Conditions: Idiopathic Pulmonary Fibrosis (IPF)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 41
Healthy volunteers: no

Brief summary:
The primary objective of this study is to evaluate the safety and tolerability of subcutaneously (SC) administered multiple, escalating doses of BG00011 (a humanized monoclonal antibody directed against the alpha v beta 6 (αvβ6) integrin, formerly known as STX-100) in participants with IPF. The Secondary objectives are to estimate the pharmacokinetic (PK) parameters after the 1st dose and after the last dose of multiple, escalating doses of BG00011 in participants with IPF, to assess the immunogenicity of BG00011 in participants with IPF, and to assess the effect of BG00011 on biomarkers isolated from bronchoalveolar lavage (BAL) and peripheral blood in participants with IPF.

Detailed description:
This study was previously posted by Stromedix, Inc. In April, 2014, sponsorship of the trial was transferred to Biogen. The study drug name was changed from STX-100 to BG00011 and the study number was changed from STX-003 to 203PF201, to align with sponsor conventions.

Arms:
arm 1: Participants will receive 8 consecutive weekly doses of BG00011 arm 2: Participants will receive 8 consecutive weekly doses of placebo.

Interventions: intervention 1: BG00011 intervention 2: Placebo
Intervention descriptions: intervention 1: BG00011 will be administered at varying doses via subcutaneous (SC) injection intervention 2: Sterile normal saline (0.9% Sodium Chloride for Injection) via Subcutaneous (SC) injections.

Protocol document:
Prot_001.pdf: 
7 October 2009  
Stromedix–STX-003  
1 
 
PROTOCOL 
 
Title: 
Randomized, Double-Blind, Placebo-Controlled, 
Multiple Dose, Dose-Escalation Study of STX-100 in 
Patients with Idiopathic Pulmonary Fibrosis (IPF)  
Protocol Number: 
203PF201 (Formerly STX-003)  
Product: 
BG00011 (Formerly STX-100) 
Phase of Development: 
2a 
Sponsor: 
Biogen MA Inc. 
250 Binney Street 
Cambridge, MA 02142 
United States  
Date of Protocol: 
16 July 2015 
Version: 
4 
 
Final 
Supersedes previous version 3 dated 01 June 2015.




Protocol 203PF201 
Version 4 
Phase 2a Multiple-Dose IPF Protocol 
CONFIDENTIAL 
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TABLE OF CONTENTS 
1. 
SPONSOR INFORMATION .......................................................................................8 
2. 
LIST OF ABBREVIATIONS.......................................................................................9 
3. 
SYNOPSIS .................................................................................................................11 
4. 
INTRODUCTION ......................................................................................................22 
4.1. 
Background .................................................................................................................22 
4.2. 
Rationale for Clinical Use of BG00011......................................................................22 
4.3. 
Population To Be Studied ...........................................................................................23 
4.3.1. 
Diagnostic Criteria for IPF .........................................................................................24 
4.3.1.1. 
HRCT Imaging Criteria for UIP pattern .....................................................................26 
4.3.1.2. 
Surgical Lung Biopsy Criteria for UIP pattern ...........................................................26 
4.3.1.3. 
Treatment in IPF subjects on Approved Therapy .......................................................27 
4.3.2. 
TGF- Activation and v6 Expression in IPF .........................................................27 
4.3.3. 
Evaluating the Impact of BG00011 on Biomarkers in IPF .........................................28 
4.4. 
BG00011 Nonclinical Experience ..............................................................................29 
4.4.1. 
Functional Analysis of αvβ6 Integrin in β6 Null Mice ...............................................29 
4.4.2. 
Pharmacology Models ................................................................................................29 
4.4.3. 
Toxicology Summary .................................................................................................29 
4.4.4. 
BG00011 Pharmacokinetics .......................................................................................30 
4.5. 
Previous Experience in Humans .................................................................................30 
4.5.1. 
Safety and Tolerability ...............................................................................................30 
4.5.2. 
BG00011 Pharmacokinetics .......................................................................................31 
4.5.3. 
Immunogenicity ..........................................................................................................31 
4.6. 
Dose and Dose Interval Rationale ..............................................................................32 
4.7. 
Potential Risks of Human Use ....................................................................................33 
4.8. 
GCP Compliance Statement .......................................................................................34 
5. 
STUDY OBJECTIVES ..............................................................................................35 
5.1. 
Primary Objective: ......................................................................................................35 
5.2. 
Secondary Objectives: ................................................................................................35 
6. 
INVESTIGATIONAL PLAN .....................................................................................36 
6.1. 
Nomenclature for Study Periods and Study Days ......................................................36 


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6.2. 
Overall Study Duration  and Follow-up .....................................................................37 
6.2.1. 
Duration of Study .......................................................................................................37 
6.2.2. 
Screening ....................................................................................................................37 
6.2.3. 
Multiple-Dose Period ..................................................................................................37 
6.2.4. 
Follow-up Period ........................................................................................................38 
6.3. 
Discontinuation or Temporary Suspension of the Study ............................................38 
6.4. 
Blinding Procedure .....................................................................................................39 
7. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................40 
7.1. 
Inclusion Criteria ........................................................................................................40 
7.2. 
Exclusion Criteria .......................................................................................................41 
7.3. 
Withdrawal Criteria ....................................................................................................42 
8. 
INVESTIGATIONAL PRODUCT ............................................................................44 
8.1. 
Identity of Investigational Product .............................................................................44 
8.2. 
Reference Product .......................................................................................................44 
8.3. 
Drug Accountability ...................................................................................................44 
8.4. 
Drug Handling Guidelines ..........................................................................................44 
9. 
TREATMENT ............................................................................................................45 
9.1. 
Dosing Schedule .........................................................................................................45 
9.2. 
Study Medication Administration...............................................................................45 
9.3. 
Safety Monitoring and Dose Escalation .....................................................................45 
9.3.1. 
Safety Monitoring .......................................................................................................45 
9.3.1.1. 
Multiple-Dose Period ..................................................................................................45 
9.3.1.2. 
Follow-up Period ........................................................................................................45 
9.3.2. 
Dose Escalation ..........................................................................................................45 
9.4. 
Prior and Concomitant Medications ...........................................................................46 
9.5. 
Subject Compliance ....................................................................................................47 
10. 
SAFETY, PHARMACODYNAMICS, AND PHARMACOKINETICS 
ASSESSMENTS.........................................................................................................48 
10.1. 
Safety Assessments .....................................................................................................48 
10.1.1. 
Adverse Events ...........................................................................................................48 
10.1.2. 
Clinical Laboratory Tests ...........................................................................................48 
10.1.3. 
Pulmonary Function Tests ..........................................................................................48 


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10.1.4. 
Bronchoalveolar Lavage .............................................................................................49 
10.1.5. 
High Resolution Computed Tomography ...................................................................49 
10.1.6. 
Other Safety Assessments ...........................................................................................49 
10.2. 
Efficacy Assessments .................................................................................................50 
10.3. 
Pharmacodynamic Assessments .................................................................................50 
10.3.1. 
Peripheral Blood Biomarkers .....................................................................................50 
10.3.2. 
Bronchoalveolar Lavage .............................................................................................50 
10.4. 
Pharmacokinetic Assessments ....................................................................................50 
11. 
STUDY PROCEDURES AND SCHEDULE ............................................................52 
11.1. 
Subject Management ..................................................................................................52 
11.2. 
Timing of Visits and Missed Visits ............................................................................52 
11.3. 
Randomization ............................................................................................................53 
11.4. 
Screening ....................................................................................................................53 
11.5. 
Multiple-dose Treatment ............................................................................................53 
11.6. 
Follow-up Period ........................................................................................................54 
11.7. 
Early Termination .......................................................................................................54 
12. 
SCHEDULE OF EVENTS .........................................................................................55 
13. 
STATISTICS ..............................................................................................................60 
13.1. 
Analysis Populations ..................................................................................................60 
13.2. 
Statistical Analysis ......................................................................................................60 
13.2.1. 
Subject Accountability and Demographics ................................................................60 
13.2.2. 
Safety Analysis ...........................................................................................................60 
13.2.3. 
Pharmacodynamic Analyses .......................................................................................61 
13.2.4. 
Pharmacokinetic Analyses ..........................................................................................61 
13.2.5. 
Immunogenicity Analyses ..........................................................................................61 
13.3. 
Determination of Sample Size ....................................................................................61 
13.4. 
Interim Analysis ..........................................................................................................62 
14. 
ADVERSE EVENTS..................................................................................................63 
14.1. 
Adverse Event Definitions ..........................................................................................63 
14.1.1. 
Serious Pretreatment Event .........................................................................................63 
14.1.2. 
Adverse Event .............................................................................................................63 
14.1.3. 
Serious Adverse Event ................................................................................................63 


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14.2. 
Adverse Event Classification ......................................................................................64 
14.3. 
Documentation and Reporting of Adverse Events by Investigator ............................64 
14.4. 
Notification of Serious Adverse Events .....................................................................65 
14.4.1. 
Expectedness of Events ..............................................................................................65 
14.4.2. 
Suspected Unexpected Serious Adverse Reactions ....................................................65 
15. 
PROCEDURES FOR HANDLING SPECIAL CIRCUMSTANCES ........................66 
15.1. 
Medical Emergency ....................................................................................................66 
15.2. 
Emergency Contact .....................................................................................................66 
15.3. 
Emergency Identification of Study treatment .............................................................66 
15.4. 
Pregnancy ...................................................................................................................66 
15.5. 
Procedure for Death ....................................................................................................67 
16. 
ETHICS ......................................................................................................................68 
16.1. 
Institutional Review Board or Independent Ethics Committee ..................................68 
16.2. 
Ethical Conduct of the Study ......................................................................................68 
16.3. 
Subject Information ....................................................................................................68 
16.3.1. 
Informed Consent .......................................................................................................68 
16.3.2. 
Subject Data Protection ..............................................................................................68 
17. 
STUDY ADMINISTRATION ...................................................................................69 
17.1. 
Investigator Responsibilities .......................................................................................69 
17.2. 
Biogen Responsibilities ..............................................................................................69 
17.3. 
Data Quality Control and Quality Assurance .............................................................69 
17.4. 
Case Report Form Completion ...................................................................................70 
17.5. 
Retention of Study Records ........................................................................................70 
17.6. 
Confidentiality ............................................................................................................70 
17.7. 
Publication Policy .......................................................................................................71 
17.8. 
Direct Access to Source Data .....................................................................................71 
17.9. 
Protocol Amendments ................................................................................................71 
18. 
REFERENCES ...........................................................................................................72 
19. 
SIGNED AGREEMENT OF THE STUDY PROTOCOL .........................................75 
 


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LIST OF TABLES 
Table 1 
HRCT and Histopathological UIP Patterns and the Level of Confidence for 
the Diagnosis of IPF (Adapted from the ATS/ERS/JRA/ALAT Guidelines) ............25 
Table 2 
Dosing Cohorts ...........................................................................................................36 
Table 3 
Schedule of Events .....................................................................................................55 
 
LIST OF FIGURES 
Figure 1 
Subject Disposition During Study 203PF201 .............................................................21 
Figure 2 
v6–Mediated TGF- Activation and BG00011 Mechanism of Action .................23 
Figure 3 
Diagnostic Algorithm for IPF (Adapted from the ATS/ERS/JRA/ALAT 
Guidelines) ..................................................................................................................24 
Figure 4 
Simulation Plot of BG00011 After 13 Doses, Once Weekly Dosing .........................33 
 


Protocol 203PF201 
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1. 
SPONSOR INFORMATION 
Biogen MA Inc. 
250 Binney Street 
Cambridge, MA  02142 
United States 
 
Biogen Idec Research Limited 
Innovation House 
70 Norden Road 
Maidenhead, Berkshire  
SL6 4AY 
United Kingdom 
 
 
For 24-hour emergency medical support contact 
 
 
For urgent medical issues in which the study’s Medical Director should be contacted, please 
refer to the Study reference manual for complete contact information. 
 
Biogen MA Inc. may transfer any or all of its study-related responsibilities to a contract research 
organization (CRO) and other third parties; however, Biogen MA Inc. retains overall 
accountability for these activities. 


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2. 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
αvβ6 
alpha v beta 6 
AE 
adverse event 
ALAT 
Latin American Thoracic Association 
ALT 
alanine transaminase 
AST 
aspartate transaminase 
ATS 
American Thoracic Society 
AUC 
area under the concentration-time curve 
BAL 
bronchoalveolar lavage 
BG00011 
humanized anti-αvβ6 monoclonal antibody 
CBC 
complete blood count 
Cmax 
maximum observed concentration 
Col1A1 
collagen type 1 alpha 1 
CRF 
case report form 
DEFA1-3 
alpha defensins 
DLCO 
carbon monoxide diffusion capacity 
DSMB 
data safety monitoring board 
ECG 
electrocardiogram 
ERS 
European Respiratory Society 
FDA 
Food and Drug Administration 
FEV1 
forced expiratory volume over 1 second 
FU 
follow-up 
FVC 
forced (expiratory) vital capacity 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C antibody 
HIV 
human immunodeficiency virus 
HRCT 
high resolution computed tomography  
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 


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Abbreviation 
Definition 
IFN- 
interferon-gamma 
IPF 
idiopathic pulmonary fibrosis  
IRB 
institutional review board 
JRS 
Japanese Respiratory Society 
LAP 
latency-associated protein 
LLOQ 
lower limit of quantification 
MD 
Multiple-dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMP 
matrix metalloproteinase  
mRNA 
messenger RNA 
NOAEL 
no observable adverse effect level 
NOEL 
no observable effect level 
OPN 
osteopontin 
PAI-1 
plasminogen activator inhibitor-1 
PFT 
pulmonary function test 
PHI 
protected health information 
PK 
pharmacokinetic(s) 
SAE 
serious adverse event 
SC 
subcutaneous(ly) 
SP-A 
surfactant A 
SP-D 
surfactant D 
SUSAR 
suspected unexpected serious adverse reaction 
t1/2 
half-life 
TE 
Treatment-emergent 
TGF-β 
transforming growth factor-beta 
TIMP-1 
tissue inhibitor of metalloproteinase 1 
TLC 
total lung capacity 
UIP 
usual interstitial pneumonia 
WBC 
white blood cell 
 


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3. 
SYNOPSIS 
Title of study:  
Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Dose-Escalation Study of 
STX-100 in Patients with Idiopathic Pulmonary Fibrosis (IPF)  
Protocol number: 203PF201(Formerly STX-003) 
Sponsor:  
Biogen MA Inc. 
250 Binney Street 
Cambridge, MA  02142 
United States 
Contract research organization: 
 
 
 
Investigators and study centers:  
Approximately 15 centers in North America will participate. 
Phase: 2a 
Primary objective:  
 
To evaluate the safety and tolerability of subcutaneously (SC) administered multiple, 
escalating doses of BG00011 (humanized monoclonal antibody directed against the v6 
integrin, formerly known as STX-100) in subjects with IPF 
Secondary objectives:  
 
To estimate the pharmacokinetic (PK) parameters after the first dose and after the last dose 
of multiple, escalating doses of BG00011 in subjects with IPF 
 
To assess the immunogenicity of BG00011 in subjects with IPF  
 
To assess the effect of BG00011 on biomarkers isolated from bronchoalveolar lavage 
(BAL) and peripheral blood in subjects with IPF 
Study design: 
This is a multi-center, randomized, double-blind, placebo-controlled, multiple-dose, 
dose-escalation study designed to evaluate the safety, tolerability, PK, immunogenicity, and impact 
on BAL and peripheral blood biomarkers of BG00011 in subjects with IPF.  Approximately 
40 subjects will be enrolled into 5 sequential ascending dose cohorts.  All cohorts will include 8 


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subjects randomized to receive either BG00011 (6 subjects) or placebo (2 subjects).  The Data 
Safety Monitoring Board (DSMB) may require that additional subjects be included in a cohort if 
needed to better understand safety prior to dose escalation.   
The doses to be administered are shown below: 
Cohort 
Dose-level 
Number of Subjects 
BG00011 
Placebo 
1 
0.015 mg/kg 
6 
2 
2 
0.1 mg/kg 
6 
2 
3 
0.3 mg/kg 
6 
2 
4 
1.0 mg/kg 
6 
2 
5 
3.0 mg/kg 
6 
2 
Total Number of Subjects 
30 
10 
Subjects with clinical symptoms and features consistent with IPF prior to screening; forced vital 
capacity (FVC)  50% of predicted value; diffusing capacity of the lung for carbon monoxide 
(DLco), corrected for hemoglobin,  30% of predicted value; oxygen (O2) saturation > 90% at rest 
while breathing ambient air or receiving ≤ 2 L/minute of supplemental oxygen; residual 
volume  120% of predicted value; a ratio of the forced expiratory volume in 1 second (FEV1) to 
FVC  0.65 after the use of a bronchodilator on screening pulmonary function tests (PFTs); high 
resolution computed tomography (HRCT) consistent with usual interstitial pneumonia (UIP) 
pattern, and who meet the other inclusion/exclusion criteria are eligible to enroll in the study.  
Subjects with IPF who do not otherwise qualify for study eligibility may be rescreened at the 
discretion of the Principal Investigator.   
Concomitant medications: 
Subjects should not be receiving high dose corticosteroid (i.e., > 15 mg/day of prednisone or its 
equivalent), cytotoxic therapy (e.g., chlorambucil, azathioprine, cyclophosphamide, methotrexate), 
nintedanib (Ofev®), vasodilator therapy for pulmonary hypertension (e.g., bosentan), unapproved 
(e.g., interferon gamma, penicillamine, cyclosporine, mycophenolate, N-acetylcysteine), and/or 
investigational therapy for IPF while participating in this study, nor can they have received such 
within 5 half-lives of the agent prior to initial screening.   
Use of pirfenidone (Esbriet®) is permitted, provided that the subject has been on a stable dose for 
at least 4 weeks prior to randomization.   
Pirfenidone should be kept at a stable dose, if possible.  Dose decreases in response to adverse 
events are permitted and should be done in a manner consistent with the prescribing information 
for pirfenidone.  Dose increases of pirfenidone, including an increase back to baseline dose after a 
dose decrease, are prohibited. 
Following enrollment into the study, every attempt should be made to avoid changes in the 
subject’s drug regimen.  Exceptions would include episodes of infections requiring treatment 
(e.g., antibiotics or antiviral drugs), exacerbations of their underlying disease requiring 
immediate intervention, or any other situation requiring modification of the subject’s therapy for 
their safety at the discretion of the treating physician. 


