationale for the Study Design ...............................................................................30
1.6.3.
Rationale for Selecting FVC as the Primary Endpoint.............................................30
1.6.4.
Rationale for Dose, Schedule and Regimen Selection .............................................31
1.6.4.1.
Biological Activity .................................................................................................31
1.6.5.
Rationale for Placebo Comparator ..........................................................................32
1.6.7.
Rationale for Patient-Reported Outcomes ...............................................................33
1.7.
Potential Risks of CC-90001 and the Study Population...........................................34
2.
STUDY OBJECTIVES AND ENDPOINTS...........................................................36
3.
OVERALL STUDY DESIGN ................................................................................46
3.1.
Study Design ..........................................................................................................46
3.1.1.
Progressive Pulmonary Fibrosis Substudy...............................................................47
3.1.2.
Adjudication Committee.........................................................................................48
3.2.
Study Duration for Subjects....................................................................................50
3.3.
End of Trial ............................................................................................................50
4.
STUDY POPULATION.........................................................................................51
4.1.
Number of Subjects ................................................................................................51
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4.2.
Inclusion Criteria....................................................................................................51
4.2.1.
Inclusion Criteria for Idiopathic Pulmonary Fibrosis Subjects.................................51
4.2.2.
Inclusion Criteria for Progressive Pulmonary Fibrosis Substudy Only ....................53
4.3.
Exclusion Criteria...................................................................................................54
5.
TABLE OF EVENTS.............................................................................................57
6.
PROCEDURES......................................................................................................64
6.1.
Screening Phase......................................................................................................64
6.2.
Treatment Phase .....................................................................................................69
6.2.1.
End of Treatment....................................................................................................70
6.3.
Post-treatment Observational Follow-up Phase .......................................................71
6.4.
Efficacy Assessment...............................................................................................72
6.4.1.
Pulmonary Function Tests ......................................................................................72
6.4.1.1.
Spirometry..............................................................................................................72
6.4.1.2.
DLCO .....................................................................................................................72
6.4.2.
Pulse Oximetry.......................................................................................................73
6.4.3.
6-Minute Walk Test................................................................................................73
6.4.5.
Chest High-resolution Computed Tomography.......................................................73
6.7.
Patient-reported Outcomes......................................................................................75
7.
DESCRIPTION OF STUDY TREATMENTS........................................................77
7.1.
Description of Investigational Product(s)................................................................77
7.2.
Treatment Administration and Schedule .................................................................77
7.2.1.
Overdose ................................................................................................................79
7.2.2.
Dose Modification/Interruptions .............................................................................79
7.2.2.1.
Dose Interruptions for Planned Surgical Procedures................................................79
7.2.3.
Method of Treatment Assignment...........................................................................79
7.3.
Packaging and Labeling..........................................................................................80
7.4.
Investigational Product Accountability and Disposal ..............................................80
7.5.
Investigational Product Compliance........................................................................80
8.
CONCOMITANT MEDICATIONS .......................................................................81
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8.1.
Permitted Concomitant Medications .......................................................................81
8.1.1.
Permitted Concomitant Medications Throughout the Entire Study..........................81
8.1.2.
Permitted Medications to Treat New or Worsening Shortness of Breath..................82
8.1.3.
Permitted Concomitant Medications Only During the 80-Week Active 
Treatment Extension Phase.....................................................................................82
8.2.
Medications that Require Careful Monitoring .........................................................82
8.2.1.
Statins.....................................................................................................................82
8.3.
Prohibited Concomitant Medications ......................................................................83
8.3.1.
Prohibited Medications Throughout the Entire Study..............................................83
8.3.2.
Prohibited Medications During the 24-week Double-blind Placebo-
controlled Treatment Phase.....................................................................................84
8.4.
Required Concomitant Medications ........................................................................84
9.
STATISTICAL CONSIDERATIONS ....................................................................85
9.1.
Overview................................................................................................................85
9.2.
Study Population Definitions ..................................................................................85
9.3.
Sample Size and Power Considerations...................................................................85
9.4.
Background and Demographic Characteristics........................................................86
9.5.
Subject Disposition.................................................................................................86
9.6.
Efficacy Analysis....................................................................................................86
9.6.1.
Analysis of the Primary Efficacy Endpoint for the IPF Study..................................86
9.6.2.
Analysis of Secondary Efficacy Endpoints..............................................................87
9.6.2.1.
24-Week Double-blind Placebo-controlled Treatment Phase...................................87
9.6.2.2.
80-Week Active Treatment Extension Phase...........................................................88
9.7.
Safety Analysis.......................................................................................................88
9.7.2.
Disease Progression................................................................................................89
9.8.
Interim Analysis .....................................................................................................89
9.9.
Other Topics...........................................................................................................90
9.9.3.
Analysis of Dose-Response ....................................................................................91
9.9.4.
External Data Monitoring Committee .....................................................................91
9.9.5.
Celgene Safety Management Team.........................................................................91
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10.
ADVERSE EVENTS..............................................................................................92
10.1.
Monitoring, Recording and Reporting of Adverse Events .......................................92
10.2.
Evaluation of Adverse Events.................................................................................92
10.2.1.
Seriousness.............................................................................................................92
10.2.2.
Severity/Intensity....................................................................................................93
10.2.3.
Causality ................................................................................................................94
10.2.4.
Duration .................................................................................................................95
10.2.5.
Action Taken..........................................................................................................95
10.2.6.
Outcome.................................................................................................................95
10.3.
Abnormal Laboratory Values..................................................................................95
10.4.
Pregnancy...............................................................................................................95
10.4.1.
Females of Childbearing Potential: .........................................................................96
10.4.2.
Male Subjects.........................................................................................................96
10.5.
Reporting of Serious Adverse Events......................................................................96
10.5.1.
Safety Queries ........................................................................................................97
10.6.
Expedited Reporting of Adverse Events..................................................................97
11.
DISCONTINUATIONS .........................................................................................99
11.1.
Treatment Discontinuation......................................................................................99
11.2.
Discontinuation Criteria for Elevation of Hepatic Transaminases............................99
11.3.
Study Discontinuation ............................................................................................99
12.
EMERGENCY PROCEDURES...........................................................................101
12.1.
Emergency Contact...............................................................................................101
12.2.
Emergency Identification of Investigational Products ...........................................101
13.
REGULATORY CONSIDERATIONS.................................................................102
13.1.
Good Clinical Practice..........................................................................................102
13.2.
Investigator Responsibilities .................................................................................102
13.3.
Subject Information and Informed Consent...........................................................103
13.4.
Confidentiality......................................................................................................103
13.5.
Protocol Amendments...........................................................................................103
13.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ..............................................................................................................103
13.7.
Ongoing Information for Institutional Review Board/ Ethics Committee ..............104
13.8.
Termination of the Study ......................................................................................104
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14.
DATA HANDLING AND RECORDKEEPING...................................................105
14.1.
Data/Documents...................................................................................................105
14.2.
Data Management.................................................................................................105
14.3.
Record Retention..................................................................................................105
15.
QUALITY CONTROL AND QUALITY ASSURANCE......................................107
15.1.
Study Monitoring and Source Data Verification....................................................107
15.2.
Audits and Inspections..........................................................................................107
15.3.
Product Quality Complaint ...................................................................................107
16.
PUBLICATIONS .................................................................................................109
17.
REFERENCES.....................................................................................................110
18.
APPENDICES......................................................................................................115
Appendix A:
Table of Abbreviations ....................................................................................115
Appendix B:
St. George’s Respiratory Questionnaire ...........................................................120
Appendix C:
University of California San Diego Shortness of Breath Questionnaire ............124
Appendix E:
6-Minute Walk Test Protocol ...........................................................................132
Appendix F:
Borg Scale........................................................................................................138
Appendix G:
Diagnostic Categories of UIP Based on HRCT Patterns and 
Histopathological Criteria For UIP in IPF.............................................................139
Appendix H:
Examples Of Drugs That Are Substrates For Selected Transporters .................141
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LIST OF TABLES
Table 1:
Study Objectives.....................................................................................................36
Table 2:
Idiopathic Pulmonary Fibrosis Study Endpoints......................................................39
Table 3:
Progressive Pulmonary Fibrosis Substudy Endpoints..............................................43
Table 4:
Summary of Criteria for Diagnosis of Idiopathic Pulmonary Fibrosis Based 
on High Resolution Computed Tomography and Lung Biopsy................................52
Table 5:
Table of Events.......................................................................................................57
Table 6:
Abbreviations and Specialist Terms......................................................................115
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LIST OF FIGURES
Figure 1:
Overall Study Design (Idiopathic Pulmonary Fibrosis Study) .................................49
Figure 2:
Overall Study Design (Progressive Pulmonary Fibrosis Substudy)..........................49
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1.
INTRODUCTION 
1.1.
Disease Background 
1.1.1.
Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and often lethal fibrosing interstitial 
lung disease of unknown etiology characterized by a poor prognosis (Raghu, 2011). 
The reported prevalence of IPF varies geographically; for example, the published prevalence of 
IPF per 100,000 people ranges from 13-63 in the United States of America (USA) and from 3-23 
in Europe (Ley, 2013). Approximately half of IPF patients either die or undergo lung 
transplantation within 3 to 5 years of diagnosis (Ley, 2013).  The disease typically occurs in 
people between the ages of 40 and 70 years (median age is 66 years) and affects men more 
frequently than women. Most patients are former smokers. There are no proven risk factors for 
IPF, but < 5% of patients have a family history of interstitial lung disease (Raghu, 2011).
The diagnosis of IPF is made after excluding other conditions associated with pulmonary fibrosis 
and is based on a characteristic clinical presentation, radiographic features, and sometimes 
pathologic specimens (Raghu, 2011).  The diagnosis of IPF requires information from several 
sources to be interpreted and integrated, and this can pose significant challenges in patient 
selection for this trial. Since the publication of the 2011 ATS/ERS guidelines (Raghu, 2011), 
diagnosing IPF continues to evolve through ongoing research and clinical experience. Very 
recently, a Fleischner Society White paper on the diagnostic criteria of IPF was published 
(Lynch, 2018).  In this paper, a new category in the interpretation of high resolution computed
tomography (HRCT) patterns, “computed tomography (CT) pattern indeterminate for usual 
interstitial pneumonia (UIP),” was proposed to encompass an HRCT that may be consistent with 
IPF and that lacks features most consistent with a non-IPF diagnosis.  This new category can be 
considered a refinement of the 2011 ATS/ERS criteria, in which an HRCT classified as 
“inconsistent with UIP” did not distinguish between patients whose scans were insufficient to 
secure this diagnosis in the absence of additional information (eg, lung biopsy), from patients 
who were unlikely to have IPF.
IPF is characterized by interstitial fibrosis, which typically results in chronic irreversible 
scarring. These pathological changes are associated with a progressive decline in pulmonary 
function, which may lead to respiratory failure and death; some patients may experience episodes 
of acute respiratory worsening despite previous stability (Raghu, 2011).  
The precise biological basis of IPF remains unclear.  Over a lifetime, the lungs are exposed to 
repetitive injury from a variety of exogenous and endogenous stimuli. Several local and systemic 
factors (eg, fibroblasts, circulating fibrocytes, chemokines, growth factors, and clotting factors) 
contribute to tissue healing and functional recovery. Dysregulation of this intricate network,
through genetic predisposition, autoimmune conditions, or superimposed diseases are proposed 
to lead to aberrant wound healing that may culminate in pulmonary fibrosis. Alternatively, 
excessive injury to the lung may overwhelm reparative mechanisms and may lead to pulmonary 
fibrosis (Nicholson, 2002; King, 2001).
In the recent past, the pharmacological treatment of IPF has changed considerably. Two 
approved treatments, pirfenidone and nintedanib, both appear to have modest effects on 
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progression-free survival and decline in pulmonary function (Noble, 2011; King, 2014; Richeldi, 
2014).  To date, lung transplantation has been shown to improve mortality in carefully selected 
patients (Kistler, 2014). Despite these advances, there remains a large unmet need for a safe and 
effective therapy for IPF that delays disease progression, improves pulmonary function, and 
reduces the mortality rate.
1.1.2.
Progressive Forms of Pulmonary Fibrosis Other Than IPF
Besides IPF, other interstitial lung diseases (ILDs) can manifest as a progressive fibrosing 
phenotype (Wells, 2018; Cottin, 2018).  The chest HRCT appearance in such individuals is 
variable and may conform to a UIP pattern similar to that in patients with IPF but can also be 
distinctive and be described as “indeterminate” for UIP or most consistent with a non-IPF 
diagnosis. Such cases would represent a radiological subset of “progressive-fibrosing ILD,” a 
recently described term that recognizes the progressive nature of such ILDs (Flaherty, 2017;
Cottin, 2018).  Progressive fibrosis of the lung parenchyma causes progressive deterioration in 
lung function, respiratory symptoms and quality of life and therefore increases the risk of early 
death (Olson, 2016; Cottin, 2018).
1.2.
Compound Background 
 CC-90001 is a potent inhibitor of JN
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1.6.
Rationale
1.6.1.
Study Rationale and Purpose
Most treatment strategies for fibrotic disorders like IPF have been based on eliminating or 
suppressing the inflammatory factors involved in the disease with immunosuppressive drugs, 
such as corticosteroids and cytotoxic agents. Although these drugs may reduce the inflammatory 
cascade by blocking the proliferation of cells and the recruitment of inflammatory leukocytes, or 
by killing recruited cells, these drugs do not necessarily target the underlying fibrotic response
well, which typically involves both local cells (stromal cells) and recruited cells (inflammatory 
leukocytes) (Wynn, 2004). By inhibiting JNK, CC-90001 is hypothesized to interrupt both areas 
of this process.  More recently, two pharmacological therapies, pirfenidone and nintedanib, 
commercially available in some regions of the world, have demonstrated modest effects on 
progression-free survival and decline in pulmonary function in patients with IPF (Noble, 2011; 
King, 2014; Richeldi, 2014). The relatively modest benefits associated with these agents for a 
disease as serious as IPF indicate that there remains an important, unmet need in the treatment of 
IPF.  Based on recent insights into the pathogenesis of IPF, the underlying rationale for the 
current protocol is that JNK plays a pivotal role in the progression of pulmonary fibrosis and that 
inhibition of JNK, by CC-90001, will lead to improved lung function and other outcomes in 
patients with IPF.
1.6.2.
Rationale for the Study Design
The Phase 3 pirfenidone and nintedanib trials demonstrated benefits on FVC in patients 
receiving active treatment, compared with placebo, after 52 weeks (King, 2014; Richeldi, 2014) 
and 72 weeks (Noble, 2011) of treatment, respectively.  Apparent benefits in FVC were observed 
as early as 24 weeks following onset of treatment (Noble, 2011; King, 2014; Richeldi, 2014). 
Therefore, it is anticipated that a treatment response with CC-90001 in IPF should occur as early 
as 24 weeks after initiation of treatment, especially if the effect is robust. The 24-week Double-
blind Placebo-controlled Treatment Phase should provide the shortest study duration to 
reasonably assess the efficacy and safety of CC-90001 with or without (±) standard of care 
(SOC) in IPF subjects. The 80-week Active Treatment Extension Phase will provide additional
 long-term safety and efficacy information for CC-90001 ± SOC.  It will also provide 
those subjects randomized to the placebo treatment without SOC the opportunity to receive 
active CC-90001 (200 mg or 400 mg PO QD).
1.6.3.
Rationale for Selecting FVC as the Primary Endpoint 
Change in FVC was selected as the primary endpoint because of its widespread clinical use and 
the clinical relevance of irreversible loss of lung function.  Change in FVC is currently accepted 
by health authorities as a primary endpoint in IPF trials in part because it is a reliable, responsive 
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measurement. Deterioration in FVC ≥ 10% from baseline over 6 months has been shown to 
predict mortality in IPF patients (du Bois, 2011).
1.6.4.
Rationale for Dose, Schedule and Regimen Selection
The 200 mg and 400 mg QD doses of CC-90001 were selected based on preclinical and clinical 
data in addition to simulation that supports adequate target engagement at clinically tolerated 
doses with sufficient PK distribution between doses.  Additionally, exposures in this dose range 
are consistent with exposures required for efficacy in preclinical models. 
1.6.4.1.
Biological Activity
 CC-930, a JNK inhibitor, was previously 
evaluated for activity in both UVB-induced phospho-c-Jun expression in healthy volunteers, and 
for safety in IPF subjects. In IPF subjects treated with CC-930, a dose-dependent trend in 
reducing plasma MMP-7 was observed, and changes in plasma MMP-7, SP-A, SP-D, and TNC 
levels significantly correlated with changes in FVC (Schafer, 2013; van der Velden, 2016). 
 
 
  Thus, the 200 and 400 mg doses 
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of CC-90001, which significantly inhibited the JNK pathway 
, phospho-c-Jun, are 
in a range that is expected to have an effect on the IPF 
.
1.6.5.
Rationale for Placebo Comparator
A placebo control is needed in this Phase 2 trial to accurately determine the clinical benefits and 
safety profile of CC-90001.
The study embodies neither expectation nor intent that patients discontinue indicated and well-
tolerated treatment to participate.  Although both pirfenidone and nintedanib have demonstrated 
clinical benefits compared to placebo, these benefits have been modest and variable; many 
patients receiving these medications may fail to demonstrate clinically meaningful benefits 
and/or may experience significant tolerability issues or adverse reactions that limit their clinical 
utility.  Clinical experience with CC-90001 thus far suggests that gastrointestinal-related AEs
may occur in IPF, similar to those that occur following administration of pirfenidone and 
nintedanib.  After Week 24 of this study, all subjects will be given the opportunity to receive 
CC-90001 (200 mg or 400 mg PO QD).  In addition, if deemed appropriate by the Investigator,
all subjects not receiving concurrent protocol-allowable SOC therapy will be permitted to receive
allowed SOC
.
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1.6.7.
Rationale for Patient-Reported Outcomes
In chronic, progressive and ultimately fatal diseases like IPF, assessment of health-related quality 
of life is especially useful in providing the patients’ perspective on treatment benefit. These 
instruments are used to directly measure treatment benefit that is of greatest relevance to the 
patient. Patient-reported outcome instruments have been included in this study to document the 
effect of CC-90001 on symptoms and quality of life.
This study will implement three patient-reported outcomes, SGRQ, 
and UCSD-SOBQ, 
to obtain preliminary information that will inform on which tools to use in the Phase 3 program.
The SGRQ has been chosen as it has demonstrated acceptable psychometric characteristics in 
patients with IPF, including construct validity, reliability, and ability to detect change over 
time (Yorke, 2010; Swigris, 2010).
 
 SGRQ 
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possess reasonable validity for differentiating subjects whose IPF disease severity changes over 
time (Swigris, 2010). The UCSD-SOBQ demonstrates content validity (Gries, 2013) and is able 
to detect changes in symptoms over time (Gries, 2013; Swigris, 2012) in patients with IPF
(Swigris, 2012a).
1.7.
Potential Risks of CC-90001 and the Study Population
Based on the Phase 1 studies in healthy subjects and the Phase 1b study in pulmonary fibrosis 
subjects, the TEAEs associated with administration of CC-90001 are mostly gastrointestinal in 
nature. Gastrointestinal TEAEs reported in these studies included nausea, diarrhea, indigestion, 
abdominal discomfort/cramping, emesis, and constipation. Headache, rash, dermatitis, fatigue 
and musculoskeletal pain TEAEs were also reported. The majority of the reported TEAEs were 
mild or moderate in severity. Some subjects who experienced nausea in the Phase 1 studies have 
reported less nausea when the IP was taken with food. There were no SAEs reported in the Phase 
1 studies.
The Sponsor has instituted extensive safety monitoring into this protocol based upon potential 
risks associated with CC-90001 and the disease under study. 
!
Frequent study visits to assess safety laboratory results, including, but not limited to,
liver function, white blood cell (WBC) count, hemoglobin, total cholesterol, high
density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, pulmonary 
function and arterial oxygen saturation (SpO2).
!
Individual subject dose stopping rules and study stopping rules to ensure subjects are 
discontinued from CC-90001 in the event of severe liver toxicity. In a study 
conducted with the structurally unrelated pan-JNK inhibitor, CC-930, IPF subjects
treated with high doses of CC-930 demonstrated abnormal liver function tests after 
approximately 8-12 weeks of daily dosing. In order to support this Phase 2 study with
chronic dosing, the CC-90001-CP-003 study in pulmonary fibrosis subjects was
conducted to understand the safety profile after a 12-week treatment duration. 
!
CC-90001 may be an inhibitor of liver transporters (eg, OATP1B1 and OATP1B3) 
and breast cancer resistance protein (BCRP). Therefore, subjects taking statins 
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concomitantly with CC-90001 may experience increased plasma concentrations of 
statins with prescribed doses.  To ensure the safety of the subjects, concomitant 
statins will be dose adjusted to a therapeutic level (see Section 8.2.1).
!
Urine cytology to examine for abnormal cellular findings.
!
Electrocardiograms (ECGs) with centralized over-read and blood pressure 
measurements will be performed to monitor for potential cardiovascular effects.
!
Required and frequent Investigator/Celgene safety review meetings to ensure 
appropriate and timely intervention (such as study discontinuation) in the event that a 
safety signal is identified.
Celgene is confident that the safety monitoring plan included within this protocol is sufficient to
monitor for potential safety risks of CC-90001. In addition, provisions for monitoring for 
disease-specific complications, such as hypoxemia and decline in pulmonary function secondary 
to disease progression, have also been included as part of the protocol design.
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2.
STUDY OBJECTIVES AND ENDPOINTS
Table 1:
Study Objectives
Primary Objective
To evaluate the effect of CC-90001, 200 mg and 400 mg, when orally administered (PO) once 
daily (QD), compared with placebo, on percent of predicted forced vital capacity (FVC) after 
24 weeks of treatment in subjects with idiopathic pulmonary fibrosis (IPF).
Secondary Objectives
To evaluate the effects of CC-90001, 200 mg and 400 mg PO QD, compared to placebo, after 
24 weeks of treatment in subjects with IPF, on: 
!
FVC (milliliters [mL])
!
Six-minute Walk Test (6MWT)
!
Disease progression
!
Health-related quality of life: St. George’s Respiratory Questionnaire (SGRQ) and 
University of California San Diego-Shortness of Breath Questionnaire (UCSD-
SOBQ)
!
Dose response
!
Safety and tolerability
To examine the effect of CC-90001 PO QD, compared to placebo, in subjects with progressive 
pulmonary fibrosis (PPF), on:
!
Safety and tolerability
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Table 1:
Study Objectives (Continued)
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Table 1:
Study Objectives (Continued)
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Table 2:
Idiopathic Pulmonary Fibrosis Study Endpoints
Endpoint
Name
Description
Timeframe
Primary 
Forced vital 
capacity (FVC)
Percentage point difference in % 
predicted FVC
Baseline to Week 24
Secondary
FVC
Absolute change and rate of decline 
in FVC (expressed in mL)
Baseline through Week 24
Secondary
6-minute Walk 
Test (6MWT) 
with Borg Scale
Change in the distance walked 
during the 6MWT as measured in 
meters (m)
Change in dyspnea rating on Borg 
Scale
Baseline to Week 24;
Baseline to Week 52;
Baseline to Week 76;
Baseline to Week 104;
Week 24 to Week 52;
Week 24 to Week 104
Secondary
Disease 
progression
Disease progression is defined as 
one or more of the following:
!
Death from respiratory failure, 
or
!
Absolute decrease of ≥ 10% 
from baseline in % predicted 
FVC at two consecutive 
evaluations at a minimum of 4 
weeks between evaluations, or
!
Decrease from baseline of ≥ 50 
meters in 6MWT distance (in 
the absence of a readily 
explainable cause, such as 
injury or trauma), or
!
Unexplained worsening 
hypoxemia (an absolute 
decrease from baseline of 4% or 
more in arterial oxygen 
saturation by pulse oximetry
[SpO2]).
Baseline through Week 24
Secondary
Quality of life
Change from Baseline in total score 
and domains on the Saint George’s 
Respiratory Questionnaire (SGRQ)
Baseline through Week 24
Change from Baseline in the 
University of California San Diego 
Shortness of Breath Questionnaire 
(UCSD- SOBQ)
Baseline through Week 24
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Table 2:
Idiopathic Pulmonary Fibrosis Study Endpoints (Continued)
Endpoint
Name
Description
Timeframe
Secondary 
Safety and 
tolerability
Type, frequency, severity, and 
relationship of adverse events 
(AEs), clinical laboratory tests 
including urine cytology, 12-lead 
electrocardiogram (ECG), vital 
signs, and physical examination 
Signing of the informed 
consent form through Week 
108 (4-week post-treatment 
observational follow-up)
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Table 3:
Progressive Pulmonary Fibrosis Substudy Endpoints
Endpoint
Name
Description
Timeframe
Secondary
Safety and 
tolerability
Type, frequency, severity, and 
relationship of adverse events 
(AEs), clinical laboratory tests 
including urine cytology, 12-lead 
electrocardiogram (ECG), vital 
signs, and physical examination 
Signing of the informed 
consent form through Week 
108 (4-week post-treatment 
observational follow-up)
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3.
OVERALL STUDY DESIGN
3.1.
Study Design
This is a Phase 2, multicenter, multinational, double-blind, randomized, placebo-controlled study 
evaluating the efficacy, safety, 
 quality of life 
 of 
two oral (PO) treatment doses of CC-90001 (200 mg and 400 mg QD), compared with placebo,
for an initial 24 weeks of treatment, in subjects with IPF.  This study will also assess the efficacy 
and long-term safety in the 80-week Active Treatment Extension Phase when all IPF subjects 
will receive CC-90001 (200 mg or 400 mg PO QD). This study is designed to assess response to 
treatment by using measures of lung function, disease progression, fibrosis on radiography, and 
patient-reported outcomes, including cough, dyspnea, and quality of life assessments. It will also 
assess dose response.
Approximately 165 adult male and female subjects with a diagnosis of IPF (Lynch, 2018) will be 
randomized 1:1:1 (55 subjects per arm) to treatment with CC-90001 (200 mg or 400 mg PO QD) 
or matching placebo for an initial 24 weeks.  Subjects receiving concurrent protocol-allowable 
standard of care (SOC) therapy are eligible to participate in the study.  Approximately 75 
subjects (25 subjects per arm) receiving protocol-allowable SOC are to be enrolled in the study.  
The randomization will be stratified based on the concurrent administration of protocol-
allowable SOC (Yes/No).  Subjects not receiving concurrent protocol-allowable SOC therapy 
will also be stratified by previous exposure to either pirfenidone or nintedanib (Yes/No).  
 
 Subjects 
completing 24 weeks of treatment will continue onto the 80-week Active Treatment Extension 
Phase. Subjects who enter and complete the 80-week Active Treatment Extension Phase will 
receive treatment for a total of 104 weeks (Figure 1).
Following an initial screening at Visit 1, eligible IPF subjects will be randomized to receive 
either CC-90001 200 mg or 400 mg PO QD or matching placebo beginning on Day 1 (Baseline 
[Visit 2]) of the study. At Week 24, all subjects originally randomized to receive placebo will be 
re-randomized 1:1 to blinded CC-90001 (200 mg or 400 mg PO QD) via interactive web 
response system (IWRS).  All IPF subjects originally randomized to CC-90001 (200 mg or 400 
mg PO QD) will remain on that same blinded treatment assignment during the 80-week Active 
Treatment Extension Phase. During the 80-week Active Treatment Extension Phase, all subjects 
not on concurrent protocol-allowable SOC therapy will have the opportunity, if deemed 
appropriate by the Investigator, to receive allowed SOC
 
.
An interim analysis will be conducted when approximately 50 non-SOC IPF subjects have 
completed 24 weeks of treatment.  If the safety and efficacy of CC-90001 are favorable, a 
separate 
substudy in subjects with progressive pulmonary fibrosis (PPF) will be 
initiated (refer to Section 3.1.1).  
A second interim analysis is planned after approximately 40 SOC IPF subjects have completed 
24 weeks of treatment. The purpose of the additional interim analysis is to evaluate safety, 
tolerability and efficacy of CC-90001 in SOC IPF subjects, along with all study subjects enrolled 
into the study, and to determine if any treatment group should be discontinued.  
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All subjects who complete the study treatment phases and those subjects who discontinue 
investigational product (IP) prior to the completion of the study will participate in the 4-week 
Post-treatment Observational Follow-up Phase.
To ensure the safety of all subjects in the study, the external Data Monitoring Committee (DMC) 
and SMT will review safety data as described in the DMC charter and SMT plan.  Close 
monitoring of safety data for all subjects will be conducted throughout the study and will 
include, but not be limited to, labs, ECGs, pulmonary function testing, and adverse events.
The blind should be maintained for persons responsible for the ongoing conduct of the study
from first subject enrolled through last subject/last visit of the 4-week Post-Treatment Follow-up 
Phase of the study. Blinded persons may include but are not limited to: Clinical Research 
Physician, Clinical Research Scientist, Clinical Trial Manager, Study Statistician, Data Manager, 
Programmers, Clinical Research Associates.
The study will be conducted in compliance with the International Council for Harmonisation 
(ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good 
Clinical Practice (GCP) and applicable regulatory requirements.
3.1.1.
Progressive Pulmonary Fibrosis Substudy
The exploratory substudy is a Phase 2, multicenter, multinational, double-blind, randomized, 
placebo-controlled study evaluating the efficacy, safety, 
 
of one PO treatment dose regimen of CC-90001 (400 mg QD, unless review of benefit-risk 
favors 200 mg PO QD), compared with placebo, for an initial 24 weeks of treatment, in subjects 
with PPF.  This substudy will also assess the efficacy and long-term safety in the 80-week Active 
Treatment Extension Phase when all PPF subjects will receive CC-90001.  
 
  This PPF substudy allows non-SOC subjects who were screened and did not 
receive a confirmed IPF diagnosis following central reading of HRCT and lung biopsy, if 
obtained, to be considered for the substudy. Enrollment into this substudy will not begin until 
after the first interim analysis and confirmation is received from the DMC that the overall main 
study in IPF subjects should continue as planned (Section 9.8).
Approximately 45 non-SOC subjects qualifying for enrollment into the substudy will be 
randomized in a 2:1 ratio (approximately 30 subjects in the CC-90001 arm and approximately 15 
subjects in the placebo arm), for an initial 24 weeks.  Subjects who enter and complete the 
80-week Active Treatment Extension Phase will receive treatment for a total of 104 weeks.  
Refer to Figure 2 for the PPF substudy design and Section 4.2.2 for specific inclusion criteria.
Following an initial screening at Visit 1, eligible PPF subjects will be randomized to receive 
either CC-90001 or matching placebo beginning on Day 1 (Baseline [Visit 2]) of the study. At 
Week 24, all subjects originally randomized to receive placebo will receive CC-90001.  All 
subjects originally randomized to CC-90001 will remain on that same blinded treatment 
assignment during the 80-week Active Treatment Extension Phase.  The decision to receive 
additional treatments for pulmonary fibrosis 
 during the 80-week Active 
Treatment Extension Phase is at the discretion of the Investigator.
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3.1.2.
Adjudication Committee
This study will employ an independent adjudication committee that will adjudicate 
 
 hospitalizations and deaths. The adjudication committee will determine whether 
death(s) is associated with respiratory failure 
 
. Details regarding the process and actions of this committee will be 
described in a separate charter.
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Figure 1: Overall Study Design (Idiopathic Pulmonary Fibrosis Study)
Abbreviations: EOFU = end of follow-up; EOT = end of treatment; PBO = placebo;
SOC = standard of care
.
Figure 2: Overall Study Design (Progressive Pulmonary Fibrosis Substudy)
Abbreviations: EOFU = end of follow-up; EOT = end of treatment; PBO = placebo.
* CC-90001 400 mg orally (PO) once daily (QD) is the intended dose regimen, unless review of benefit-risk favors 
200 mg PO QD.
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3.2.
Study Duration for Subjects
The study will have a total duration of up to 116 weeks. The study will consist of an up to 
8-week Screening Phase; a 24-week Double-blind Placebo-controlled Treatment Phase; an 
80-week Active Treatment Extension Phase; and a 4-week Post-treatment Observational Follow-
up Phase.
3.3.
End of Trial
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary 
 analysis, as prespecified in the protocol, 
whichever is the later date.
Approved
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4.
STUDY POPULATION
4.1.
Number of Subjects 
Approximately 210 subjects will be randomized worldwide.  Approximately 165 subjects 
diagnosed with IPF will be randomized into the study and approximately 45 additional subjects
will be randomized into the PPF substudy.
4.2.
Inclusion Criteria
4.2.1.
Inclusion Criteria for Idiopathic Pulmonary Fibrosis Subjects
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject is male or female ≥ 40 years of age at the time of signing the informed consent 
form (ICF)
2. Subject must understand and voluntarily sign an ICF prior to any study-related 
assessments/procedures being conducted
3. Subject is willing and able to adhere to the study visit schedule and other protocol 
requirements
4. Investigator has considered all available IPF treatment options with the potential subject 
before consenting the subject for participation in the study
5. Diagnosis of IPF is supported by HRCT, as described in Table 4 and Appendix G.
Note: Historical lung biopsy (surgical lung biopsy [SLB] or lung cryobiopsy) may be used for 
eligibility, if available.  HRCT scan performed within 18 months of randomization may be used if 
it meets image acquisition guidelines and scan is reviewed by centralized review. For sites 
subject to regulatory restrictions that do not permit HRCT within this time period, a previous 
HRCT scan is permissible if the scan is deemed sufficient for centralized review.
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Table 4:
Summary of Criteria for Diagnosis of Idiopathic Pulmonary Fibrosis Based 
on High Resolution Computed Tomography and Lung Biopsy
UIP Pattern on 
HRCTa
Histopathological Criteria for UIP in IPF (UIP-IPF)a
Lung Biopsy 
Not Available 
Or Non-
Diagnostic
Definite
UIP-IPF
Probable
UIP-IPF
Indeterminate
UIP-IPF
Features Most 
Consistent 
With An 
Alternative 
Diagnosis
Typical
Eligible
Eligible
Eligible
Eligible
Ineligible
Probable, ≤60 
years of age
Ineligible
Eligible
Eligible
Ineligible
Ineligible
Probable, > 60 
years of age
Eligible
Eligible
Eligible
Eligible
Ineligible
Indeterminate
Ineligible
Eligible
Eligible
Ineligible
Ineligible
Most consistent 
with non-IPF 
diagnosis
Ineligible
Ineligible
Ineligible
Ineligible
Ineligible
Abbreviations:  HRCT = high resolution computed tomography; IPF = idiopathic pulmonary fibrosis; 
UIP = usual interstitial pneumonia.
a Criteria are described in Appendix G; adapted from Lynch, 2018 and Chung, 2018.
6. Extent of fibrotic changes (eg, honeycombing, reticular changes) greater than the extent 
of emphysema on HRCT scan, as determined by centralized review
7. No features supporting an alternative diagnosis on transbronchial biopsy, bronchoalveolar 
lavage (BAL), or SLB, if performed prior to Screening
8. Percent predicted forced vital capacity (FVC) ≥ 45% and ≤ 95% at Screening confirmed 
by centralized review
9. Change in FVC (measured in milliliters [mL]) between Screening and Day 1 less than a 
10% relative difference, calculated as: the absolute value of 100% * (Screening FVC 
[mL] - Day 1 FVC [mL]) / Screening FVC (mL)
10. Hemoglobin-corrected percent predicted diffusion capacity of the lung for carbon 
monoxide (DLCO) ≥ 25% and ≤90% predicted at Screening
11. Able to walk ≥150 meters during the 6-minute walk test (6MWT) at Screening
12. Females of childbearing potential (FCBP) 1 must:
a.
Have two negative pregnancy tests as verified by the Investigator prior to starting IP. 
She must agree to ongoing pregnancy testing during the course of the study, and after 
end of study treatment. This applies even if the subject practices true abstinence* 
from heterosexual contact.
                                               
1 A female of childbearing potential is a sexually mature female who 1) has not undergone a hysterectomy (the surgical removal 
of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been postmenopausal for at least 
24 consecutive months (that is, has had menses at any time during the preceding 24 consecutive months).
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b. Either commit to true abstinence* from heterosexual contact (which must be 
reviewed on a monthly basis and source documented) or agree to use two effective 
birth control methods (one of which is highly effective) at the same time, and be able 
to comply with, effective contraception without interruption, 28 days prior to starting 
IP, during the study therapy (including dose interruptions), and for 28 days after 
discontinuation of IP.
Approved options for birth control are:
!
Any one of the following highly effective methods: Hormonal 
contraception (for example, birth control pills, intravaginal ring, 
transdermal patch, injection, implant); intrauterine device (IUD); tubal 
ligation (tying your tubes); or a partner with a vasectomy.  
Note: Certain drugs may reduce the effectiveness of hormonal 
contraceptives during and up to one month after discontinuation of these 
concomitant therapies.
!
Any effective method, for example, condoms.
13. Male subjects must:
Practice true abstinence# (which must be reviewed on a monthly basis) or agree to use a 
latex condom or nonlatex condom not made out of natural (animal) membrane (eg,
polyurethane) during sexual contact with a pregnant female or a female of childbearing 
potential while participating in the study, during dose interruptions and for at least 28 
days following IP discontinuation, even if he has undergone a successful vasectomy.
14. For subjects stratified to the protocol-allowable standard of care therapy group (only):
Subjects must be receiving and agree to maintain the same dose of protocol-allowable
standard of care (SOC) therapy for at least 8 weeks prior to Screening Visit 1 and must 
agree to continue this dose through Visit 9/Week 24. 
 
4.2.2.
Inclusion Criteria for Progressive Pulmonary Fibrosis Substudy Only
Progressive pulmonary fibrosis subjects must satisfy the following criteria to be enrolled in the 
substudy:
15. Met all inclusion criteria described for IPF subjects in Section 4.2.1 other than Inclusion 
Criterion 5 (ie, not received an “eligible” designation based on Table 4)
16. Features of diffuse fibrosing lung disease of > 10% on HRCT by central reading
                                               
# True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. (Periodic 
abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable 
methods of contraception).
Approved
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17. Investigator-documented ≥5% annualized relative decline in FVC in past 24 months 
from Screening Visit 1 (Examples: ≥10% relative decline in past 2 years; ≥5% relative 
decline in past year; ≥2.5% relative decline in past 6 months)
4.3.
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1. Subject has any significant medical condition, laboratory abnormality, or psychiatric 
illness that would prevent the subject from participating in the study
2. Subject has any condition including the presence of laboratory abnormalities, which 
places the subject at unacceptable risk if he/she were to participate in the study
3. Subject has any condition that confounds the ability to interpret data from the study
4. Significant clinical worsening of pulmonary fibrosis between Screening and Baseline
(Visit 2), in the opinion of the Investigator
5. Subjects with any of the following laboratory criteria:
!
White blood cell count (WBC) < 3500/mm3 (< 3.5 X 109/L) or > 14,000/mm3
(> 14 X 109/L)
!
Platelet count < 120,000/μL (< 120 X 109/L) 
!
Serum creatinine > 1.5 mg/dL (> 132.6 μmol/L)
!
Aspartate aminotransferase (AST/SGOT) > 1.5 X upper limit of normal (ULN)
!
Alanine aminotransferase (ALT/SGPT) > 1.5 X upper limit of normal (ULN)
!
Total bilirubin > 2 mg/dL (> 34.2 μmol/L)
!
Hemoglobin < 10 g/dL (< 100 g/L)
6. Subject with a QTcF > 450 msec
7. Any condition other than pulmonary fibrosis that in the opinion of the Investigator is 
likely to result in the death of the subject within the next year
8. Inability to obtain reproducible, high-quality pulmonary function tests.
9. Evidence of clinically relevant airways obstruction (ie, FEV1/FVC < 0.7) at Screening 
and/or significant respiratory disorder/pathology (eg, pulmonary arterial hypertension
requiring treatment, asthma, tuberculosis, sarcoidosis, hypersensitivity pneumonitis, 
aspergillosis, asbestosis, neoplastic disease, cystic fibrosis or other interstitial lung 
disease) other than IPF
Note: Following central readings of HRCTs and central reviews of lung biopsies, if 
performed, underlying causes of pulmonary fibrosis in subjects enrolled in the PPF 
substudy may include fibrotic lung diseases other than IPF.
10. Subject is likely to have lung transplantation during the first 24 weeks of the study (being 
on transplantation list is acceptable for participation)
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11. Impairment (other than dyspnea) limiting the ability to comply with study requirements 
(eg, pulmonary function tests, 6-minute walk test)
12. Subjects using the following medications:
 endothelium receptor antagonists 
(eg, bosentan, ambrisentan), interferon gamma-1b, imatinib mesylate, N-acetylcysteine, 
azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil, cyclosporine, and 
oral steroids (eg, prednisone > 12.5 mg/day or equivalent) within 4 weeks prior to the 
Screening Visit. 
Note: Subjects should not discontinue any of these therapies for the sole purpose of 
participating in this study.
13. Use of any cytokine modulator/biologic, such as etanercept, adalimumab, efalizumab, 
infliximab, or rituximab within 12 weeks of randomization 
14. Use of an inhaled long-acting bronchodilator within 24 hours of the Screening Visit or 
short-acting bronchodilator within 8 hours of the Screening Visit
15. Use of drugs that are known to cause hepatotoxicity, such as, but not limited to, 
acetaminophen (paracetamol) at dosages of > 3 grams/day and niacin dosage of > 2 
grams/day while on study or within 2 weeks of first dose of IP
16. Use of any medications that are substrates of one or more of the transporters P-gp, BCRP, 
OAT3, OATP1B1, OATP1B3, and OCT2 and have a narrow therapeutic index (eg, 
digoxin, mycophenolate mofetil)
17. History of recent (within 6 months of Screening) deep vein thrombosis (DVT) or 
pulmonary embolism (PE) and/or recurrent DVT or recurrent PE
18. History of cardiac valve replacement requiring chronic anticoagulation therapy
19. History of congenital and/or acquired immunodeficiencies (eg, common variable 
immunodeficiency, human immunodeficiency virus [HIV], etc)
20. History of hepatitis B and/or hepatitis C, including those considered successfully
treated/cured
21. Active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections 
(including, but not limited to, atypical mycobacterial disease and herpes zoster), or any 
major episode of infection requiring hospitalization or treatment with intravenous or oral 
antibiotics within 4 weeks of the Screening Visit and at any time during the Screening 
Phase, up through the first dose of IP
22. History of active or latent tuberculosis (TB) infection, unless there is medical record 
documentation of successful completion of a standard course of treatment considered 
appropriate, based on local prevalence of multi-drug resistant TB and consistent with 
World Health Organization guidelines
Note: If a subject has adequate documentation of successful treatment for either latent or 
active TB, the QuantiFERON-TB Gold test is not needed. Instead, a chest radiograph, 
obtained within the 12 weeks prior to Screening or during Screening, without changes 
suggestive of active TB infection as determined by a qualified radiologist, will be 
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sufficient to permit further participation in the study for these subjects. Documentation 
of adequate treatment for TB must be obtained prior to randomization.
23. Subject has had a household contact with a person with active TB and subject did not 
receive appropriate and documented prophylaxis for TB
Note: Household contact is a person who shared the same enclosed living space as the 
index case for one or more nights or for frequent or extended daytime periods during the 
3 months before the start of current treatment.
24. Clinical diagnosis of any connective tissue disease, including, but not limited to,
scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, and 
rheumatoid arthritis
25. History of end-stage renal disease requiring dialysis
26. History of severe hepatic impairment or end-stage liver disease
27. History of Gilbert’s syndrome
28. History of alcohol or drug abuse within 6 months prior to Screening
29. Use of tobacco products (cigarettes, pipes and cigars), vapes, e-cigarettes or marijuana
use within 3 months of Screening and/or unwillingness to avoid the use of these products
throughout the study
30. History of malignancy (exceptions: excised and cured basal/squamous cell skin 
carcinomas or cervical carcinoma in situ with no recurrence in 5 years)
31. Pregnancy or lactation
32. Use of any investigational drug within one month of Screening, or 5 PD/PK half-lives 
(whichever is longer)
Approved
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5.
TABLE OF EVENTS
Table 5:
Table of Events
Screening
Phase
24-Week
Double-Blind Placebo-
Controlled Treatment 
Phase
80-Week Active
Treatment Extension Phase
Early 
Termination 
Visit
Post-
Treatment 
Observational 
Follow-up
Visit(s)k
1
Screening
2
Baselinea
3
4-9
Every 4 
Weeks
10E
11E-17E
Every 4 
Weeks
18E-25E
Every 6 
Weeks
26E
End of 
Treatment
27E
Week(s)
-8 to -1
0
1
± 3 
days
4, 8, 12, 
16, 20, 
24 ± 3 
days
25
± 3 
days
28, 32, 36, 
40, 44, 48, 
52
± 3 days
58, 64, 70, 
76, 82, 88, 
94, 100
± 3 days
104
± 3 days
108
4-weeks post-
treatment
± 3 days
Main Informed 
Consent
X
-
-
-
-
-
-
-
-
-
Inclusion/Exclusion 
Criteria
X
X
-
-
-
-
-
-
-
-
Demographics
X
-
-
-
-
-
-
-
-
-
Complete Medical 
History
X
-
-
-
-
-
-
-
-
-
Prior IPF Disease 
History
X
-
-
-
-
-
-
-
-
-
Prior IPF Therapies
X
-
-
-
-
-
-
-
-
-
Approved
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Table 5:
Table of Events (Continued)
Screening
Phase
24-Week
Double-Blind Placebo-
Controlled Treatment 
Phase
80-Week Active
Treatment Extension Phase
Early 
Termination 
Visit
Post-
Treatment 
Observational 
Follow-up
Visit(s)k
1
Screening
2
Baselinea
3
4-9
Every 4 
Weeks
10E
11E-17E
Every 4 
Weeks
18E-25E
Every 6 
Weeks
26E
End of 
Treatment
27E
Week(s)
-8 to -1
0
1 
± 3 
days
4, 8, 12, 
16, 20, 
24 ± 3 
days
25 
± 3 
days
28, 32, 36, 
40, 44, 48, 
52
± 3 days
58, 64, 70, 
76, 82, 88, 
94, 100
± 3 days
104
± 3 days
108
4-weeks post-
treatment
± 3 days
Prior/ Concomitant 
Medication Evaluation
Continuous starting after the informed consent form is signed through 28 days after treatment 
Prior/Concomitant 
Procedures Evaluation
Continuous starting after the informed consent form is signed through 28 days after treatment. 
Postmenopausal 
testing: estradiol and 
follicle-stimulating 
hormone (for women 
without a menses for 1 
year and/ or 
undocumented status)
X
-
-
-
-
-
-
-
-
-
QuantiFERON® -TB 
Gold Test or Chest 
Radiograph for TB 
when appropriate l, 
Hepatitis B & C Tests
X
-
-
-
-
-
-
-
-
-
SAFETY ASSESSMENTS
Adverse Event 
Evaluation
Continuous starting after the informed consent form is signed through 28 days after treatment.
Approved
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Table 5:
Table of Events (Continued)
Screening
Phase
24-Week
Double-Blind Placebo-
Controlled Treatment 
Phase
80-Week Active
Treatment Extension Phase
Early 
Termination 
Visit
Post-
Treatment 
Observational 
Follow-up
Visit(s)k
1
Screening
2
Baselinea
3
4-9
Every 4 
Weeks
10E
11E-17E
Every 4 
Weeks
18E-25E
Every 6 
Weeks
26E
End of 
Treatment
27E
Week(s)
-8 to -1
0
1 
± 3 
days
4, 8, 12, 
16, 20, 
24 ± 3 
days
25 
± 3 
days
28, 32, 36, 
40, 44, 48, 
52
± 3 days
58, 64, 70, 
76, 82, 88, 
94, 100
± 3 days
104
± 3 days
108
4-weeks post-
treatment
± 3 days
Complete Physical 
Examination
X
-
-
-
X
-
-
X
X
X
Targeted Physical 
Examination
-
X
X
X
-
X
X
-
-
-
Vital Signs
X
X
-
Week 
24
-
Week 52
Week 76
X
X
X
Weight
X
-
-
Week 
24
-
-
-
X
X
X
Height
X
-
-
-
-
-
-
-
-
-
12-Lead ECG
X
-
-
Weeks 
4, 12, 
24
-
Week 52
-
X
X
X
Hematology 
Laboratory
X
X
X
X
X
X
X
X
X
X
Chemistry Laboratory
X
X
X
X
X
X
X
X
X
X
Approved
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CC-90001-IPF-001 Amendment 3.0 Final:  28 Aug 2019
Table 5:
Table of Events (Continued)
Screening
Phase
24-Week
Double-Blind Placebo-
Controlled Treatment 
Phase
80-Week Active
Treatment Extension Phase
Early 
Termination 
Visit
Post-
Treatment 
Observational 
Follow-up
Visit(s)k
1
Screening
2
Baselinea
3
4-9
Every 4 
Weeks
10E
11E-17E
Every 4 
Weeks
18E-25E
Every 6 
Weeks
26E
End of 
Treatmen
t
27E
Week(s)
-8 to -1
0
1 
± 3 
days
4, 8, 12, 
16, 20, 
24 ± 3 
days
25 
± 3 
days
28, 32, 36, 
40, 44, 48, 
52
± 3 days
58, 64, 70, 
76, 82, 88, 
94, 100
± 3 days
104
± 3 days
108
4-weeks post-
treatment
± 3 days
PT and INR (for 
subjects receiving 
vitamin K antagonist 
[eg, warfarin] therapy, 
only)b
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
-
Weeks 32, 
52
Week 76
X
X
X
Urine cytology
X
-
-
Weeks 
12, 24
-
Weeks 32, 
52
X
X
X
-
Urine β-hCG
-
Xc
-
-
-
-
-
-
-
-
Serum β-hCGd
X
X
-
X
-
X
X
X
X
X
Pregnancy counseling 
for FCBP
X
X
X
X
X
X
X
X
X
X
EFFICACY ASSESSMENTS
HRCTe,
Xf
-
-
Week 24
-
-
-
Xf
Xf
-
SGRQ
-
X
-
Weeks 
12, 24
-
-
-
X
X
-
Approved
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Table 5:
Table of Events (Continued)
Screening
Phase
24-Week
Double-Blind Placebo-
Controlled Treatment 
Phase
80-Week Active
Treatment Extension Phase
Early 
Termination 
Visit
Post-
Treatment 
Observational 
Follow-up
Visit(s)k
1
Screening
2
Baselinea
3
4-9
Every 4 
Weeks
10E
11E-17E
Every 4 
Weeks
18E-25E
Every 6 
Weeks
26E
End of 
Treatmen
t
27E
Week(s)
-8 to -1
0
1 
± 3 
days
4, 8, 12, 
16, 20, 
24 ± 3 
days
25 
± 3
days
28, 32, 36, 
40, 44, 48, 
52
± 3 days
58, 64, 70, 
76, 82, 88, 
94, 100
± 3 days
104
± 3 days
108
4-weeks post-
treatment
± 3 days
Spirometryg
X
X
X
X
X
X
X
X
X
X
SpO2 g
X
X
X
X
X
X
X
X
X
X
UCSD-SOBQ
-
X
-
Weeks 
12, 24
DLCOg
X
X
-
Week 24
-
Week 52
-
X
X
X
6MWT with Borg 
Scale
X
X
-
Week 24
-
Week 52
Week 76
X
X
X
Assessment for New 
or Worsening 
Shortness of Breath 
X
X
X
X
X
X
X
X
X
X
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Table 5:
Table of Events (Continued)
Screening
Phase
24-Week
Double-Blind Placebo-
Controlled Treatment 
Phase
80-Week Active
Treatment Extension Phase
Early 
Termination 
Visit
Post-
Treatment 
Observational 
Follow-up
Visit(s)k
1
Screening
2
Baselinea
3
4-9
Every 4 
Weeks
10E
11E-17E
Every 4 
Weeks
18E-25E
Every 6 
Weeks
26E
End of 
Treatmen
t
27E
Week(s)
-8 to -1
0
1 
± 3 
days
4, 8, 12, 
16, 20, 
24 ± 3 
days
25 
± 3 
days
28, 32, 36, 
40, 44, 48, 
52
± 3 days
58, 64, 70, 
76, 82, 88, 
94, 100
± 3 days
104
± 3 days
108
4-weeks post-
treatment
± 3 days
INVESTIGATIONAL PRODUCT (IP)
Dispense IPi
-
X
X
X
X
X
X
Xj
-
-
Return and Count IP 
-
-
X
X
X
X
X
X
X
-
Abbreviations: β-hCG = beta human chorionic gonadotropin; DLCO = diffusion capacity of the lung for carbon monoxide; E= Extension; ECG = electrocardiogram; FCBP= 
female of childbearing potential; HRCT = high resolution computed tomography; INR = international normalized ratio; IP = investigational product; IPF = idiopathic pulmonary 
fibrosis; 
 PT = prothrombin time; 
 