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Study periods: 
Screening: 
Qualifying assessments including medical history, physical examination, vital signs, 12-lead 
electrocardiogram (ECG), and clinical laboratory tests including pregnancy testing (if applicable) 
and testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and 
hepatitis C (HCV) antibody will be performed within 5 weeks or 35 days (8 weeks or 56 days, for 
cohorts 4 and 5 only) prior to dosing.  Pulmonary function tests (PFTs), HRCT and BAL are also 
included as part of the screening process and must be performed within 5 weeks (35 days) prior to 
dosing in all cohorts.  It is recommended that the BAL and PFTs be performed after the 
subject has met the other inclusion criteria, including the screening HRCT.  Following 
confirmation of eligibility on a screening PFT, subjects will perform 1 additional PFT, which can 
be performed at any time up to and including Day 1 of the MD period (Day 1-MD) provided it is at 
least 1 day after the screening PFT, to establish their baseline lung function.  Screening 
assessments (e.g., clinical laboratory tests or PFTs) may be repeated if there are questionable 
results or if abnormalities are felt to be due to inherent variability of the test procedure.  If the 
subject must be rescreened for study entry, results from previous screening assessments may be 
used, as long as the screening windows for those assessments are met and all spirometry data used 
for subject qualification are derived from a single day.   
Upon fulfilling all of the inclusion and none of the exclusion criteria, subjects will be randomized 
to receive either BG00011 or placebo.  The subject will be instructed to return to the clinic on 
Day 1-MD for baseline, pre-dose evaluations and to ensure that they still qualify for the study by 
meeting all criteria with the exception of PFTs.  If a subject’s PFT values from the Screening visit 
meet the inclusion criteria, they should not be excluded from the study based upon their baseline 
PFT values.   
MD Period 
On Day 1-MD, the subject’s medical history, physical examination, inclusion/exclusion criteria, 
vital signs, oxygen saturation, and pregnancy status (if applicable) will be assessed, as well as 
blood samples collected for baseline laboratory, biomarker, PK, and antibody assessments.  The 
first dose of study treatment will then be administered and the subject will remain in the clinic for 
at least 8 hours for monitoring, with a PK sample obtained 8 hours following dosing.  The subject 
will be discharged with instructions to return to the clinic for follow-up visits on Days 2-MD, 
3-MD, and 5-MD for safety evaluations and PK sampling.   
Study treatment will be administered once weekly for 8 doses on Days 1-MD, 8-MD, 15-MD, 
22-MD, 29-MD, 36-MD, 43-MD, and 50-MD.  Prior to dosing on Days 8-MD, 15-MD, 29-MD, 
and 43-MD, a physical examination, vital signs, oxygen saturation, laboratory assessments, and PK 
blood draws will be performed, and then the study treatment will be administered.  On Days 
22-MD, 36-MD, and 50-MD, pre-dose vital signs and oxygen saturation will be performed and a 
trough PK level will be drawn prior to administration of study medication.  An ECG will be 
performed at the Day 15-MD visit, and PFTs will be performed at the Day 29-MD visit.  Serum for 
biomarkers will be obtained on Days 29-MD and 50-MD.  All subjects will be observed at the 
study center for a minimum of 30 minutes following dosing at each study visit, after which vital 
signs will be checked, instructions will be provided, and the subject will be discharged.  After the 
final (8th) dose of study treatment, Day 50-MD PK samples will be collected at 8 hours following 
dose administration, and the subject will be discharged with instructions for procedures during the 
FU period.   
FU Period 
After completing the MD period of the study, each subject will be monitored for an additional 12 


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weeks (8 weeks for subjects in cohorts 4 or 5).  Study days during the FU period will be dependent 
on when the last dose of study medication is administered, which will be Day 50 if all doses are 
received on schedule.  The day of the last dose of study treatment is designated as Day 1 of the FU 
period (Day 1-FU).  Visits during the FU period will occur on Days 2-FU, 3-FU, 5-FU, 8-FU, 
15-FU, 22-FU, 29-FU, 57-FU (8 weeks), and, for those in cohorts 1 to 3 only, 85-FU.  Vital signs, 
PK levels, and monitoring of health status will be assessed at each visit.  An ECG will be 
performed on Days 8-FU and 85-FU (Day 57-FU for cohorts 4 and 5).  The Day 8-FU visit 
assessments will include BAL, PFTs and HRCT; the BAL should be performed between Day 3-FU 
and Day 8-FU, and PFTs and HRCT scan should be performed within 21 days following 
administration of the last dose of study medication.  If performed on the same day, HRCT and 
PFTs must be performed prior to BAL.  If a BAL is performed first, at least 2 days must have 
elapsed before PFTs or HRCT are performed.  Serum for assessment of antibody development to 
BG00011 will be collected on Days 29-FU (all cohorts) and 57-FU (cohorts 4 and 5 only) or 85-FU 
(cohorts 1 to 3).  Serum for biomarkers will be obtained and additional safety assessments will be 
performed on Days 8-FU, 29-FU, 57-FU, and 85-FU (12 weeks after the final dose for cohorts 1 to 
3 only), which is the final study visit.  At Day 57-FU the Investigator will also record their 
assessment of the subject’s respiratory status relative to baseline: better, worse or the same (for 
cohorts 4 and 5 only).  Following this visit, the subject will be discharged from study participation.   
Subjects who discontinue prior to Day 8-FU should undergo all assessments described for the 
Day 8-FU visit, if possible, including BAL, PFTs, and HRCT that are to be performed within a 
specified period after the subject receives their last dose of study medication.  Also, samples should 
be collected for serum pregnancy testing (if applicable) and anti-BG00011 antibody testing.  
Subjects who discontinue subsequent to having Day 8-FU assessments performed should have 
Day 85-FU (Day 57-FU for cohorts 4 and 5) assessments performed at the time of termination.  
Dose escalation: 
This study comprises 5 sequential escalating dose cohorts.  The independent DSMB will review 
unblinded safety and PK data from each dose cohort.  The DSMB members’ responsibilities and 
the process for data review are described in the DSMB charter.   
Dose escalation will be based on the DSMB’s review of PK and safety data through Day 15 for the 
initial 4 subjects in each cohort administered BG00011 or placebo (3:1, respectively) in each 
cohort.  Safety assessments will include a review of adverse events (AEs), vital signs, physical 
examination, clinical laboratory tests, ECG, and pulse oximetry from these visits.  Therefore, it is 
anticipated that the DSMB will convene approximately 7-8 weeks after the first 4 subjects in the 
previous cohort are dosed, in order to allow for compilation and evaluation of the data.  A DSMB 
meeting will not occur for the final cohort except on an ad hoc basis, as no dose escalation decision 
needs to be made.   
After reviewing the safety and PK data, the DSMB may recommend initiation of the next dose 
escalation cohort.  Alternatively, the DSMB may recommend monitoring subjects within a cohort 
for a longer period of time or reviewing safety and PK data from additional subjects prior to 
recommending dose escalation.  If indicated, another cohort may be enrolled at a dose level similar 
to or lower than prior cohorts (see the section below titled “Criteria for stopping or temporarily 
suspending the study”). 
Updated safety (including BAL, PFTs, and HRCT results) and PK information on all participants 
will be provided in each subsequent DSMB data package.  Additionally, information on serious 
adverse events (SAEs) will be provided to the DSMB on an ongoing basis throughout the study. 


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Criteria for stopping or temporarily suspending the study: 
 
If 2 subjects receiving study medication in a cohort experience an SAE that is considered 
possibly or probably related to study treatment by the Investigator, the DSMB will 
determine whether the nature, severity, or the number of AEs would permit 1 of the 
following: 
o Continuation of enrollment and dosing of the current cohort 
o Initiation of the next dose escalation cohort 
o Enrollment of an additional 4 subjects in that cohort 
o Enrollment of an intermediate dose cohort 
o Discontinuation of dose escalation 
 
If 2 subjects receiving study medication in a cohort experience a clinically significant, 
sustained decrease from baseline respiratory status as determined by both the Investigator 
and the DSMB. 
 
If 2 subjects receiving study medication demonstrate a significant increase in matrix 
metalloproteinase (MMP)-12 levels between baseline and post-treatment BAL assessments 
as determined by the DSMB. 
 
Exposure as measured by area under the concentration-time curve (AUC) is greater than 
the comparable systemic exposure at the no observable effect level observed in nonhuman 
primate studies. 
 
The DSMB feels there is a need to temporarily suspend subject enrollment until further 
assessments are made. 
Inclusion criteria: 
 
1. 
Male or female subjects, 45 to 84 years old, inclusive.   
 Subjects 18 to 44 years of age are eligible if they have a histopathological 
diagnosis of UIP based upon a surgical lung biopsy in the appropriate clinical 
setting, and meet all other inclusion/exclusion criteria. 
2. 
Clinical features consistent with IPF prior to screening (based on the American Thoracic 
Society/European Respiratory Society/Japanese Respiratory Society/Latin American 
Thoracic Association consensus criteria for the diagnosis of IPF. 
3. 
FVC ≥ 50% of predicted value. 
4. 
DLco (corrected for hemoglobin)  30% predicted value.   
5. 
Oxygen saturation > 90% at rest by pulse oximetry while breathing ambient air or 
receiving  2 L/minute of supplemental oxygen 
6. 
Residual volume  120% predicted value. 
7. 
Ratio of FEV1 to FVC ≥ 0.65 after the use of a bronchodilator. 
8. 
Other known causes of interstitial lung disease have been excluded (e.g., drug toxicities, 
environmental exposures, connective tissue diseases).   
9. 
HRCT image fulfills the criteria for ‘UIP pattern’ (surgical lung biopsy not required.  The 
radiographic diagnosis of UIP must be confirmed on the screening HRCT by an 
independent central radiologist experienced in the evaluation of interstitial lung diseases.   
10. 
If the HRCT image does not fulfill the criteria for ‘UIP pattern’ a surgical lung biopsy is 


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necessary for the diagnosis of IPF (lung biopsy performed prior to screening is 
acceptable).  In this setting the HRCT image must meet the criteria for ‘possible UIP 
pattern’ and the lung biopsy must fulfill the histopathological criteria for either ‘UIP 
pattern’ or ‘probable UIP pattern’.  If the HRCT image fulfills the criteria for UIP pattern, 
results from a surgical lung biopsy are not necessary.  If however, a lung biopsy has been 
performed, it must fulfill the histopathological criteria for either ‘UIP pattern’ or ‘probable 
UIP pattern’ with the appropriate HRCT correlate. 
11. 
Adequate bone marrow and liver function as demonstrated by: 
 Hemoglobin ≥ 10 g/dL  
 White blood cell (WBC) count ≥ 3.00 x 103/µL 
  Neutrophils ≥ 1.50 x 103/µL 
  Platelets ≥ 80 x 103/µL 
 Total bilirubin ≤ 1.5 mg/dL 
 Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times upper 
limit of normal 
12. 
Subject has a life expectancy of at least 12 months. 
13. 
Subject must provide written informed consent.  If required by local law, candidates must 
also authorize the release and use of protected health information (PHI).   
14. 
Female subjects must be surgically sterile, postmenopausal (minimum 1 year without 
menses), or agree to use 1 or more of the following forms of contraception from the time 
of signing the ICF through 12 weeks following the last injection of study medication: 
hormonal (i.e., oral, transdermal, implant, or injection); double barrier (i.e., condom, 
diaphragm with spermicide); intrauterine device; vasectomized partner (6 months 
minimum); or abstinence.  Male subjects must also agree to use 1 or more of the above 
forms of birth control for either themselves or their partner(s), as appropriate, from the 
time of signing the ICF through 12 weeks following the last injection of study medication.  
Exclusion criteria:  
1. Unable to perform PFTs. 
2. Findings that are diagnostic of a condition other than UIP on surgical lung biopsy (performed 
either before or after screening), HRCT imaging, transbronchial lung biopsy, or BAL.   
3. Currently receiving high dose corticosteroid, cytotoxic therapy (e.g., chlorambucil, 
azathioprine, cyclophosphamide, methotrexate), nintedanib (Ofev®), vasodilator therapy for 
pulmonary hypertension (e.g., bosentan), unapproved (e.g., INF-, penicillamine, cyclosporine, 
mycophenolate, N-acetylcysteine), and/or investigational therapy for IPF or administration of 
such therapeutics within 5 half-lives of the agent prior to initial screening in this study. 
A current dose of  15 mg/day of prednisone or its equivalent is acceptable if it is anticipated 
that the dose will remain stable during enrollment. 
Pirfenidone (Esbriet®) is permitted, provided that the subject has been on a stable dose for at 
least 4 weeks prior to randomization and it is anticipated that the dose will remain stable during 
enrollment. 
4. History of malignancy, including carcinoma during the preceding 5 years.  However, subjects 
with a history of excised or treated basal cell, squamous cell, or cervical carcinomas are 
eligible to participate in this study. 


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5. Significant cardiac disease (e.g., New York Heart Association Class 3 or 4; myocardial 
infarction within the past 6 months; unstable angina; coronary angioplasty or coronary artery 
bypass graft within the past 6 months; or uncontrolled atrial or ventricular cardiac 
arrhythmias). 
6. Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) within 3 
months prior to screening. 
7. Significant reaction to previous injection of a monoclonal antibody. 
8. Female who is pregnant or breastfeeding. 
9. Male or female planning a pregnancy during the duration of this study.  A serum pregnancy 
test will be performed on all female subjects of childbearing potential. 
10. Fever (body temperature > 38°C) or symptomatic viral or bacterial infection within 1 week 
prior to screening.   
11. Positive test for HBsAg, HCV antibody (if confirmed by HCV RNA), or HIV antibody at 
screening. 
12. Drug or alcohol abuse (as defined by the Investigator).   
13. Treatment with another investigational drug, investigational device, or approved therapy for 
investigational use within 5 half-lives of the agent prior to screening in this study 
14. End-stage fibrotic disease requiring organ transplantation within 6 months.   
15. Any other condition that, in the opinion of the Investigator, may compromise the safety or 
compliance of the subject or would preclude the subject from successful completion of the 
study. 
Test product, dose, and mode of administration:  
BG00011 is a humanized monoclonal antibody (human immunoglobulin G1 subgroup III, kappa) 
and consists of 2 heavy and 2 light chains connected by inter-chain disulfide bonds.  The molecular 
weight of the intact BG00011 molecule is 148,000 daltons, including its carbohydrate moiety.   
BG00011 is provided as a lyophilized drug product in vials, must be kept refrigerated (2C to 8C), 
be protected from light and may not be frozen. 
BG00011 will be administered as an SC injection (e.g., in the upper arm) after reconstitution.  Each 
BG00011 lyophilized drug product vial is reconstituted using 1.3 mL of preservative-free sterile 
water for injection/USP to yield a final concentration of 75.0 mg/mL.   
Additional dilution is required for lower doses and instructions for dilution will be provided to the 
pharmacy.  The reconstituted drug product does not contain a preservative and should be used 
within 4 hours. 
Dose cohorts are 0.015, 0.1, 0.3 1.0 mg/kg, and 3.0 mg/kg.  Placebo subjects will be injected with 
normal saline (0.9% Sodium Chloride for Injection) at a volume equivalent to that administered if 
they were assigned to BG00011.  An injection volume greater than 1.5 mL should be split between 
2 injection sites.   
Study medication for each subject will be double-blinded.  An unblinded pharmacist not associated 
with the operational conduct of the study will prepare appropriate medication for injection 
according to the provided randomization code and instructions for preparation.  This individual 
will keep the randomization code locked in a secure place and will not disclose the code to anyone 
else (except for a quality assurance person in the pharmacy) or discuss subject information with 
study staff.  In the event of a medical emergency, when knowledge of the subject’s treatment 


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18 
assignment may influence the subject’s clinical care, the Investigator or designee may open the 
code-break envelope for the subject experiencing the emergency.  
Duration of study 
In cohorts 1 to 3, each subject’s participation in the study will be for approximately 24 weeks (~5.5 
months), i.e., up to 5 weeks to perform screening/entry evaluations, followed by 7 weeks of 
double-blind study dosing (8 doses) and a Follow-up period of 12 weeks.  For subjects in cohorts 4 
or 5, the subject’s participation in the study will be approximately 23 weeks (~5.5 months), i.e., up 
to 8 weeks to perform screening/entry evaluations, followed by 7 weeks of double-blind study 
dosing (8 doses) and Follow-up period of 8 weeks.   
Reference therapy, dose, and mode of administration  
Sterile normal saline (0.9% Sodium Chloride for Injection) administered as an SC injection.   
Criteria for evaluation: 
Safety  
- 
AEs, including injection site assessment 
- 
SAEs 
- 
Physical examinations  
- 
Vital signs 
- 
12-lead ECGs  
- 
Hematology: complete blood count (CBC) with differential and platelet counts.  CBC 
includes red blood cells, WBCs, hemoglobin, hematocrit, mean corpuscular volume, mean 
corpuscular hemoglobin, and mean corpuscular hemoglobin concentration 
- 
Serum chemistry: albumin, alkaline phosphatase, ALT, AST, blood urea nitrogen, calcium, 
chloride, carbon dioxide, creatinine, direct bilirubin, gamma-glutamyl transferase, glucose, 
lactate dehydrogenase, magnesium, phosphorus, potassium, sodium, total bilirubin, total 
cholesterol, total protein, uric acid 
- 
Urinalysis: including determination of the presence of protein, glucose, ketones, occult 
blood, and WBCs by dipstick, with microscopic examination if indicated 
- 
Pulse oximetry 
- 
PFTs: 2 PFTs will be performed during the screening period (within 5 weeks prior to 
dosing).  The first of these tests (Screening) will be performed both before and after 
bronchodilator administration to determine if the subject qualifies for the study, whereas 
the second, will be performed without bronchodilator administration and will establish the 
subject’s baseline values; these 2 PFT sets must be performed on separate days during the 
screening period up to and including Day 1-MD.  PFTs will also be performed at the 
Day 29 visit during the MD period and within 21 days after receiving the last dose of study 
medication.   
- 
PFT parameters include: 
FVC 
FEV1 
TLC (total lung capacity)  


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DLCO 
Residual volume 
PFTs may be performed prior to but not within 2 days after BAL. 
- 
BAL: BAL will be performed during the screening period (within 5 weeks prior to dosing) 
and between Day 3-FU and Day 8-FU after receiving the last dose of study medication.  
Analysis of the BAL macrophage MMP-12 mRNA levels (which are increased when 
macrophages are activated) will be performed at a central laboratory. 
- 
HRCT scans will be performed during screening to establish the pre-dosing pattern and 
extent of disease.  HRCT will be repeated within 21 days after receiving the last dose of 
study medication during the MD period.  An independent central radiologist experienced in 
the evaluation of diffuse lung diseases and blinded to treatment assignment will read all 
scans during the MD and FU periods.   
Formation of antibodies to BG00011:  
Blood samples for immunogenicity testing will be collected during screening, on Day 1-MD prior 
to dosing, and at Day 29-FU and Day 85-FU (Day 57-FU for subjects in cohorts 4 or 5) after the 
last dose of study medication 
Pharmacokinetics:  
Blood samples for standard PK measures will be collected prior to the initial dose of study 
treatment (screening and pre-dose on Day 1) and 8 hours after dosing.  Samples for PK measures 
will be collected at the same times, relative to dosing, at the final administration of study treatment 
on Day 50-MD (i.e., prior to dosing and 8 hours after dosing).  Additional PK samples will be 
collected on Days 2-MD and 2-FU (24 hours following dosing), Days 3-MD and 3-FU (72 hours 
after dosing), Days 5-MD and 5-FU, and Days 8-MD and 8-FU at approximately the same time of 
day.  Trough serum levels (samples obtained prior to dosing) will be obtained weekly during the 
dosing period.  PK samples will also be obtained during all subsequent follow-up visits for 
subjects, i.e., Days 15-FU, 22-FU, 29-FU, 57-FU and 85 FU (cohorts 1 to 3, only). 
PK parameters include: 
- 
Cmax (maximum observed concentration) 
- 
Time to reach Cmax 
- 
Area under the concentration-time curve from time zero (just prior to dose) to the last 
measurable concentration 
- 
Area under the concentration-time curve from time zero to infinity 
- 
Area under the concentration-time curve from time zero (time of dosing) to tau (within a 
dosing interval) 
- 
Terminal elimination rate constant 
- 
t½ (elimination half-life) 
- 
Clearance (unadjusted for bioavailability) 
- 
Volume of distribution (unadjusted for bioavailability) 
Efficacy 
There are no efficacy objectives in this study. 
Pharmacodynamics  
Blood samples for blood biomarkers will be collected at screening and on Days 1-MD, 29-MD, 
50-MD, 8-FU, 29-FU, 57-FU, and for subjects in cohorts 1 to 3 only, 85-FU.   


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Peripheral blood biomarkers may include, but are not limited to the following:  
- 
MMP-7 
- 
Osteopontin  
- 
Tissue inhibitor of metalloproteinase 1  
- 
Collagen type 1 alpha1  
- 
Surfactant A  
- 
Alpha defensins (DEFA1-3) 
BAL will be performed during screening and between Day 3-FU and Day 8-FU, and analyses of 
BAL fluid and cell pellet will be performed at a central laboratory.  Biomarkers, which may 
include mRNA levels for plasminogen activator inhibitor-1 and osteopontin, as well as protein 
levels for phosphorylated SMAD, will be measured in macrophages isolated from BAL.  
Additional biomarkers may be added prior to the initiation of analysis and will be included in the 
statistical analysis plan.   
Statistical methods: 
 
Data for BG00011 treated subjects will be grouped by dose cohort.  Data for all placebo subjects, 
regardless of dosing cohort, will be treated as 1 group.  Exposure to study treatment and reasons for 
discontinuation of study treatment will be tabulated, and demographics will be presented using 
descriptive statistics (i.e., mean, standard deviation, median, and range).  Safety variables will be 
tabulated and presented for all subjects who receive BG00011 or placebo.  AEs will be coded using 
the Medical Dictionary for Regulatory Activities (MedDRA) version 10.1 or higher.  The incidence 
of treatment-emergent AEs (TEAEs) will be presented by system organ class and preferred term.  
TEAEs will also be presented by severity and relationship to study treatment.  For each treatment 
group, descriptive statistics will be used to summarize and present subject demographics, vital 
signs, and clinical laboratory parameters within each protocol-specified visit.   
Shift tables will be presented for selected laboratory parameters.  Physical examination results, 
oxygen saturation, PFT results and ECG parameters will be presented in listings.  The incidence of 
antibodies to BG00011 will be tabulated by treatment group and dose cohort for each subject.  
Listing of individual subject serum BG00011 concentrations, actual blood sampling times, and PK 
parameters as well as graphs of concentration versus time will be prepared by dose cohort.  Serum 
concentrations and PK parameters will be summarized through descriptive statistics and compared 
among dosing cohorts (and to placebo) using mixed effects models.  Dose proportionality will be 
assessed following log-transformation and dose normalized AUC and Cmax will be analyzed using 
mixed modeling.  Exploratory exposure-response relationship will be evaluated post-hoc and as 
applicable for both safety and pharmacodynamics to assist with determining the appropriate dosing 
regimen for BG00011 in this clinical setting. 
BAL and peripheral blood biomarkers will be tabulated and presented for all BG00011 subjects 
within a dose cohort (or placebo).  Changes from baseline in BAL and blood biomarkers will be 
compared among treatment groups and to the placebo group. 
Interim Analysis: An administrative interim analysis may be performed on all subject data up to 
and including the Day 8-FU visit for the last subject in cohort 4.  The interim analysis will provide 
safety, PK, and PD information to aid in internal (Biogen MA Inc) decision-making only and will 
not affect the study design of the current protocol. 


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Figure 1 
Subject Disposition During Study 203PF201 


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4. 
INTRODUCTION 
4.1. 
Background 
BG00011 (formerly known as STX-100) [anti-alpha v beta 6 [αvβ6] monoclonal antibody] 
previously in development by Stromedix, Inc, is currently being developed by Biogen MA Inc, 
as a novel therapeutic for patients with idiopathic pulmonary fibrosis (IPF).  In fibrotic disease, 
active transforming growth factor-beta (TGF-β) is thought to be critical to the initiation and 
maintenance of fibrosis.  BG00011 blocks the binding of αvβ6 to the latent form of TGF-β, 
thereby inhibiting its activation in response to tissue injury or inflammation.  The clinical 
development plan for BG00011 is designed to demonstrate that inhibition of TGF- activation 
by BG00011 in patients with idiopathic pulmonary fibrosis (IPF) can prevent or reduce alveolar 
epithelial injury and the progression of fibrosis, resulting in preservation of pulmonary function.  
The objective of this Phase 2a study is to evaluate the safety, tolerability, pharmacokinetics (PK), 
immunogenicity, and impact on bronchoalveolar lavage (BAL) and peripheral blood biomarkers 
of multiple doses of BG00011 in subjects with IPF.   
4.2. 
Rationale for Clinical Use of BG00011  
There is a strong rationale for targeting the TGF-β pathway as a means of inhibiting fibrosis.  
The TGF-β cytokine is central to the initiation and maintenance of fibrosis, a pathological 
process characterized by the replacement of diseased tissue with excess extracellular matrix, 
leading to organ scarring and failure [Bartram and Speer 2004; Border and Noble 1994; Shihab 
1995; Yamamoto 1993; Yamamoto 1996].  TGF-β is synthesized as a latent precursor protein 
that is cleaved and secreted with the N-terminal latency-associated protein (LAP) non-covalently 
associated with the mature active C-terminal TGF-β cytokine (Figure 2).  This complex cannot 
bind to the TGF-β receptor and is not biologically active.   
A critical regulator of TGF- activation is the v6 integrin, which binds to LAP, leading to 
localized activation of this cytokine [Munger 1999].  The v6 integrin is expressed at low or 
undetectable levels in healthy adult tissues; but is highly upregulated on epithelial cells during 
tissue injury and fibrosis [Breuss 1995; Breuss 1993; Häkkinen 2000; Trevillian 2004; Zambruno 
1995].  By blocking the binding of v6 to latent TGF-, anti-v6 antibodies (including 
BG00011) prevent TGF- activation and inhibit the development of tissue fibrosis.  By 
inhibiting local activation of TGF- only in v6-expressing tissues, BG00011 offers a 
potentially safer alternative to systemic inhibition of TGF- in diseases where the v6 integrin 
is upregulated.   


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Figure 2 
v6–Mediated TGF- Activation and BG00011 Mechanism of Action 
 
4.3. 
Population To Be Studied 
Idiopathic pulmonary fibrosis is a chronic, progressive, and fibrosing disease of the lungs that 
typically strikes the middle aged and elderly (median age at diagnosis: 66 years) with male 
predominance (1.5 to 1.7:1) [Adamali and Maher 2012; King 2011].  The annual incidence of 
IPF is between 4.6 and 16.3 per 100,000 and has been rising over the past 30 years [Adamali and 
Maher 2012].  The most common symptoms that patients with IPF experience include shortness 
of breath, cough, and fatigue.   
Idiopathic pulmonary fibrosis is diagnosed based on the appearance of usual interstitial 
pneumonia, either histologically after lung biopsy or via high resolution computerized 
tomography) [American Thoracic Society/European Respiratory Society 2002].  Usual interstitial 
pneumonia is characterized by spatially and temporally heterogeneous fibrosis with 
honeycombing within the lung.  The disease pattern is often diffuse with loci of fibrosis, often at 
varying stages, interspersed with healthy tissue.  The median survival for patients is between 2.5 
and 3.5 years after diagnosis of IPF, with a 5-year survival rate of 20% [Adamali and Maher 
2012]. 
Progression of disease is the rule in untreated patients, and there are currently 2 approved 
therapies, pirfenidone and nintedanib, that slow progression of, but do not arrest, the disease.  
Other agents including nonspecific anti-inflammatory or immunosuppressive therapy have been 
tried.  Corticosteroids alone, as well as azathioprine or cyclophosphamide as single agents or in 
combination with corticosteroids have shown limited efficacy.  Methotrexate, colchicine, 
penicillamine, and cyclosporine have been combined with prednisone with poor results.  In 2 
large Phase 3 studies, interferon gamma-1b (IFN-1b) treatment did not improve lung function or 
survival [Raghu 2004].   


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4.3.1. 
Diagnostic Criteria for IPF 
The diagnostic criteria for IPF used in this protocol are based on the evidence-based guidelines 
developed by the American Thoracic Society/European Respiratory Society/Japanese 
Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) joint task 
force for the diagnosis and management of IPF (originally presented May 17, 2010 at the ATS 
Conference, New Orleans, LA) [Raghu 2011]. 
IPF is a chronic, progressive fibrosing interstitial pneumonia of unknown cause occurring in 
adults and limited to the lungs.  Evidence of restrictive physiology and impaired gas exchange on 
pulmonary function studies is characteristic, although pulmonary function may be normal or only 
slightly impaired in the early stages of IPF.  The diagnosis requires histopathological and/or 
radiologic evidence of usual interstitial pneumonia (UIP) and exclusion of other causes of 
idiopathic interstitial pneumonia and interstitial lung diseases (e.g., occupational or 
environmental exposures, drug toxicities, and collagen vascular diseases).   
The ATS/ERS/JRS/ALAT joint task force concludes that in the appropriate clinical setting the 
diagnosis of IPF is ascertained if the high resolution computed tomography (HRCT) image 
fulfills the criteria for ‘UIP pattern’ (surgical lung biopsy is not required).  However, if the 
HRCT image differs from the ‘UIP pattern’, a surgical lung biopsy is necessary and specific 
combinations of the HRCT and histopathological criteria are required for the diagnosis of IPF 
(lung biopsy performed prior to screening is acceptable) (Figure 3).  The task force also 
recommends that multidisciplinary discussions between pulmonologists, radiologists, and 
pathologists experienced in the diagnosis of interstitial lung diseases be conducted to increase the 
accuracy of the diagnosis of IPF. 
Figure 3 
Diagnostic Algorithm for IPF (Adapted from the ATS/ERS/JRA/ALAT 
Guidelines) 
Suspected IPF
Identifiable Causes for ILD?
HCRT
No
Surgical Biopsy
Multi-disciplinary 
Discussion
IPF/Not IPF per Tables
IPF
Not IPF
Possible UIP
Inconsistent with UIP
UIP
Probable UIP/Possible
Non-classifiable 
fibrosis
UIP
Yes
Not UIP
 


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It is imperative that all subjects enrolled in Study 203PF201 have a confident diagnosis of 
IPF.  Therefore, only subjects who meet the following HRCT imaging and/or lung histology 
criteria for UIP (in addition to the other inclusion/exclusion criteria) are eligible for this 
study: 
 The HRCT image fulfills the criteria for ‘UIP pattern’ (i.e., surgical lung biopsy is not 
required [see Figure 3 and Table 1]).   
 If the HRCT image does not fulfill the criteria for ‘UIP pattern’ a surgical lung biopsy 
is necessary for the diagnosis of IPF (lung biopsy performed prior to screening is 
acceptable).  In this setting the HRCT image must meet the criteria for ‘possible UIP 
pattern’ and the lung biopsy must fulfill the histopathological criteria for either ‘UIP 
pattern’ or ‘probable UIP pattern’ (see Table 1 and histopathological criteria 
summarized below). 
Therefore only patients who meet the radiographic and/or histopathological criteria 
resulting in ‘Yes’ for the ‘Diagnosis of IPF (see Table 1) are eligible to participate in this 
study; i.e., individuals with a ‘probable’ or ‘possible’ diagnosis of IPF do not qualify for 
this study.  However, if the HRCT and/or surgical lung biopsy are repeated due to concern 
regarding the adequacy of the HRCT technique or sampling error on the lung biopsy, the patient 
may be rescreened for eligibility at the Principal Investigator’s discretion. 
Table 1 
HRCT and Histopathological UIP Patterns and the Level of Confidence for 
the Diagnosis of IPF (Adapted from the ATS/ERS/JRA/ALAT Guidelines) 
HRCT Pattern 
Histopathology Pattern 
Diagnosis of IPF?
1 
UIP 
UIP 
Probable UIP 
Possible UIP 
Non-classifiable fibrosis
2 
Yes 
Not UIP 
No 
Possible UIP 
UIP 
Probable UIP 
Yes 
Possible UIP 
Non-classifiable fibrosis2 
Probable
3 
Not UIP 
No 
Inconsistent with UIP 
UIP 
Possible3 
Probable UIP 
Possible UIP 
Non-classifiable fibrosis2 
Not UIP 
No 
1 The accuracy of the diagnosis increases with the use of a multidisciplinary team decision, particularly where 
radiologic and histopathological patterns are discordant. 
2 Non-classifiable fibrosis: a pattern of fibrosis that does not meet the criteria for UIP pattern or other idiopathic 
interstitial pneumonias. 
3 Multidisciplinary discussion among interstitial lung disease experts should include the potential for sampling error 
on lung biopsy and re-evaluation of the adequacy of the HRCT technique. 


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4.3.1.1. 
HRCT Imaging Criteria for UIP pattern 
As described in the recently updated ATS/ERS/JRA/ALAT guidelines for the diagnosis and 
management of IPF, HRCT lung imaging can be categorized in descending order of confidence 
as: 1) UIP pattern, 2) possible UIP pattern, or 3) inconsistent with UIP pattern. 
If the following four features are present, the HRCT image fulfills the criteria for ‘UIP pattern’:  
 Subpleural, basal predominance  
 Reticular abnormalities 
 Honeycombing with or without traction bronchiectasis  
 Absence of features listed as inconsistent with UIP pattern  
If each of these features is present except for honeycombing, then the HRCT image fulfills the 
criteria for ‘possible UIP pattern’.   
Conversely, if any of the following 7 features are present, the HRCT would be classified as 
‘inconsistent with UIP pattern’: 
 Upper or mid lung predominance 
 Peri-bronchovascular predominance 
 Extensive ground glass abnormality (extent greater than reticular abnormality) 
 Profuse micro nodules (bilateral, predominantly upper lobes) 
 Discrete cysts (multiple, bilateral, away from areas of honeycombing) 
 Diffuse mosaic attenuation/air trapping (bilateral, in 3 or more lobes) 
 Consolidation in bronchopulmonary segments(s)/lobe(s) 
4.3.1.2. 
Surgical Lung Biopsy Criteria for UIP pattern  
If the HRCT image does not fulfill the criteria for the ‘UIP pattern’, then a surgical lung biopsy 
is necessary and assessment of both the HRCT image and lung histopathology is required for the 
diagnosis of IPF (lung biopsy performed prior to screening is acceptable).  Histopathology on 
surgical lung biopsy can be categorized in descending order of confidence as: 1) UIP pattern, 2) 
probable UIP pattern, 3) possible UIP pattern, or 4) not UIP pattern.   
The histopathological criteria for ‘UIP pattern’ include the following four features:  
 Evidence of marked fibrosis/architectural distortion, +/- honeycombing in a 
predominantly subpleural/paraseptal distribution 
 Presence of patchy involvement of lung parenchyma by fibrosis  
 Presence of fibroblast foci 
 Absence of features against a diagnosis of UIP, suggesting an alternate diagnosis 
The histopathological criteria for ‘probable UIP pattern’ are summarized below:  
 Evidence of marked fibrosis/architectural distortion, +/- honeycombing  


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 Absence of either patchy involvement or fibroblastic foci, but not both 
 Absence of features against a diagnosis of UIP, suggesting an alternate diagnosis 
OR 
 Honeycomb changes only  
 This scenario usually represents end-stage fibrotic lung disease where honeycombed 
segments have been sampled but where a UIP histopathological pattern might be present 
in other areas.  Such areas are usually represented by overt honeycombing on HRCT and 
can be avoided by pre-operative targeting of biopsy sites away from these areas using 
HRCT. 
The histopathological criteria for ‘not UIP pattern’ include any of the six following features: 
 Hyaline membranes  
  Can be associated with acute exacerbation of IPF. 
 Organizing pneumonia  
 Can be associated with acute exacerbation of IPF. 
 An isolated or occasional granuloma and/or a mild component of organizing pneumonia 
pattern may rarely be coexisting in lung biopsies with an otherwise UIP pattern. 
 Granulomas 
 An isolated or occasional granuloma and/or a mild component of organizing pneumonia 
pattern may rarely be coexisting in lung biopsies with an otherwise UIP pattern. 
 Marked interstitial inflammatory cell infiltrate away from honeycombing 
 Predominant airway centered changes 
 Other features suggestive of an alternate diagnosis 
4.3.1.3. 
Treatment in IPF subjects on Approved Therapy 
Cohorts 4 and 5 will allow for the inclusion of subjects who are on a stable dose of pirfenidone 
(Esbriet®).  Pirfenidone is one of two approved therapies for patients with IPF and 
understanding the safety, PK and PD of BG00011 in subjects on background pirfenidone 
treatment is important.   
4.3.2. 
TGF- Activation and v6 Expression in IPF 
In human disease, the αvβ6 integrin is highly upregulated in alveolar epithelium from patients 
with IPF and other inflammatory and/or fibrotic lung diseases, such as scleroderma, 
radiation-induced fibrosis, and bronchiolitis obliterans with organizing pneumonia [Breuss 1995; 
Sheppard 2003].  TGF- is also abundant on the alveolar epithelium in focal areas of fibrosis 
[Broekelmann 1991; Khalil 1996], and the pattern of αvβ6 expression mirrors that of TGF- in 
lung tissue from patients with IPF.  Moreover, progression of pulmonary fibrosis has been 
observed in patients with higher levels of TGF- [Bartram and Speer 2004].  TGF- plays a 
central role in the initiation and maintenance of fibrosis and both 6 null mice [Hahm 2007; Ma 