 SGRQ = St. 
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George’s Respiratory Questionnaire; 6MWT = Six-minute Walk Test; SpO2 = oxygen saturation; TB = tuberculosis; UCSD-SOBQ = University of California San Diego Shortness 
of Breath Questionnaire.
a The Baseline value is defined as the last assessment prior to or on the date of the first dose of IP in the study.
b PT and INR will only be done on those subjects who require monitoring for vitamin K antagonist levels (eg, warfarin).
c Urine pregnancy test will be performed to assess subject eligibility prior to the first administration of IP, if the initial serum pregnancy test did not already occur within 72 hours 
of dosing (negative results required for IP administration).
d Serum pregnancy testing during the 80-week Active Treatment Extension Phase occurs every 4 weeks for females of child bearing potential. 
e HRCT used to qualify subjects for inclusion can be performed between Visits 1 and 2, inclusive, or can utilize historical HRCT images (within 18 months of randomization) 
which still require review by a central reader. For sites subject to regulatory restrictions that do not permit HRCT within this time period, a previous HRCT scan is permissible if 
the scan is deemed sufficient for centralized review.
g Spirometry, DLCO, and pulse oximetry will be assessed as part of the safety assessments for those subjects who discontinue for progressive disease during the 24-Week Double-
blind Placebo-controlled and 80-Week Active Treatment Extension Phases.
i Blinded IP will be packaged in 32 tablet-count, 16-day blister cards (16-day card includes IP for two additional days in the event the subject is unable to return for their 
scheduled visit). 
!
On Visits 2 and 3, one blister card will be dispensed to the subject. Remaining IP from the blister card issued on Visit 2 will be reissued to the subject along with a 
new card on Visit 3. The subject should be instructed to finish the remaining IP in the blister card issued at Visit 2 before starting the new blister card issued at Visit 3.
!
On Visits 4 to 8, two blister cards will be dispensed to the subject per visit. 
!
On Visits 9 and 10E, one blister card will be dispensed to the subject. Remaining IP from the blister card issued on Visit 9 will be reissued to the subject along with a 
new card on Visit 10E. The subject should be instructed to finish the remaining IP in the blister card issued at Visit 9 before starting the new blister card issued at 
Visit 10E.
!
On Visits 11E to 16E, two blister cards will be dispensed to the subject per visit.  
!
On Visit 17E to 24E, three blister cards will be dispensed to the subject per visit.
!
On Visit 25E, two blister cards will be dispensed to the subject per visit.  
j Final dose of IP administered at the investigative site.
k For all subsequent visits, an administrative window of ± 3 days is permitted.  Scheduling of Visits 3 to 9 is based on Visit 2 (randomization date) and scheduling of Visits 10E to 
26E is based on Visit 9 (re-randomization date).  The Post-treatment Observational Follow-up Visit is scheduled 28 days (4 weeks) after the date of the last dose of IP ± 3 days.
l If a subject has adequate documentation of successful treatment for either latent or active TB, the QuantiFERON-TB Gold test is not needed. Instead, a chest radiograph, 
obtained within the 12 weeks prior to Screening or during Screening, without changes suggestive of active TB infection as determined by a qualified radiologist, will be 
sufficient to permit further participation in the study for these subjects. Documentation of adequate treatment for TB must be obtained prior to randomization.
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6.
PROCEDURES
Any questions regarding the protocol should be directed to the Medical Monitor or designee.
Signed informed consent forms (ICFs) must be obtained before any study evaluations are 
performed and any samples are collected per local regulations during the course of the study.
6.1.
Screening Phase
Screening evaluations will be performed for all subjects to determine study eligibility. These 
evaluations must be completed within 8 weeks after Screening (Visit 1) unless noted 
otherwise below. Subjects are permitted to be re-screened once should they fail to meet the 
study entry criteria; however, all re-screened subjects must be re-consented for the study.
Note: Subjects who fail the entry criteria due to a positive hepatitis B, hepatitis C or TB test 
result should not be rescreened for the study. Subjects who received hepatitis B vaccination 
and who test positive for hepatitis B surface antibody and negative for both hepatitis B 
surface antigen and hepatitis B core antibody are not excluded from the study.
Waivers to the protocol will not be granted during the conduct of this trial, under any 
circumstances.
Safety laboratory analyses will be performed by the contracted central laboratory. The central 
laboratory will provide a separate manual for the collection and processing of the samples for 
this study.  Screening laboratory values must demonstrate subject eligibility, but may be 
repeated within the Screening window, if necessary.
The following assessments will be performed at Screening as specified in the Table of 
Events, Table 5, after the informed consent has been obtained.
!
The Screening Visit should be registered in the interactive web response system 
(IWRS).
!
Demographics (eg, date of birth, sex, race, and ethnicity-if allowed by local 
regulations)
!
Disease history, including specific information regarding diagnosis of IPF
!
Complete Medical History: All relevant medical conditions diagnosed/occurring 
prior to Screening should be recorded, including smoking and alcohol history, as 
well as previous relevant surgeries.
!
Prior Procedures: All procedures occurring up to 35 days prior to Screening Visit 
should be recorded.
!
Prior and Current Medication Evaluation:
∀
All IPF/PPF therapies used by the subjects should be recorded.
∀
All medications (prescription and nonprescription, including vitamins) taken 
by the subject up to 35 days prior to Screening Visit should be recorded, 
including the stop dates for medications prohibited in the study. All 
medications taken by the subject at any time during the study must also be 
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recorded. Other key medications and therapies, such as previous treatment for 
tuberculosis or relevant diseases, should also be recorded. 
Additional instructions can be found in the electronic case report form (CRF) 
Completion Guidelines.
!
Washout of all disallowed therapies defined in Sections 4.3 and 8.2 if required 
should commence after the informed consent is signed on the initial day of 
Screening (Visit 1).
!
Complete Physical Examination: Complete physical examinations will include 
evaluation of the skin, nasal cavities, eyes and ears, respiratory, cardiovascular, 
abdominal, neurological, lymphatic, and musculoskeletal systems. Gynecological, 
urogenital and rectal examinations will not be performed unless for cause.
!
Vital Signs, Height and Weight: Vital signs, including body temperature, pulse 
rate, respiration rate, and seated blood pressure will be taken. Height and weight 
(to be done in street clothes, no shoes) will also be measured and recorded.
!
12-lead electrocardiogram (ECG): All ECG recordings will be manually over-
read on an ongoing basis by a cardiologist at the core ECG laboratory for QT 
measurement and QTc calculation using Fridericia’s formula (QTcF). The central 
cardiologist will interpret all ECGs with respect to PR interval, QRS duration, 
heart rate and R-R interval, QT and QTcF intervals and for arrhythmia, ischemia
or any relevant finding. Details regarding the ECG recordings are described in a 
separate manual.
!
Spirometry: Spirometry for FVC (volume of air that can forcibly be blown out 
after full inspiration) and FEV1 (maximum volume of air that can forcibly be 
blown out in the first second during the FVC maneuver) will be performed at 
prespecified times. Sites are required to use the spirometry equipment provided by 
the Sponsor.  Spirometers must meet the American Thoracic Society/European 
Respiratory Society (ATS/ERS) criteria (Miller, 2005).
For each subject, all subsequent pulmonary function testing should start at 
approximately the same time of the day (in the morning with ±1 hour maximum 
difference; time will be recorded).  Subjects must refrain from strenuous activity 
at least 12 hours prior to testing.
Details of the procedure will be described in a separate manual.
DLCO: The DLCO will be measured at prespecified times. DLCO will be measured 
after the spirometry testing is completed.  DLCO equipment will be calibrated 
centrally to meet ATS/ERS criteria (MacIntyre, 2005). The same tester should be 
employed during the study. Details of the procedure will be described in a 
separate manual.
Note: For data analysis, all DLCO values will be corrected for hemoglobin.
!
Pulse oximetry will be used to measure arterial oxygen saturation.
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!
Historical lung biopsy (surgical lung biopsy [SLB] or lung cryobiopsy) if used for 
study eligibility must be sent to the central pathologist selected by the Sponsor for 
expertise in the scoring of IPF-related histologic findings (Appendix G).
!
Chest HRCT: For confirmation of diagnosis, chest HRCT is required for all 
subjects. HRCT may be obtained during screening or historical HRCT (within 18 
months of randomization) may be used to qualify the subject for study entry. All 
HRCT images will be reviewed by a central reader. In the event a historical HRCT 
does not meet study eligibility (as determined by the central reader), a new HRCT 
must be obtained.  For sites subject to regulatory restrictions that do not permit 
HRCT within this time period, a previous HRCT scan is permissible if the scan is
deemed sufficient for centralized review.  Diagnosis of IPF by HRCT and lung 
biopsy, if obtained, will be assessed according to Lynch, 2018 (Appendix G).
Details regarding the analyses and handling of the HRCT images and historical 
lung biopsies for central reading will be provided in a separate manual.  
Note: A new lung biopsy should not be obtained at the Screening Visit in order to 
qualify the subject for the study.
!
6MWT: A 6MWT will be performed in accordance with the ATS guidelines 
(ATS, 2002) and as described in Appendix E. The 6MWT measures the distance a 
subject is able to walk on a hard, flat surface, over a total of six minutes. In 
conjunction with the 6MWT, the subject will also complete the Borg Scale 
(Appendix F), assesses dyspnea.
!
Assessment for new or worsening shortness of breath.  
The standard requirements to perform the above procedures will be outlined in the separate
operations manual.
!
The following laboratory specimens will be collected:
∀
Hematology panel including complete blood count (CBC) with differential, 
including red blood cell (RBC) count, hemoglobin, hematocrit, mean 
corpuscular volume, mean corpuscular hemoglobin, mean corpuscular
hemoglobin concentration, WBC count (with differential), neutrophil count 
(percent and absolute), and platelet count
∀
Chemistry panel will include albumin, alanine aminotransferase (ALT; serum 
glutamic pyruvic transaminase [SGPT]), alkaline phosphatase, aspartate 
aminotransferase (AST; serum glutamic oxaloacetic transaminase [SGOT]), 
gamma-glutamyl transferase (GGT), bicarbonate, blood urea nitrogen, 
calcium, chloride, creatinine, glucose, lactate dehydrogenase, magnesium, 
phosphorus, potassium, sodium, total bilirubin, direct bilirubin, indirect 
bilirubin, total cholesterol, HDL, LDL, total protein, triglycerides, and uric 
acid.
∀
Prothrombin time (PT) and international normalized ratio (INR) will be 
obtained only in those subjects receiving vitamin K antagonists (eg, warfarin).
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∀
Urinalysis: semiquantitative testing via dipstick (specific gravity, pH, glucose, 
erythrocytes, leukocytes, protein, and nitrite) will be performed by the central 
laboratory.  Microscopic urinalysis (epithelial cells, RBC, WBC, and casts) 
will be performed only if the dipstick urinalysis is abnormal.
Note: If the Screening Visit 1 urinalysis test results are positive (eg, leukocyte 
esterase or nitrite present), a urine culture test is required and the subject 
must have a confirmatory negative urine culture test to rule out urinary tract 
infection (UTI) prior to randomization, which can be performed using the 
provided central laboratory urine culture kits or a local laboratory at the site.
∀
In addition to the routine urinalysis, urine cytology will be done for the 
detection of abnormal cells. The urine cytology specimen will be evaluated by 
a pathologist at the central laboratory.
Note: “Abnormal, clinically significant” results should be recorded in the 
Medical History CRF if found prior to first dose of IP, or in the AE CRF if 
found after the first dose of IP. Clinical laboratory evaluations do not require
subjects to be fasting. However, the site will record on the lab requisition form
whether a clinical laboratory evaluation was obtained in the fasting or 
nonfasting state.
∀
Mycobacterium tuberculosis (TB) testing: Testing will be done at the 
Screening Visit via QuantiFERON®-TB Gold.
Note: A positive QuantiFERON-TB Gold test or 2 successive indeterminate 
QuantiFERON-TB Gold tests will disqualify the subject from further 
participation in the study.
Note: If a subject has adequate documentation of successful treatment for 
either latent or active TB, the QuantiFERON-TB Gold test is not needed.
Instead, a chest radiograph, obtained within the 12 weeks prior to Screening 
or during Screening, without changes suggestive of active TB infection as 
determined by a qualified radiologist, will be sufficient to permit further 
participation in the study for these subjects. Documentation of adequate 
treatment for TB must be obtained prior to randomization.
∀
Viral tests: Hepatitis B surface antigen (HBsAg) and hepatitis C antibody 
(HCV Ab) testing:  testing will be performed at Screening.  The hepatitis
screen includes testing for hepatitis B surface antigen and antibody, hepatitis B 
core antibodies (IgG/IgM), and antibodies to hepatitis C.  A positive result for 
one or more of these tests will disqualify the subject from further participation 
in the study.  The Investigator should refer the subject to his/her general 
practitioner or other appropriate healthcare provider for further follow-up.
Note: Subjects who received hepatitis B vaccination and who test positive for 
hepatitis B surface antibody and negative for both hepatitis B surface antigen 
and hepatitis B core antibody are not excluded from the study.
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∀
Pregnancy test: Testing is required for all female subjects of childbearing 
potential.  Serum beta human chorionic gonadotropin (β-hCG) pregnancy test 
will be performed at the Screening Visit.  
Note: Urine pregnancy test will be performed to assess subject eligibility prior 
to the first administration of IP, if the initial serum pregnancy test did not 
already occur with 72 hours of dosing (negative results required for IP 
administration).
∀
Counseling about pregnancy precautions and the potential risks of fetal 
exposure must be conducted. 
∀
Postmenopause test: Estradiol and follicle-stimulating hormone (FSH) levels 
are required for all females who have not had a menses for at least one year,
and do not have documentation confirming their postmenopausal status.
!
Adverse Events: Adverse event assessment begins when the subject signs the 
informed consent form and is assessed continuously throughout the study, until 28
days following the last dose of IP.
All abnormal ECG, laboratory and physical exam findings identified during the 
Screening period will be captured on the medical history page of the CRF.
Of note, minor fluctuations of symptoms (eg, cough and dyspnea) that reflect the 
underlying disease should not necessarily be recorded as an AE if they are similar 
in intensity and duration to prior such fluctuations. However, more marked and/or 
sustained worsening of such symptoms should be recorded as an AE.
Refer to Section 10 for details pertaining to AEs. Adverse event assessment begins 
when the subject signs the informed consent form. If a subject is hospitalized for a 
serious adverse event, additional information will be collected regarding reason 
and duration of hospitalization and to which unit the subject was admitted.
!
Information to be collected on Screening Failures: At a minimum, the information 
to be collected should include the informed consent date, demographics, and 
reason why the subject did not qualify for the study will be collected for all 
subjects determined to be screen failures. Adverse events experienced by screen 
failure subjects will be collected from the date of signing consent to the day the 
subject is confirmed to be a screen failure. This information will be captured in the 
subject’s source documents and appropriate CRF(s).
Note:
!
For purposes of study eligibility, inclusion and exclusion criteria/results should be 
reviewed again prior to randomization (Baseline [Visit 2]) to ensure the subject 
continues to meet criteria for entry into the study. Additionally, FVC must be 
repeated at the Baseline (Visit 2) and should be the first assessment done at that 
visit.
!
If the subject does not receive IP within 8 weeks after Screening (Visit 1), the 
subject must be screen failed, and all screening assessments with the exception of 
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the HRCT, if previously done, must be repeated.  Details on how to handle screen 
failures will be described in the CRF operations manual.
6.2.
Treatment Phase
The subject will begin treatment upon confirmation of eligibility at the Baseline (Visit 2).  
For all subsequent visits, an administrative window of ± 3 days is permitted.  Scheduling of 
Visits 3 to 9 is based on Visit 2 (randomization date) and scheduling of Visits 10E to 26E is 
based on Visit 9 (re-randomization date).
The following evaluations will be performed at the frequency specified in the Table of 
Events, Table 5 and in the order described below.  The evaluations should be performed prior 
to dosing on the visit day, unless otherwise specified.
!
Adverse event evaluation
!
Concomitant medications reviewed with the subject
!
Concomitant procedures reviewed with the subject
!
Patient-reported outcome questionnaires will be completed as described 
in Section 6.7
!
Assessment for new or worsening shortness of breath
As part of the routine assessments during the study visit, subjects will be assessed for 
new or worsening of shortness of breath (SOB).  The Investigator should use his/her 
clinical judgement to decide how to further assess and treat such subjects.
Subjects who experience and receive adequate treatment for SOB with permitted 
drugs (see Section 8.1.2) but demonstrate further clinical decline and/or decrease of
≥10% from baseline in % predicted FVC at two consecutive evaluations at a 
minimum of 4 weeks between evaluations should discontinue IP and enter the 4-week 
Post-treatment Observational Follow-up Phase (Table of Events, Table 5). Whether to 
discontinue a subject from study treatment who experiences unexplained worsening in 
hypoxemia (an absolute decrease from baseline of 4% or more in SpO2) will be left up 
to the Investigator’s discretion. Treatment of subjects during the Post-treatment 
Observational Follow-up Phase is at the discretion of the Investigator.
All relevant clinical data (summary on clinical course, signs and symptoms; 
laboratory, lung function and imaging results; and treatment provided) relating to new 
or worsening shortness of breath must be collected by the Investigator. Changes in 
respiratory status that are considered by the Investigator as possibly or likely due to 
 
disease progression will be reviewed further by the independent 
Adjudication Committee. Details regarding the adjudication process will be described 
in a separate charter.
!
Efficacy assessments as described in Section 6.4
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!
12-lead ECG will be performed as described in Section 6.1
!
Complete/targeted physical examination (source documented only): Complete 
physical examinations will include evaluation of the skin, nasal cavities, eyes and 
ears, respiratory, cardiovascular, abdominal, neurological, lymphatic, and 
musculoskeletal systems. Gynecological, urogenital and rectal examinations will 
not be performed unless for cause.
A targeted physical examination includes evaluation of the respiratory, 
cardiovascular, abdominal systems.  Clinically significant abnormal findings 
identified during the physical examinations will be recorded on the CRF as 
adverse events.  Gynecological, urogenital and rectal examinations will not be 
done unless for cause.
!
Vital signs: Vital sign measurements (body temperature, pulse rate, respiration 
rate, and seated blood pressure) will be taken.  If an abnormal (out of range) value 
constitutes an adverse finding, it should be reported as an AE if appropriate.
!
Weight (to be done in street clothes, no shoes) will be measured and recorded.
!
Clinical laboratory safety tests will be performed as described in Section 6.1, with 
the exception of those labs performed only at Screening (eg, QuantiFERON-TB 
Gold®, hepatitis test, and postmenopausal testing).
!
Counseling about pregnancy precautions and the potential risks of fetal exposure 
must be conducted. 
!
Study IP dispensation (refer to Section 7.2 and the Table of Events, Table 5), 
returns (all used and unused blister cards) and IP compliance will be assessed.
A more detailed description of the order of the procedures for each visit will be provided in 
the operations manual.
6.2.1.
End of Treatment
An end of treatment (EOT) evaluation will be performed for subjects who are withdrawn 
from treatment for any reason as soon as possible after the decision to permanently 
discontinue treatment has been made. 
The following evaluations will be performed as specified in the Table of Events, Table 5 and 
in the order described below:
!
Adverse event evaluation
!
Review of concomitant medications
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!
Review of concomitant procedures
!
Patient-reported outcome questionnaires will be completed as described in 
Section 6.7
!
Assessment for new or worsening SOB
!
Efficacy assessments as described in Section 6.4
!
12-lead ECG as described in Section 6.1
!
Complete physical examination (source documented only) in Section 6.1
!
Vital signs as described in Section 6.2. All abnormal (out of range) value that 
constitutes an adverse finding (event), should be reported as an AE if appropriate
!
Weight (to be done in street clothes, no shoes) will also be measured and recorded
!
Clinical laboratory safety tests as described in Section 6.1, with the exception of 
those labs performed only at Screening (eg, QuantiFERON-TB Gold, hepatitis 
test, and postmenopausal testing)
!
Counseling about pregnancy precautions and the potential risks of fetal exposure 
must be conducted. 
 
!
Study IP returned (all used and unused blister cards) and IP compliance will be
assessed
6.3.
Post-treatment Observational Follow-up Phase
All subjects will be followed for 28 days after the last dose of IP for AE reporting, as well as 
SAEs made known to the Investigator at any time thereafter that are suspected of being 
related to IP, as described in Section 10.1.  The Post-treatment Observational Follow-up Visit 
is scheduled 28 days (4 weeks) after the date of the last dose of IP ± 3 days.
The following evaluations will be performed as specified in the Table of Events, Table 5 and 
in the order described below:
!
Adverse event evaluation (monitored through 28 days after the last dose of IP or 
until the last study visit, whichever is longer).
!
Concomitant medications reviewed with the subject
!
Concomitant procedures reviewed with the subject
!
Assessment for new or worsening SOB
!
Pulmonary function tests (for safety only):
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∀
Spirometry (FEV1, FVC)
∀
DLCO
∀
Pulse oximetry
!
6MWT
!
12-lead ECG as described in Section 6.1
!
Complete physical examination (source documented only). Refer to Section 6.1
!
Vital signs including weight
!
Clinical laboratory safety tests as described in Section 6.1, with the exception of 
those labs only performed only at Screening (eg, QuantiFERON-TB Gold, 
hepatitis test, and postmenopausal testing)
!
Counseling about pregnancy precautions and the potential risks of fetal exposure 
must be conducted
6.4.
Efficacy Assessment
Efficacy assessments should be performed in the order presented below.
6.4.1.
Pulmonary Function Tests
Information regarding the potential effect of treatment on lung function, including FVC and 
DLCO will be collected.  FVC and DLCO have been reported to correlate with survival in 
patients with IPF (Latsi, 2003; Collard, 2003; Flaherty, 2003; Noble, 2011; King, 2014).
6.4.1.1.
Spirometry
Spirometry will be measured as described in Section 6.1 and will be performed at multiple 
time points throughout the treatment phase of the study. Prior to spirometry testing, subjects 
must adhere to the washout periods indicated below if the following concomitant medications 
are being used:
!
Short-acting bronchodilator: ≥8 hours
!
Long-acting bronchodilator: ≥24 hours
For each subject, pulmonary function testing must occur at approximately the same time of day
(in the morning with ±1 hour maximum difference, time will be recorded) relative to IP 
dosing in the clinic. On days of clinic visits (including the Screening Visit), subjects must
refrain from strenuous activity at least 12 hours prior to pulmonary function testing.
Spirometry will be the first physiologic efficacy assessment performed at each visit.
Details regarding the process and handling of the spirometric tests will be described in the
separate operations manual.
6.4.1.2.
DLCO
Evaluation of the DLCO will be done by a single breath DLCO according to task force 
recommendations (MacIntyre, 2005). The DLCO, which represents carbon monoxide uptake
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into the blood from a single inspiration in 10 seconds, will be measured at the same visits 
when spirometry is being assessed.  Note: in some regions throughout the world, DLCO is 
referred to as TLCO [transfer factor for carbon monoxide].  In this protocol, DLCO will be 
the only nomenclature used. The DLCO will measure the ability of the lungs to transfer gas 
from inhaled air to the red blood cells in pulmonary capillaries. All sites will use their own 
calibrated equipment per taskforce recommendations for DLCO.  DLCO will be performed 
after the spirometry assessment is done. Details regarding the process and handling of the 
DLCO tests will be described in a separate operation manual. 
Note: For data analysis, all DLCO values will be corrected for hemoglobin. 
6.4.2.
Pulse Oximetry
Pulse oximetry will be used to measure arterial oxygen saturation (SpO2).  Hypoxemia is a
component of the definition of disease progression (Section 9.7.2). All sites will provide their 
own oximeter.
6.4.3.
6-Minute Walk Test 
The 6MWT has been shown to be a predictor of mortality in IPF (Lederer, 2006; Caminati, 
2009).  Changes in the 6MWT demonstrate strong correlations with changes in lung function 
and quality of life (Nathan, 2015). Therefore, this measurement may be an important, 
clinically relevant outcome parameter in patients treated with CC-90001.
A 6MWT will be performed as described in Section 6.1.
6.4.5.
Chest High-resolution Computed Tomography
!
Eligibility HRCT for all subjects
∀
Historical (obtained within 18 months of randomization visit) or a new HRCT 
will be obtained for study eligibility.  In the event a historical HRCT is 
determined by the central reader as not meeting study eligibility, a new HRCT 
must be done. 
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Note: For sites subject to regulatory restrictions that do not permit HRCT 
within this time period, a previous HRCT scan is permissible if the scan is 
deemed sufficient for centralized review. 
Details regarding the performance of HRCT will be described in the separate operations
manual.
 