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2003; Munger 1999; Pittet 2001; Puthawala 2008], and mice treated with αvβ6-blocking 
antibodies[Hahm 2007; Horan 2008; Puthawala 2008] are protected from fibrosis in lung and 
kidney models of disease.  Therefore, selective inhibition of the αvβ6/TGF- pathway by 
BG00011, a novel anti-fibrotic agent directed against the αvβ6 integrin, may be an effective 
treatment for IPF and other fibrotic diseases.   
4.3.3. 
Evaluating the Impact of BG00011 on Biomarkers in IPF 
Identification of biomarkers associated with IPF has been challenging, in part due to limited 
access to lung tissue, heterogeneity of disease involvement, and safety concerns related to 
performing repeated lung biopsies in this patient population.   
Increased blood levels of surfactant proteins-A and -D (SP-A and SP-D), KL-6, soluble Fas 
ligand (sFasL), and -defensins (DEFA1-3), have been reported in patients with IPF and other 
interstitial lung diseases [Greene 2002; Kuwano 2002; Mukae 2002; Yokoyama 1998].  Elevated 
serum levels of SP-A and SP-D were predictive of mortality risk, and KL-6 (MUC1 mucin, a 
sensitive indicator of damage to alveolar type II cells) has been reported to be correlated with 
disease activity and prognosis in patients with IPF.  Plasma -defensin levels were inversely 
correlated with arterial oxygen tension and lung function (i.e., percent predicted forced vital 
capacity (FVC), forced expiratory volume over 1 second [FEV1], and carbon monoxide diffusion 
capacity [DLCO]) suggesting they may be useful as biomarkers of disease severity and activity in 
patients with IPF [Mukae 2002].  Two matrix metalloproteinases (MMPs), MMP-1 and MMP-7, 
implicated in the pathogenesis of IPF, were significantly increased in lung tissue, BAL fluid, and 
blood from patients with IPF, suggesting that increased levels in peripheral blood reflect the 
pathologic changes in the IPF alveolar micro-environment [Rosas 2008].  Moreover, serum 
MMP-7 concentrations in patients with subclinical IPF were significantly elevated when 
compared with control patients; while significantly lower than observed in patients with 
symptomatic IPF.  Finally, serum MMP-7 was negatively correlated with lung function as 
measured by percent predicted FVC and DLCO.   
MMP-12 is a matrix-degrading metalloproteinase that is expressed only by tissue macrophages 
and placental trophoblasts.  Since MMP-12 is highly upregulated in alveolar macrophages of 6-
null mice and is mechanistically linked to the mild empysema-like histologic changes observed 
in later life [Morris 2003], the doses where m3G9 (the murine form of BG00011) treatment 
induced expression of this marker of macrophage activation were determined.  Analysis of lung 
mRNA collected from mice treated with m3G9 (0.3 to 30 mg/kg/week for 4 weeks) revealed a 
significant increase in MMP-12 mRNA expression at doses of 10 and 30 mg/kg, but not at doses 
of 3 mg/kg or lower [Horan 2008].  All of the molecular changes induced by high-dose m3G9 
treatment (including MMP-12) reverted to baseline after discontinuing m3G9 treatment.   
In contrast to mice, no significant change in the expression of inflammatory genes (including 
MMP-12) or proteins in lung tissue and BAL fluid were observed in cynomolgus monkeys 
receiving vehicle, 0.1 or 10 mg/kg BG00011 weekly for 4 weeks (see BG00011 Investigator’s 
Brochure).  Conversely, the expression of TGF--inducible proteins tissue inhibitor of 
metalloproteinase 1, plasminogen activator inhibitor-1, and endothelin-1 were significantly 
downregulated in BAL fluid in both the 0.1 and 10 mg/kg BG00011 treatment groups, 
suggesting that the antibody was attenuating profibrotic activity at these doses.  This observation 


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suggests that in monkeys, as in mice, the potential inhibition of profibrotic activity by BG00011 
is seen at lower doses than the potential proinflammatory activity. 
In summary, BAL and peripheral blood biomarkers may provide a means to assess treatment-
associated changes in IPF patients in a minimally invasive manner. 
4.4. 
BG00011 Nonclinical Experience 
4.4.1. 
Functional Analysis of αvβ6 Integrin in β6 Null Mice 
Evaluation of β6 null mice has provided direct insight into the function of the αvβ6 integrin and 
its role in disease (see BG00011 Investigator’s Brochure).  The β6 null mice are protected from 
fibrosis in models of lung, liver, and kidney disease.  The 6 null mice develop mild pulmonary 
inflammation, defined as minimally increased numbers of lymphocytes, neutrophils, eosinophils, 
and enlarged vacuolated (foamy) macrophages in the lungs and in bronchoalveolar lavage (BAL) 
fluid. In later life, the 6 null mice develop mild emphysema-like histologic changes that are 
functionally correlated with increased matrix-metalloproteinase (MMP)-12 expression and 
directly linked to inactivation of TGF-[Morris 2003]. 
4.4.2. 
Pharmacology Models 
Nonclinical pharmacology studies to determine the biological activity and safety of BG00011 
have been conducted using a murine anti-αvβ6 antibody (m3G9) in mice and BG00011 in 
cynomolgus monkeys.  Several rodent models of fibrosis show increased αvβ6 expression in 
epithelial cells of the affected tissue, including the lung, kidney, and liver.  Efficacy of m3G9 has 
been demonstrated in models of lung, kidney, and liver fibrosis, as measured by markers of 
tissue fibrosis, including collagen production and accumulation of -smooth muscle actin (SMA) 
positive fibroblasts [Hahm 2007; Horan 2008; Puthawala 2008](BG00011 Investigator’s 
Brochure).   
4.4.3. 
Toxicology Summary 
Nonclinical toxicology studies of up to 26-weeks in duration were conducted in the CD-1 mouse 
and cynomolgus monkey.  Murine studies used m3G9, while monkey studies used BG00011.  
BG00011 had no treatment-related safety pharmacology changes (CNS, cardiovascular and 
respiratory).  In the SC repeat-dose mouse studies with m3G9, treatment-related findings were 
observed in the lung and the injection site.  Pulmonary findings of greater lung weights and 
histologic changes of alveolar histiocytosis (greater number and increased size of macrophages), 
minimal inflammation, and necrosis were observed at 10 mg/kg.  Alveolar histiocytosis and 
inflammation were partially reversed after the recovery period.  At the injection sites (1 and 
10 mg/kg), a higher incidence of minimal to mild fibroplasia was observed compared with the 
control group.  After repeat-dose of m3G9, the NOAEL was 1 mg/kg in mice.   
In the SC repeat-dose studies in monkeys, clinical signs of watery feces and dry skin were 
observed.  The only other treatment-related finding was minimal to mild alveolar macrophage 
infiltration in the 1 and 10 mg/kg dose groups.  The histologic change in the lung was observed 
at a lower incidence and was reversible.  The NOAEL in monkeys was 10 mg/kg. 


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In repeat-dose mouse studies with m3G9, low incidences of tumors (bronchoalveolar adenoma, 
lymphoma) were observed sporadically and in a non-dose-related manner.  Spontaneous 
bronchoalveolar lesions have been reported in mouse historical control data.  No tumors were 
noted in monkey studies.   
In the mouse reproductive development studies, m3G9 did not have any effect on the male or 
female fertility, and there was no treatment-related malformation in fetuses. 
4.4.4. 
BG00011 Pharmacokinetics 
In mice, systemic exposure of m3G9 after SC administration was highly not dose-proportional.  
BG00011 exhibited a high bioavailability following SC administration in the monkey.  In 
a 26-week monkey toxicity study, BG00011 showed a slightly greater than dose-proportional 
increase in systemic exposure.   
4.5. 
Previous Experience in Humans 
A Phase 1 randomized, double-blind, placebo-controlled, single-dose, dose escalation study has 
conducted to evaluate the safety, tolerability, and PK of SC administered BG00011 in healthy 
volunteers.  Forty subjects were enrolled into 5 ascending dose cohorts (6 active: 2 placebo 
subjects per cohort) to receive a single SC dose of BG00011 (range: 0.003 mg/kg to 0.3 mg/kg) 
or placebo (saline injection) and were monitored for 3 months after dosing.  Dose escalation was 
based on the data safety monitoring board’s (DSMB’s) review of safety and PK data through 
Day 8 post-dose.  One subject in the placebo group was prematurely withdrawn from the study at 
14 days post-dosing due to non-compliance with the protocol. 
The mean age across all dose cohorts was 32 years of age (range: 19 to 48 years), the majority of 
enrolled subjects were white (90%; 36 of 40 subjects), and slightly more than half of the subjects 
were female (58%; 23 of 40 subjects).  The placebo group and 5 BG00011 dose cohorts were 
generally balanced for baseline demographic characteristics including age, gender, height, 
weight, and body mass index. 
4.5.1. 
Safety and Tolerability 
Single SC doses of BG00011 from 0.003 to 0.3 mg/kg were well tolerated in this healthy 
volunteer study.  In general, subjects in the Phase 1 trial reported mild to moderate adverse 
events (AEs).  There were no SAEs, including deaths, or premature discontinuations related to an 
AE.  No dose-related trends were noted for any safety measures, including AEs, and no 
dose-related changes were noted in physical examinations, vital signs, or clinical laboratory 
parameters.  Pulmonary function parameters remained stable after dosing across all dose levels.   
Seventy-nine AEs were reported by 29 subjects during the study.  Twenty-one of 30 subjects 
(70%) who received BG00011 and 8 of 10 subjects (80%) who received placebo reported an AE.   
Four subjects experienced 7 AEs assessed as possibly related to study treatment.  Three of these 
AEs were reported in 2 BG00011-treated subjects (abdominal discomfort and hyperhidrosis in 1 
subject and pain in the extremity in 1 subject).  Four AEs were reported as possibly related to 
study treatment in 2 subjects who received placebo (diarrhea, gastroenteritis, and rash in 1 
subject and pedal flushing in another subject).   


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The majority of AEs were mild to moderate in severity.  Severe events included headache 
(1 subject in the placebo group); elevated blood potassium (1 subject in the placebo group); neck 
muscle spasms, neck pain, and headache (1 subject in the 0.01 mg/kg dose group); and elevated 
serum cholesterol (1 subject in the 0.03 mg/kg dose cohort).  None of the events were considered 
related to study treatment, all resolved, and the incidence of these AEs did not appear related to 
dose. 
PFTs were monitored frequently during the Phase 1 study; i.e., 3 assessments prior to dosing and 
then at 1, 4, and 12 weeks following administration of study treatment.  PFT parameters 
remained stable following dosing across all dose levels.  AEs related to the respiratory system 
were mild to moderate in severity, and assessed as unrelated to study treatment.  Similarly, 
changes in respiratory rate and pulse oximetry were unremarkable following dosing in all 
cohorts. 
In summary, single SC doses of BG00011 over the range of 0.003 to 0.3 mg/kg were well 
tolerated in the healthy volunteer population with the incidence and severity of AEs, or changes 
in physical examination, vital signs, or clinical laboratory parameters comparable to the placebo 
treated subjects.   
4.5.2. 
BG00011 Pharmacokinetics 
The PK parameters of a single SC dose of BG00011 administered to healthy volunteers was 
evaluated with assessment of serum levels for 12 weeks following administration of study 
treatment.  The lower limit of quantitation for the validated enzyme-linked immunosorbent assay 
in humans is 25 ng/mL.   
Serum levels were not quantifiable in the initial 2 dose cohorts (0.003 and 0.01 mg/kg).  For 
cohorts 3 to 5 (0.03, 0.1, or 0.3 mg/kg doses, respectively), the data fit a one compartment first 
order, no lag time, first order elimination model well.  For cohorts 3 to 5, in which serum levels 
were above the limit of quantitation, the AUC from time 0 to time of the last measurable 
concentration and Cmax exhibited dose proportionality (R2 = 0.99 and 0.98, respectively).  Based 
on the PK parameters from cohorts 4 and 5 (i.e., 0.1 and 0.3 mg/kg), the serum t½ of BG00011 
was approximately 6 days, and serum concentrations peaked at approximately 5 days.  The 
maximum observed exposure was 319,693 ng*hr/mL.   
4.5.3. 
Immunogenicity 
In the Phase 1 study, serum was collected predose and at 1, 2, and 3 months following 
administration of study treatment and tested for the presence of anti-BG00011 antibodies using a 
validated electrochemiluminescence  method.  Three of 30 subjects receiving BG00011 tested 
positive for anti-BG00011 antibodies.  Two subjects (0.01 and 0.03 mg/kg dose cohorts) tested 
positive at the 2- and 3-month time points, and these antibodies were neutralizing.  The 
remaining subject (0.1 mg/kg dose cohort) tested positive at all time points (including predose); 
however, the samples from this subject were negative in the neutralization assay.  Neither the 
incidence nor severity of AEs appeared to be correlated with the presence of antibodies to 
BG00011, and no hypersensitivity reactions were observed in the Phase 1 study.   


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4.6. 
Dose and Dose Interval Rationale 
The selection of once weekly SC dosing of BG00011 at doses of 0.015, 0.1, 0.3, 1.0, and 
3.0 mg/kg in this study is based on the nonclinical toxicology, PK, and research studies as well 
as the Phase 1 study in healthy volunteers.   
In the nonclinical models of lung, liver and kidney fibrosis, the efficacious dose range for m3G9 
was 0.2 mg/kg to 10 mg/kg with an effective dose 50% range of 0.2 to < 1 mg/kg (Table 3 in the 
Investigator Brochure).  In the 3-month GLP toxicology studies, the NOEL in non-human 
primates receiving BG00011 was 10 mg/kg (see Section 4.4.3).   
BG00011 was well tolerated in healthy volunteers following single SC doses ranging from 0.003 
mg/kg to 0.3 mg/kg.  The lowest dose of BG00011 that provided reliable estimates of PK 
parameters was 0.1 mg/kg (assay LLOQ = 25 ng/mL).  Based on PK parameters from the 0.1 and 
0.3 mg/kg dose cohorts, the serum half-life of BG00011 was approximately 6 days, supporting 
once weekly administration (see Section 4.5.2).  In addition, the serum BG00011 AUC exhibited 
dose proportionality in the 3-month monkey toxicology study (up to 10 mg/kg) and in humans 
(up to the highest dose tested, 0.3 mg/kg).   
Using the PK parameters from the 0.3 mg/kg dose group in the healthy volunteer study, 
modeling was performed to predict the steady-state PK parameters following once weekly 
administration for 5 different doses (range: 0.03 mg/kg to 3.0 mg/kg).  The modeling and 
simulations with once weekly SC dosing indicate that steady-state BG00011 concentrations were 
achieved by the 8th dose (i.e., 2 months) and accumulation was estimated to be approximately 
2.5 fold (Figure 4).  At the highest anticipated dose of 3.0 mg/kg in the current study, the 
estimated AUC exposure ratios (monkey/human) indicate that the human exposure is 
approximately 7 times lower than the estimated exposure at the NOAEL in the 6-month monkey 
toxicology study.  Therefore, repeat dosing to subjects in this protocol is anticipated to achieve 
tolerable, steady-state levels for all dose cohorts that encompass the anticipated therapeutic 
range. 
The initial dose of 0.015 mg/kg was selected to provide BG00011 exposure in humans 
comparable to the AUC observed at the NOAEL in the 3-month murine toxicology study.  After 
the first dose increase, dose escalation will proceed by half-log increments between dose cohorts.  
In summary, the dose escalation regimen selected for this study is 8 once weekly SC 
administrations of BG00011 at doses of 0.015, 0.1, 0.3, 1.0 and 3.0 mg/kg. 


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Figure 4 
Simulation Plot of BG00011 After 13 Doses, Once Weekly Dosing 
  
 
4.7. 
Potential Risks of Human Use 
BG00011 was well tolerated following administration of a single dose in the Phase 1 healthy 
volunteer study.  No dose-related trends were noted for AEs, vital signs, physical examination, or 
laboratory safety parameters including PFTs (see Section 4.5.1).   
As with any protein therapeutic, BG00011 may be immunogenic.  Two of 30 subjects (7%) 
receiving BG00011 in the Phase 1 healthy volunteer study tested positive following negative 
pre-dose testing for anti-BG00011 antibodies.  There was no observed correlation between the 
incidence and severity of AEs with the presence of anti-BG00011 antibodies, nor were any 
hypersensitivity reactions observed.  Ultimately, the presence of neutralizing antibodies may 
affect the safety, PK, or efficacy profile of BG00011.   
Based on data from animal studies, there is a risk that repeated doses of BG00011 may induce 
pulmonary inflammation.  Therefore, exposure to BG00011 in this study will be limited to drug 
exposure below which no observable effects have been reported in the 6-month monkey 
toxicology study (Section 4.4.3).  Subjects’ respiratory status will be monitored throughout the 
study (e.g., clinical symptoms and signs, pulse oximetry and PFTs), while status of lung disease 
will be monitored by HRCT.  In addition, β6 knockout mice developed emphysema with an 
associated increase in MMP-12 levels.  As such, MMP-12 mRNA levels (which are increased 
when macrophages are activated) will be assessed in pulmonary macrophages isolated from BAL 
in an attempt to validate this test as a safety biomarker for use with this agent.   
In the repeat-dose mouse studies with m3G9, low incidences of tumors (bronchoalveolar 
adenoma, lymphoma) were observed sporadically and in a non-dose-related manner.  
Spontaneous bronchoalveolar lesions have been reported in mouse historical control data 
(Section 4.4.3).  An increased incidence of benign and malignant tumors has also been reported 
in 6 null mice [Ludlow 2005].  No tumors were noted in monkeys treated for 3 or 6 months 
with BG00011 or after 4 months of recovery.  The relevance of the reported tumor findings in 
mice to humans is not clear. 


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The reproductive toxicity of BG00011 in humans is unknown.  Women of childbearing potential 
must use contraception from the time of signing the informed consent form (ICF) through the 
end of the 12-week follow-up (FU) period and must be informed that there are potential hazards 
to the fetus should pregnancy occur during treatment.  Male subjects must also agree to use 
contraception for either themselves or their partners throughout the duration of the study. 
BG00011 is an investigational therapy and human exposure has been limited to date.  Thus, there 
may be unforeseen or unknown risks for this patient population either from administration of 
BG00011 alone or in combination with other medications the patient may be receiving.   
The potential risks of lung inflammation, emphysema, transplant rejection and malignancy based 
on the nonclinical findings described above will be conveyed to subjects in the ICF.  The ICF 
also identifies procedures that may pose a risk to the subject beyond the potential systemic 
effects of administering BG00011.  Risks due to phlebotomy may include bruising, localized 
bleeding or swelling, infection, syncope, and pain associated with the procedure.  Risks 
associated with SC injection of study treatment may include pain, erythema, swelling, 
tenderness, inflammation, and/or bruising at the site of injection.  Injection site reactions were 
not observed in the Phase 1 healthy volunteer study.  An HRCT exposes the patient to a small 
dose of radiation.  The risks of BAL include sore throat, cough, hoarseness, fever, chills, nausea, 
vomiting, myalgia, hypoxia, bronchospasm, infection, arrhythmias, hypotension, and/or 
myocardial infarction (rare).  Aspiration may occur if the patient has not fasted adequately prior 
to the procedure.   
4.8. 
GCP Compliance Statement 
This trial will be conducted in compliance with all instructions, regulations, and agreements in 
this protocol and in the applicable International Conference on Harmonisation (ICH) and Good 
Clinical Practice (GCP) guidelines, and must also be conducted in accordance with local 
regulations.   