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, 
6.7.
Patient-reported Outcomes
All questionnaires listed on the Table of Events, Table 5 will be completed by subjects using 
an electronic site pad. The SGRQ, UCSD-SOBQ 
 questionnaires are 
incorporated as endpoints in this study to assess the subjects’ perception of how IPF affects 
their quality of life and to measure overall disease burden.
At each visit the subject will complete the SGRQ first, followed by the UCSD-SOBQ 
 
before any other procedures. The person administering the questionnaires 
should check for completeness but should never help the subject in choosing a response. 
Subjects will not have access to any data collected, or the results of the previous 
questionnaires.
!
St. George’s Respiratory Questionnaire (Appendix B):  The SGRQ is a quality of 
life health questionnaire that has been validated in IPF.  It consists of 76 items in 
three domains:
∀
Symptoms
∀
Activity
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∀
Impact of disease on daily life
A total score is calculated from 0 (no health impairment) to 100 (maximum health 
impairment). In addition to the total score, there is also a score for each domain: 
symptoms, activity, and impact which are scored 0-100.
!
The University of California San Diego Shortness of Breath Questionnaire 
(Appendix C):  The UCSD-SOBQ is a 24-item dyspnea questionnaire that asks 
subjects to rate themselves from 0 (“Not at all”) to 5 (“Maximally or unable to do 
because of breathlessness”) in two areas: 1) how short of breath they are while 
performing various activities (21 items); and 2) how much shortness of breath, 
fear of hurting themselves by overexerting, and fear of shortness of breath limit 
them in their daily lives (3 items).  If the subject does not routinely perform the 
activity, they are asked to estimate the degree of shortness of breath anticipated. 
The UCSD-SOBQ is scored by summing responses across all 24 items to form a 
total score. Scores range from 0 to 120.
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7.
DESCRIPTION OF STUDY TREATMENTS
7.1.
Description of Investigational Product(s)
CC-90001 will be supplied as film-coated 200 mg tablets by the Sponsor and labeled 
appropriately as IP for this study.
Applicable doses of CC-90001 will be provided as blinded 32 tablet-count, 16-day blister 
cards according to local clinical study agreement and in accordance with local guidelines.  
Please refer to the clinical label for more details on storage condition.  CC-90001 is not 
approved for any indication. CC-90001 can be taken with or without food.  The dosing 
schedule is described in Section 7.2.
7.2.
Treatment Administration and Schedule
All IP treatment allocation will be handled via interactive web response system (IWRS).
Subjects are instructed to take 2 tablets once daily, approximately the same time of day, 
with or without food.  
The IPF study subjects are provided with the following IP treatments:  
!
24-week Double-blind, Placebo-controlled Treatment Phase: Baseline (Visit 2) to
Week 24 (Visit 9)
Subjects will receive 2 tablets once daily as follows:
∀
CC-90001 400 mg PO QD (two 200 mg tablets)
∀
CC-90001 200 mg PO QD (one 200 mg tablet and one placebo tablet)
∀
Placebo PO QD (two placebo tablets)
Note: The first dose of IP is taken on the day of Visit 2 and the last dose of IP is 
taken on the day of Visit 9.
!
80-week Active Treatment Extension Phase: Week 24 + 1 Day (Day After Visit 9)
to Week 104 (Visit 26E)
Subjects will receive 2 tablets once daily as follows:
∀
CC-90001 400 mg PO QD (two 200 mg tablets)
∀
CC-90001 200 mg PO QD (one 200 mg tablet and one placebo tablet)
Note: The first dose of IP is taken on the day after Visit 9 and the last dose is 
taken at Visit 26E.
At Visit 9/Week 24, all IPF subjects originally randomized to placebo at baseline during the 
24-week Double-blind Placebo-controlled Treatment Phase will be re-randomized 1:1 to 
receive blinded CC-90001 (200 mg or 400 mg PO QD) via IWRS during the 80-week Active
Treatment Extension Phase.  All subjects originally randomized to CC-90001 (200 mg or 400 
mg PO QD) will remain on that same blinded treatment assignment.  Subjects begin the 
blinded-dose active treatment the day after Visit 9 (ie, Week 24 + 1 day).  During the 
80-week Active Treatment Extension Phase, all subjects not on concurrent protocol-allowable 
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SOC therapy will have the opportunity, if deemed appropriate by the Investigator, to receive 
allowed SOC
.
The PPF substudy subjects are provided with the following IP treatments:  
!
24-week Double-blind, Placebo-controlled Treatment Phase: Baseline (Visit 2) to 
Week 24 (Visit 9)
Subjects will receive 2 tablets once daily as follows:
∀
CC-90001 PO QD (400 mg PO QD [two 200 mg tablets], unless review of 
benefit-risk favors 200 mg PO QD)
∀
Placebo PO QD (two placebo tablets)
Note: The first dose of IP is taken on the day of Visit 2 and the last dose of IP is 
taken on the day of Visit 9.
!
80-week Active Treatment Extension Phase: Week 24 + 1 Day (Day After Visit 9) 
to Week 104 (Visit 26E)
Subjects will receive 2 tablets once daily as follows:
∀
CC-90001 PO QD (400 mg PO QD [two 200 mg tablets], unless review of 
benefit-risk favors 200 mg PO QD)
Note: The first dose of IP is taken on the day after Visit 9 and the last dose is 
taken at Visit 26E.
At Visit 9/Week 24, all PPF subjects originally randomized to placebo at baseline during the 
24-week Double-blind Placebo-controlled Treatment Phase will receive blinded CC-90001 
(400 mg PO QD, unless review of benefit-risk favors 200 mg PO QD) via IWRS during the 
80-week Active Treatment Extension Phase. All subjects originally randomized to CC-90001
(400 mg PO QD, unless review of benefit-risk favors 200 mg PO QD) will remain on that 
same blinded treatment assignment.  Subjects begin the blinded-dose active treatment the day 
after Visit 9 (ie, Week 24 + 1 day).  During the 80-week Active Treatment Extension Phase, 
the decision for PPF subjects to receive additional treatments for pulmonary fibrosis 
 
 is at the discretion of the Investigator.
Blinded IP will be packaged in 32 tablet-count, 16-day blister cards. The 16-day blister cards
include IP for two additional days in the event the subject is unable to return for their 
scheduled visit. 
!
On Visits 2 and 3, one blister card will be dispensed to the subject. Remaining IP 
from the blister card issued on Visit 2 will be reissued to the subject along with a new 
card on Visit 3. The subject should be instructed to finish the remaining IP in the 
blister card issued at Visit 2 before starting the new blister card issued at Visit 3.
!
On Visits 4 to 8, two blister cards will be dispensed to the subject per visit. 
!
On Visits 9 and 10E, one blister card will be dispensed to the subject. Remaining IP 
from the blister card issued on Visit 9 will be reissued to the subject along with a new 
card on Visit 10E. The subject should be instructed to finish the remaining IP in the 
blister card issued at Visit 9 before starting the new blister card issued at Visit 10E.
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!
On Visits 11E to 16E, two blister cards will be dispensed to the subject per visit.  
!
On Visit 17E to 24E, three blister cards will be dispensed to the subject per visit.
!
On Visit 25E, two blister cards will be dispensed to the subject.  
7.2.1.
Overdose
Overdose, as defined for this protocol, applies to protocol-required dosing of the IP 
(CC-90001) only. Therefore, for a drug to meet the overdose definition it must be both 
required and an IP. In this study the only required IP is CC-90001 and placebo, hence the 
overdose definition will apply to only CC-90001 (or matching placebo). Other required or 
optional non-IP intended for prophylaxis of certain side effects, to treat the disease, etc, are 
excluded from this definition.  Overdose for this protocol is defined as ingestion of > 2 tablets 
within the same calendar day, whether by accident or intentionally. Adverse Events 
associated with an overdose must be collected on the Adverse Events page of the CRF for all 
overdosed subjects, but the overdose itself is not considered an AE.
Detailed information about any CC-90001 overdose in this study, regardless of whether the 
overdose was accidental or intentional, should be reported on the drug exposure CRF page.
7.2.2.
Dose Modification/Interruptions
This is a dose-finding study therefore no dose reductions will be permitted. However, in the 
event the subject experiences a study drug-related adverse event, a temporary IP interruption 
for up to 4 days will be permitted anytime during the study.  The Sponsor should be notified 
in advance of the dosage interruption; however, the decision to interrupt IP dosing will be 
based on the Investigator’s clinical judgment.  If the subject misses 4 or more consecutive 
days of dosing, Celgene must be contacted to decide whether dosing should resume or 
whether the subject should be terminated from the study IP and enter the Post-treatment 
Observational Follow-up Phase.
If a dose of IP is missed, it should be taken as soon as possible on the same day, provided it 
occurs within 36 hours of the previous dose.  The dose should be skipped if the timing of the 
dose occurs > 36 hours of the previous dose.  
Note: If the dose is missed for the entire day, the subject should not take an extra dose the 
next day or take an unscheduled dose.
7.2.2.1.
Dose Interruptions for Planned Surgical Procedures
It is unknown if CC-90001 affects wound healing in humans.  Subjects should interrupt IP 
7 to 10 days prior to and restart 7 days after any surgical procedures.
7.2.3.
Method of Treatment Assignment
An IWRS will be used to track IP assignments for all subjects and treatment groups through 
the 24-week Placebo-controlled Treatment Phase and 80-week Active Treatment Extension 
Phase.
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7.3.
Packaging and Labeling
The label(s) for IP will include the Sponsor name, address and telephone number, the 
protocol number, IP name, dosage form and strength (where applicable), amount of IP per 
container, lot number, expiry date (where applicable), medication identification/kit number, 
dosing instructions, storage conditions, and required caution statements and/or regulatory 
statements as applicable. Additional information may be included on the label as applicable 
per local regulations.
7.4.
Investigational Product Accountability and Disposal 
Celgene (or designee) will review with the Investigator and relevant site personnel the 
process for investigational product return, disposal, and/or destruction including 
responsibilities for the site versus Celgene (or designee).
7.5.
Investigational Product Compliance
The Investigator(s) or designee(s) is responsible for accounting for all study IP that is issued 
to and returned by the subject during the course of the study.  Accurate recording of all study 
drug administration (including dispensing and dosing) will be made in the appropriate section 
of the subject’s CRF and source documents. Study personnel will review the instructions 
printed on the package with the study subjects prior to dispensing the IP. Investigational 
product will be dispensed as noted in the Table of Events, Table 5. The subjects will be 
instructed to return the IP containers, including any unused IP, to the study site at each visit 
for tablet counts and reconciliation. Subjects will be asked whether they have taken their IP as 
instructed at each study visit. Any problems with IP compliance will be reviewed with the 
subject. If the subject misses 4 or more consecutive days of dosing, Celgene must be 
contacted to decide whether dosing should resume or whether the subject should be 
terminated from the study IP and enter the Post-treatment Observational Follow-up Phase.
Gross compliance problems (eg, missing 4 or more consecutive days of dosing or taking less 
than 80% of the doses between study visits) should be discussed with Celgene. Compliance 
will be categorized into 4 classes: < 50%, ≥50% to ≤80%, > 80% to ≤120%, > 120%. 
IP compliance will be calculated at each visit as:
Compliance (%) =      Number of tablets actually taken between visits                 X 100
                                Number of tablets that should have been taken between visits
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8.
CONCOMITANT MEDICATIONS 
Over the course of this study, additional medications may be required to manage aspects of 
the disease state of a subject, including side effects from treatments or progressive disease. 
All medications (prescription and non-prescription), treatments, and therapies taken by the 
subject from Screening throughout his/her entire participation in the study, including those
initiated prior to the start of the study, must be recorded on the subject’s source document and 
on the appropriate page of the CRF. The dose, unit, frequency, route, indication, date the 
medication was started, and date the medication was stopped (if not ongoing) must be 
recorded. 
8.1.
Permitted Concomitant Medications
8.1.1.
Permitted Concomitant Medications Throughout the Entire Study
Subjects may take any medication that is not restricted by the protocol and would not be 
expected to interfere with the conduct of the study. Chronic medication should be dosed on a 
stable regimen throughout the study.
!
Subjects in the concurrent protocol-allowable SOC therapy group must be 
receiving the same dose of medication for IPF at least 8 weeks prior to Screening
Visit 1 and through Visit 9/Week 24.  
 
  
!
During the 80-week Active Treatment Extension Phase, all subjects not on 
concurrent protocol-allowable SOC therapy will have the opportunity, if deemed 
appropriate by the Investigator, to receive allowed SOC
.
!
Oral corticosteroid(s) at stable dose ≤ 12.5 mg/day prednisone or equivalent will 
be permitted throughout the study.  Inhaled corticosteroids at approved doses will
be permitted throughout the study. 
!
The following commonly used products are acceptable for use during the study: 
acetaminophen (≤ 3 grams/day), ibuprofen, naproxen sodium, NSAIDs, 
loratadine, pseudoephedrine, guaifenesin, calcium, histamine-receptor antagonists, 
proton-pump inhibitors, antidepressants, and hypertension drugs.
!
Supplemental oxygen is permitted as indicated (eg, new or worsening SOB, etc).
!
Subjects may take statins (HMG-CoA reductase inhibitors) on the study however 
will require careful monitoring. To ensure the safety of the subjects, statins will be 
dose adjusted to an appropriate therapeutic level while being taken during the 
study (Section 8.2.1).
!
Bronchodilators:
∀
Short-acting bronchodilator may be used provided it does not occur within 8 
hours of the study visit.
∀
Inhaled long-acting bronchodilator may be used provided it does not occur 
within 24 hours of the study visit
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!
All medications required to treat adverse events or medical emergencies that occur 
throughout the study are permitted (eg, antibiotics).
8.1.2.
Permitted Medications to Treat New or Worsening Shortness of Breath
Medications, such as prednisone (> 12.5 mg/day or equivalent), azathioprine, and 
cyclophosphamide can be initiated or increased at Investigator’s discretion for the treatment of
an exacerbation.  Subjects may be given supplemental oxygen to alleviate hypoxemia. These
drugs should be discontinued at the Investigator’s discretion upon resolution of the 
exacerbation. If an exacerbation has not improved within 6 weeks or a subject has shown 
signs of further clinical decline despite adequate treatment, the subject should be discontinued
from study IP and enter the Post-treatment Observational Follow-up Phase, as per the Table of 
Events, Table 5.
8.1.3.
Permitted Concomitant Medications Only During the 80-Week Active 
Treatment Extension Phase
For subjects not in the SOC group, an antifibrotic therapy that is considered by the 
country/Investigator as SOC
will be permitted after Week 24 
 
 
.
8.2.
Medications that Require Careful Monitoring
High doses of CC-90001 may moderately induce CYP3A4. Subjects receiving drugs that 
utilize this enzyme in their metabolic pathway (eg, warfarin) should be closely monitored 
during co-administration. All subjects receiving vitamin K antagonists (eg, warfarin) should 
be carefully monitored for changes in INR.
CC-90001 may inhibit the transporters P-gp, BCRP, OAT3, OATP1B1, OATP1B3, and 
OCT2
. Drugs considered to be substrates of these transporters should 
be closely monitored for potential drug interactions while subjects are participating in the 
study. Additional substrates of these transporters can be found in Appendix H. Questions 
regarding potential co-administration of CC-90001 and drugs that are substrates for these 
transporters should be discussed with the Sponsor.
8.2.1.
Statins
Due to the potential for DDIs, the following must be done to ensure the safety of subjects 
taking statins while on the study:
!
During the Screening phase of the study, all subjects receiving statins should be 
prescribed the lowest approved statin dose for adults approximately 1 week before 
Visit 2 (Baseline). For example, a subject receiving atorvastatin 20 mg during the 
Screening Period should be instructed to begin taking atorvastatin 10 mg, instead, 
approximately 1 week prior to randomization.
Note: Subjects who are already receiving the lowest approved statin dose for 
adults should remain on that dose.
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!
At Visit 2 (Baseline), eligible subjects will begin treatment with CC-90001.
Following multiple oral doses of CC-90001, the steady state should be achieved 
on approximately Day 5.  
!
At Visit 3, the lipid profile will be assessed. Based on results of the subjects’ lipid 
profile at Visit 3, the statin dose may be increased to the next highest approved 
dose, if indicated. 
Note: If the lipid profile at Visit 3 is comparable to the lipid profile from Visit 1 
(Screening), the statin dose should not be increased.
!
At Visit 4, the lipid profile will be assessed. Based on the subjects’ lipid profile at 
Visit 4, the statin dose may be increased to the next approved dose, if indicated.
Note: If the lipid profile at Visit 4 is comparable to the lipid profile from Visit 1 
(Screening), the statin dose should not be increased.
The Investigator should use his/her clinical judgement to decide when/if the further 
increase in the statin dose is warranted and how to assess these subjects. In 
particular, Investigators should monitor closely for AEs associated with 
increased statin exposures (eg, myalgia, liver function test abnormalities). If 
needed, the Investigator should refer the subject to his/her general practitioner or other 
appropriate healthcare provider for further follow-up.
8.3.
Prohibited Concomitant Medications
8.3.1.
Prohibited Medications Throughout the Entire Study
The following medications cannot be administered for the specified times prior to the 
initiation of study IP and for the duration of the study.
!
!
Use of any cytotoxic/immunosuppressive agent including azathioprine, 
cyclophosphamide, methotrexate, mycophenolate mofetil, cyclosporine, oral 
corticosteroids whose dose exceeds > 12.5 mg/day (prednisone or equivalent).
Note: Medications, such as prednisone (> 12.5 mg/day or equivalent), 
azathioprine, and cyclophosphamide can be initiated or increased at 
Investigator’s discretion for the treatment of new or worsening shortness of breath 
(an exacerbation as described above [Section 8.1.2]).
!
Use of any cytokine modulators/biologics, such as etanercept, adalimumab, 
efalizumab, infliximab, or rituximab within 12 weeks of randomization.
!
Use of any medications associated with hepatotoxicity risk, such as, but not 
limited to, acetaminophen > 3 grams/day and niacin > 2 grams/day while on study 
or within 2 weeks of first study dose. 
!
Use of marijuana within 3 months of Screening and during the study.
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Note: Drugs considered to be substrates of these transporters and without a 
narrow therapeutic index (eg, OATP1B1/3 substrates statins, OCT2 substrate 
metformin [Section 8.2.1]) should be closely monitored for potential drug 
interactions while subjects are participating in the study. Additional substrates of 
these transporters can be found in Appendix H.
Exceptions may be made if, in the opinion of the Investigator, the medication
 
is needed to support best medical practice in the time frame of study participation 
AND such medication will not interfere with subject safety or the interpretation of study 
results. In such instances, the Sponsor’s Medical Monitor and Investigator must concur.
8.3.2.
Prohibited Medications During the 24-week Double-blind Placebo-controlled
Treatment Phase
The following medications cannot be administered for the specified times prior to the 
initiation of study IP and for the duration of the 24-week Double-blind Placebo-controlled
Treatment Phase of the study. Subjects taking the following medications must adhere to the 
following minimum washout period:
!
Medications to treat IPF/PPF including, but not limited to,
D-penicillamine, endothelium receptor antagonists (eg, bosentan, ambrisentan), 
interferon gamma-1b, imatinib mesylate, and N-acetylcysteine [NAC], within 4 weeks 
prior to Screening Visit 1 and through Visit 9/Week 24.
8.4.
Required Concomitant Medications
There are no required concomitant medications for inclusion in this study.  
 
 
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9.
STATISTICAL CONSIDERATIONS
9.1.
Overview
This is a double-blind, randomized, placebo-controlled study with two treatment arms of oral 
CC-90001 (200 mg or 400 mg PO QD), or one treatment arm in the PPF substudy, compared 
to placebo.  This study consists of a 24-week Double-blind Placebo-controlled Treatment 
Phase, an 80-week Active Treatment Extension Phase, and a 4-week Post-treatment 
Observational Follow-up Phase.  The primary efficacy analysis of percentage point difference 
in the percent predicted FVC at Week 24 and the secondary analyses will be performed after 
all IPF subjects complete the 24-week Double-blind Placebo-controlled Treatment Phase 
(Weeks 0 to 24) or terminate early prior to the Week 24 visit, and similarly but separately for 
the PPF subjects.  Additional analyses will also be performed after the final database lock 
when all subjects complete the study or terminate early. This section outlines the statistical 
analysis strategy and details will be documented in a separate Statistical Analysis Plan (SAP) 
prior to unblinding of the treatment assignments for the 24-week Double-blind Placebo-
controlled Treatment Phase of the study. The randomization schedule will be generated and 
implemented by the IWRS vendor.
9.2.
Study Population Definitions
The safety population will include all randomized subjects who received at least one dose of 
IP.  The analysis of safety data in this study will be based on the safety population and 
subjects will be included in the treatment group they actually received.
The Full Analysis Set (FAS) will include all randomized subjects who received at least one 
dose of IP. The analysis of efficacy data in this study will be primarily based on the FAS and 
subjects will be included in the treatment group to which they are randomized.
The Per Protocol (PP) population will include all randomized subjects who received at least 
one dose of IP, have Baseline (Visit 2) and at least one post-Baseline FVC evaluation, and 
have no important protocol deviation during the 24-week Double-blind Placebo-controlled
Treatment Phase.  The final determination of important protocol deviation criteria will be 
made prior to the unblinding of the database and will be separately documented.
The FAS and PP populations will be analyzed separately for the IPF study and the PPF 
substudy.
9.3.
Sample Size and Power Considerations
The primary objective of the study is to estimate the effect of CC-90001 in subjects with IPF 
either not receiving SOC or currently receiving SOC.
Approximately 165 subjects (55 subjects for CC-90001 200 mg ± SOC, 55 subjects for 
CC-90001 400 mg ± SOC, and 55 subjects for placebo ± SOC) provides 75% power for 
testing an overall difference of 2.2 percentage points in the Week 24 mean change from 
Baseline of percent predicted FVC value between either active treatment group ± SOC and 
the placebo group ± SOC (two-sided t-test; α = 0.1; standard deviation [SD] = 5%), assuming 
that approximately 45% of subjects will be receiving concurrent protocol-allowable SOC
based on the projected enrollment.  The group size estimate is based on an assumed treatment 
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difference of 3 in percent predicted FVC in the non-SOC cohort and 1.3 in percent predicted 
FVC in the SOC cohort at Week 24 from Baseline.  The study will also estimate the effect of 
CC-90001 in the PPF cohort.
9.4.
Background and Demographic Characteristics
Subject’s age, height, weight, and baseline characteristics will be summarized using 
descriptive statistics, while sex, race and other categorical variables will be provided using 
frequency tabulations.  Medical history data will be summarized using frequency tabulations 
by the Medical Dictionary for Regulatory Activities (MedDRA) system organ class and 
preferred term.
9.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, completed, discontinued, along 
with primary reason for discontinuation) will be summarized using frequency and percent by 
study phase.  A summary of subjects enrolled by site will be provided.  Protocol deviations 
will be summarized using frequency tabulations.
9.6.
Efficacy Analysis
9.6.1.
Analysis of the Primary Efficacy Endpoint for the IPF Study
A mixed-effect model of repeated measures (MMRM) will be used as the method for the 
primary efficacy analysis.  The MMRM model will use the percent predicted FVC value as 
the dependent variable.
The MMRM model will include dose, time on treatment, current SOC (Yes/No), and
interactions as fixed effects covariates. The model will also include the stratification factor
applied to the non-SOC cohort, previous exposure to either pirfenidone or nintedanib 
(Yes/No), and Baseline percent predicted FVC value as fixed effects covariates.  Time will be 
treated as a categorical variable in the MMRM model and will be considered as a repeated 
effect.
All post-baseline measurements up to Week 24 of percent predicted FVC values will be 
included in this analysis with no imputation of missing data other than that inherent in the 
MMRM model.
In addition to point estimates, 95% confidence intervals (CIs) for the differences calculated 
from the model (overall active treatment minus overall control, or active versus control within 
each cohort) of the least squares (LS) mean change from Baseline percent predicted FVC 
value and nominal p-values will also be provided, separately for each dose versus placebo 
comparison and also combining the 200 and 400 mg doses versus placebo comparison if both 
active treatment groups demonstrate efficacy. P-values and 95% CIs are considered
descriptive measures of strength of association between dose and endpoint, rather than formal 
criteria to claim statistical significance.
In addition to the primary efficacy analysis of MMRM, non-parametric analysis of Rank-
ANCOVA (Stokes, 2000) with a baseline FVC as a covariate for pair-wise comparisons with 
imputation of percent predicted FVC value for deaths to the worst rank will be applied as a 
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sensitivity analysis for the primary endpoint. Non-death discontinuation will be imputed in a 
different scheme; the details of the methods will be specified in the Statistical Analysis Plan.
To determine whether the treatment effect is consistent across various subgroups, the primary 
endpoint will be summarized by category of some classification variables observed at 
baseline including variables based on FVC (% predicted), age, time since first diagnosis of 
IPF, and prior therapy.
No multiplicity adjustment is planned for this study.
In addition to the above primary method of analysis on the primary endpoint, a Bayesian 
posterior probability that the effect ratios are greater than 1 (transformed on the log scale), 
within the naïve cohort and the SOC cohort separately, will be calculated using priors built 
from the current literature.  The information from the literature may allow for a more precise 
estimate of the treatment effects.
 