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5. 
STUDY OBJECTIVES  
5.1. 
Primary Objective:  
 To evaluate the safety and tolerability of subcutaneously (SC) administered multiple, 
escalating doses of BG00011 in subjects with IPF 
5.2. 
Secondary Objectives:  
 To estimate the pharmacokinetic (PK) parameters after the first dose and after the last 
dose of multiple, escalating doses of BG00011 in subjects with IPF 
 To assess the immunogenicity of BG00011 in subjects with IPF  
 To assess the effect of BG00011 on biomarkers isolated from bronchoalveolar lavage 
(BAL) and peripheral blood in subjects with IPF 


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6. 
INVESTIGATIONAL PLAN 
This is a multi-center, randomized, double-blind, placebo-controlled, multiple-dose, 
dose-escalation study designed to evaluate the safety, tolerability, PK, immunogenicity, and 
impact on BAL and peripheral blood biomarkers of BG00011 in subjects with IPF.  
Approximately 40 subjects will be enrolled into 5 sequential ascending dose cohorts.  All 
cohorts will include 8 subjects randomized to receive either BG00011 (6 subjects) or placebo 
(2 subjects).  The DSMB may require that additional subjects be included in a cohort if needed to 
better understand safety prior to dose escalation.   
Doses to be administered are shown in Table 2: 
Table 2 
Dosing Cohorts  
Cohort 
Dose 
Number of Subjects 
BG00011 
Placebo 
1 
0.015 mg/kg 
6 
2 
2 
0.1 mg/kg 
6 
2 
3 
0.3 mg/kg 
6 
2 
4 
1.0 mg/kg 
6 
2 
5 
3.0 mg/kg 
6 
2 
Total Number of Subjects 
30 
10 
Subjects with clinical symptoms and features consistent with IPF prior to screening, FVC  50% 
of predicted value; DLco, corrected for hemoglobin,  30% of predicted value; oxygen (O2) 
saturation > 90% at rest while breathing ambient air or receiving ≤ 2 L/minute of supplemental 
oxygen; residual volume  120% of predicted value; a ratio of the forced expiratory volume in 1 
second (FEV1) to FVC  0.65 after the use of a bronchodilator on screening pulmonary function 
tests (PFTs); HRCT consistent with UIP pattern, and who meet the other inclusion/exclusion 
criteria are eligible to enroll in the study.  Subjects with IPF who do not otherwise qualify for 
study eligibility may be rescreened at the discretion of the Principal Investigator. 
6.1. 
Nomenclature for Study Periods and Study Days 
Days for the MD period are designated with an “MD” and days for the FU period are designated 
with an “FU”.  
 Day 1-MD is the day the subject receives the first dose during the MD period of the 
study. 
 Day 1-FU is first day of the follow-up period, which should coincide with the day of 
last dose during the MD period (Day 50-MD).   
See the Schedule of Events in Table 3 which illustrates the sequence of study visits and treatment 
periods. 


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6.2. 
Overall Study Duration  and Follow-up 
6.2.1. 
Duration of Study 
In cohorts 1 to 3, each subject’s participation in the study will be for approximately 24 weeks 
(~5.5 months), i.e., up to 5 weeks to perform screening/entry evaluations, followed by 7 weeks 
of double-blind study dosing (8 doses) and a Follow-up period of 12 weeks.  For cohorts 4 and 5,  
the subject’s participation in the study will be for approximately 23 weeks (~5.5 months), i.e., up 
to 8 weeks to perform screening/entry evaluations, followed by 7 weeks of double-blind study 
dosing (8 doses) and Follow-up period of 8 weeks.   
6.2.2. 
Screening 
Subjects will undergo screening assessments within 5 weeks or 35 days (8 weeks or 56 days, for 
cohorts 4 and 5 only) prior to dosing.  Pulmonary function tests (PFTs), HRCT and BAL are also 
included as part of the screening process and must be performed within 5 weeks (35 days) prior 
to dosing in all cohorts.  Qualifying assessments including medical history, physical 
examination, vital signs, 12-lead electrocardiogram (ECG), oxygen saturation, PFTs (before and 
after bronchodilator administration), HRCT, and clinical laboratory tests including pregnancy 
testing (if applicable) and testing for human immunodeficiency virus (HIV), hepatitis B surface 
antigen (HBsAg), and hepatitis C (HCV) antibody will be performed.  It is recommended that 
the BAL and PFTs be performed after the subject has met the other inclusion criteria, 
including the screening HRCT.  Following confirmation of eligibility on a screening PFT, 
subjects will perform 1 additional set of PFTs without bronchodilator administration to establish 
their baseline lung function which can be performed at any time up to and including Day 1-MD 
of the study provided it is at least 1 day after the screening PFT.  Screening assessments (e.g., 
clinical laboratory assessments or PFTs) may be repeated if there are questionable results or if 
abnormalities are felt to be due to inherent variability of the test procedure.  If a subject must be 
rescreened for study entry, results from previous screening assessments may be used, as long as 
the screening windows for those assessments are met and all spirometry data used for subject 
qualification are derived from a single day.   
Upon fulfilling all of the inclusion and none of the exclusion criteria, subjects will be 
randomized to receive either BG00011 or placebo.  Subjects will be instructed to return to the 
clinic on Day 1-MD for baseline, pre-dose evaluations and to ensure that they still qualify for the 
study by meeting all criteria with the exception of PFTs.  If a subject’s Screening PFT values 
meet the inclusion criteria, they should not be excluded from the study based upon their baseline 
PFT values.   
6.2.3. 
Multiple-Dose Period 
On Day 1-MD the subject’s medical history, physical examination, inclusion/exclusion criteria, 
vital signs, oxygen saturation, and pregnancy status (if applicable) will be assessed, as well as 
blood samples collected for baseline laboratory, biomarker, PK, and antibody assessments.  The 
first dose will be administered and the subject will be observed at the study center for at least 8 
hours for monitoring and laboratory tests.  A PK sample will be collected at 8 hours after dosing.  
The subject will then be discharged with instructions to return to the study center for follow-up 


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visits on Days 2-MD, 3-MD, 5-MD, and at each of the weekly dosing visits for safety 
evaluations and PK sampling. 
Study treatment will be administered weekly on Days 1-MD, 8-MD, 15-MD, 22-MD, 29-MD, 
36-MD, 43-MD, and 50-MD, for a total of 8 doses.  Prior to dosing on Days 1-MD, 8-MD, 15-
MD, 29-MD, and 43-MD, a physical examination, oxygen saturation, vital signs, laboratory 
assessments, and a PK blood draw will be performed, and then the study medication will be 
administered.  On Days 22-MD, 36-MD and 50-MD, pre-dose vital signs and oxygen saturation 
will be obtained, and a trough PK level will be drawn prior to administration of study 
medication.  Serum for biomarkers will be obtained on Days 29-MD and 50-MD, and other 
assessments (e.g., ECG) will be performed as indicated in the Schedule of Events (Table 3) 
Following dosing at each study visit, subjects will be observed at the study center for a minimum 
of 30 minutes, vital signs will be checked, instructions will be given, and the subject will be 
discharged. 
After administration of the final (8th) dose of study treatment in the MD period (Day 50-MD), 
PK samples will be collected at 8 hours, and the subject will be discharged with instructions for 
procedures during the FU period.  
Except for the first and eighth (last) doses, there are no scheduled interim visits between dosing 
days, but subjects should be assessed if there are clinical concerns.   
6.2.4. 
Follow-up Period  
After completing the MD period of the study, each subject will be followed up for an additional 
12 weeks (8 weeks for subjects in cohorts 4 or 5).  Study days during the follow-up period will 
be dependent on when the last dose of study medication is administered.  The day of the last dose 
of study treatment is designated as Day 1 of the FU period (Day 1-FU).  Visits during the FU 
period will occur on Days 2-FU, 3-FU, 5-FU, 8-FU, 15-FU, 22-FU, 29-FU, 57-FU (8 weeks), 
and, for those in cohorts 1 to 3 only, 85-FU. 
Vital signs, PK levels, and monitoring of health status will be assessed at each visit.  The BAL 
should be performed between Day 3-FU and Day 8-FU, and PFTs and HRCT scan should be 
performed within 21 days following administration of the last dose of study medication.  If 
performed on the same day, HRCT and PFTs must be performed prior to BAL.  If a BAL is 
performed first, at least 2 days must have elapsed before PFTs and HRCT are performed.  Serum 
for assessment of antibody development to BG00011 will be collected on Days 29-FU (all 
cohorts) and 57-FU (cohorts 4 and 5 only) or 85-FU (cohorts 1 to 3).  Serum for biomarkers will 
be obtained and additional safety assessments will be performed on Days 8-FU, 29-FU, 57-FU, 
and 85-FU (12 weeks after the final dose for cohorts 1 to 3 only), which is the final study visit.  
At Day 57-FU the Investigator will also record their assessment of the subject’s respiratory status 
relative to baseline: better, worse or the same (for cohorts 4 and 5 only).  Following this visit, the 
subject will be discharged from study participation. 
6.3. 
Discontinuation or Temporary Suspension of the Study 
Biogen MA Inc. may terminate this study at any time for safety or administrative reasons.  
Biogen MA Inc. will terminate the study if the occurrence of AEs or other findings suggests an 
unacceptable risk to the health of the subjects.   


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Criteria for stopping or temporarily discontinuing the study include: 
1. If 2 subjects receiving study medication in a cohort experience an SAE that is considered 
possibly or probably related to the study treatment by the Investigator, the DSMB will 
determine whether the nature, severity, or the number of AEs would permit 1 of the 
following: 
 Continuing enrollment and dosing of the current cohort 
 Initiation of the next dose escalation cohort 
 Enrollment of an additional 4 subjects in that cohort 
 Enrollment of an intermediate dose cohort 
 Discontinuation of dose escalation 
2. If 2 subjects receiving study medication in a cohort experience a clinically significant, 
sustained decrease from baseline respiratory status as determined by both the Investigator 
and the DSMB. 
3. If 2 subjects receiving study medication demonstrate a significant increase in MMP-12 
levels between baseline and post-treatment BAL assessments as determined by the 
DSMB. 
4. Exposure as measured by AUC is greater than the comparable systemic exposure at the 
NOEL observed in nonhuman primate studies. 
5. The DSMB feels there is a need to temporarily suspend subject enrollment until further 
assessments are made. 
6.4. 
Blinding Procedure 
This study is double-blinded.  The study execution contract research organization, site investigators, 
site staff, and subjects will remain blinded throughout the entirety of the study with the exception of 
designated pharmacy staff and other key individuals as listed in the unblinding plan.  An unblinded 
pharmacist at each site, not associated with the operational conduct of the study, will prepare 
appropriate medication for injection according to the provided unblinded randomization code and 
instructions for preparation.  This individual will keep the unblinded code locked in a secure place 
and will neither disclose the code to anyone else (except for an unblinded quality assurance person to 
monitor the pharmacy) nor discuss the subjects with site staff.  Members of the DSMB will be 
unblinded to review safety and available PK data, to assess safety and tolerability, and to make 
informed decisions regarding dose escalation.   
An administrative interim analysis may be performed on all subject data up to and including the 
Day 8-FU visit for the last subject in cohort 4.  The analysis will include a review of unblinded data 
that will be limited to a core unblinded team as specified in the unblinding plan. 
See Section 15.3 for a description of unblinding procedures in case of a medical emergency.  If a 
subject’s treatment assignment is unblinded accidentally, this should be noted in the study file 
and reported to the Sponsor.  The subject should remain in the study and continue the 
protocol-specified dosing and follow-up evaluations. 


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7. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
7.1. 
Inclusion Criteria 
To be eligible to participate in this study, candidates must meet the following eligibility criteria 
at Screening: 
1. Consenting male or female subjects, 45 to 84 years old, inclusive.   
 Subjects 18 to 44 years of age are eligible if they have a histopathological 
diagnosis of UIP based upon a surgical lung biopsy in the appropriate clinical 
setting, and meet all other inclusion/exclusion criteria.   
2. Clinical features consistent with IPF prior to screening (based on the 
ATS/ERS/JRS/ALAT consensus criteria for the diagnosis of IPF [see Section 4.3.1]).   
3. FVC ≥ 50% of predicted value. 
4. DLco (corrected for hemoglobin) ≥ 30% predicted value.   
5. Oxygen saturation > 90% by pulse oximetry while breathing ambient air at rest or 
receiving 2 L/minute of supplemental oxygen.   
6. Residual volume  120% predicted value. 
7. Ratio of FEV1 to FVC ≥ 0.65 after the use of a bronchodilator. 
8. Other known causes of interstitial lung disease have been excluded (e.g., drug toxicities, 
environmental exposures, connective tissue diseases).   
9. HRCT image fulfills the criteria for ‘UIP pattern’ (surgical lung biopsy not required [see 
Section 4.3.1]).  The radiographic diagnosis of UIP must be confirmed on the screening 
HRCT by an independent central radiologist experienced in the evaluation of interstitial 
lung diseases.   
10. If the HRCT image does not fulfill the criteria for ‘UIP pattern’ a surgical lung biopsy is 
necessary for the diagnosis of IPF (lung biopsy performed prior to screening is 
acceptable).  In this setting the HRCT image must meet the criteria for ‘possible UIP 
pattern’ and the lung biopsy must fulfill the histopathological criteria for either ‘UIP 
pattern’ or ‘probable UIP pattern’ (see Section 4.3.1).  If the HRCT image fulfills the 
criteria for UIP pattern, results from a surgical lung biopsy are not necessary.  If however, 
a lung biopsy has been performed, it must fulfill the histopathological criteria for either 
‘UIP pattern’ or ‘probable UIP pattern’ with the appropriate HRCT correlate.   
11. Adequate bone marrow and liver function as demonstrated by: 
 Hemoglobin ≥ 10 g/dL  
 White blood cell (WBC) count ≥ 3,000/mm3 
 Neutrophils ≥ 1,500/mm3 
 Platelets ≥ 80,000/mm3 


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 Total bilirubin ≤ 1.5 mg/dL 
 Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times upper 
limit of normal 
12. Subject has a life expectancy of at least 12 months. 
13. Subject must provide written informed consent.  If required by local law, candidates must 
also authorize the release and use of protected health information (PHI).   
14. Female subjects must be surgically sterile, postmenopausal (minimum 1 year without 
menses), or agree to use 1 or more of the following forms of contraception from the time 
of signing the ICF through 12 weeks following the last injection of study medication: 
hormonal (i.e., oral, transdermal, implant, or injection); double barrier (i.e., condom, 
diaphragm with spermicide); intrauterine device; vasectomized partner (six months 
minimum); or abstinence.  Male subjects must also agree to use 1 or more of the above 
forms of birth control for either themselves or their partner(s), as appropriate, from the 
time of signing the ICF through 12 weeks following the last injection of study 
medication. 
7.2. 
Exclusion Criteria 
Candidates will be excluded from study entry if any of the following exclusion criteria exist at 
Screening: 
1. Unable to perform PFTs. 
2. Findings that are diagnostic of a condition other than UIP on surgical lung biopsy 
(performed either before or after screening) HRCT imaging, transbronchial lung biopsy, 
or BAL 
3. Currently receiving high dose corticosteroid, cytotoxic therapy (e.g., chlorambucil, 
azathioprine, cyclophosphamide, methotrexate), nintedanib (Ofev®), vasodilator therapy 
for pulmonary hypertension (e.g., bosentan), unapproved (e.g., IFN-, penicillamine, 
cyclosporine, mycophenolate, N-acetylcysteine), and/or investigational therapy for IPF or 
administration of such therapeutics within 5 half-lives of the agent prior to initial 
screening in this study.  A current dose of  15 mg/day of prednisone or its equivalent is 
acceptable if it is anticipated that the dose will remain stable during the study.  
Pirfenidone (Esbriet®) is permitted, provided that the subject has been on a stable dose 
for at least 4 weeks prior to randomization and it is anticipated that the dose will remain 
stable during enrollment. 
4. History of malignancy, including carcinoma during the preceding 5 years.  However, 
subjects with a history of excised or treated basal cell, squamous cell, or cervical 
carcinomas are eligible to participate in this study. 
5. Significant cardiac disease (e.g., New York Heart Association Class 3 or 4; myocardial 
infarction within the past 6 months; unstable angina; coronary angioplasty or coronary 
artery bypass graft within the past 6 months; or uncontrolled atrial or ventricular cardiac 
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6. Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) 
within 3 months prior to screening. 
7. Significant reaction to previous injection of a monoclonal antibody. 
8. Female who is pregnant or breastfeeding. 
9. Male or female planning a pregnancy during the duration of this study.  A serum 
pregnancy test will be performed on all female subjects of childbearing potential. 
10. Fever (body temperature > 38°C) or symptomatic viral or bacterial infection within 1 
week prior to screening.   
11. Positive test for HBsAg, HCV antibody (if confirmed by HCV RNA), or HIV antibody at 
screening. 
12. Drug or alcohol abuse (as defined by the Investigator).   
13. Treatment with another investigational drug, investigational device, or approved therapy 
for investigational use within 5 half-lives of the agent prior to initial screening in this 
study. 
14. End-stage fibrotic disease requiring organ transplantation within 6 months.   
15. Any other condition that, in the opinion of the Investigator, may compromise the safety 
or compliance of the subject or would preclude the subject from successful completion of 
the study. 
7.3. 
Withdrawal Criteria 
Subjects will be informed that they have the right to withdraw from the study at any time for any 
reason without prejudice to their medical care. 
Subjects must be withdrawn from the study for any of the following reasons: 
 Subject request 
 Subject is unwilling or unable to comply with the protocol 
 Medical reason, at the discretion of the Investigator and/or the Medical Monitor 
The reasons for subject withdrawal must be recorded in the subject’s case report form (CRF) and 
in the source records.  The Investigator must notify Biogen MA Inc. and the Medical Monitor 
immediately when a subject has been discontinued/withdrawn due to an AE.   
Subjects who discontinue prior to Day 8-FU should undergo all assessments described for the 
Day 8-FU visit, if possible, including BAL, PFTs, and HRCT that are to be performed within a 
specified period after the subject receives their last dose of study medication.  Also, samples 
should be collected for serum pregnancy testing (if applicable) and anti-BG00011 antibody 
testing.  Subjects who discontinue the FU period subsequent to having Day 8-FU assessments 
performed should have Day 85-FU (Day 57-FU for cohorts 4 and 5) assessments performed at 
the time of termination.   
Subjects who discontinue participation during the MD period of the study for reasons unrelated 
to the study or study treatment (e.g., withdraw consent, lost to follow-up) may be replaced as 


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required for the study to meet its objectives.  Replacement subjects will be assigned unique 
identification numbers.   


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8. 
INVESTIGATIONAL PRODUCT 
8.1. 
Identity of Investigational Product 
BG00011 is a humanized monoclonal antibody (human immunoglobulin G1 subgroup III, kappa) 
and consists of 2 heavy and 2 light chains connected by inter-chain disulfide bonds.  The 
molecular weight of the intact BG00011 molecule is 148,000 daltons, including its carbohydrate 
moiety.   
BG00011 is provided as a lyophilized drug product in vials, must be kept refrigerated (2C to 
8C), be protected from light, and may not be frozen.  BG00011 will be administered as an SC 
injection (e.g., in the upper arm) after reconstitution.   
Each BG00011 lyophilized drug product vial is reconstituted using 1.3 mL of preservative-free 
sterile water for injection/USP to yield a final concentration of 75.0 mg/mL BG00011 in 15 mM 
sodium citrate, 7.5% (w/v) sucrose, 0.0075 % polysorbate 80, at pH 6.1. 
Additional dilution is required for lower doses and instructions for dilution will be provided to 
the pharmacy.  The reconstituted drug product does not contain a preservative and should be 
used within 4 hours.   
8.2. 
Reference Product 
The placebo (control agent) to be used in this study will be sterile normal saline (0.9% Sodium 
Chloride for Injection) administered as an SC injection.  The investigational site’s pharmacist 
will supply sterile, normal saline.  The manufacturer’s directions for material storage and 
handling are to be followed, as are standard clinical practices for ensuring sterility of the 
material.  The volume will be calculated as if the subject was to receive BG00011, and the 
equivalent amount of saline will be administered. 
8.3. 
Drug Accountability 
Accountability for study medication is the responsibility of the Principal Investigator.   
Investigational clinical supplies must be received by a pharmacist or other designated person at 
the study site and kept in a secured location.  The investigational site or pharmacy associated 
with the site must maintain accurate records indicating dates and quantity of study medication 
received, to whom it was dispensed (subject-by-subject accounting), and accounts of any study 
medication accidentally or deliberately destroyed.  Unless otherwise notified, all study 
medication, both used and unused, must be saved for drug accountability.  The Investigator must 
return all unused vials of study medication to the Sponsor at the end of the study, unless local 
destruction is agreed to in writing.   
8.4. 
Drug Handling Guidelines 
Please refer to the pharmacy instructions, provided in a separate document, for detailed drug 
handling, preparation, administration, and storage instructions.   


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9. 
TREATMENT 
9.1. 
Dosing Schedule 
BG00011 will be administered as an SC injection.  Doses will be 0.015 mg/kg, 0.1 mg/kg, 0.3 
mg/kg, 1.0 mg/kg, and 3.0 mg/kg.  Weight obtained at initial screening will be used to calculate 
dose throughout the MD period. 
At the end of Screening, eligible subjects will return for dosing on Day 1-MD.  Study treatment 
will be administered once weekly for 8 doses (7 weeks), i.e., on Days 1-MD, 8-MD, 15-MD, 
22-MD, 29-MD, 36-MD, 43-MD, and 50-MD. 
9.2. 
Study Medication Administration 
Investigational product (reconstituted monoclonal antibody BG00011) and the placebo control 
(saline solution) will be administered via SC injections (e.g., in the upper arm).  Study 
medication must be administered within 4 hours after preparation.  An injection volume greater 
than 1.5 mL should be split between 2 injection sites.   
9.3. 
Safety Monitoring and Dose Escalation 
The Sponsor is committed to assuring subject safety during this study and the Phase 2a IPF 
protocol was designed with input from leading physicians experienced with conducting clinical 
trials in this setting.  Eligibility criteria stipulate that subjects are clinically stable, meet accepted 
criteria for the diagnosis of IPF, and have PFTs consistent with moderate disease severity (e.g., 
FVC  50% and DLCO  30% of predicted values, respectively).   
9.3.1. 
Safety Monitoring 
Subjects will be closely monitored during the study periods as described below.   
9.3.1.1. 
 Multiple-Dose Period 
After receiving the first dose of study treatment, subjects are observed for 8 hours and then 
discharged with additional visits on Days 2-MD, 3-MD, 5-MD, and then weekly throughout the 
7-week dosing period. 
9.3.1.2. 
Follow-up Period 
After administration of the final (eighth) dose of study treatment, subjects  in cohorts 1 to 3 and 
subjects in cohorts 4 or 5, will have 7 visits over the subsequent 4 weeks followed by a clinic 
visit at Month 3 (Month 2 for cohorts 4 and 5). 
9.3.2. 
Dose Escalation 
An independent DSMB experienced in the oversight and monitoring of the conduct of clinical 
trials will determine whether dose escalation should proceed.  Dose escalation will be based on 
the DSMB’s review of unblinded PK and safety data through at least Day 15 from the initial 4 
subjects administered BG00011 or placebo (3:1, respectively) in each cohort.  Safety 


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assessments will include a review of AEs, vital signs, physical examination, clinical laboratory 
tests, and pulse oximetry from these visits.  Updated safety (including BAL, PFTs, and HRCT 
results) and PK information on all participants will be provided in each subsequent DSMB data 
package.  For example, at the DSMB meetings for cohorts 2 and 3, updated safety and PK data 
will be available through at least week 8 of the FU period (i.e., complete PK data through the 
dosing period and follow-up BAL, PFT, and HRCT) for all participants in cohorts 1 and 2, 
respectively.   
Reports of SAEs will be provided to the DSMB on an ongoing basis throughout the study.  In 
addition, Biogen MA Inc. will review AEs in a blinded manner on an ongoing basis and alert the 
DSMB of any safety concerns.   
In order to allow for compilation and evaluation of the data, it is anticipated that the DSMB will 
convene approximately 7 to 8 weeks after the first 4 subjects in the previous cohort are dosed.  
After reviewing the safety and PK data, the DSMB may recommend initiation of the next dose 
escalation cohort.  Alternatively, the DSMB may recommend monitoring subjects within a 
cohort for a longer period of time or reviewing safety and PK data from additional subjects prior 
to recommending dose escalation.  If indicated, another cohort may be enrolled at a dose level 
similar to or lower than prior cohorts (see Section 6.3 ‘Discontinuation or Temporary Suspension 
of the Study’).   
A DSMB meeting will not occur during the final cohort except on an ad hoc basis, as no dose 
escalation decision needs to be made. 
9.4. 
Prior and Concomitant Medications  
It is recognized that this subject population will be taking various medications.  All concomitant 
medications (including herbals, vitamins, and over-the-counter medications) taken during the 
entire study, starting with what is currently being taken by subjects at the initial screening visit 
(even if the medication is discontinued at that time), will be recorded on a CRF.  Subjects must 
not have received treatment with another investigational drug, investigational device, or 
approved therapy for investigational use within 5 half-lives of the agent prior to initial screening 
in this study, nor are they allowed to participate in another investigational study during this 
study.   
Subjects should not be receiving high dose corticosteroid (i.e., > 15 mg/day of prednisone or its 
equivalent), cytotoxic therapy (e.g., chlorambucil, azathioprine, cyclophosphamide, 
methotrexate), nintedanib (Ofev®), vasodilator therapy for pulmonary hypertension (e.g., 
bosentan), unapproved (e.g., interferon gamma, penicillamine, cyclosporine, mycophenolate, N-
acetylcysteine), and/or investigational therapy for IPF while participating in this study, nor can 
they have received such within 5 half-lives of the agent prior to initial screening.  All treatments 
previously used for treatment of IPF will be captured on a CRF.   
Use of Pirfenidone (Esbriet®) is permitted, provided that the subject has been on a stable dose 
for at least 4 weeks prior to randomization.   
Pirfenidone should be kept at a stable dose, if possible.  Dose decreases in response to adverse 
events are permitted and should be done in a manner consistent with the prescribing information 


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for pirfenidone.  Dose increases of pirfenidone, including an increase back to baseline dose after 
a dose decrease, are prohibited. 
Following enrollment into the study, every attempt should be made to avoid changes in the 
subject’s drug regimen.  Exceptions would include episodes of infections requiring treatment 
(e.g., antibiotics or antiviral drugs), exacerbations of their underlying disease requiring 
immediate intervention, or any other situation requiring modification of the subject’s therapy 
for their safety at the discretion of the treating physician. 
9.5. 
Subject Compliance 
Study medication is administered SC by site personnel while the subjects are at the study center.  
Therefore, monitoring for subject compliance with the treatment regimen is unnecessary. 


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10. 
SAFETY, PHARMACODYNAMICS, AND 
PHARMACOKINETICS ASSESSMENTS 
10.1. 
Safety Assessments 
10.1.1. 
Adverse Events  
AE information will be collected throughout the study.  See Section 14 for a full description of 
AE definitions, AE and SAE reporting procedures, and emergency procedures.   
10.1.2. 
Clinical Laboratory Tests  
The following laboratory safety assessments will be performed: 
 Hematology: complete blood count (CBC) with differential and platelet counts.  CBC 
includes red blood cells, WBCs, hemoglobin, hematocrit, mean corpuscular volume, 
mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. 
 Serum chemistry: albumin, alkaline phosphatase, ALT, AST, blood urea nitrogen 
(BUN), calcium, chloride, carbon dioxide, creatinine, direct bilirubin, gamma-
glutamyl transferase, glucose, lactate dehydrogenase, magnesium, phosphorus, 
potassium, sodium, total bilirubin, total cholesterol, total protein, and uric acid.   
 Urinalysis: including determination of the presence of protein, glucose, ketones, 
occult blood, and WBCs by dipstick, with microscopic examination, if indicated.   
A blood sample for hematology/serum chemistry testing will be collected at the following time 
points: screening, prior to dosing on Day 1-MD, and on Days 8-MD, 15-MD, 29-MD and 
43-MD, and then on Days 8-FU, 29-FU, 57-FU, and those in cohorts 1 to 3 only, 85-FU after the 
final dose.  
At screening, blood samples for HCV antibody, HBsAg, and HIV antibody will be collected to 
establish eligibility.  Appropriate referrals must be made for any positive HCV, HBsAg, or HIV 
test that is obtained according to applicable state laws.   
Collection, handling, and shipping procedures for the BAL specimens and serum samples for 
PK, antibodies to BG00011, and biomarkers are provided in the study manual.  Validated 
bioanalytical methods will be used to measure BG00011 serum levels and antibodies to 
BG00011. 
10.1.3. 
Pulmonary Function Tests  
Screening and Baseline PFTs 
Two PFTs will be performed during Screening (within 5 weeks prior to dosing).  The first of 
these tests (screening PFT) will be performed before and after bronchodilator administration and 
will be used to determine if the subject qualifies for the study, whereas the other 1 (performed 
without bronchodilator administration) will serve as the subject’s baseline value.  These 2 PFTs 
must be performed on separate days during Screening up to and including Day 1-MD.  The 
baseline PFT must not be performed until the results from the Screening PFT have been 


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received.  Additional PFTs will be performed on Day 29-MD ± 5 days and within 21 days after 
receiving the last dose of study medication.  PFT parameters include: 
 FVC  
 FEV1 
 TLC (total lung capacity)  
 DLCO 
 Residual Volume  
A subject who qualifies for inclusion in 1 cohort but is unable to participate (e.g., cohort fully 
enrolled) may be assessed for inclusion in a subsequent cohort without repeating the screening 
PFTs, unless it will fall outside the 5 week window prior to dosing.   
Assessment of PFT Changes from Baseline  
The assessment of changes in lung function during this study will be performed by comparing 
the subject’s FU PFT parameters to their baseline value.  Quality control assessment of all PFTs 
will be performed by a blinded independent expert.   
PFTs showing clinically significant change(s) from baseline should be repeated to confirm the 
change prior to reporting the observation as an AE.  Since the variability in lung function 
measurements is related to both biological and technical factors and is greater than observed in 
most other clinical laboratory tests [Jensen 2007a; Jensen 2007b; Pellegrino 2005]), when 
evaluating changes in PFTs it is important to consider the inherent variability in the PFT 
parameter being measured.  For example, a ≥ 12% change from baseline in FEV1 is considered 
significant and may be clinically important [Pellegrino 2005].  Therefore, a subject whose FEV1 
decreases by 14% from their baseline value (i.e., 86% of baseline) will be confirmed with repeat 
PFT testing, and if the decrease persists, the subject will be considered to have had an AE.  For 
TLC, FVC, and DLCO, a ≥ 8%, ≥ 12%, and ≥ 15% decline from baseline, respectively, is 
considered to be clinically meaningful [Pellegrino 2005]; personal communication with R 
Crapo).   
10.1.4. 
Bronchoalveolar Lavage  
BAL will be performed during Screening and between Day 3-FU and Day 8-FU after receiving 
the last dose of study medication.  Analysis of the BAL macrophage MMP-12 mRNA levels 
(which are increased when macrophages are activated) will be performed at a central laboratory.   
10.1.5. 
High Resolution Computed Tomography  
HRCT scans will be performed during screening to establish the pre-dosing pattern and extent of 
disease.  HRCT will be repeated within 21 days after receiving the last dose of study treatment 
during the MD period.  An independent central radiologist experienced in the evaluation of 
diffuse lung diseases and blinded to treatment assignment will read all scans during the MD and 
FU periods.   
10.1.6. 
Other Safety Assessments  
The following assessments will be performed: 


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 Medical history 
 Physical examination 
 Vital signs: oral temperature (°C), heart rate (beats/min), respiratory rate 
(breaths/min), sitting blood pressure (mmHg) after at least 5 minutes rest 
 Body weight (kg) and height (cm) 
 12-lead ECG  
 Oxygen saturation (pulse oximetry) after at least 5 minutes rest 
 Serum pregnancy test  
 Urine pregnancy test 
 Formation of antibodies to BG00011: blood samples for immunogenicity testing will 
be collected during screening, and on Day 1-MD (prior to dosing), Day 29-FU, and 
Day 85-FU (Day 57-FU for subjects in cohorts 4 or 5).   
10.2. 
Efficacy Assessments 
There are no efficacy objectives in this study.   
10.3. 
Pharmacodynamic Assessments  
10.3.1. 
Peripheral Blood Biomarkers 
Peripheral blood will be collected to determine whether administration of BG00011 has a 
beneficial effect on blood biomarkers of TGF- activation, tissue remodeling and lung injury, 
and epithelial function in subjects with IPF.  These biomarkers may include the TGF- inducible 
proteins TIMP-1 and Col1A1; matrix proteins such as osteopontin (OPN) and MMP-7; and 
indicators of epithelial function including SP-A and alpha defensins (DEFA1-3).  Additional 
biomarkers may be added prior to the initiation of the analyses and will be included in the 
statistical analysis plan.  Blood samples for blood biomarkers will be collected at screening and 
on Days 1-MD, 29-MD, 50-MD, 8-FU, 29-FU, 57-FU, and for subjects in cohorts 1 to 3 only, 
85-FU.   
10.3.2. 
Bronchoalveolar Lavage 
Biomarkers which may include mRNA levels for PAI-1 and OPN, as well as protein levels for 
phosphorylated SMAD, will be measured in macrophages isolated from BAL.  BAL will be 
performed during screening and between Day 3-FU and Day 8-FU following administration of 
the last dose of study treatment.  Analyses of BAL fluid and cell pellet will be performed at a 
central laboratory. 
10.4. 
Pharmacokinetic Assessments  
The following parameters will be assessed during the study to evaluate the PK profile of 
BG00011. 
PK parameters include: 


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 Cmax 
 Time to reach Cmax 
 Area under the concentration-time curve from time zero (time of dosing) to the last 
measurable concentration 
 Area under the concentration-time curve from time zero (time of dosing) extrapolated 
to infinity 
 Area under the concentration-time curve from time zero (time of dosing)  to 
tau (within a dosing interval) 
 Terminal elimination rate constant 
 t½: elimination half-life 
 Clearance (unadjusted for bioavailability) 
 Volume of distribution (unadjusted for bioavailability) 
Blood samples for PK evaluation will be collected at screening, prior to dosing on Day 1-MD 
and at 8 hours after dosing; and prior to dosing on Days 2-MD (24 hours), 3-MD, 5-MD, 8-MD, 
15-MD, 22-MD, 29-MD, 36-MD, 43-MD, and 50-MD.  After the final dose of the MD period, 
PK samples will be obtained at 8 hours, and on Days 2-FU, 3-FU, 5-FU, 8-FU, 15-FU, 22-FU, 
29-FU, 57-FU, and, for cohorts 1 to 3 only, 85-FU during the FU period.  BG00011 PK samples 
should be drawn as close as possible to the sampling times shown in the Schedule of Events 
(Table 3). 
Exposure-response relationships will be explored for both safety and pharmacodynamics to assist 
with determining the appropriate dosing regimen for BG00011 in this clinical setting. 


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11. 
STUDY PROCEDURES AND SCHEDULE 
11.1. 
Subject Management 
Female subjects of childbearing potential must practice effective contraception for the entire 
study period, i.e., from the time of signing the ICF through 12 weeks following the last injection 
of study treatment.  Female subjects are exempt from contraception requirements if they are 
postmenopausal for a least 1 year before dosing or are surgically sterile (i.e., no uterus or no 
ovaries).  Females who have their fallopian tubes tied or cut are not considered surgically sterile.  
Male subjects must have had a vasectomy performed at least 6 months prior to screening or must 
agree to use contraception for either themselves or their partner(s) from the time of signing the 
ICF through 12 weeks following the last injection of study treatment. 
Subjects will undergo screening assessments within 5 weeks (8 weeks for selected assessments 
in cohorts 4 and 5) prior to dosing.  Upon fulfilling all of the inclusion and none of the exclusion 
criteria, subjects will be randomized to receive either BG00011 or placebo.   
Subjects will receive 8 doses of their assigned medication at weekly intervals, with visits and 
assessments as detailed below and in the Schedule of Events.  Subjects will be followed for 
12 weeks (8 weeks for cohorts 4 and 5) after their final dose of study treatment.   
11.2. 
Timing of Visits and Missed Visits 
As described in Section 6.1, to help prevent confusion between the periods of the study, days 
specific to the MD dosing period will be designated as “Day X-MD”.  The follow-up period 
begins at the visit where the last dose of study treatment is administered, and study days after the 
final dose of study treatment is administered are designated as “Day X-FU.”  
Table 3 shows specific days for each visit.  If a dosing visit is delayed during the multiple-dose 
period the dose should be administered as soon as possible thereafter.  If a missed dose is 
delayed no more than 2 days beyond the protocol-specified visit date, i.e., within the allowed ± 2 
day window, all subsequent doses should still be administered on the originally scheduled day 
(e.g., Day 22, Day 29).  If a dose is delayed by 3 or more days beyond the specified visit date 
then either 1) the missed dose should be omitted and dosing should then resume as per the 
Schedule of Events, or 2) the subsequent dosing visit dates should be adjusted appropriately, if 
this can still be done within the allowed visit windows, to ensure there is always an interval of at 
least 5 days between doses. 
Subjects who discontinue prior to Day 8-FU should undergo all assessments described for the 
Day 8-FU visit, if possible, including BAL, PFTs, and HRCT that are to be performed within a 
specified period after the subject receives their last dose of study treatment.  Also, samples 
should be collected for serum pregnancy testing (if applicable) and anti-BG00011 antibody 
testing.  Subjects who discontinue the study subsequent to having Day 8-FU assessments 
performed should have Day 85-FU (57-FU for subjects in cohorts 4 or 5) assessments performed 
at the time of termination.   


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11.3. 
Randomization  
A central randomization will be used that is blinded to the Sponsor, site staff, subject, and 
personnel responsible for data verification, entry, and analysis.  An unblinded statistician for the 
contract research organization who is independent of study conduct will develop the 
randomization scheme.  The subject randomization number indicates the cohort and 
randomization sequence that is unique to each subject (e.g., Number 101 indicates cohort 1, 
Subject 1).  If the subject qualifies for randomization based on results obtained during Screening, 
central randomization may be contacted and the randomization number assigned.  A subject will 
be considered randomized once a randomization number has been assigned and the subject 
receives the first dose of study treatment.   
The unblinded pharmacist will be notified of the randomization number and treatment 
assignment and will prepare appropriate medication for injection according to the provided 
randomization code and instructions for preparation.  The unblinded pharmacist will keep the 
randomization code locked in a secure place and will not disclose the code to anyone else (except 
for a quality assurance person in the pharmacy) or discuss subject information with study staff.  
A sealed blind break envelope will be completed by the unblinded statistician for the contract 
research organization and provided to the study staff in the event emergency unblinding is 
necessary.  If there has been a significant change in the subject’s condition on Day 1-MD, the 
Medical Monitor should be consulted before dosing occurs.   
11.4. 
Screening  
Visit 1 – Within 5 Weeks (8 weeks for Cohorts 4 and 5) Prior to Dosing 
Subjects will be required to sign an ICF prior to any study related procedures, including 
screening evaluations that are not part of their routine medical follow-up.  After written informed 
consent is obtained, the subject will be given a screening number.  Subjects who are screened 
and fail the inclusion/exclusion criteria will not be allowed in the study.  “Screening” is 
designated as Visit 1, but it is recognized that these procedures may encompass more than 1 visit. 
Screening assessments (e.g., clinical laboratory tests or PFTs) may be repeated if there are 
questionable results or if abnormalities are felt to be due to inherent variability of the test 
procedure.  If a subject must be rescreened for study entry, results from previous screening 
assessments may be used, as long as the screening windows for those assessments are met and all 
spirometry data used for subject qualification are derived from a single day.  It is recommended 
that the BAL and PFTs be performed after the subject has met the other inclusion criteria, 
including the screening HRCT. 
A detailed list of screening procedures is provided in Table 3.  
Further details regarding the PFT procedures may be found in Section 10.1.3.   
11.5. 
Multiple-dose Treatment  
If the laboratory and other tests performed during screening indicate continued eligibility, 
subjects will return to the study center during the morning of Day 1-MD and remain there for 8 
hours after dose administration.   