9.6.2.
Analysis of Secondary Efficacy Endpoints
9.6.2.1.
24-Week Double-blind Placebo-controlled Treatment Phase
Descriptive statistics for change from Baseline, frequencies, or median time to event in 
efficacy measures will be summarized by visit for each treatment group, and for the treatment 
difference between each CC-90001 treatment group ± SOC and the placebo treatment group
± SOC. In addition, 95% CIs for the treatment differences will be provided to indicate the 
variability.
The analysis of most of the continuous secondary efficacy endpoints during the Double-blind 
Placebo-controlled Treatment Phase will be performed using an MMRM model in a manner 
similar to the primary analysis as specified in Section 9.6.1.
A random coefficient mixed effect model will be used to analyze the rate of decline of FVC. 
The usual FVC predictors, such as age, sex, height, and race, along with treatment and time 
interaction, will be included as fixed effects in the model, in which time will be treated as a 
numerical variable. In addition, intercept and slope of the linear relationship between FVC 
and time will be assumed to be subject-specific and treated as random coefficients.  
Comparisons of mean yearly decrease of FVC between treatment groups will be performed 
using appropriate contrasts. 
A Cochran-Mantel-Haenszel (CMH) test will be used for the pair-wise comparisons of the 
proportions of subjects who experience disease progression at Week 24 between the two 
active treatment groups ± SOC and the placebo ± SOC. For the time to even data, such as 
time-to-first acute exacerbation and time to disease worsening, log-rank test will be provided 
by treatment, and a Kaplan-Meier estimate for the survival function will be provided for all 
the time to event data.  For the time to event data (on-treatment time to death endpoint, time 
to first acute exacerbation and time to disease worsening while on treatment), Kaplan-Meier 
estimates for the survival function will be provided by treatment groups (CC-90001 200 mg 
PO QD ± SOC, CC-90001 400 mg PO QD ± SOC, and placebo ± SOC).  The number and 
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percentage of events within different time intervals during treatment will also be provided by 
treatment group.
 
9.6.2.2.
80-Week Active Treatment Extension Phase
Efficacy analyses for the 80-week Active Treatment Extension Phase will be performed based 
on subjects who received at least one dose of active treatment (200 mg PO QD or 400 mg PO 
QD) during the 80-week Active Treatment Extension Phase. The efficacy endpoints will be 
summarized with descriptive statistics by treatment group.  Continuous efficacy endpoints 
will be summarized using mean, SD, median, minimum, maximum, and number of 
observations analyzed. Binary efficacy endpoints will be summarized with counts, 
percentages, and associated 95% CIs for the percentages within each treatment group based 
on Clopper-Pearson method.   
9.7.
Safety Analysis
The safety analyses for the 24-week Double-blind Placebo-controlled Treatment Phase will 
be performed using the safety population as defined in Section 9.2 by treatment group.  The 
safety analyses will also be performed for the CC-90001 exposure period for subjects who 
receive at least one dose of CC-90001, which will include safety data during the 24-week 
Double-blind Placebo-controlled Treatment Phase and the 80-week Active Treatment 
Extension Phase.  Safety will be assessed by clinical review of all relevant parameters 
including AEs, laboratory tests, vital signs, and ECG measurements; summary of safety 
parameters will include data collected at scheduled, unscheduled, and early termination visit, 
and post-treatment observational follow-up visit. No inferential testing for statistical 
significance will be performed.
Adverse events will be classified using the MedDRA classification system.  All AEs will be 
summarized by frequency, severity and relationship to IP.  Adverse events leading to death or 
to discontinuation from treatment and serious adverse events will be listed separately.  Study 
drug-related AEs will be listed separately.  In the by-subject analysis, a subject having the 
same event more than once will be counted only once and by greatest severity.
Laboratory data will be summarized by visit descriptively (count, mean, median, standard 
deviation, and range).  In addition, shift tables showing the number of subjects with values 
below, within and above the normal ranges pretreatment versus post treatment, together with 
the number determined to be clinically significant, will be provided.  
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Vital sign measurements, including weight, will be summarized descriptively by visit (count, 
mean, median, standard deviation, and range).  
9.7.2.
Disease Progression
A subject will have met the criteria for disease progression when one or more of the 
following events have occurred:
!
Death from respiratory failure, or
!
Absolute decrease of ≥ 10% from baseline in percent predicted FVC at two 
consecutive evaluations at a minimum of 4 weeks between evaluations, or
!
Decrease from baseline of ≥50 meters in 6MWT distance (in the absence of a 
readily explainable cause, such as injury or trauma), or
!
Unexplained worsening hypoxemia (an absolute decrease from baseline of 4% or 
more in SpO2).
Subjects who experience an absolute decrease of ≥ 10% from baseline in percent predicted
FVC at two consecutive evaluations at a minimum of 4 weeks between evaluations must be 
discontinued from the study IP and enter the Post-treatment Observational Follow-up (see
Section 11.1). Example: a subject whose FVC decreases from 50% predicted at Visit 2 to 
40% predicted at Visits 4 and 5 must be discontinued from the study. Whether to discontinue 
a subject from study treatment who experiences: 1) a decrease from baseline of ≥ 50 meters in 
6MWT distance (in the absence of a readily explainable cause, such as injury or trauma), or 
2) a new or worsening hypoxemia (an absolute decrease from baseline of 4% or more in 
SpO2), is at the Investigator’s discretion.
9.8.
Interim Analysis
An initial interim analysis will be conducted after approximately 50 non-SOC subjects with 
IPF have completed 24 weeks of treatment. The purpose of this interim analysis is to 
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determine whether to terminate the study based on futility criteria and if futility criteria are 
not met, whether to discontinue any treatment group. Sample size re-estimation may be
performed based on observed standard deviation and effect size.  
If the safety and efficacy of CC-90001 from these initial IPF subjects are favorable, the study 
will continue as planned and enrollment into the PPF substudy will be initiated.  Subjects 
enrolled into the PPF substudy will be randomized to CC-90001 400 mg PO QD, unless 
review of benefit-risk favors 200 mg PO QD, or placebo.
An additional unblinded interim analysis is planned after approximately 40 SOC IPF subjects
have completed 24 weeks of treatment. The purpose of the additional interim analysis is to 
evaluate safety, tolerability and efficacy of CC-90001 in SOC IPF subjects, along with all 
study subjects enrolled into the study, and to determine if any treatment group should be 
discontinued. Sample size re-estimation may also be considered for the non-SOC group, the 
SOC group or subjects in the PPF sub-study.
If a decision at an interim analysis is made to discontinue a treatment group, that decision 
may be made separately for IPF subjects not receiving concurrent SOC and for IPF subjects 
receiving concurrent SOC.  A decision to discontinue a treatment group will be based on lack 
of efficacy (ie, futility) and/or lack of acceptable safety and tolerability. If a treatment group
is discontinued, subjects may receive a different CC-90001 dose regimen during the 80-week 
Active Treatment Extension Phase than during the 24-week Double-blind Placebo-controlled 
Phase.
Additional interim analyses may be conducted. 
The DMC will be responsible for review of the interim analyses data and will make 
recommendations to a Celgene internal review committee, who will be responsible for final 
decision-making. The Celgene internal review committee members will not play a role in the 
study conduct and the blind will be maintained for persons responsible for the ongoing 
conduct and management of the study. 
The details of these analyses, similar to analyses described in Sections 9.6.1 and 9.6.2, will be 
documented in a separate charter/analysis plan. 
9.9.
Other Topics
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9.9.3.
Analysis of Dose-Response
The primary method of analysis of dose-response for efficacy will be based on the MMRM 
model of the primary endpoint as described in Section 9.6.1.  Supportive analyses, including 
sensitivity analyses and analyses of secondary endpoints, as described in Section 9.6.2, will 
also help inform optimal dose selection.  The overall benefit-risk profile for each dose will be 
used to determine the dose(s) selected for further clinical development.
9.9.4.
External Data Monitoring Committee
Although the Celgene study staff will monitor safety on an ongoing basis throughout the 
study, formal unblinded safety and efficacy assessments of the study data will be performed 
by an independent external DMC. The DMC is comprised of independent physician experts 
and a statistician who are not affiliated with the Sponsor and for whom there is no identified 
conflict of interest. The scope, conduct, membership, processes, and accountabilities of the 
DMC are specified in the DMC charter. 
The DMC will be also responsible for review of the interim analyses data and will make 
recommendations to a Celgene internal review committee (IRC), who will be responsible for 
final decision-making. The Celgene IRC members will not play a role in the study conduct 
and the blind will be maintained for persons responsible for the ongoing conduct and 
management of the study.  The details of this analysis including the scope of distribution will 
be documented in a separate charter/analysis plan.
9.9.5.
Celgene Safety Management Team
In addition to safety monitoring conducted by Investigators, site study personnel, and by the 
Celgene study team, blinded study safety data will be reviewed by the Celgene SMT. The 
SMT is comprised of lead representatives from multiple Celgene functions engaged in the 
CC-90001 development program. 
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10.
ADVERSE EVENTS
10.1.
Monitoring, Recording and Reporting of Adverse Events
An AE is any noxious, unintended, or untoward medical occurrence that may appear or 
worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s 
health, including laboratory test values (as specified by the criteria in Section 10.3), 
regardless of etiology. Any worsening (ie, any clinically significant adverse change in the 
frequency or intensity of a pre-existing condition) should be considered an AE.  A diagnosis 
or syndrome should be recorded on the AE page of the CRF rather than the individual signs 
or symptoms of the diagnosis or syndrome. 
Abuse, withdrawal, sensitivity or toxicity to an investigational product should be reported as 
an AE. Overdose, accidental or intentional, whether or not it is associated with an AE should 
be reported on the overdose CRF. (See Section 7.2 for the definition of overdose.) Any 
sequela of an accidental or intentional overdose of an investigational product should be 
reported as an AE on the AE CRF. If the sequela of an overdose is an SAE, then the sequela 
must be reported on an SAE report form and on the AE CRF. The overdose resulting in the 
SAE should be identified as the cause of the event on the SAE report form and CRF but 
should not be reported as an SAE itself.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for CC-90001
overdose. Actual treatment should depend on the severity of the clinical situation and the 
judgment and experience of the treating physician.
All subjects will be monitored for AEs during the study.  Assessments may include 
monitoring of any or all of the following parameters:  the subject’s clinical symptoms, 
laboratory, pathological, radiological or surgical findings, physical examination findings, or 
findings from other tests and/or procedures.
All AEs will be recorded by the Investigator from the time the subject signs informed consent 
until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at 
any time thereafter that are suspected of being related to IP.  AEs and SAEs will be recorded 
on the AE page of the CRF and in the subject’s source documents.  All SAEs must be 
reported to Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event 
by facsimile, or other appropriate method, using the SAE Report Form, or approved 
equivalent form.  
10.2.
Evaluation of Adverse Events
A qualified Investigator will evaluate all adverse events as to:
10.2.1.
Seriousness 
An SAE is any AE occurring at any dose that:
!
Results in death;
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!
Is life-threatening (ie, in the opinion of the Investigator, the subject is at 
immediate risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of 
the subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life-
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.  
Medical and scientific judgment should be exercised in deciding whether such an AE should 
be considered serious.
Events not considered to be SAEs are hospitalizations for:
!
a standard procedure for protocol therapy administration.  However, 
hospitalization or prolonged hospitalization for a complication of therapy 
administration will be reported as an SAE. 
!
routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
a procedure that is planned (ie, planned prior to start of treatment on study); must 
be documented in the source document and the CRF.  Hospitalization or 
prolonged hospitalization for a complication remains a reportable SAE.
!
an elective treatment of or an elective procedure for a pre-existing condition, 
unrelated to the studied indication, that has not worsened from Baseline. 
!
emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the CRF and the SAE Report 
Form must be completed.
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to the IP, action taken regarding the IP, and outcome.
10.2.2.
Severity/Intensity
For both AEs and SAEs, the Investigator must assess the severity/ intensity of the event. 
Mild
!
Asymptomatic or mild symptoms; clinical or diagnostic observations only
!
Intervention not indicated
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!
Activities of daily life (ADLs) minimally or not affected
!
No or minimal intervention/therapy may be required 
Moderate 
!
Symptom(s) cause moderate discomfort
!
Local or noninvasive intervention indicated
!
More than minimal interference with ADLs but able to carry out daily social and 
functional activities.
!
Drug therapy may be required
Severe (could be non-serious or serious) 
!
Symptoms causing severe discomfort/pain
!
Symptoms requiring medical/surgical attention/intervention
!
Interference with ADLs including inability to perform daily social and functional 
activities (eg, absenteeism and/or bed rest)
!
Drug therapy is required
The term “severe” is often used to describe the intensity of a specific event (as in mild, 
moderate or severe myocardial infarction); the event itself, however, may be of relatively 
minor medical significance (such as severe headache).  This criterion is not the same as 
“serious” which is based on subject/event outcome or action criteria associated with events 
that pose a threat to a subject’s life or functioning.  
Seriousness, not severity, serves as a guide for defining regulatory obligations.
10.2.3.
Causality
The Investigator must determine the relationship between the administration of the IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
a causal relationship of the adverse event to IP administration is 
unlikely or remote, or other medications, therapeutic 
interventions, or underlying conditions provide a sufficient 
explanation for the observed event.
Suspected:
there is a reasonable possibility that the administration of IP 
caused the adverse event.  ‘Reasonable possibility’ means there 
is evidence to suggest a causal relationship between the IP and 
the adverse event.
Causality should be assessed and provided for every AE/SAE based on currently available 
information.  Causality is to be reassessed and provided as additional information becomes 
available.
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If an event is assessed as suspected of being related to a comparator, ancillary or additional IP 
that has not been manufactured or provided by Celgene, please provide the name of the 
manufacturer when reporting the event.
10.2.4.
Duration
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of 
the event.
10.2.5.
Action Taken
The Investigator will report the action taken with IP as a result of an AE or SAE, as 
applicable (eg, discontinuation, interruption, or dose reduction of IP, as appropriate) and 
report if concomitant and/or additional treatments were given for the event. 
10.2.6.
Outcome
The Investigator will report the outcome of the event for both AEs and SAEs.
All SAEs that have not resolved upon discontinuation of the subject’s participation in the 
study must be followed until recovered (returned to Baseline), recovered with sequelae, or 
death (due to the SAE).
10.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or
!
is judged to be of significant clinical importance, eg, one that indicates a new 
disease process and/or organ toxicity, or is an exacerbation or worsening of an 
existing condition.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the 
diagnosis or syndrome should be recorded on the AE page/screen of the CRF.  If the 
abnormality was not a part of a diagnosis or syndrome, then the laboratory abnormality 
should be recorded as the AE. If possible, the laboratory abnormality should be recorded as a 
medical term and not simply as an abnormal laboratory result (eg, record thrombocytopenia 
rather than decreased platelets).
10.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject of childbearing 
potential or partner of childbearing potential of a male subject are immediately reportable 
events.
In the event of a pregnancy occurring in a female subject of childbearing potential or female 
partner of a male subject, Celgene will follow up with the clinical investigator each trimester 
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of pregnancy and for 1 year following the birth of the infant (if applicable).  Please reference 
the pregnancy information consent (permission) forms for data collection for additional 
information.
10.4.1.
Females of Childbearing Potential:
Pregnancies and suspected pregnancies (including elevated β-hCG or positive pregnancy test 
in a female subject of childbearing potential regardless of disease state) occurring while the 
subject is on IP, or within 28 days of the subject’s last dose of IP, are considered immediately 
reportable events.  Investigational product is to be discontinued immediately and the subject 
instructed to return any unused portion of the IP to the Investigator. The pregnancy, suspected 
pregnancy, or positive pregnancy test must be reported to Celgene Drug Safety immediately 
by email, phone or facsimile, or other appropriate method, using the Pregnancy Initial Report 
Form, or approved equivalent form.  
The female subject should be referred to an obstetrician-gynecologist, preferably one 
experienced in reproductive toxicity for further evaluation and counseling.
The Investigator will follow the female subject until completion of the pregnancy, and must 
notify Celgene Drug Safety immediately about the outcome of the pregnancy (either normal 
or abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent 
form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the Investigator 
should report the abnormal outcome as an AE.  If the abnormal outcome meets any of the 
serious criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or other 
appropriate method, within 24 hours of the Investigator’s knowledge of the event using the 
SAE Report Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs.  In addition, any infant death after 28 days that the Investigator suspects is 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
facsimile, or other appropriate method, within 24 hours of the Investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
10.4.2.
Male Subjects
If a female partner of a male subject taking IP becomes pregnant, the male subject taking IP 
should notify the Investigator, and the pregnant female partner should be advised to call their 
healthcare provider immediately.
10.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form 
in addition to being recorded on the AE page/screen of the CRF.  All SAEs must be reported 
to Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event by 
facsimile, or other appropriate method (eg, via email), using the SAE Report Form, or 
approved equivalent form.  This instruction pertains to initial SAE reports as well as any 
follow-up reports.
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The Investigator is required to ensure that the data on these forms is accurate and consistent.  
This requirement applies to all SAEs (regardless of relationship to IP) that occur during the 
study (from the time the subject signs informed consent until 28 days after the last dose of IP 
or until the last study visit, whichever is longer), or any SAE made known to the Investigator 
at any time thereafter that are suspected of being related to IP.  Serious adverse events 
occurring prior to treatment (after signing the ICF) will be captured.
The SAE report should provide a detailed description of the SAE and include a concise 
summary of hospital records and other relevant documents.  If a subject died and an autopsy 
has been performed, copies of the autopsy report and death certificate are to be sent to 
Celgene Drug Safety as soon as these become available.  Any follow-up data should be 
detailed in a subsequent SAE Report Form, or approved equivalent form, and sent to Celgene 
Drug Safety.
Where required by local legislation, the Investigator is responsible for informing the 
Institutional Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with 
all relevant initial and follow-up information about the event. The Investigator must keep 
copies of all SAE information on file including correspondence with Celgene and the 
IRB/EC.
10.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail.  The response time is expected to be no more than five (5) 
business days.  Urgent queries (eg, missing causality assessment) may be handled by phone.
10.6.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness 
of events suspected of being related to CC-90001 based on the Investigator Brochure.
In the United States, all suspected unexpected serious adverse reactions (SUSARs) will be 
reported in an expedited manner in accordance with 21 CFR 312.32.
For countries within the European Economic Area (EEA), Celgene or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 
Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in 
accordance with Directive 2001/20/EC and the Detailed Guidance on collection, verification 
and presentation of adverse reaction reports arising from clinical trials on investigational 
products for human use (ENTR/CT3) and also in accordance with country-specific 
requirements.
Events of disease progression for the disease under study (including deaths due to disease 
progression for indications that are considered to be fatal) will be assessed as expected 
adverse events and will not be reported as expedited safety reports to regulatory authorities.
Celgene or its authorized representative shall notify the Investigator of the following 
information:
!
Any AE suspected of being related to the use of IP in this study or in other studies 
that is both serious and unexpected (ie, SUSAR);
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!
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or 
carcinogenicity.
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC.  (See Section 14.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event 
Report Form Completion Guidelines or to the Pregnancy Report Form Completion 
Guidelines.
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11.
DISCONTINUATIONS
11.1.
Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the
IP:
!
Adverse event
!
Withdrawal by subject
!
Disease progression
!
Acute exacerbation (has not improved within 6 weeks of treatment or the subject 
has shown evidence of further clinical decline despite appropriate treatment)
!
Death
!
Lost to follow-up
!
Lung transplantation
!
Other, to be specified on the CRF (eg, noncompliance, important protocol 
deviation)
The reason for discontinuation of treatment should be recorded in the CRF and in the source 
documents.
The decision to discontinue a subject from treatment remains the responsibility of the treating 
physician, which will not be delayed or refused by the Sponsor.  However, prior to
discontinuing a subject, the Investigator may contact the Medical Monitor and forward 
appropriate supporting documents for review and discussion.
11.2.
Discontinuation Criteria for Elevation of Hepatic Transaminases
Subjects should be carefully monitored for changes in liver function:
∀
ALT > 3 × upper limit of normal (ULN) 
∀
AST > 3 × ULN 
A history of alcohol use and or biliary colic as potential causes of the above findings should 
be elicited. For subjects experiencing either of the above, use of IP should be interrupted and 
subjects should undergo repeat testing, including ALT, AST, total bilirubin, and alkaline 
phosphatase, within 48 to 72 hours of the original test to confirm or refute the finding. If the 
ALT or AST lab result(s) is confirmed to be > 3 x ULN, the subject should not be re-
challenged with IP. The subject should be discontinued from the study IP and enter the
4-week Post-treatment Observational Follow-up Phase and hepatic enzyme(s) should be 
followed until resolution. 
11.3.
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
study:
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Screen failure
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Adverse event
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Withdrawal by subject
!
Death
!
Lost to follow-up
!
Lung transplantation
!
Other, to be specified on the CRF (eg, noncompliance, important protocol 
deviation)
The reason for discontinuation of treatment should be recorded in the CRF and in the source 
documents.
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12.
EMERGENCY PROCEDURES
12.1.
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research 
Physician/Medical Monitor or designee by telephone at the number(s) listed on the 
Emergency Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee 
cannot be reached, please contact the global Emergency Call Center by telephone at the 
number listed on the Emergency Contact Information page of the protocol (after title page).
This global Emergency Call Center is available 24 hours a day and 7 days a week. The 
representatives are responsible for obtaining your call-back information and contacting the 
on-call Celgene/contract research organization Medical Monitor, who will then contact you 
promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you 
are not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls.
12.2.
Emergency Identification of Investigational Products
The blind must not be broken during the course of the study unless in the opinion of the 
Investigator, it is absolutely necessary to safely treat the subject.  If it is medically imperative 
to know what IP the subject is receiving, IP should be temporarily discontinued if, in the 
opinion of the Investigator, continuing IP can negatively affect the outcome of the subject’s 
treatment.
The decision to break the blind in emergency situations remains the responsibility of the 
treating physician, which will not be delayed or refused by the Sponsor.  However, the 
Investigator may contact the Medical Monitor prior to breaking the blind to discuss 
unblinding, mainly in the interest of the subject.
The Investigator should ensure that the code is broken only in accordance with the 
protocol. The Investigator should promptly notify the Medical Monitor of the emergency 
unblinding and the reason for breaking the blind, which should be clearly documented by the 
Investigator in the subject’s source documentation.
Emergency unblinding should only be performed by the Investigator through the Interactive 
Web Response System (IWRS).
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13.
REGULATORY CONSIDERATIONS
13.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative, 
and Investigator abide by Good Clinical Practice (GCP), as described in International Council 
for Harmonisation (ICH) Guideline E6 and in accordance with the general ethical principles 
outlined in the Declaration of Helsinki. The study will receive approval from an IRB/EC prior 
to commencement. The Investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
13.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations.  Celgene staff or an authorized representative will evaluate and approve 
all Investigators who in turn will select their staff.
The Investigator should ensure that all persons assisting with the study are adequately 
informed about the protocol, amendments, study treatments, as well as study-related duties 
and functions, including obligations of confidentiality of Celgene information. The 
Investigator should maintain a list of Sub-investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.
The Investigator is responsible for keeping a record of all subjects who sign an informed 
consent form (ICF) and are screened for entry into the study.  Subjects who fail screening 
must have the reason(s) recorded in the subject’s source documents.
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records 
(eg, medical records, office charts, hospital charts, and study-related charts) for source data 
verification.  The Investigator must ensure timely and accurate completion of CRFs and 
queries.
The information contained in the protocol and amendments (with the exception of the 
information provided by Celgene on public registry websites) is considered Celgene 
confidential information.  Only information that is previously disclosed by Celgene on a 
public registry website may be freely disclosed by the Investigator or its institution, or as 
outlined in the Clinical Trial Agreement.  Celgene protocol, amendment and IB information 
is not to be made publicly available (for example on the Investigator’s or their institution’s 
website) without express written approval from Celgene.  Information proposed for posting 
on the Investigator’s or their institution’s website must be submitted to Celgene for review 
and approval, providing at least 5 business days for review.
At the time results of this study are made available to the public, Celgene will provide 
Investigators with a summary of the results that is written for the lay person. The Investigator 
is responsible for sharing these results with the subject and/or their caregiver as agreed by the 
subject.
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13.3.
Subject Information and Informed Consent
The Investigator must obtain informed consent of a subject and/or a subject’s legal 
representative prior to any study related procedures.
Documentation that informed consent occurred prior to the study subject’s entry into the 
study and of the informed consent process should be recorded in the study subject’s source 
documents including the date.  The original ICF signed and dated by the study subject and by 
the person consenting the study subject prior to the study subject’s entry into the study, must 
be maintained in the Investigator’s study files and a copy given to the study subject.  In 
addition, if a protocol is amended and it impacts on the content of the informed consent, the 
ICF must be revised.  Study subjects participating in the study when the amended protocol is 
implemented must be re-consented with the revised version of the ICF.  The revised ICF 
signed and dated by the study subject and by the person consenting the study subject must be 
maintained in the Investigator’s study files and a copy given to the study subject.
13.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene 
requires the Investigator to permit Celgene's representatives and, when necessary, 
representatives from regulatory authorities, to review and/or copy any medical records 
relevant to the study in accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the Investigator to obtain such permission in 
writing from the appropriate individual.
13.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor.  Amendments will be submitted to the IRB/EC for written 
approval.  Written approval must be obtained before implementation of the amended version 
occurs.  The written signed approval from the IRB/EC should specifically reference the 
Investigator name, protocol number, study title and amendment number(s) that is applicable. 
Amendments that are administrative in nature do not require IRB/IEC approval but will be 
submitted to the IRB/IEC for information purposes.
13.6.
Institutional Review Board/Independent Ethics Committee 
Review and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents 
will be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, 
their dates of issue, and the site (or region or area of jurisdiction, as applicable) for which 
approval is sought. If applicable, the documents will also be submitted to the authorities in 
accordance with local legal requirements.
IP can only be supplied to an Investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received 
by Celgene or its authorized representative. This documentation must also include a list of the 
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members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not 
disclose the names, occupations and qualifications of the committee members, it should be 
asked to issue a statement confirming that the composition of the committee is in accordance 
with GCP. For example, the IRB General Assurance Number may be accepted as a substitute 
for this list. Formal approval by the IRB/EC should mention the protocol title, number, 
amendment number (if applicable), study site (or region or area of jurisdiction, as applicable), 
and any other documents reviewed. It must mention the date on which the decision was made 
and must be officially signed by a committee member. Before the first subject is enrolled in 
the study, all ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be 
revised.
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and 
the IRB/EC prior to use.  
13.7.
Ongoing Information for Institutional Review Board/ Ethics 
Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
13.8.
Termination of the Study
Celgene reserves the right to terminate this study prematurely at any time for reasonable 
medical or administrative reasons. Any premature discontinuation will be appropriately 
documented according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the Investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons, such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
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14.
DATA HANDLING AND RECORDKEEPING 
14.1.
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the 
study and the distribution of the investigational product are complete, accurate, filed and 
retained.  Examples of source documents include: hospital records; clinic and office charts; 
laboratory notes; memoranda; subject’s diaries or evaluation checklists; dispensing records; 
recorded data from automated instruments; copies or transcriptions certified after verification 
as being accurate copies; microfiche; x-ray film and reports; and records kept at the 
pharmacy, and the laboratories, as well as copies of CRFs or CD-ROM.
14.2.
Data Management
Data will be collected via CRF and entered into the clinical database per Celgene standard 
operating procedures (SOPs). This data will be electronically verified through use of 
programmed edit checks specified by the clinical team.  Discrepancies in the data will be 
brought to the attention of the clinical team, and investigational site personnel, if necessary.  
Resolutions to these issues will be reflected in the database.  An audit trail within the system 
will track all changes made to the data.
14.3.
Record Retention
Essential documents must be retained by the Investigator according to the period of time 
outlined in the Clinical Trial Agreement. The Investigator must retain these documents for the 
time period described above or according to local laws or requirements, whichever is longer. 
Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the Investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the Investigator, Celgene, and their 
authorized representative(s);
!
List of Sub-investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles 
in the study, curriculum vitae, and their signatures;
!
Copies of CRFs (if paper) and of documentation of corrections for all subjects;
!
IP accountability records;
!
Record of any body fluids or tissue samples retained;
!
All other source documents (subject records, hospital records, laboratory records, 
etc); 
!
All other documents as listed in Section 8 of the ICH consolidated guideline on 
GCP (Essential Documents for the Conduct of a Clinical Trial).
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The Investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified 
period.  The Investigator must obtain approval in writing from Celgene prior to destruction of 
any records. If the Investigator is unable to meet this obligation, the Investigator must ask 
Celgene for permission to make alternative arrangements. Details of these arrangements 
should be documented. 
All study documents should be made available if required by relevant health authorities. 
Investigator or institution should take measures to prevent accidental or premature destruction 
of these documents.
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15.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized 
representative for compliance with applicable government regulations with respect to current 
GCP and SOPs.
15.1.
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and 
after the study.  All aspects of the study are reviewed with the Investigator and the staff at a 
study initiation visit and/or at an Investigators’ Meeting.  Prior to enrolling subjects into the 
study, a Celgene representative will review the protocol, CRFs, procedures for obtaining 
informed consent, record keeping, and reporting of AEs/SAEs with the Investigator.  
Monitoring will include on-site visits with the Investigator and his/her staff as well as any 
appropriate communications by mail, email, fax, or telephone.  During monitoring visits, the 
facilities, investigational product storage area, CRFs, subject’s source documents, and all 
other study documentation will be inspected/reviewed by the Celgene representative in 
accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison 
of the entries made onto the CRFs against the appropriate source documentation.  Any 
resulting discrepancies will be reviewed with the Investigator and/or his/her staff.  Any 
necessary corrections will be made directly to the CRFs or via queries by the Investigator 
and/or his/her staff. Monitoring procedures require that informed consents, adherence to 
inclusion/exclusion criteria and documentation of SAEs and their proper recording be 
verified.  Additional monitoring activities may be outlined in a study-specific monitoring 
plan.
15.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene.  Representatives of this unit will conduct audits of clinical 
research activities in accordance with Celgene SOPs to evaluate compliance with Good 
Clinical Practice guidelines and regulations.
The Investigator is required to permit direct access to the facilities where the study took 
place, source documents, CRFs and applicable supporting records of study subject 
participation for audits and inspections by IRB/ECs, regulatory authorities (eg, Food and 
Drug Administration [FDA], European Medicines Agency [EMA], Health Canada) and 
company authorized representatives.  The Investigator should make every effort to be 
available for the audits and/or inspections.  If the Investigator is contacted by any regulatory 
authority regarding an inspection, he/she should contact Celgene immediately.
15.3.
Product Quality Complaint
A Product Quality Complaint (PQC) is any written, electronic, or oral communication that
alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, 
purity, or performance of any drug product manufactured by or on behalf of Celgene 
Corporation after it is released for distribution. PQCs may reduce the usability of the product 
for its intended function or affect performance of the product and therefore pose a significant 
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risk to the patient. Examples of PQCs include (but are not limited to): mixed product, 
mislabeling, lack of effect, seal/packaging breach, product missing/short/overage, 
contamination, suspected falsified, tampered, diverted or stolen material, and general 
product/packaging damage. If you become aware of a suspected PQC, you are obligated to 
report the issue immediately. You can do so by emailing 
 