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A detailed list of pre-dose assessments, with recommendations for timing, is provided in Table 3.  
Actual times will be recorded in the subject’s CRF. 
The dosing schedule and regimen are described in Section 9.1. 
11.6. 
Follow-up Period  
A detailed list of follow-up assessments, with recommendations for timing, is provided in Table 
3.   
Actual times will be recorded in the subject’s CRF. 
11.7. 
Early Termination  
If a subject terminates at Day 8-FU or before, all Day 8-FU assessments need to be performed, as 
well as the following:  
 Serum pregnancy test (if applicable) 
 Sample collection for anti-BG00011 antibody analysis 
 BAL (between Day 3 and Day 8 [i.e., 48 hours to 168 hours] after the last dose of 
study treatment) 
 PFTs (within 21 days after the last dose of study treatment); PFTs should not be 
performed within 2 days after BAL 
 HRCT (within 21 days after the last dose of study treatment), HRCT should not be 
performed within 2 days after BAL  
 Completion of the Study Termination form 
If a subject terminates during the follow-up period after Day 8-FU (and all Day 8-FU 
assessments were performed), all Day 85-FU (Day 57-FU for cohorts 4 and 5) assessments 
should be performed at the time of termination, if possible. 


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12. 
SCHEDULE OF EVENTS 
Table 3 
Schedule of Events 
Tests and Evaluations 
 
SCREENING1  
MD Period 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Day 1-MD (Day of first Dose) 
Day 2-MD 
Day 3-MD 
Day 5-MD   
Qualification 
assessments  
Pre-dose 
Dosing with 
BG00011 
Post-dose  
2 h (±10 min) 
4 h (±10 min) 
8 h (±10 min) 
24 h (±4 h) 
48 h(±4 h) 
96 h(±4 h) 
Informed Consent  
X 
 
 
 
 
 
 
 
 
Medical History 
X 
X2 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X3 
 
 
 
 
 
 
 
Physical Examination 
X 
X 
 
 
 
 
X 
 
 
Vital Signs4 
X 
X5 
 
X 
X 
X 
X 
X 
X 
Body Weight and Height 
X6 7 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
BAL 
X8 
 
 
 
 
 
 
 
 
Pulmonary Function Tests 
X9 
 
 
 
 
 
 
 
 
Oxygen Saturation10 
X 
X 
 
 
 
 
X 
 
 
HRCT 
X11 
 
 
 
 
 
 
 
 
Serum Pregnancy 
X12 
 
 
 
 
 
 
 
 
Urine Pregnancy 
 
X13 
 
 
 
 
 
 
 
Blood Chemistry 
X 
X 
 
 
 
 
 
 
 
Hematology 
X 
X 
 
 
 
 
 
 
 
Urinalysis 
X 
X 
 
 
 
 
 
 
 
HIV, HCV, HBsAg Testing 
X 
 
 
 
 
 
 
 
 
Serum for Biomarkers 
X 
X 
 
 
 
 
 
 
 
Serum for BG00011 PK 
X 
X 
 
 
 
X14 
X 
X 
X 
Serum for anti-BG00011 Ab 
X 
X 
 
 
 
 
 
 
 
Study treatment Administration 
 
 
X 
 
 
 
 
 
 
Investigator assessment of  subject’s  
respiratory status 
 
 
 
 
 
 
 
 
 
Monitoring of AEs 
 
Monitor and record throughout the study15 
Monitoring of Concomitant Therapy 
Monitor and record throughout the study16 


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Tests and Evaluations 
MD Period 
 
Visit 6 
Dose 2 
Visit 7 
Dose 3 
Visit 8 
Dose 4 
Visit 9 
Dose 5 
Day 8-MD 
 (±1 day) 
 
Day 15-MD  
(±2 days) 
 
Day 22-MD 
(±2 days) 
Day 29-MD 
(±2 days) 
Pre-dose 
Post-dose 
Pre-dose 
Post-dose 
Pre-dose 
Post-dose 
Pre-dose 
Post-dose 
Informed Consent  
 
 
 
 
 
 
 
 
Medical History 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
 
 
 
 
 
 
 
 
Physical Examination 
X 
 
X 
 
 
 
X 
 
Vital Signs4 
X5 
X17 
 X5 
X17 
X5 
X17 
X5 
X17 
Body Weight and Height 
 
 
 
 
 
 
 
 
12-lead ECG 
 
 
X 
 
 
 
 
 
BAL 
 
 
 
 
 
 
 
 
Pulmonary Function Tests 
 
 
 
 
 
 
X18 
 
Oxygen Saturation10 
X5 
 
X5 
 
X5 
 
X5 
 
HRCT 
 
 
 
 
 
 
 
 
Serum Pregnancy 
 
 
 
 
 
 
 
 
Urine Pregnancy 
 
 
 
 
 
 
 
 
Blood Chemistry 
X 
 
X 
 
 
 
X 
 
Hematology 
X 
 
X 
 
 
 
X 
 
Urinalysis 
X 
 
X 
 
 
 
X 
 
HIV, HCV, HBsAg Testing 
 
 
 
 
 
 
 
 
Serum for Biomarkers 
 
 
 
 
 
 
X 
 
Serum for BG00011 PK 
X 
 
X 
 
X 
 
X 
 
Serum for anti-BG00011 Ab 
 
 
 
 
 
 
 
 
Study treatment Administration 
X 
X 
X 
X 
Investigator assessment of  subject’s  
respiratory status 
 
 
 
 
Monitoring of AEs 
Monitor and record throughout the study15 
Monitoring of Concomitant Therapy 
Monitor and record throughout the study16 


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Tests and Evaluations 
MD Period 
FU Period 
Visit 10 
Dose 6 
Visit 11 
Dose 7 
Visit 12 
Dose 8 
Visit 13 
Visit 14 
Day 36-MD 
(±2 days) 
Day 43-MD 
(±2 days) 
Day 50-MD (1-FU)  
(±2 days) 
Day 2-FU 
 
Day 3-FU 
 
Pre-dose 
Post-dose 
Pre-dose 
Post-dose 
Pre-dose 
Post-dose 
24 h  
 (±4 h) 
48 h 
(±4 h) 
Informed Consent  
 
 
 
 
 
 
 
 
Medical History 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
 
 
 
 
 
 
 
 
Physical Examination 
 
 
X 
 
 
 
 
 
Vital Signs4 
X5 
X17 
X5 
X17 
 X5 
X19 
X 
X 
Body Weight and Height 
 
 
 
 
 
 
 
 
12-lead ECG 
 
 
 
 
 
 
 
 
BAL 
 
 
 
 
 
 
 
X20 
Pulmonary Function Tests 
 
 
 
 
 
 
 
 
Oxygen Saturation10 
X5 
 
X5 
 
X5 
 
 
X 
HRCT 
 
 
 
 
 
 
 
 
Serum Pregnancy 
 
 
 
 
 
 
 
 
Urine Pregnancy 
 
 
 
 
 
 
 
 
Blood Chemistry 
 
 
X 
 
 
 
 
 
Hematology 
 
 
X 
 
 
 
 
 
Urinalysis 
 
 
X 
 
 
 
 
 
HIV, HCV, HBsAg Testing 
 
 
 
 
 
 
 
 
Serum for Biomarkers 
 
 
 
 
X 
 
 
 
Serum for BG00011 PK 
X 
 
X 
 
X 
X14 
X 
X 
Serum for anti-BG00011 Ab 
 
 
 
 
 
 
 
 
Study treatment Administration 
X 
X 
X 
 
 
Investigator assessment of  subject’s  
respiratory status 
 
 
 
 
 
Monitoring of AEs 
Monitor and record throughout the study15 
Monitoring of Concomitant Therapy 
Monitor and record throughout the study16 


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Tests and Evaluations 
FU Period 
 
Visit 15 
Visit 16 
Visit 17 
Visit 18 
Visit 19 
Visit 20 
Visit 21 
Day 5-FU 
 
Day 8-FU 
(or early 
termination) 
Day 15-FU 
 
Day 22-FU 
 
Day 29-FU 
 
Day 57-FU21 
 
Day 85-FU 
(for Cohorts 1 to 3 only) 
96 h (±4 h) 
(±1 day) 
(±2 days) 
(±2 days) 
(±3 days) 
(±7 days) 
(±7 days) 
Informed Consent  
 
 
 
 
 
 
 
Medical History 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
 
 
 
 
 
 
 
Physical Examination 
 
X 
X 
 
X 
X 
X 
Vital Signs4 
X 
X 
X 
X 
X 
X 
X 
Body Weight and Height 
 
X 
 
 
 
X22 
X 
12-lead ECG 
 
X 
 
 
 
X22 
X 
BAL 
 
X20 
 
 
 
 
 
Pulmonary Function Tests 
 
X23 
 
 
 
 
 
Oxygen Saturation10 
 
X 
 
 
X 
X 
X 
HRCT 
 
X23 
 
 
 
 
 
Serum Pregnancy 
 
X 
 
 
 
X22 
X 
Urine Pregnancy 
 
 
 
 
 
 
 
Blood Chemistry 
 
X 
 
 
X 
X 
X 
Hematology 
 
X 
 
 
X 
X 
X 
Urinalysis 
 
X 
 
 
X 
X 
X 
HIV, HCV, HBsAg Testing 
 
 
 
 
 
 
 
Serum for Biomarkers 
 
X 
 
 
X 
X 
X 
Serum for BG00011 PK 
X 
X 
X 
X 
X 
X 
X 
Serum for anti-BG00011 Ab 
 
 
 
 
X 
X22 
X 
Study treatment Administration 
 
 
 
 
 
 
 
Investigator assessment of subject’s 
respiratory status 
 
 
 
 
 
X22 
 
Monitoring of AEs 
Monitor and record throughout the study15 
Monitoring of Concomitant Therapy 
Monitor and record throughout the study16 
Ab = antibody; AE = adverse event; BAL = bronchoalveolar lavage; ECG = electrocardiogram; FU = follow-up; HBsAg = Hepatitis B surface antigen; HCV = 
hepatitis C antibody; HIV = human immunodeficiency virus; HRCT = high resolution computed tomography; MD = Multiple-dose; PK = pharmacokinetics  
1 Within 5 weeks for cohorts 1 to 3 and 8 weeks for cohorts 4 and 5 
2 Update medical history with any changes prior to dosing, including existing conditions.   


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3 Entry criteria re-checked prior to dosing on Day 1-MD to confirm eligibility. 
4 Vital signs include blood pressure, pulse, temperature, and respiration rate.  Blood pressure to be performed sitting, after at least 5 minutes rest. 
5 To be performed within 30 minutes prior to study treatment administration. 
6 Weight obtained at initial screening will be used to calculate dose throughout the study. 
 7 Height will be measured at initial screening only.   
8 BAL must be performed within 5 weeks prior to the first dose.   
9 A screening PFT (before and after bronchodilator) will be performed to determine eligibility.  If the subject qualifies for the study, 1 subsequent PFT, without 
bronchodilator administration, (may be performed on the same day prior to a BAL or at least 2 days after a BAL) will be performed during screening (up to 
Day 1-MD) and used for baseline values, all within 5 weeks of dosing.   
10 Using pulse oximeter, oxygen saturation will be measured after at least 5 minutes at rest.  The amount of supplemental oxygen the subject is receiving, if any, 
should be noted. 
11 Historical HRCT scan is acceptable for determining subject eligibility; however, an HRCT is required to also be performed within 5 weeks prior to the initial 
dose 
12 Serum pregnancy test for females of childbearing potential.  Results must be negative for inclusion into the study.   
13 Urine pregnancy test for females of childbearing potential must be performed and determined negative prior to dosing. 
14 Obtain samples at 8 h (± 10 min) after dose administration. 
15 AEs are captured after first dose of study treatment.  Events prior to dosing should be entered on the Medical History CRF. 
16 All concomitant medications being taken at the time of initial screening (including medications discontinued at that time) through the termination visit are to be 
recorded on the CRF. 
17 To be performed at 30 ± 10 minutes post injection. 
18 To be performed on Day 29 (± 5 days) of the dosing period. 
19 To be performed at 30 ± 10 minutes post injection and 8 hours ± 10 minutes post injection.  
20 To be performed between Day 3-FU and Day 8-FU 
21 End of Study for subjects in cohorts 4 or 5. 
22 For subjects in cohorts 4 or 5 only. 
23 Must be performed within 21 days of last administration of study drug.  


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13. 
STATISTICS 
The objectives of this Phase 2a study are to evaluate the safety, tolerability, PK, immunogenicity, 
and impact on BAL and peripheral blood biomarkers of multiple-doses of BG00011 in subjects 
with IPF. 
13.1. 
Analysis Populations 
All subjects who have received at least 1 dose of BG00011 or placebo will be included in the 
safety analyses.  All subjects who received at least 1 dose of BG00011 and have a corresponding 
sample collected for BAL and/or blood biomarkers (e.g., Day 8-FU) will be considered for the 
pharmacodynamic analyses.  All subjects who received study treatment will be included in the 
PK analyses, provided that a pre-dose and at least 1 post-dose blood sample with detectable drug 
concentrations were collected during the specified sampling period. 
13.2. 
Statistical Analysis 
13.2.1. 
Subject Accountability and Demographics 
Data will be summarized and presented by dose cohort, defined as each of the BG00011 dose 
groups and the combined placebo group.  Data will be listed by cohort. 
Exposure to study treatment and reasons for discontinuation of study treatment will be tabulated 
by dosing cohort and study period.  Demographics will be presented using descriptive statistics 
(i.e., mean, standard deviation, median, and range). 
13.2.2. 
Safety Analysis 
Data for BG00011 treated subjects will be grouped by dose cohort and study period.  Data for all 
placebo subjects, regardless of dosing cohort, will be treated as 1 group.   
An AE or SAE will be considered treatment-emergent (TE) if it was newly acquired or worsened 
during or after the administration of investigational drug.  Descriptive analysis of 
treatment-emergent AEs (TEAEs) and treatment-emergent SAEs (TESAEs) will include the 
following: 
 Incidence of all TEAEs, and of TESAEs. 
 TEAEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) version 10.1 or higher.   
 TEAEs will be grouped by system organ class and preferred term. 
 TEAEs will be presented by severity and relationship to study treatment (see 
Section 14.2). 
 Individual listing of all TEAEs (including accompanying symptoms). 
 Descriptive statistics will be tabulated for all TEAEs. 


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For each treatment group, descriptive statistics will be used to summarize and present vital signs 
and clinical laboratory parameters within each protocol-specified visit.  Shift tables will be 
presented for selected laboratory parameters.  Physical examination results, oxygen saturation, 
BAL, PFT, HRCT, and ECG parameters will be presented in listings.   
13.2.3. 
Pharmacodynamic Analyses 
Variables related to potential pharmacodynamics (i.e., biomarkers in BAL and peripheral blood) 
will be tabulated and presented for all BG00011 subjects within a dose cohort (or placebo).  
Changes from baseline in the pharmacodynamic variables will be compared among treatment 
groups and with the placebo group.   
Peripheral blood biomarkers may include, but will not be limited to tissue remodeling markers, 
such as MMP-7 and OPN; TGF--inducible markers, such as TIMP-1 and Col1A1; and 
epithelial injury markers, including SP-A, and DEFA1-3.  mRNA for tissue remodeling markers 
which may include PAI-1 and osteopontin, and protein levels for the TGF--inducible marker 
phosphorylated SMAD, will be measured in macrophages isolated from BAL.  Additional 
biomarkers may be added prior to the initiation of analysis.  The complete list of peripheral 
blood and BAL biomarkers will be provided in the statistical analysis plan.   
13.2.4. 
Pharmacokinetic Analyses 
Listings of individual subject serum BG00011 concentrations, actual blood sampling times, and 
PK parameters as well as graphs of concentration vs. time will be prepared by dosing cohort.  
Serum concentrations and PK parameters will be summarized through descriptive statistics and 
compared among dosing cohorts (and to placebo) using mixed effects models.  Dose 
proportionality will be assessed following log-transformation, and dose normalized AUC and 
Cmax will be analyzed using mixed modeling.  Exposure-response relationships will be evaluated 
post-hoc and as applicable, for both safety and pharmacodynamics, to assist with determining the 
appropriate dosing regimen for BG00011 in this clinical setting.   
13.2.5. 
Immunogenicity Analyses 
The incidence of antibodies to BG00011 will be tabulated for each subject by treatment group 
and dose cohort using descriptive statistics.  A test for trend will be conducted to assess the 
relationship between dose level and incidence.  The antibody titer and natural-log transformed 
results will be summarized and presented using descriptive statistics.  Samples that test positive 
for antibodies to BG00011 will be further assessed to determine if these antibodies are 
neutralizing.  The effect of anti-BG00011 antibodies on PK parameters will also be explored. 
13.3. 
Determination of Sample Size 
No formal statistical justification for the sample size was performed for this Phase 2a study.  
Cohort size was determined based on requirements for PK analyses and safety assessments.  
With 6 subjects per cohort administered BG00011 the probability of observing an event is 82% if 
the actual probability of such an event is 25%. 


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13.4. 
Interim Analysis 
An administrative interim analysis may be performed on all subject data up to and including the 
Day 8-FU visit for the last subject in cohort 4.  The interim analysis will provide safety, PK, and 
PD information to aid in internal (Biogen MA Inc.) decision-making only and will not affect the 
study design of the current protocol. 


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14. 
ADVERSE EVENTS 
Throughout the course of the study, every effort must be made to remain alert to possible AEs.  
If an AE occurs, the first concern should be for the safety of the subject.  If necessary, 
appropriate medical intervention should be provided. 
At the signing of the ICF, each subject must be given the names and telephone numbers of study 
site staff for reporting of AEs and medical emergencies. 
14.1. 
Adverse Event Definitions 
14.1.1. 
Serious Pretreatment Event 
A serious pretreatment event is any event that meets the criteria for SAE reporting (as defined in 
Section 14.1.3) and occurs after the subject signs the ICF, but before administration of study 
treatment. 
14.1.2. 
Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product and that does not necessarily have a causal relationship 
with this treatment.  An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. 
Determination of whether an abnormal laboratory value meets the definition of an AE will be 
made by the Investigator.  The following laboratory abnormalities should be captured as AEs: 
 Any laboratory test result that meets the criteria for an SAE (Section 14.1.3). 
 Any laboratory test result that requires the subject to receive specific corrective 
therapy. 
 Any laboratory abnormality that the Investigator considers to be clinically significant. 
14.1.3. 
Serious Adverse Event 
An SAE is any untoward medical occurrence that at any dose: 
 results in death 
 in the view of the Investigator, places the subject at immediate risk of death (a 
life-threatening event); however, this does not include an event that, had it occurred 
in a more severe form, might have caused death 
 requires inpatient hospitalization or prolongation of existing hospitalization 
 results in persistent or significant disability/incapacity, or 
 results in a congenital anomaly/birth defect. 