or by contacting the Celgene Customer Care Center 
.
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16.
PUBLICATIONS
As described in Section 13.2, all protocol- and amendment-related information, with the 
exception of the information provided by Celgene on public registry websites, is considered 
Celgene confidential information and is not to be used in any publications.  Celgene protocol-
related information proposed for use in a publication must be submitted to Celgene for review 
and approval and should not be utilized in a publication without express written approval 
from Celgene, or as described in the Clinical Trial Agreement.
Celgene will ensure Celgene-sponsored studies are considered for publication in the scientific 
literature in a peer-reviewed journal, irrespective of the results.  At a minimum, this applies to 
results from all Phase 3 clinical studies, and any other study results of significant medical 
importance.  This also includes results relating to investigational medicines whose 
development programs have been discontinued.
Study results may also be presented at one or more medical congresses and may be used for 
scientific exchange and teaching purposes.  Additionally, this study and its results may be 
submitted for inclusion in all appropriate health authority study registries, as well as 
publication on health authority study registry websites, as required by local health authority 
regulations.
Eligibility for external authorship, as well as selection of first authorship, will be based on 
several considerations, including, but not limited to, contribution to protocol development, 
study recruitment, data quality, participation in data analysis, participation in study steering 
committee (when applicable) and contribution to abstract, presentation and/or publication 
development.
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17.
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Flaherty KR, Brown KK, Wells AU, Clerisme-Beaty E, Collard HR, Cottin V, et al. Design 
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nintedanib in patients with progressive fibrosing interstitial lung disease. BMJ Open Respir
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Serum surfactant proteins -A and -D as biomarkers in idiopathic pulmonary fibrosis. Eur 
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Gries KS, Esser D, Wiklund I. Content validity of CASA-Q cough domains and UCSD-
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King TE Jr. Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. 
A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med.
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MacIntyre N, Crapo RO, Viegi G, Johnson DC, van der Grinten CPM, Brusasco V. 
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Eur Respir J. 2005;26:720-35.
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of test performance characteristics and minimal clinically important difference of the 6-
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Nicholson AG, Fulford LG, Colby TV, du Bois RM, Hansell DM, Wells AU.  The 
relationship between individual histologic features and disease progression in idiopathic 
pulmonary fibrosis.  Am J Respir Crit Care Med. 2002;166:173-77.
Noble PW, Albera C, Bradford WZ, Costable U, Glassberg MK, Kardatzke D, et al.  
Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised 
trials. Lancet. 2011;377:1760-769.
Olson AL, Brown, KK, Swigris, JJ. Understanding and optimizing health-related quality of 
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Pirfenidone NDA 22-535 Briefing Document.  US Food and Drug Administration, 
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Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An official 
ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines 
for diagnosis and management. Am J Respir Crit. Care Med. 2011;183:788-24.
Raghu G, Rochberg B, Zhang Y, Cuello Garcia CA, Azuma A, et al. An official 
ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. 
An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192:e3-
e19.
Raghu G, Wells AU, Nicholson AG, Richeldi L, Flaherty KR, Le Maulf F, et al. Effect of 
nintedanib in subgroups of idiopathic pulmonary fibrosis by diagnostic criteria. Am J Respir 
Crit Care Med. 2017;195:78-85.
Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and 
safety of nintedanib in idiopathic pulmonary fibrosis. New Engl J Med.2014;370:2071-82.
Schafer PH, Ye Y, Chen P, Liu Y, Bennett B, Sutherland D, et al. Pharmacodynamic and 
pharmacokinetic assessment of the c-Jun N-terminal kinase inhibitor CC-930 in a phase 2 
sequential ascending dose study in idiopathic pulmonary fibrosis. Am J Respir Crit Care 
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Stokes ME, Davis CS, Koch GG. Categorical data analysis using the SAS system, 2nd ed.
Cary (NC): SAS Institute Inc;2000.
Swigris JJ, Brown KK, Behr J, du Bois RM, King TE, Raghu G, et al. The SF-36 and SGRQ: 
validity and first look at minimum important differences in IPF. Respir Med. 2010;104:296-
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Swigris JJ, Fairclough D. Patient-reported outcomes in idiopathic pulmonary fibrosis 
research. Chest. 2012;142:291-97.
Swigris JJ, Han M, Vij R, Noth I, Eisenstein EL, Anstrom KJ, et al. The UCSD shortness of 
breath questionnaire has longitudinal construct validity in idiopathic pulmonary fibrosis. 
Respir Med. 2012a;106:1447–55.
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van der Velden JL, Ye Y, Nolin J, Hoffman SM, Chapman DG, Lahue KG, et al. JNK 
inhibition reduces lung remodeling and pulmonary fibrotic systemic markers. Clin Transl 
Med. 2016;5:36-54.
Wells AU, Brown KK, Flaherty KR, Kolb M, Thannickal VJ. IPF Consensus Working 
Group. What’s in a name? That which we call IPF, by any other name would act the same. 
Eur Respir J. 2018; 51:1800692.
Wynn TA.  Fibrotic disease and the TH1/TH2 paradigm.  Nat Rev Immunol. 2004;4(8):583-
94.
Yorke J, Jones PW, Swigris J.  Development and validity testing of an IPF-specific version of 
the St. George’s Respiratory Questionnaire. Thorax. 2010;65(10):921-6.
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18.
APPENDICES
Appendix A:
Table of Abbreviations
Table 6:
Abbreviations and Specialist Terms
Abbreviation or 
Specialist Term
Explanation
ADL
Activity of daily life
AE
Adverse event
ALT
Alanine aminotransferase (SGPT)
AST
Aspartate aminotransferase (SGOT)
ATS
American Thoracic Society
BAL
Bronchoalveolar lavage
BCRP
ATP Binding Cassette Protein G2 /ABCG2
β-hCG
Beta-subunit of human chorionic gonadotropin
BID
Twice daily
CBC
Complete blood count
CI(s)
Confidence interval(s)
Cmax
Maximum plasma concentration of drug
CMH
Cochran-Mantel-Haenszel
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Appendix A:
Table of Abbreviations (continued)
Table 6:
Abbreviations and Specialist Terms (Continued)
Abbreviation or 
Specialist Term
Explanation
CRF
Case report form
CYP
Cytochrome p450
DLCO
Diffusion capacity of the lung for carbon monoxide
DMC
Data Monitoring Committee
DVT
Deep vein thrombosis
EC
Ethics Committee
ECG
Electrocardiogram
EEA
European Economic Area
EOT
End of treatment
ERS
European Respiratory Society
ETC
Et cetera
FAS
Full analysis set
FCBP
Females of childbearing potential
FDA
Food and Drug Administration
FEV1
Forced exhaled volume in 1 second
FSH
Follicle-stimulating hormone
FVC
Forced vital capacity
GCP
Good Clinical Practice
GD
Gestation Day
GGT
Gamma-glutamyltransferase
GI
Gastrointestinal
GLP
Good Laboratory Practice
HDL
High density lipoprotein
HIV
Human immunodeficiency virus
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Appendix A:
Table of Abbreviations (continued)
Table 6:
Abbreviations and Specialist Terms (Continued)
Abbreviation or 
Specialist Term
Explanation
HRCT
High resolution computed tomography
IB
Investigator’s Brochure
IC50
50% inhibitory concentration
ICF
Informed consent form
ICH
International Council for Harmonisation
ILD
Interstitial lung disease
IND
Investigational New Drug
INR
International normalized ratio
IP
Investigational product
IPF
Idiopathic pulmonary fibrosis
IRB
Institutional Review Board
IRC
Internal review committee
IWRS
Interactive web response system
JNK
c-Jun N-terminal kinase
LDL
Low density lipoprotein
LS
Least squares 
MAD
Multiple ascending dose
MedDRA
Medical Dictionary for Regulatory Activities
MMP
Matrix metalloproteinase
MMRM
Mixed-effect model of repeated measures
MS
Millisecond
NAC
N-acetylcysteine
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Appendix A:
Table of Abbreviations (continued)
Table 6:
Abbreviations and Specialist Terms (Continued)
Abbreviation or 
Specialist Term
Explanation
NOAEL
No observed adverse effect level
OATP1B1
Organic anion transporting polypeptide 1B1
OATP1B3
Organic anion transporting polypeptide 1B3
OCT2
Organic cation transporter 2
PD
Pharmacodynamics
PE
Physical examination or pulmonary embolism
P-gp
P-glycoprotein
Phospho-c-Jun
Phosphorylated (Ser 63) c-Jun
PIN
Personal identification number
PK
Pharmacokinetics
PO
Per os (oral or orally)
PP
Per-protocol
PPF
Progressive pulmonary fibrosis
QD
Quoque die (once a day or once daily)
QTcB
QTc calculation using Bazett’s formula
QTcF
QTc calculation using Fridericia’s formula
RBC
Red blood cell count
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SD
Standard deviation
SGOT
Serum glutamic oxaloacetic transaminase 
SGPT
Serum glutamic pyruvic transaminase
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Appendix A:
Table of Abbreviations (continued)
Table 6:
Abbreviations and Specialist Terms (Continued)
Abbreviation or 
Specialist Term
Explanation
SGRQ
St. George’s Respiratory Questionnaire
6MWT
Six-minute walk test
SLB
Surgical lung biopsy
SOB
Shortness of breath
SOC
Standard of care
SOP
Standard operating procedure
SpO2
Arterial oxygen saturation by pulse oximetry
SP
Surfactant protein
SUSAR
Suspected unexpected serious adverse reaction
t1/2
Half-life
TB
Tuberculosis
TEAE
Treatment-emergent adverse event
UCSD-SOBQ
University of California San Diego Shortness of Breath Questionnaire
UIP
Usual interstitial pneumonia
ULN
Upper limit of normal
USA
United States of America
UVB
Ultraviolet B
VC
Vital capacity
WBC
White blood cell count
±
With or without
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Appendix B:
St. George’s Respiratory Questionnaire
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Appendix B:
St. George’s Respiratory Questionnaire (SGRQ) 
(Continued)
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Appendix B:
St. George’s Respiratory Questionnaire (SGRQ) 
(Continued)
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Appendix B: St. George’s Respiratory Questionnaire (SGRQ) 
(Continued)
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Appendix C: University of California San Diego Shortness of Breath
Questionnaire
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Appendix C:
University of California San Diego Shortness of Breath 
Questionnaire (Continued)
Eakin, 1998.
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Appendix E:
6-Minute Walk Test Protocol
The 6-minute walk test (6MWT) measures the distance that a patient can walk on a measured, 
flat hard surface in a period of 6 minutes. The objective is for patients to walk as far as 
possible during 6 minutes. The 6MWT evaluates the global and integrated responses of all 
body systems involved during walking. The instructions below incorporate the guidelines 
provided in the ATS statement for the 6MWT (ATS, 2002). It is imperative to follow the 
procedures in this document in order to ensure patient safety and control procedural sources 
of variability in the 6MWT.
Location
The 6MWT should be performed indoors, along a flat, long, and straight corridor with a hard 
surface with little traffic. A process for controlling traffic that might interfere with the 
procedure should be in place. The walking course should be unobstructed, and between 20–
40 meters in length, but as close to the standard of 30 meters (100 feet) as possible. The 
course should be marked with visible markers (eg, small traffic cones or chairs). A starting 
line, which marks the beginning and end of each approximately 60-meter lap, should be 
marked on the floor. The 6MWT course will be approved by the Sponsor during the 
qualification visit.
Patient Safety
The walking test should be performed by trained personnel with experience and knowledge in 
exercise testing, basic cardiopulmonary resuscitation, O2 therapy, blood pressure monitoring, 
and the application and limitations of pulse oximeters. Physicians are not required to be 
present during all tests. The primary Investigator (PI) will decide whether physician 
attendance is required. Patients with a history of unstable angina or myocardial infarction 
during the previous 6 months should not participate in a 6MWT. Blood pressure and pulse 
rate should be measured before the test. Relative contraindications to participation in the 
6MWT include:
!
Resting heart rate >120 beats per minute (bpm) or <60 bpm
!
Systolic blood pressure >200 mm Hg or <80 mm Hg
!
Diastolic blood pressure >110 mm Hg
Patients with any of these findings should be referred to the PI or designee, for clinical 
assessment and a decision about the conduct of the test. Supplies that must be available in 
proximity to the 6MWT course include O2, sublingual nitroglycerine, aspirin and albuterol 
(metered dose inhaler or nebulizer). A telephone or other means should be in place to enable 
a call for help. The appropriate location of a crash cart should be determined by the PI. 
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Appendix E:
6-Minute Walk Test Protocol (Continued)
Indications for immediate termination of the O2 titration or the 6MWT procedure include the 
following (American Association for Respiratory Care, 1992; ATS, 2002):
!
Angina
!
Light headedness
!
Intolerable dyspnea
!
Leg cramps
!
Staggering
!
Diaphoresis
!
Pale or ashen appearance
!
Mental confusion or headache
The test administrators must be trained to recognize these problems and to respond 
appropriately should they occur. If a test is terminated for any of the above reasons, the 
patient should sit or lie supine as appropriate depending on the severity of the event, the test 
administrator’s assessment of the severity of the event, and the risk of syncope. Once the 
patient is sitting or supine, blood pressure, pulse rate, and O2 saturation should be obtained, 
and a physician evaluation performed.
Personnel Performing the 6MWT
It is essential that the personnel performing the 6MWT do not receive or solicit any 
information from the patient regarding adverse events or pulmonary symptoms. In order to 
minimize within-patient variability, if possible, the same person should perform the 6MWT 
for any given patient.
Equipment
The following equipment is used for the 6MWT:
!
A stopwatch
!
Mechanical lap counter
!
Markers to identify the course
!
Chair(s) or wheel chair that can be easily moved along the course
!
Pad of worksheets on a clipboard
!
Pulse oximeter
!
Sphygmomanometer (blood pressure measurement device)
!
Patient’s usual O2 supply and nasal cannula/tubing in addition to a back-up 
supply; back-up supply is preferably lightweight
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Appendix E:
6-Minute Walk Test Protocol (Continued)
!
Measuring tape for precise determination of the distance walked
!
Stethoscope
Patient Preparation
!
Patients should wear comfortable clothing and shoes.
!
In order to minimize intra-individual variability, the 6MWT should be performed 
as close to the same time of day as possible.
!
A light meal is permitted before tests.
!
The patient’s usual medication regimen should be maintained the day of the 
walking test. If the patient routinely uses bronchodilators before a walk, then the 
patient should self-administer such bronchodilators 5–30 minutes before the 
6MWT.
!
A “warm-up” period before the test should not be performed.
!
If the patient uses supplemental O2, his/her delivery device and/or O2 conserving 
system should be used if possible.
Oxygen Titration Procedure (conducted only during the Screening Visit)
At the time of the screening visit, the patient will undergo an O2 titration procedure. The goal 
of the procedure is to objectively determine the necessary O2 flow, up to and including 6 
L/min, that the patient needs to complete the 6MWT without developing O2 desaturation 
(SpO2 <83%, where SpO2 is O2 saturation measured by pulse oximetry). This flow rate will 
represent the patient’s baseline O2 flow rate for the subsequent 6MWT procedures conducted 
at baseline and during the Study Period.
All increases in O2 flow during the titration procedure will be in 2 L/min increments, such 
that all patients will start on 0 L/min, then sequentially increase to 2, 4, and then 6 L/min if 
necessary. This procedure includes a resting O2 titration followed by a walking O2 titration 
during the 6MWT. The O2 flow rate determined during the walking O2 titration procedure 
will be the O2 flow rate that the patient receives for all subsequent 6MWT conducted during 
the study.
STEP 1. Resting O2 Titration
A) The patient should be seated for at least 10 minutes, instructed to sit still and not to talk, 
and O2 should be stopped. If the resting SpO2 decreases to <83% in 5 minutes of rest off 
supplemental O2, then start O2 at 2 L/min. If following the initiation of O2 at 2 L/min, the 
resting SpO2 is <83% in 5 minutes, then increase O2 to 4 L/min. If following the increase 
in O2 to 4 L/min, the resting SpO2 is <83% in 5 minutes, then increase O2 to 6 L/min. If 
while on 6 L/min O2, the resting SpO2 is <83% in 5 minutes in Step 1, then the O2
titration procedure should be terminated and the patient is not eligible for study 
participation. 
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Appendix E:
6-Minute Walk Test Protocol (Continued)
B) The lowest flow for which a patient can maintain a resting SpO2 ≥83% for 5 minutes will 
be the initial flow rate in the walking portion (STEP 2) of the O2 titration procedure.
STEP 2. Walking O2 Titration
A) Before starting the exercise evaluation, the patient should be seated and resting for at least 
10 minutes on the flow rate determined during the resting O2 titration procedure.
B) The test administrator should follow the actual 6MWT procedure (see below) during the 
walking O2 titration for each level of O2 flow evaluated.
C) After the patient begins walking, if the patient’s SpO2 decreases to below 83% at any 
time:
!
The walk should be terminated,
!
The patient’s O2 flow should be increased by 2 L/min,
!
The patient should then be seated and allowed to rest for 5 minutes.
!
If the resting SpO2 after 5 minutes is not ≥83%, then the O2 flow rate should be 
increased another 2 L/min and the resting SpO2 reassessed after 5 minutes. This 
should be repeated until the resting SpO2 is ≥83% for 5 minutes.
D) The walking O2 titration procedure should then be repeated at the higher O2 flow rate. If 
the patient’s SpO2 decreases to below 83% at any time, Steps 2C and 2D will be repeated.
E) If a patient is titrated during the walking O2 titration to 6 L/min of O2, and within 
6 minutes of the 6MWT on 6 L/min of O2 the SpO2 drops below 83%, then the Walking 
O2 titration should be terminated and the patient is not eligible for study participation.
F) The lowest flow on which a patient can complete the 6MWT without developing a SpO2
< 83% will be the patient’s O2 flow for all subsequent 6MWT conducted during the 
course of the study.
6MWT Procedure:
1. The 6MWT will be performed during the oxygen titration procedure at screening, on the 
day of randomization, and every 24 weeks during the study.
2. Seat the patient in a chair near the starting line, deliver the baseline O2 flow rate 
determined during the oxygen titration procedure at the screening visit, apply pulse 
oximetry probe, and have the patient rest for at least 10 minutes. If the patient’s resting 
SpO2 after 10 minutes of rest on the baseline O2 flow rate is <83%, then the patient 
should not participate in the 6MWT. Ensure patient’s vital signs are in compliance with 
the guidelines in patient safety section. 
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Appendix E:
6-Minute Walk Test Protocol (Continued)
3. Instruct the patient as follows:
“The object of this test is to walk as far as possible for 6 minutes. You will walk back and 
forth in this hallway. Six minutes is a long time to walk, so you will be exerting yourself. 
You will probably get out of breath or become exhausted. You are permitted to slow 
down, to stop, and to rest as necessary. You may lean against the wall while resting, but 
resume walking as soon as you are able. You will be walking back and forth around the 
markers. You should turn briskly around the markers and continue back the other way 
without hesitation. Now, I’m going to show you so please watch the way I turn without 
hesitation.” The walk administrator should demonstrate by walking one lap. “Are you 
ready to do that? I am going to use this counter to keep track of the number of times you
complete a lap. Remember that the object is to walk as far as possible for 6 minutes, but 
don’t run or jog. I am going to walk behind you and watch your oxygen saturation. When 
I say stop, I want you to stop walking and stand where you are. I will bring you a chair if 
you need to sit down.”
4. Have the patient stand and use the Borg scale (see below) before walking to measure 
perceived dyspnea and record SpO2 and pulse rate (from pulse oximeter).
5. The patient, and not the test administrator, should carry and/or pull his/her O2 delivery 
device and/or conserving system, as they do in everyday life. The patient should use 
his/her own O2 delivery device and/or conserving system whenever possible. If the patient 
does not have his/her own equipment, attempts should be made to use equipment the 
patient is familiar with and to use the lightest weight equipment possible. Patients should 
use the same equipment during all 6MWTs performed during the Study Period. The test 
administrator will carry and monitor the pulse oximeter.
6. Position the patient at the starting line.
7. As soon as the patient starts to walk, start the timer. The test administrator should walk 
behind the patient to monitor the pulse oximeter and should not influence the pace. The 
test administrator should monitor for the lowest SpO2 measured during the 6-minute time 
interval following the start of the walk and this value will be recorded on the CRF.
8. During the walk test, the administrator should not talk to anyone else except the patient. 
Use an even tone of voice when using the following standard phrases of encouragement. 
The test administrator should watch the patient and not get distracted. 
9. It is important that only the following standard phrases of encouragement be used for all 
the 6MWTs:
!
After the first minute: “You are doing well. You have 5 min to go.”
!
After the 2nd minute: “Keep up the good work. You have 4 min to go.”
!
After the 3rd minute: “You are doing well. You are halfway done.”
!
After the 4th minute: “Keep up the good work. You have only 2 min left.”
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Appendix E:
6-Minute Walk Test Protocol (Continued)
!
After the 5th minute: “You are doing well. You have only 1 min to go.”
!
With 15 seconds to go: “In a moment I’m going to tell you to stop. When I do, just 
stop right where you are and I will come to you.”
10. The test should terminate when any of the following occur:
!
Six minutes are up
!
SpO2 is <83%
!
Patient develops signs or symptoms requiring test termination (see above patient 
safety section)
At the time of termination, the test administrator should say “Stop!”, and mark the spot they 
stopped by placing a bean bag or piece of tape on the floor. If the test is terminated for 
reasons other than the completion of 6 minutes of walking, the guidelines outlined above in 
the patient safety section should be followed.
11. The test administrator should record the post-walk dyspnea score using the Borg scale   
immediately following the completion of the 6MWT, and the lowest SpO2 observed 
during the 6MWT.
12. The number of laps traveled and the additional distance covered (number of meters in the 
final partial lap) should be recorded.
13. The test administrator should calculate the total distance walked in meters, rounding to 
the nearest meter.
14. The test administrator should congratulate the patient on good effort, and offer a drink of 
water.
NOTE: If the patient stops during the test and needs to rest, they should be told, “You can 
lean against the wall if you would like; then continue walking whenever you feel you are 
able.”
The timer should continue to run. If the patient stops before the 6 minutes are up and does not 
wish to continue, or the test administrator determines that they should not continue, a chair 
should be taken to the patient to sit on. The reason the 6MWT was terminated, the time of 
termination, and the distance walked at termination should be recorded in all cases.
References
American Association for Respiratory Care, 1992; ATS, 2002.
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Appendix F:
Borg Scale
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Appendix G:
Diagnostic Categories of UIP Based on HRCT Patterns and Histopathological Criteria For 
UIP in IPF  
A. Diagnostic Categories of UIP Based on HRCT Patterns
Typical UIP HRCT 
pattern
Probable UIP HRCT pattern
HRCT pattern 
indeterminate for 
UIP
HRCT features most consistent 
with non-IPF diagnosis
Distribution
Basal predominant 
(occasionally diffuse), 
and subpleural
predominant; distribution 
is often heterogeneous
Basal and subpleural 
predominant;
distribution is often
heterogeneous
Variable or diffuse
Upper-lung or mid-lung 
predominant fibrosis; 
peribronchovascular predominance 
with subpleural sparing
Features
Honeycombing; reticular 
pattern usually associated 
with peripheral traction
bronchiectasis or 
bronchiolectasisa;
absence of features to 
suggest an alternative
diagnosis
Reticular pattern with peripheral
traction bronchiectasis or
bronchiolectasisa; 
honeycombing is absent; 
absence of features to suggest 
an alternative diagnosis
Evidence of fibrosis 
with some 
inconspicuous
features suggestive of 
non-UIP pattern
Any of the following:
predominant consolidation, 
extensive pure ground glass opacity 
(without acute exacerbation), 
extensive mosaic attenuation with 
extensive sharply defined lobular air 
trapping on expiration, diffuse 
nodules or cysts
Abbreviations: HRCT=high resolution computed tomography; IPF=idiopathic pulmonary fibrosis; UIP=usual interstitial pneumonia.
a Reticular pattern is superimposed on ground glass opacity, and in these cases, it is usually fibrotic. Pure ground glass opacity, however, would be against the 
diagnosis of UIP or IPF and would suggest acute exacerbation, hypersensitivity pneumonitis, or other conditions.
Adapted from Lynch, 2018.
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Appendix G:
Diagnostic Categories of UIP Based on HRCT Patterns and Histopathological Criteria For 
UIP in IPF (Continued)
B. Histopathological Criteria for UIP in IPF (UIP-IPF)
Definite UIP-IPF
Probable UIP-IPF
Indeterminate for UIP-IPF
Features most consistent with an alternative 
diagnosis
General 
comments
Patients show features 
with all four criteria, 
and do not show
features that might 
suggest an alternative 
diagnosis (eg, non-
UIP)
Patients show either honeycomb 
fibrosis only, or a severe 
fibrosing process that falls short 
of showing all four criteria for 
definite UIP-IPF and do not 
show features that might suggest 
an alternative diagnosis
Patients show evidence of a fibrosing 
process but with features that are more in 
favor of either a non-UIP pattern, or UIP 
in a setting other than IPF
Patients show either a UIP pattern with ancillary 
features strongly suggesting an alternative diagnosis, or 
a non-UIP pattern (see cell below)
Specific    
criteria
Dense fibrosis causing 
architecture 
remodeling with 
frequent 
honeycombing; patchy 
lung involvement by 
fibrosis; subpleural or 
paraseptal distribution, 
or both; fibroblast foci 
at the edge of dense 
scars
Honeycomb fibrosis only or; 
dense fibrosis causing 
architecture remodeling with 
frequent honeycombing; patchy 
lung involvement by fibrosis; 
fibroblast foci at the edge of 
dense scars may or may not be 
present
Patients have less compelling histological 
changes than those classified by the final 
column (eg, occasional foci of 
centrilobular injury or scarring, rare 
granulomas or giant cells, only a minor 
degree of lymphoid hyperplasia or diffuse 
inflammation, or diffuse homogenous 
fibrosis favoring fibrotic non-specific 
interstitial pneumonia); these features, and 
the differential diagnoses they call to 
mind, become part of the multidisciplinary 
discussion and decision with regard to a 
multidisciplinary diagnosis of IPF, or not
Non-UIP pattern: patients with features of other fibrotic 
disorders, eg, fibrotic hypersensitivity pneumonitis, 
fibrotic non-specific interstitial pneumonia, fibrosing 
organizing pneumonia, pleuroparenchymal
fibroelastosis, pulmonary Langerhans cell histiocytosis, 
or smoking-related interstitial fibrosis; UIP pattern with 
ancillary features strongly suggesting an alternative 
diagnosis: eg, prominent diffuse alveolar damage or 
organizing pneumonia (consider acute exacerbation of 
UIP), granulomas, (consider hypersensitivity 
pneumonitis, sarcoid, infection), marked interstitial 
inflammatory cell infiltrate away from areas of UIP 
(consider hypersensitivity pneumonitis)
Abbreviations: HRCT=high resolution computed tomography; IPF=idiopathic pulmonary fibrosis; UIP=usual interstitial pneumonia.
Adapted from Lynch, 2018.
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Appendix H:
Examples Of Drugs That Are Substrates For Selected 
Transporters
Examples of In Vivo Substrates for Selected Transporters
Transporter
Gene
Substrate
P-gp
ABCB1
aliskiren, colchicine, dabigatran etexilate, digoxin, 
everolimus, fexofenadine, ranolazine, saxagliptin, 
sirolimus, sitagliptin, talinolol, tolvaptan
OATP1B1
SLCO1B1
atorvastatin, ezetimibe, fluvastatin, glyburide, rosuvastatin, 
simvastatin acid, pitavastatin, pravastatin, repaglinide, 
valsartan, olmesartan 
OATP1B3
SLCO1B3
atorvastatin, rosuvastatin, pitavastatin, telmisartan, 
valsartan, olmesartan 
BCRP
ABCG2
rosuvastatin, sulfasalazine
Abbreviations: BCRP = ATP binding cassette protein G2/ABCG2; OAT1B1 = organic anion 
transporting polypeptide 1B1; OAT1B3 = organic anion transporting polypeptide 1B3; P-gp = p-
glycoprotein.
Examples of Substrates of One or More Transporters with a Narrow Therapeutic Index
Substrate
digoxin
mycophenolate mofetil
procainamide
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Celgene Signing Page
This is a representation of an electronic record that was signed electronically in Livelink.
This page is the manifestation of the electronic signature(s) used in compliance with
the organizations electronic signature policies and procedures.
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'DWH7KXUVGD\$XJXVW30(DVWHUQ'D\OLJKW7LPH
0HDQLQJ$SSURYHGQRFKDQJHVQHFHVVDU\
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CC-90001
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1.
JUSTIFICATION FOR AMENDMENT
The primary purpose of this amendment is to allow subjects with idiopathic pulmonary fibrosis 
(IPF) receiving protocol-allowable standard of care (SOC) treatment to be enrolled in the study. 
Consequently, the number of subjects planned for enrollment was increased from 135 to 165 to 
obtain an adequate number of subjects receiving SOC.  
Significant changes included in this amendment are summarized below:
!
Inclusion of subjects with IPF receiving protocol-allowable standard of care (SOC) 
treatment
This change was instituted to determine whether subjects already receiving SOC demonstrate 
a treatment benefit from CC-90001, as compared to placebo. The number of randomized IPF 
subjects was increased from 135 to 165 to allow for an adequate estimation of efficacy, 
safety and tolerability in subjects receiving SOC.
 
∀
Protocol Summary (Study Design and Statistical Methods);
∀
Section 1.6.2 (Rationale for the Study Design) – was originally Section 1.7.2;
∀
Section 1.6.5 (Rationale for Placebo Comparator) – was originally Section 1.7.5;
∀
Section 3.1 (Study Design and Figure 1: Overall Study Design [Idiopathic Pulmonary 
Fibrosis Study]);
∀
Section 4.1 (Number of Subjects);
∀
Section 7.2 (Treatment Administration and Schedule);
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∀
Section 8.4 (Required Concomitant Medications);
∀
Section 9.3 (Sample Size and Power Considerations);
∀
Section 9.6.1 (Analysis of the Primary Efficacy Endpoint for the IPF Study);
∀
Section 9.6.2.1 (24-Week Double-blind Placebo-controlled Treatment Phase);
∀
Section 9.8 (Interim Analysis)
!
Exploratory PPF Substudy
A separate, exploratory substudy in subjects with PPF will be initiated after a decision allows 
continuation of the IPF study as planned from an interim analysis.  Subjects who were 
initially screened for the IPF study and did not meet eligibility based on the central reader 
criteria for IPF based on high resolution computed tomography (HRCT) and lung biopsy, if 
provided, but met the PPF inclusion criteria will be considered for the PPF substudy.  The 
rationale for studying these subjects is that they may also benefit from anti-fibrotic 
treatments, such as CC-90001.  Approximately 45 qualifying non-SOC PPF subjects will be 
enrolled into the substudy.
∀
Revised or newly added content in the following sections based on the inclusion of the 
PPF substudy: 
∀
Protocol Summary (Secondary Objectives, 
 Study Design, 
Study Treatments and Statistical Methods);
∀
Section 1.1.2 (Progressive Forms of Pulmonary Fibrosis Other Than IPF) – a newly 
added section;
∀
Section 2 (Study Objectives and Endpoints) – Secondary Objectives 
 
 related to the PPF substudy were added to Table 1;
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∀
Section 2 (Study Objectives and Endpoints) – Table 3 (Progressive Pulmonary 
Fibrosis Substudy Endpoints) was added;
∀
Section 3 (Overall Study Design) with newly added Figure 2 (Overall Study Design 
[Progressive Pulmonary Fibrosis Substudy]);
∀
Section 3.1 (Study Design);
∀
Section 3.1.1 (Progressive Pulmonary Fibrosis Substudy) – newly added section;
∀
Section 4.1 (Number of Subjects);
∀
Section 4.2.2 (Inclusion Criteria for Progressive Pulmonary Fibrosis Substudy Only) 
– newly added section;
∀
Section 4.3 (Exclusion Criteria) – Some of the wording was updated so that it applies 
to both IPF and PPF populations.  Also, Exclusion Criterion No. 9 has a newly added 
“Note” that only applies to the PPF population;
∀
Section 6.1 (Screening Phase);
∀
Section 7.2 (Treatment Administration and Schedule);
∀
Section 9.1 (Overview);
∀
Section 9.2 (Study Population Definitions);
∀
Section 9.3 (Sample Size and Power Considerations);
∀
Section 9.6.1 (Analysis of the Primary Efficacy Endpoint for the IPF Study);
∀
Section 9.6.2.1 (24-Week Double-blind Placebo-controlled Treatment Phase);
∀
Section 9.8 (Interim Analysis)
!
Inclusion Criteria Revised
Section 4.2 (Inclusion Criteria) was updated to include two sub-sections, Sections 4.2.1 and 
4.2.2, as described below.
∀
Section 4.2.1 (Inclusion Criteria for Idiopathic Pulmonary Fibrosis Subjects) was added 
as a subsection for IPF subjects.
∀
Inclusion Criterion No. 5 (original) – was deleted to allow subjects with a prior IPF 
diagnosis longer than 5 years to be considered for participation in the study.  Some 
patients with IPF have a more protracted course of disease
 
 and there is no reason to suspect that CC-90001 would not be 
potentially beneficial in these patients.
∀
Inclusion Criterion No. 12 (originally Inclusion Criterion No. 13) – was revised with 
updated program-wide female contraception language, based on the latest updated
Celgene template.
∀
Inclusion Criterion No. 13 (originally Inclusion Criterion No. 14) – was revised with
updated program-wide male contraception language, based on the latest updated
Celgene template.
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∀
Section 4.2.2 (Inclusion Criteria for Progressive Pulmonary Fibrosis Substudy Only) was 
added as a subsection for PPF subjects.
!
Exclusion Criteria Revised 
∀
Section 4.3 (Exclusion Criteria) 
 
∀
Exclusion Criterion No. 22 – was revised to account for allowing subjects with 
documentation of adequately treated latent or active tuberculosis (TB) to participate 
in the study.  Also, a “Note” was added to this Criterion and Section 6.1 (Screening) 
to describe when the QuantiFERON-TB Gold test is not required for adequately 
treated subjects, provided there is a chest radiograph taken prior to or during 
Screening to rule out latent/active TB and there is documentation of adequate 
treatment for TB prior to randomization.
∀
Exclusion Criterion No. 23 (newly added) – was added for excluding subjects who 
had household contact with a person with active TB and the subject did not receive 
appropriate and documented prophylaxis for TB.
!
Dose Interruptions for Planned Surgical Procedures
Section 7.2.2.1 (Dose Interruptions for Planned Surgical Procedures) was added to emphasize 
that subjects with planned surgical procedures should interrupt investigational product (IP)
7 to 10 days prior to and restart 7 days after any surgical procedures, since it is unknown if 
CC-90001 affects wound healing in humans.
!
Changes to Statistical Sections
The study is no longer powered at 80% since the proposed IPF patient population will 
include both non-SOC and SOC IPF subjects and benefits of CC-90001 in subjects already 
receiving anti-fibrotic therapy are expected to be reduced.  The inclusion of a PPF substudy 
population will be analyzed as a separate population.  Additional supportive analyses (eg, 
efficacy analysis of both active treatment groups, considered together, versus placebo, and a 
Bayesian approach to efficacy analysis) are specified.
∀
Revised content in the following sections based on the changes to the statistical section: 
∀
Protocol Summary (Study Design and Statistical Methods); 
∀
The original Section 1.6 (Study Hypothesis) was removed since it no longer applies, 
and the purpose of the study is to estimate the effect of CC-90001 in IPF subjects 
either not receiving SOC or currently receiving SOC.  As a result, sections previously 
labeled as 1.7, 1.7.1, 1.7.2, 1.7.3, etc, are re-numbered accordingly.
∀
Section 9.2 (Study Population Definitions);
∀
Section 9.3 (Sample Size and Power Considerations);
∀
Section 9.6.1 (Analysis of the Primary Efficacy Endpoint for the IPF Study);
∀
Section 9.6.2.1 (24-Week Double-blind Placebo-controlled Treatment Phase);
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∀
Section 9.8 (Interim Analysis);
∀
Section 9.9.3 (Analysis of Dose-Response) – was newly added to briefly describe the 
analysis approach used to inform optimal dose selection.
This amendment also includes other administrative, corrective and/or minor changes,
which are summarized below: 
!
In multiple sections throughout the amendment, the term “Placebo-controlled” was 
appropriately added to previous phrase, “24-week Double-blind Treatment Phase,” to
emphasize that the first 24 weeks of the study are placebo-controlled. “24-week 
Double-blind Placebo-controlled Treatment Phase” is now consistently stated 
throughout the protocol.
!
In Protocol Summary (Study Design, Length of Study and Study Treatments), 
Section 3.1 (Study Design), Section 3.2 (Study Duration for Subjects), and Section 
7.2 (Treatment Administration and Schedule), detailed descriptions regarding 
Protocol Amendments 1.0 and 2.0 that no longer apply were deleted.
!
Section 1.7 (Potential Risks of CC-90001 and the Study Population) which was 
previously Section 1.7.8, and Section 8.1.1 (Permitted Concomitant Medications 
Throughout the Entire Study) were revised with minor word changes for a better 
description regarding concomitant statins, which will be dose adjusted to a 
therapeutic level during the study.
!
Sections 2 and 3 (Study Objectives and Endpoints and Overall Study Design) had 
Table 2 and Figure 1 titles relabeled to specifically define the endpoints in Table 2 as 
the “Idiopathic Pulmonary Fibrosis Study Endpoints” and Figure 1 as the Overall 
Study Design “Idiopathic Pulmonary Fibrosis Study,” since a separate Table 3 and 
Figure 2 were added to define the “Progressive Pulmonary Fibrosis Substudy 
Endpoints” and Overall Study Design “Progressive Pulmonary Fibrosis Substudy,” 
respectively.  Also, Table 2 (Idiopathic Pulmonary Fibrosis Study Endpoints) has 
been updated with additional timeframes for analysis of endpoints.
!
Section 3.1.2 (Adjudication Committee), which was previously Section 3.1.1, and 
Protocol Summary (Adjudication Committee) were slightly revised to include the 
same content and minor word changes for a better description of the content within 
both sections.
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!
Section 4.2 (Inclusion Criteria, newly labelled as Inclusion Criterion No. 5), Section 5 
(Table of Events, Table 5, which was previously Table 4) Footnote “e”, Section 6.1 
(Screening Phase), and Section 6.4.5 (Chest High-resolution Computed Tomography)
were slightly revised for a clearer description regarding eligible historical HRCT 
scans. The wording “if it meets image acquisition guidelines and scan is reviewed 
by” centralized review was changed to “if the scan is deemed sufficient for” 
centralized review in the following paragraph:  
HRCT scan performed within 18 months of randomization may be used if it meets 
image acquisition guidelines and scan is reviewed by centralized review.  For sites 
subject to regulatory restrictions that do not permit HRCT within this time period, a 
previous HRCT scan is permissible “if the scan is deemed sufficient for” centralized 
review.
!
Section 5 (Table of Events, Table 5, which was previously Table 4) Footnote “h” was 
revised to remove the erroneous letter “E” after Weeks 12, 16, 20, and 24.
!
Section 5 (Table of Events, Table 5, which was previously Table 4) has a newly 
added Footnote “k” and Section 6.2 (Treatment Phase) and Section 6.3 (Post-
treatment Observational Follow-up Phase) were revised to better describe the 
scheduling of visits.  For all subsequent visits, an administrative window of ± 3 days 
is permitted.  Scheduling of Visits 3 to 9 is based on Visit 2 (randomization date) and 
scheduling of Visits 10E to 26E is based on Visit 9 (re-randomization date).  The 
Post-treatment Observational Follow-up Visit is scheduled 28 days (4 weeks) after 
the date of the last dose of IP ± 3 days.
!
Section 5 (Table of Events, Table 5, which was previously Table 4) has a newly 
added Footnote “l” and Section 6.1 (Screening Phase) was updated with a new “Note” 
to describe when the QuantiFERON-TB Gold test is not required for a subject, 
provided there is a chest radiograph taken prior to or during Screening to rule out 
latent/active TB, and documentation of adequate treatment for TB prior to 
randomization.  
Also, within Table 5 (Table of Events), the QuantiFERON® -TB Gold Test, Hepatitis 
B & C Tests assessment row was updated to include “or Chest Radiograph for TB 
when appropriate.”
!
Section 6.1 (Screening Phase) was revised with corrections in the following 
2 sentences: 
∀
A correction to note that screening evaluations must be completed within 8 weeks 
“after Screening (Visit 1)” and not within 8 weeks “of Baseline (Visit 2).”
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∀
A correction to note that if the subject does not receive IP within 8 weeks “after 
Screening (Visit 1),” the subject must be screen failed.  Previously, it was stated 
as “if the subject does not receive IP within 8 weeks of Baseline (Visit 2)” which 
was incorrect.
!
Section 6.1 (Screening Phase), first paragraph, last sentence was revised with an 
additional statement to emphasize that all re-screened subjects must be re-consented 
for the study. 
!
For Section 6.1 (Screening Phase), the following new “Note” was added to emphasize 
to the site to perform a urine culture test, if the Screening Visit 1 urinalysis test results 
are positive for leukocyte esterase or nitrite present:  
Note: If the Screening Visit 1 urinalysis test results are positive (eg, leukocyte 
esterase or nitrite present), a urine culture test is required, and the subject must have 
a confirmatory negative urine culture test to rule out urinary tract infection (UTI)
prior to randomization, which can be performed using the provided central 
laboratory urine culture kits or a local laboratory at the site.  
!
For Section 6.3 (Post-treatment Observational Follow-up Phase), the order of the 
assessments for concomitant medications and concomitant procedures were adjusted
to match the order in Section 6.2 (Treatment Phase) for consistency.  
!
The IP sections, Section 7.2 (Treatment Administration and Schedule) and Protocol 
Summary (Study Design and Study Treatments) were updated with summarized 
information to better describe the IP treatments and the number and type of tablets 
taken by subjects during the 24-week Double-blind, Placebo-controlled Treatment 
Phase versus the 80-week Active Treatment Extension Phase.  Also, a clear 
description of when the IP is taken during each phase was provided in Section 7.2.
!
Section 9.7.2 (Disease Progression) was revised to clarify that the Investigator’s 
discretion to discontinue the subject can also apply if the subject experiences a 
decrease from baseline of ≥ 50 meters in 6-minute Walk Test (6MWT) distance (in 
the absence of a readily explainable cause, such as injury or trauma). 
!
In Section 9.8 (Interim Analysis), Section 9.9.4 (External Data Monitoring 
Committee) and Protocol Summary (External Data Monitoring Committee), content 
was added to describe the Data Monitoring Committee’s (DMC’s) role and 
responsibility in reviewing the interim analyses data.  The DMC will make 
recommendations to a Celgene Internal Review Committee, who will remain 
independent from the Study Team, and will be responsible for final decision making.
!
Section 10.4 (Pregnancy) was updated with language regarding the new process for
Celgene to obtain consent for collecting pregnancy information from a female subject 
of childbearing potential, or female partner of a male subject, in the event that a 
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Summary of Changes CC-90001-IPF-001
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pregnancy occurs during the study, which requires the release of the new Celgene 
pregnancy-specific information consent forms.
!
Section 17 (References) was updated with additonal citations based on newly added 
content.
!
Section 18 (Appendix E. 6-Minute Walk Test Protocol) was updated with a correction 
in the instructions for Step 2: Walking O2 Titration Procedure, bullet E.  The Walking 
O2 titration should be terminated and the patient deemed not eligible for study 
participation if a patient is titrated during the walking O2 titration to 6 L/min of O2
and within the “6 minutes” of the 6MWT the oxygen saturation (SpO2) drops below 
83%.
!
Other minor editorial changes were made throughout the document.
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Summary of Changes CC-90001-IPF-001
Celgene Corporation
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CC-90001-IPF-001 Amendment 2.0 Final: 18 Jul 2018
1.
JUSTIFICATION FOR AMENDMENT
The rationale for the following changes is to allow idiopathic pulmonary fibrosis (IPF) subjects 
who were randomized to placebo the opportunity to receive CC-90001 (200 mg or 400 mg orally 
[PO] once a day [QD]) after 24 weeks of treatment.  In the current study design, these subjects 
are not given the opportunity to receive CC-90001.  It will also afford all subjects to receive 
active treatment for an additional 52 weeks (80-week Active Treatment Extension Phase).
Significant changes included in this amendment are summarized below:
!
Protocol Title (Title Page and Protocol Summary)
The title was changed to: “A Phase 2, 24-Week, Randomized, Double-blind, Placebo-
controlled, Multicenter Study, With an 80-Week Active Treatment Extension, to 
Evaluate the Efficacy and Safety of CC-90001 in Subjects With Idiopathic Pulmonary 
Fibrosis.”
!
Study Design (Protocol Summary and Section 3.1)
The study design was changed to include an 80-week Active Treatment Extension 
Phase. The 80-week Active Treatment Extension Phase will provide subjects who 
were randomized to placebo the opportunity to receive CC-90001 (200 mg or 400 mg 
PO QD) after completing Week 24 of the study.
∀
Added a description of how subjects who were enrolled under the original 
protocol and Protocol Amendment 1.0 will continue in the study under Protocol 
Amendment 2.0 and may receive treatment for up to 132 weeks.
∀
The length of the study was revised to 116 weeks; 8-week Screening Phase, 24-
week Double-blind Placebo-controlled Treatment Phase, 80-week Active 
Treatment Extension Phase and 4-week Post-treatment Observational Follow-up 
Phase. 
∀
Added text that describes the randomization of subjects stratified by previous 
exposure to pirfenidone, nintedanib or no prior exposure to either drug.
!
Study Duration and Length of Study (Protocol Summary, Figure 1, and Section 
3.2)
∀
The study figure was revised to reflect an 80-week Active Treatment Extension 
Phase.
∀
The study duration was revised based upon the 80-week Active Treatment 
Extension Phase to include a total duration of up to 116 weeks for those subjects 
enrolled under Protocol Amendment 2.0.
∀
Clarified that subjects enrolled under the original protocol or under Protocol 
Amendment 1.0 can have a total study duration of up to 141 weeks.
∀
Screening Phase: The Screening Phase was revised to permit screening for up to 
8 weeks.
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Summary of Changes CC-90001-IPF-001
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The 8-week screening will prevent subjects from falling out of the screening 
window due to scheduling conflicts within institutions’ radiology (high resolution 
computerized tomography [HRCT]) and pulmonary departments (spirometry and 
diffusion capacity of the lung for carbon monoxide [DLCO]).
!
Study Endpoints (Section 2, Table 2)
∀
Revised the timeframe for several endpoints described in Table 2.
Due to the change in the study design, the timeframe for several study endpoints 
needed to be adjusted.  
!
Inclusion Criteria (Section 4.2)
∀
Revised inclusion criterion number 5 regarding years since the diagnosis of IPF at 
screening from within 4 years to within 5 years.
The median survival rate for IPF is 3 to 5 years from the time of diagnosis (Ley, 
2013).  Therefore, the inclusion of patients with a history of IPF within 5 years is 
still representative of the general population of IPF patients.  More recent IPF 
trials (eg, pirfenidone [King, 2014], nintedanib [Richeldi, 2014], pamrevlumab
[NCT01890265] and KD025 [NCT02688647]) have included a 5-year window 
from the time of diagnosis for study eligibility.
∀
Revised inclusion criterion number 6 and Section 6.1 regarding the diagnosis of 
IPF. Appendix G and Table 3 that is referenced in inclusion criterion number 6
were also revised.
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Summary of Changes CC-90001-IPF-001
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Criteria to establish the diagnosis of IPF have continued to evolve since 
publication of the ATS/ERS/JRS/ALAT statement in 2011.  It has become 
increasingly recognized that the absence of honeycombing has a poor negative 
predictive value for the diagnosis of IPF in many patients.  In patients without an
environmental exposure history or evidence of a collagen vascular disease, an 
HRCT pattern suggestive of IPF even in the absence of honeycombing has a high 
positive predictive value for IPF and a lung biopsy is considered unnecessary 
(Raghu, 2014).  A recent analysis of the INPULSIS trial further substantiates that 
IPF in patients with and without honeycombing on HRCT behave similarly.  In 
the INPULSIS trials, there was no difference in the rate of decline in FVC 
between patients with and without honeycombing who received placebo.  
Furthermore, there was no difference in the treatment response to nintedanib 
among patients with and without honeycombing (Raghu, 2017).
A Fleischner Society White paper on the diagnostic criteria of IPF was recently 
published (Lynch, 2018). In this paper, a new category in the interpretation of 
HRCT patterns, “Computerized tomography (CT) pattern indeterminate for usual 
interstitial pneumonia (UIP),” was proposed to encompass an HRCT that may be 
consistent with IPF and that lacks features most consistent with a non-IPF 
diagnosis. This new category can be considered a refinement of the 2011 
ATS/ERS/JRS/ALAT criteria (Raghu, 2011), in which an HRCT classified as 
“inconsistent with UIP” did not distinguish between patients whose scans were 
insufficient to secure this diagnosis in the absence of additional information (eg, 
lung biopsy), from patients who were unlikely to have IPF.
Based upon the findings cited above, the incorporation of the modified IPF 
algorithm will permit the inclusion of those patients diagnosed with IPF who 
would not have qualified for the current study under the 2011 
ATS/ERS/JRS/ALAT guidelines (Raghu, 2011).
In addition, lung cryobiopsy was added as an alternative diagnostic tool to 
surgical lung biopsy (SLB) since pathologic analysis of lung cryobiopsy showed 
that a UIP pattern identified using the same criteria used when analyzing the SLB 
samples may be identified with high confidence in almost 80% of the cases and 
the interobserver consistency is similar to that obtained with surgical specimens
(Colby, 2017).
∀
Revised inclusion criterion number 8 to clarify that transbronchial biopsy, 
bronchoalveolar lavage (BAL), or surgical lung biopsy (SLB), must have been
performed prior to Screening.
∀
Revised inclusion criterion number 9 and Protocol Summary Study Population to 
include an upper limit for percent predicted forced vital capacity (% FVC) of ≤ 
95%.  
Including a cap for the upper limit of % predicted FVC will exclude rare, atypical
IPF subjects from the study who are unlikely to demonstrate a treatment benefit, 
regardless of the treatment.
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Summary of Changes CC-90001-IPF-001
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∀
Revised inclusion criterion number 11 and Protocol Summary Study Population 
regarding the upper limit for hemoglobin-corrected DLCO.  
In response to recommendations of several investigators, the upper limit for 
hemoglobin-corrected percent predicted DLCO was changed from 85% to 90%
predicted.
!
Exclusion Criteria (Section 4.3)
∀
Clarified in exclusion criterion number 10 that lung transplantation should not 
occur within the first 24 weeks of the study.
Since it is difficult to predict when a subject will receive a lung transplant while 
participating in the study, the study will only exclude those subjects who are 
expected to be transplanted before Week 24 (the time when the primary endpoint 
is assessed).
∀
Revised exclusion criterion number 12 regarding IPF targeted therapies.
Mycophenolate mofetil was added to the list of excluded medications as it may be 
used off-label to treat IPF.  This revision is also reflected in Sections 8.1.3 and 
8.3.1 in the protocol.
∀
Revised exclusion criterion number 13 regarding cytokine modulators/biologics.
Revised criterion to include the term “biologic” as rituximab is a biologic that 
targets B cells, rather than a cytokine.
∀
Removed exclusion criterion number 15 regarding supplemental oxygen use.
Use of continuous supplemental oxygen is considered standard practice for many 
IPF patients in parts of the world located at higher altitudes. 
∀
Clarified that exclusion criterion number 20 regarding history of hepatitis B and 
/or hepatitis C applies even to those subjects who were considered successfully 
treated/cured.
Currently it is unknown if CC-90001 has the potential to reactivate the hepatitis B 
and /or hepatitis C viruses.
!
Revised the Protocol Summary Study Treatments, Section 7.2 Treatment 
Administration and Schedule, and Section 7.2.3 Method of Treatment 
Assignment
∀
Sections were revised to reflect an 80-week Active Treatment Extension Phase;
clarified how the subjects who received placebo in the 24-week Treatment Phase 
will be provided active drug in the 80-week Active Treatment Extension Phase, 
and revised the timing and the number of blister cards to issue in the 80-week
Active Treatment Extension Phase (Section 7.2 only).
∀
Described how the subjects that were enrolled under Protocol Amendment 1.0 
will continue in the study under Protocol Amendment 2.0. 
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∀
Revised the number of blister cards to be dispensed based upon the 80-week 
Active Treatment Extension Phase.
!
Revised Section 1.7.8 Potential Risks of CC-90001 and the Study Population
A description of why statins require close monitoring while subjects are on the study
was added.
!
Revised text in Section 8.1 Permitted Concomitant Medications and added New 
Section 8.2.1 Statins
New preliminary data suggest that CC-90001 is an inhibitor of three transporters, 
organic anion transporting polypeptides (OATP1B1 and OATP1B3) and breast 
cancer resistance protein (BCRP).  Concomitant use of a statin with CC-90001 may 
increase plasma concentrations of statins. Therefore, to ensure the safety of the 
subjects taking statins concomitantly with CC-90001 the procedure for how statins 
are to be dosed on the study is described in the protocol.
!
Revised Section 8.1.1 Permitted Concomitant Medications Throughout the Study
Added new bullet to further describe the use of oral corticosteroids in the study.
!
Revised Section 11.1 Treatment Discontinuations
The term “Disease progression” was substituted for “Absolute decrease of ≥ 10% 
from baseline in percent predicted FVC at two consecutive evaluations at a minimum 
of 4 weeks between evaluations.” The revised text clarifies that evidence of disease 
progression other than decrease in FVC (e.g., worsening hypoxemia or a decrease
from baseline in 6-minute walk test (6MWT) distance, as defined in Table 2, Study 
Endpoints) may be reasons to discontinue treatment at the Investigator’s discretion.  
However, “Absolute decrease of ≥ 10% from baseline in percent predicted FVC at 
two consecutive evaluations at a minimum of 4 weeks between evaluations” remains 
a mandatory requirement for treatment discontinuation.
!
Revised Section 11.2 Discontinuation Criteria for Elevation of Hepatic 
Transaminases  
 it was clarified in Section 11.2 that 
subjects who experience elevated alanine aminotransferase (ALT) or aspartate 
aminotransferase (AST) > 3 x upper limit of normal (ULN) should also have repeat 
testing that includes AST, ALT, total bilirubin, and alkaline phosphatase testing and 
that the elevated hepatic enzymes should be followed until resolution.
!
Revised the Table of Events, Table 4
To be consistent with the 80-week Treatment Extension, the visit spacing and timing 
of some of the assessments were revised (vital signs, weight, electrocardiogram, 
clinical labs, 
 St. George’s Respiratory Questionnaire (SGRQ), 
 
spirometry, arterial oxygen saturation by pulse oximetry (SpO2), DLCO, 6MWT, 
assessment of shortness of breath, 
 
 and return of investigational product [IP]). The abbreviations 
in the table were also revised to reflect the revised table.
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CC-90001-IPF-001 Amendment 2.0 Final: 18 Jul 2018
Protocol Template Revisions
!
To comply with the latest protocol template revisions, the following items were 
addressed in the protocol:
∀
Added to Section 3.1 the additional language to document blinding status of the 
study team roles.
∀
Moved Patient-reported Outcomes description to the newly defined Section 6.7.  
As a result of this template change, several sections within Section 6 required new
sub-section renumbering.
∀
Added Section 15.3 Product Quality Complaint to provide information to 
investigators regarding the definition of a product quality complaint (PQC) and 
how to notify the Sponsor of a suspected PQC.
The amendment also includes other minor clarifications and corrections including: 
!
Section 1.6 was revised to remove 400 mg PO QD dose as this hypothesis should 
include both studied doses.
!
Sections 1.7.2 and 1.7.5 were revised to reflect the 80-week treatment extension 
where all subjects will be receiving active CC-90001.
!
Removed “inhaled steroids” from the list of excluded IPF targeted therapies as 
inhaled corticosteroids are permitted for use throughout the study. 
!
Revised parts of Section 6.1, Screening Phase:
∀
Clarified that subjects who were previously vaccinated for hepatitis B are eligible 
for the study.
∀
Removed the verbiage regarding the order of the assessments.
∀
Revised the HRCT diagnosis criteria according to Lynch, 2018.  Rationale for this 
change is described above, under inclusion criterion number 6 and Table 3.
∀
Postmenopause test: Estradiol and follicle-stimulating hormone (FSH) levels are 
required for all females who have not had a menses for at least one year, and do 
not have documentation confirming their postmenopausal status.  The original 
text mentioned females 50 to 55 years of age.  Because females can reach
menopause in their forties, the language was simplified to address all females who 
have not had a menses for at least one year.
∀
Revised Section 6.1 to reflect 8 weeks of the Baseline visit.
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!
Clarified text related to treatment administration in Section 7.2.
!
Revised the timeframe for the overdose definition in Sections 7.2.1 and 7.2.2.  
Overdose is defined within the same calendar day and no longer within a 24-hour 
period as ingestion of “> 2 tablets within the same calendar day” instead of “> 4 
tablets within a 24-hour period”.  To be consistent with the revised definition of 
overdose, the window of time of when an IP dose could be taken within the same day 
was changed from “12 hours” to “36 hours” from the previous dose taken. 
!
Table of Events and Section 7.2.3 were revised to read 80-week Active Treatment 
Extension Phase.
!
Clarified in Table 4 footnote c  that pregancy testing during the 80-week treatment 
extension for females of childbearing potential will be done as an unscheduled visit.
!
Revised the statistical Sections 9.1, 9.6.2.2, and 9.7 to reflect the 80-week Active 
Treatment Extension Phase.  
!
Revised Section 9.2 to comply with new protocol deviation convention and to further 
define the Full Analysis Set (FAS).
!
Clarified in Section 9.6.1 why there is no adjustment for multiplicity.
!
Revised Section 9.8 to reflect the timing of the interim analysis to occur when 40% to 
50% of subjects complete 24 weeks of treatment.
!
Revised Sections 11.1 and 11.3 last bullet to read important protocol deviation to 
comply with new protocol deviation convention. 
!
Renamed the table for Selected Transporters in Appendix H, and provided an 
additional table that provides examples of substrates of one or more transporters with 
a narrow therapuetic index.  
!
Updated the email addresses for the 
 personnel
!
Minor editorial changes
New references cited in the protocol:
Chung J H, Oldham JM, Montner SM, Vij R, Adegunsoye A, Husain AN, et al. CT-
pathologic correlation of major types of pulmonary fibrosis: insights for revisions to 
current guidelines. AJR Am J Roentgenol. 2018;210:1034-41. 
Lynch DA, Sverzellati N, Travis WD, Brown KK, Colby TV, Galvin JG, et al. 
Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. 
Lancet Respir Med. 2018;6(2):138-153.
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References cited above:
Colby TV, Tomassetti S, Cavazza A, Dubini A, Poletti V.  Transbronchial cryobiopsy in 
diffuse lung disease. Update for the pathologist. Arch Pathol Lab Med. 2017;141:891-
900.
King TE Jr. Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et 
al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J 
Med. 2014; 370(22):2083-92.
Ley B, Collard HR. Epidemiology of idiopathic pulmonary fibrosis. Clin Epidemiol. 
2013; 5: 483-92.
Lynch DA, Sverzellati N, Travis WD, Brown KK, Colby TV, Galvin JG, et al. 
Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. 
Lancet Respir Med. 2018;6(2):138-153.
Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An official 
ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based 
guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:  
788-824.
Raghu G, Lynch D, Godwin JD, Webb R, Colby TV, Leslie KO, et al. Diagnosis of 
idiopathic pulmonary fibrosis with high-resolution CT in patients with little or no 
radiological evidence of honeycombing: secondary analysis of a randomised, controlled 
trial. Lancet Respir Med 2014;2(4):277–84.
Raghu G, Wells AU, Nicholson AG, Richeldi L, Flaherty KR, Le Maulf F, et al. Effect of 
nintedanib in subgroups of idiopathic pulmonary fibrosis by diagnostic criteria. Am J 
Respir Crit Care Med. 2017;195(1):78–85.
Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and 
safety of nintedanib in idiopathic pulmonary fibrosis. New Engl J Med.2014; 370:2071-
82.
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CC-90001-IPF-001 Amendment 1.0 Final: 25 Aug 2017
1.
JUSTIFICATION FOR AMENDMENT
Significant changes included in this amendment are summarized below:
!
Inclusion Criteria (Section 4.2)
∀
Added new inclusion criterion #4 regarding consideration of treatment options for 
idiopathic pulmonary fibrosis (IPF)
“Investigator has considered all available IPF treatment options with the potential 
subject before consenting the subject for participation in the study”
∀
Revised inclusion criterion #6 regarding the diagnosis of IPF via high resolution 
computerized tomography (HRCT)
Increased the time prior to randomization for acceptance of historical HRCT from 
12 months to 18 months.  
This change in the window for use of a historical HRCT reflects standard 
practices in many regions regarding the frequency of HRCT for IPF patients, 
particularly in those regions that do not permit periodic HRCT due to radiation 
restrictions (eg, Germany).
∀
Revised inclusion criterion #11 and Protocol Summary regarding the lower limit 
for diffusion capacity of the lung for carbon monoxide (DLCO)
In response to recommendations of investigators, the lower limit for hemoglobin-
corrected percent predicted DLCO was changed from ≥30% to ≥ 25%.
A substantial number of patients with IPF may have forced vital capacity (FVC)
values of 45% predicted or greater but with relatively low DLCO (eg, in the 25% 
to 30% predicted range).  Increasing the range of acceptable DLCO by reducing 
the lower limit to of ≥25% predicted DLCO will enable recruitment of IPF 
patients to more closely reflect the spectrum of IPF who might be eligible for 
treatment. The amended protocol also clarifies that percent predicted DLCO
values used will be corrected for hemoglobin, to better standardize this 
measurement.
!
Exclusion Criteria (Section 4.3)
∀
Revised exclusion criterion #9 regarding respiratory disorder
Added to the term pulmonary arterial hypertension, requiring treatment to exclude
those patients with more advanced disease.
∀
Revised exclusion criterion #12 regarding IPF targeted therapies
Mycophenolate mofetil was added to the list of excluded medications as it may be 
used off-label to treat IPF.
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∀
Revised exclusion criterion #13 regarding cytokine modulators/biologics
Revised criterion to include the term biologic as rituximab is a biologic that 
targets B cells, rather than a cytokine.
Alefacept was removed from the list of cytokine modulators as it is no longer a 
marketed drug.
∀
Revised exclusion criterion #15 regarding supplemental oxygen use
Clarified that subjects who receive continuous supplemental oxygen as part of 
standard of care for all IPF patients residing at high altitudes are not excluded 
from participation in the trial.
∀
Clarified in exclusion criterion #19 regarding valve replacement
Replaced the term “artificial” with “cardiac” valve replacement requiring 
anticoagulation therapy.
∀
Revised exclusion criterion #29 regarding use of smoking products
Revised this criterion to exclude subjects who smoke pipes, cigars, vapes,                    
e-cigarette and marijuana, in addition to cigarettes.
!
Included External Data Monitoring Committee (DMC) (Section 9.9.3 and 
Protocol Summary)
∀
the internal DMC 
was replaced by an external DMC.
!
Mandatory Discontinuation Due to Unsuccessful Treatment of Acute 
Exacerbation (Sections 8.1.2 and 11.1)
∀
The duration of time required for mandatory discontinuation due to unsuccessful 
treatment of acute exacerbation was increased from 2 weeks to 6 weeks.  This 
change was recommended by multiple study investigators, who stated that many 
patients with an acute IPF exacerbation who eventually recover do not begin to 
demonstrate improvement within a 2-week time period.
!
Revised the Discontinuation Criteria for Elevated Liver Function Tests (Sections 
1.7.8, 6.2, and 11.2)
∀
 the fold-elevation of alanine 
aminotransferase (ALT) and aspartate aminotransferase (AST) requiring 
withholding study drug and potential discontinuation was lowered.  The reference 
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CC-90001-IPF-001 Amendment 1.0 Final: 25 Aug 2017
to the DHHS guidance document was removed from Sections 1.7.8 and 17 in the 
protocol.
!
6-minute walk test (6MWT) (Appendix E)
∀
Study investigators requested that the 6MWT to follow be included as an 
appendix in the protocol.  This will ensure greater uniformity in how the 6MWT
is performed across sites.  Added new reference in Section 17, American 
Association for Respiratory Care. Clinical practice guideline. Exercise testing for 
evaluation of hypoxemia and/or desaturation. Respir Care 1992;37:907–912.
The amendment also includes other minor clarifications and corrections including: 
∀
Corrected the title of the Celgene Therapeutic Area Head Signature page to read 
Clinical Research and Development, Immunology and Inflammation.
∀
The medical monitors originally assigned to the protocol to cover the Americas, 
Canada, European Union and Asia Pacific were replaced due to a change in 
personnel at the clinical research organization (CRO).
∀
Corrected Table 4, Visit 9 to have a ± 3-day visit window.
∀
Removed the sentence that incorrectly references the cough domain in the Saint 
Georges Respiratory Questionnaire in Sections 1.7.7 
 and in Table 2.
∀
Further clarified in Section 6.1 and Table 4, that in the event that a historical 
HRCT does not meet study eligibility (as determined by the central reader), a new 
HRCT must be obtained.  For sites subject to regulatory restrictions that do not 
permit HRCT within this time period, a previous HRCT scan is permissible if it 
meets image acquisition guidelines and scan is reviewed by centralized review.  
Note: HRCT should be obtained after the subject has satisfied all of the above 
study assessments for study eligibility.
∀
Further clarified in Section 6.1, how minor fluctuations of symptoms (eg, cough 
and dyspnea) that reflect the underlying disease should not necessarily be 
recorded as an adverse event (AE) if they are similar in intensity and duration to 
prior such fluctuations. More marked and or sustained worsening of such 
symptoms should be recorded as an AE.
∀
Further clarified in Section 6.1 how positive hepatitis test results should be 
interpreted for those subjects who have been previously vaccinated for hepatitis 
B.
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Summary of Changes CC-90001-IPF-001
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CC-90001-IPF-001 Amendment 1.0 Final: 25 Aug 2017
∀
Corrected Section 7.2, Treatment Administration and Schedule and Table 4 for 
the visit timing and number of blister cards dispensed based upon drug 
configuration cards.
∀
Further clarified in Section 7.2.2, that if investigational product (IP) is missed and 
the timing occurs > 12 hours of the previous dose, the dose should be skipped.
∀
Corrected Section 12.2 for emergency unblinding of study IP, that it will occur 
via the Interactive Web Response System (IWRS).
∀
Replaced the Borg scale in Appendix F with copyrighted version.
∀
Clarified in the following sections that DLCO will be hemoglobin-corrected: 
Study population in the Protocol Summary, Table 2, inclusion criterion #11, 
Sections 6.1 and 6.5.2.2.
∀
Clarified in Table 4 and Sections 
 6.1 and 8.2 that warfarin is but one example 
of a vitamin K antagonist; in some countries, other vitamin K antagonists can be 
used instead.
∀
Clarified in Sections 1.7.8 and 6.1 that the cholesterol panel will include total,
high density lipoprotein (HDL) and low density lipoprotein (LDL).  
∀
Changed centralized to independent adjudication committee in Section 3.1.1 and 
Protocol Summary.
∀
Added in Section 8.2 a reminder to investigators to contact the sponsor if they 
have any question regarding the administration of CC-90001 with drugs that are 
substrates for the transporters described in this section.
∀
Added in Section 8.3.1 that marijuana should not be used within 3 months of 
Screening.
∀
Further clarified in Section 8.3.2 that oral anticoagulants for conditions other than 
IPF (with the exception of cardiac valve replacement) are permitted.
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