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An SAE may also be any other medically important event that, in the opinion of the Investigator, 
may jeopardize the subject or may require intervention to prevent one of the other outcomes 
listed in the definition above.  (Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or convulsions occurring at home that do not 
require an inpatient hospitalization.) 
14.2. 
Adverse Event Classification 
Relationship to Investigational Drug 
The following classifications should be used when evaluating the relationship of AEs and SAEs 
to the investigational drug. 
None: 
No relationship between the experience and the administration of study 
treatment; related to other etiologies such as concomitant medications or 
subject’s clinical state. 
Unlikely: 
The current state of knowledge indicates that a relationship is unlikely.   
Possible: 
A reaction that follows a plausible temporal sequence from administration 
of the study treatment and follows a known response pattern to the 
suspected study treatment.  The reaction might have been produced by the 
subject’s clinical state or other modes of therapy administered to the 
subject, but this is not known for sure. 
Probable: 
A reaction that follows a plausible temporal sequence from administration 
of the study treatment and follows a known response pattern to the 
suspected study treatment.  The reaction cannot be reasonably explained 
by the known characteristics of the subject’s clinical state or other modes 
of therapy administered to the subject. 
Definite: 
A reaction that follows a plausible temporal sequence from administration 
of the study treatment and follows a known response pattern to the 
suspected study treatment and can be confirmed with a positive re-
challenge test or supporting laboratory data. 
Severity 
Mild: 
Awareness of sign or symptom, but easily tolerated 
Moderate: 
Discomfort enough to cause interference with normal daily activities 
Severe: 
Inability to perform normal daily activities 
Life-threatening: 
Immediate risk of death from the reaction as it occurred 
14.3. 
Documentation and Reporting of Adverse Events by Investigator 
Subjects will be evaluated and questioned generally to identify AEs during the course of the 
study.  All AEs spontaneously reported by the subject and/or in response to an open question 
from study personnel or revealed by observation, physical examination, or other diagnostic 
procedures will be recorded on the appropriate CRF for that visit.  In all instances, the 


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65 
Investigator should follow subjects until the outcome of the AE is known, until it is considered to 
be chronic or stable, or until it is no longer considered clinically significant.  AEs will be 
reported and followed only through the subject’s final study visit. 
Events occurring after administration of the first dose of study treatment will be reported on the 
AE CRF.  Any events occurring prior to dosing will be reported on the Medical History CRF.  
Any post-dosing clinically relevant deterioration in laboratory assessments or other clinical 
findings is considered an AE and must be recorded on the AE Form.  AE information recorded 
on AE forms will be entered into the database on an ongoing basis.   
For SAEs, a SAE form must also be completed with as much information as possible and 
submitted in the time frame described in Section 14.4.  SAEs must be reported from the signing 
of the ICF through the Final Safety Visit.  When new significant information is obtained as well 
as when the outcome of an event is known, the Investigator should record the information on a 
new SAE form.  If the subject was hospitalized, a copy of the discharge summary, as well as any 
other relevant hospital records, must be included as part of the subject medical file. 
14.4. 
Notification of Serious Adverse Events 
Investigator Reporting to Sponsor 
All SAEs (including deaths) that occur from signing of the ICF through the Final Safety Visit 
must be reported by the Investigator to 
 by faxing the SAE form within 
24 hours from the point in time when the Investigator becomes aware of the SAE.  Investigators 
must report to 
 any SAE, whether or not considered drug related, including 
those listed in the protocol or Investigator Brochure.  The report must include an assessment of 
whether there is a reasonable possibility that the drug caused the event.   
SAE Reporting Contact Information 
 
DSS Hotline No.: 
  
DSS Fax No.: 
 
14.4.1. 
Expectedness of Events  
Expectedness of all AEs will be determined according to the Investigator’s Brochure. 
14.4.2. 
Suspected Unexpected Serious Adverse Reactions  
Suspected unexpected serious adverse reactions (SUSARs) are SAEs that are unexpected and 
judged by the Investigator or Biogen MA Inc. to be related to the study treatment administered.   
Biogen MA Inc. or designee will report SUSARs and other applicable SAEs to the appropriate 
regulatory authorities, central institutional review boards (IRBs)/ECs and Investigators as 
required, according to local law.   


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15. 
PROCEDURES FOR HANDLING SPECIAL CIRCUMSTANCES 
15.1. 
Medical Emergency 
In a medical emergency requiring immediate attention, study site staff will apply appropriate 
medical intervention, according to current standards of care.  The Investigator (or designee) 
should contact the 
 24-hour emergency medical support number (
)  
15.2. 
Emergency Contact 
In the event of a medical emergency (i.e., an event that requires immediate attention regarding 
the treatment of a subject, operation of the clinical study, and/or the use of investigational drug), 
investigational site personnel must immediately contact the Medical Monitor by phone, followed 
by details in a fax or e-mail.  Full contact information for the Medical Monitor may be found in 
the Study Reference Manual.   
15.3. 
Emergency Identification of Study treatment 
In the event of a medical emergency, when knowledge of the subject’s treatment assignment may 
influence the subject’s clinical care, the Investigator or designee may open the code-break 
envelope of the subject experiencing the emergency.  However, prior to unblinding, the 
Investigator should attempt to contact the Medical Monitor. 
If unblinding is necessary, the Investigator must document the reasons for unblinding in the 
subject’s source documents, but should not divulge the subject’s treatment assignment to any 
individuals except the Medical Monitor and those individuals involved in the direct medical care 
of the subject.  The date and the reasons for breaking the blind must be submitted to Biogen MA 
Inc. within 24 hours.  Any opened envelopes will be returned to the secure location. 
If a subject’s treatment assignment is unblinded, the subject should remain in the study and 
continue the protocol-specified dosing schedule and follow-up evaluations, unless the reason for 
unblinding indicates otherwise. 
Biogen MA Inc. reserves the right to review the unblinded data if required for the safe and 
proper treatment of a subject, or if the severity of an AE if drug-related, would lead to early 
termination of the study. 
15.4. 
Pregnancy 
Female subjects should not become pregnant during the study.  The Investigator must report any 
pregnancy, occurring in a female subject from the first dose of study treatment to 12 weeks post 
last dose, to 
 (DSS Fax No.: 
) within 24 hours of the study 
site staff becoming aware of the pregnancy.  All subsequent injections of the study treatment will 
be stopped and the subject will enter the standard FU period.  The Investigator or study site staff 
must follow the pregnancy until outcome and report the outcome to 
.  
Congenital abnormalities and birth defects in the offspring of male or female subjects should be 
reported as an SAE if conception occurred during the study treatment period. 


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15.5. 
Procedure for Death 
Deaths must be reported to 
 by fax using the SAE form within 24 hours of 
the investigational site’s awareness of the event.  The appropriate CRF must be completed.  
Investigators are requested to send death certificates and autopsy reports to 
 
per the SAE reporting procedures described in Section 14.4.   
If a subject’s treatment assignment is unblinded for a medical emergency that ultimately leads to 
death, the Investigator must also document the reason for unblinding in the subject’s CRF.   


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16. 
ETHICS 
16.1. 
Institutional Review Board or Independent Ethics Committee 
This protocol will be reviewed and approved by the IRB where the study is conducted.  The IRB 
will meet all Food and Drug Administration (FDA) requirements governing IRBs (Code of 
Federal Regulations, Title 21, Part 56). 
16.2. 
Ethical Conduct of the Study 
Biogen MA Inc., the Medical Monitor, and the Investigator must comply with all instructions, 
regulations, and agreements in this protocol and in the applicable ICH and GCP guidelines, and 
must also conduct the study in accordance with local regulations.   
16.3. 
Subject Information  
16.3.1. 
Informed Consent 
Informed written consent is required from each subject prior to any testing under this protocol, 
including screening tests and evaluations.  The ICF, as specified by the clinical site’s IRB, must 
follow the Protection of Human Subjects regulations listed in the Code of Federal Regulations, 
Title 21, Part 50.   
The background of the proposed study and the benefits and risks of the procedures and study 
must be explained to the subjects.  It is the responsibility of the Investigator to obtain consent 
and to provide the subject with a copy of the signed and dated ICF.  Confirmation of a subject’s 
informed consent must also be documented in the subject’s medical record prior to any testing 
under this protocol, including screening tests and evaluations. 
All ICFs used in this study must be approved by the appropriate IRB and by Biogen MA Inc. or 
its designee.  The ICF must not be altered without the prior agreement of the relevant IRB and 
Biogen MA Inc. or its designee.   
16.3.2. 
Subject Data Protection 
Prior to any testing under this protocol, including screening tests and evaluations, subjects must 
authorize the release and use of PHI, as required by local law. 
The subject will not be identified by name in the CRF or in any study reports.  These reports will 
be used for research purposes only.  Biogen MA Inc., its designee, and various government 
health agencies may inspect the records of this study.  Every reasonable effort will be made to 
keep the subject’s personal medical data confidential. 


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17. 
STUDY ADMINISTRATION 
17.1. 
Investigator Responsibilities 
The Investigator’s responsibilities include the following: 
 Monitor and record all AEs, which include SAEs occurring any time during the study 
after signing of the ICF, regardless of the severity or relationship to study treatment. 
 Determine the seriousness, relationship, and severity of each event. 
 Determine the onset and resolution dates of each event. 
 Monitor and record all pregnancies and follow-up on the outcome of the pregnancy 
and status of the infant. 
 Complete an SAE form for each SAE and fax it to 
 within 
24 hours of the Investigator becoming aware of the event. 
 Pursue SAE follow-up information actively and persistently.  Follow-up information 
must be reported to 
 within 24 hours of the Investigator 
becoming aware of new information. 
 Ensure all AE and SAE reports are supported by documentation in the subjects’ 
medical records. 
 Notify the IRB of any unexpected SAEs involving risks to human subjects.  Copies of 
appropriate IRB documentation should be retained for the site and Sponsor study 
files. 
17.2. 
Biogen Responsibilities 
The Sponsor’s (or its designee’s) responsibilities include the following: 
 Before study site activation and subject enrollment, the Clinical Monitor is 
responsible for reviewing with study site staff the definitions of AEs and SAEs, as 
well as the instructions for monitoring, recording, and reporting AEs and SAEs. 
 Biogen MA Inc. (or designee) is to notify all appropriate regulatory authorities, 
central ethics committees, and Investigators of SAEs, as required by local law, within 
required time frames.   
 Biogen MA Inc. (or designee) is responsible for forwarding copies of documents that 
are submitted to regulatory authorities to the Investigators for submission to the local 
IRB, if applicable, and for inclusion in the study site files. 
17.3. 
Data Quality Control and Quality Assurance 
The Clinical Monitor will arrange to visit the Investigators at regular intervals during the study.  
The monitoring visits must be conducted according to the applicable ICH and GCP guidelines to 
ensure protocol adherence, quality of data, drug accountability, compliance with regulatory 


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requirements, and continued adequacy of the investigational site and its facilities.  During these 
visits, CRFs and other data related to the study will be reviewed and any discrepancies or 
omissions will be resolved.  The Clinical Monitor will be given access to study-relevant source 
documents (including medical records) for purposes of source data verification. 
During and/or after completion of the study, quality assurance officers named by Biogen MA 
Inc. or the regulatory authorities may wish to perform on-site audits.  The Investigator is 
expected to cooperate with any audit and provide assistance and documentation (including 
source data) as requested. 
17.4. 
Case Report Form Completion 
It is the Investigator’s responsibility to ensure the accuracy, completeness, legibility, and 
timeliness of the data reported in the subject’s CRF.  Source documentation supporting the CRF 
data should indicate the subject’s participation in the study and should document the dates and 
details of study procedures, AEs, and subject status. 
The Investigator will maintain copies (paper or electronic) of the CRFs at the study site.  
Subjects who discontinue or terminate from the study, the CRFs will be completed as much as 
possible, and the reason for the discontinuance or termination clearly and concisely specified on 
the appropriate CRF. 
17.5. 
Retention of Study Records 
The Investigator will maintain all study records according to ICH-GCP and applicable regulatory 
requirements.  Records will be retained for at least 2 years after the last marketing application 
approval or 2 years after formal discontinuation of the clinical development of the investigational 
product or according to applicable regulatory requirements.  If the Investigator withdraws from 
the responsibility of keeping the study records, custody must be transferred to a person willing to 
accept the responsibility.  Biogen MA Inc. must be notified in writing if a custodial change 
occurs. 
17.6. 
Confidentiality 
To maintain subject privacy, all CRFs, study treatment accountability records, study reports and 
communications will identify the subject by the assigned subject number.  The Investigator will 
grant monitor(s) and auditor(s) from the Sponsor or its designee and regulatory authority(ies) 
access to the subject’s original medical records for verification of data gathered on the CRFs and 
to audit the data collection process.  The subject’s confidentiality will be maintained and will not 
be made publicly available to the extent permitted by the applicable laws and regulations. 
All information regarding the investigational product supplied by the Sponsor to the Investigator 
is privileged and confidential information and shall remain the sole property of Biogen MA Inc.  
The Investigator agrees to use this information to accomplish the study and will not use it for 
other purposes without consent from the Sponsor.  The Investigator agrees not to disclose 
Biogen’s confidential information to anyone except to people involved in the study that need 
such information to assist in conducting the study, and then only on like terms of confidentiality 
and nonuse.  It is understood that there is an obligation to provide the Sponsor with complete test 


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results and all data developed in the study.  The information obtained from the clinical study will 
be used towards the development of the investigational product and may be disclosed to 
regulatory authority(ies), other Investigators, corporate partners, or consultants as required. 
17.7. 
Publication Policy 
The Sponsor, Biogen MA Inc., has no objection to publication or public disclosure for non-
commercial purposes by Institution or Investigator of the study data in accordance with this 
section.  The parties recognize that because this is a multi-center study, there is a need for a 
coordinated approach to any publication or publicizing of the study data or results of this study.  
In this regard, there will be no publication or publicizing of study data or results prior to the 
multi-center publication.  Authorship of the multi-center publication will be based on 
contribution to the design, conduct, or analysis of the study.  Therefore, Institution and 
Investigator agree not to publish or present the study data or results on an individual basis, until 
after the first to occur of: (a) publication of the multi-center publication, (b) notification from 
Sponsor or Sponsor’s designee that a multi-center publication is no longer planned, or (c) 18 
months after completion of the study at all sites.  After completion of the study, and subject to 
the provisions of this section, the Institution and Investigator shall be free to publish or present 
the study data or results.  The Institution or Investigator will submit any proposed manuscript or 
publication to the Sponsor for comment at least 30 days prior to its release of that manuscript or 
publication or at least 14 days prior to submission for abstracts or presentations (“Review 
Period”).  The Institution or Investigator will make every reasonable attempt to incorporate 
comments received from the Sponsor, and will upon request remove any previously undisclosed 
Confidential Information, prior to publication or disclosure.  If during the Review Period, 
Sponsor notifies the Institution or Investigator that it desires patent applications to be filed on 
any Invention disclosed or contained in the disclosures, the Institution and Investigator will defer 
publication or other disclosure for a period, not to exceed an additional 90 days, sufficient to 
permit Sponsor or its designee to file or have filed any desired patent applications.   
17.8. 
Direct Access to Source Data 
The Investigator and clinical sites will permit trial-related monitoring, audits, IRB review, and 
regulatory inspections as requested by FDA or other regulatory authorities, Biogen, or Biogen’s 
designee, including direct access to source data/documents (i.e., original medical records, 
laboratory reports, hospital documents, progress reports, signed ICF, etc.) in addition to CRFs. 
17.9. 
Protocol Amendments 
All protocol amendments must be approved by the IRB and submitted to the appropriate 
regulatory authorities before implementation of such modifications to the study. 
In the event that the protocol needs to be modified immediately to eliminate an apparent hazard 
to a subject, Biogen MA Inc. will amend and implement the protocol change and subsequently 
notify the regulatory authorities and/or the IRB, as appropriate.  Most such instances that require 
immediate action for an individual subject will be handled by a protocol deviation or waiver. 


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72 
18. 
REFERENCES 
Adamali HI, Maher TM. Current and novel drug therapies for idiopathic pulmonary fibrosis. 
Drug Des Devel Ther. 2012;6:261-72. 
American Thoracic Society/European Respiratory Society. American Thoracic Society/European 
Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic 
Interstitial Pneumonias. Am J Respir Crit Care Med. 2002;165(2):277-304. 
Bartram U, Speer CP. The role of transforming growth factor beta in lung development and 
disease. Chest. 2004;125(2):754-65. 
Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 
1994;331(19):1286-92. 
Breuss JM, Gallo J, DeLisser HM, et al. Expression of the beta 6 integrin subunit in 
development, neoplasia and tissue repair suggests a role in epithelial remodeling. J Cell Sci. 
1995;108 ( Pt 6):2241-51. 
Breuss JM, Gillett N, Lu L, et al. Restricted distribution of integrin beta 6 mRNA in primate 
epithelial tissues. J Histochem Cytochem. 1993;41(10):1521-7. 
Broekelmann TJ, Limper AH, Colby TV, et al. Transforming growth factor beta 1 is present at 
sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc Natl Acad Sci U 
S A. 1991;88(15):6642-6. 
Greene KE, King TE, Kuroki Y, et al. Serum surfactant proteins-A and -D as biomarkers in 
idiopathic pulmonary fibrosis. Eur Respir J. 2002;19(3):439-46. 
Hahm K, Lukashev ME, Luo Y, et al. Alphav beta6 integrin regulates renal fibrosis and 
inflammation in Alport mouse. Am J Pathol. 2007;170(1):110-25. 
Häkkinen L, Hildebrand HC, Berndt A, et al. Immunolocalization of tenascin-C, alpha9 integrin 
subunit, and alphavbeta6 integrin during wound healing in human oral mucosa. J Histochem 
Cytochem. 2000;48(7):985-98. 
Horan GS, Wood S, Ona V, et al. Partial inhibition of integrin alpha(v)beta6 prevents pulmonary 
fibrosis without exacerbating inflammation. Am J Respir Crit Care Med. 2008;177(1):56-65. 
Jensen RL, Teeter JG, England RD, et al. Sources of long-term variability in measurements of 
lung function: implications for interpretation and clinical trial design. Chest. 2007a;132(2):396-
402. 
Jensen RL, Teeter JG, England RD, et al. Instrument accuracy and reproducibility in 
measurements of pulmonary function. Chest. 2007b;132(2):388-95. 


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Khalil N, O'Connor RN, Flanders KC, et al. TGF-beta 1, but not TGF-beta 2 or TGF-beta 3, is 
differentially present in epithelial cells of advanced pulmonary fibrosis: an immunohistochemical 
study. Am J Respir Cell Mol Biol. 1996;14(2):131-8. 
King TE, Pardo A, Selman M. Idiopathic pulmonary fibrosis. Lancet. 2011;378(9807):1949-61. 
Kuwano K, Maeyama T, Inoshima I, et al. Increased circulating levels of soluble Fas ligand are 
correlated with disease activity in patients with fibrosing lung diseases. Respirology. 
2002;7(1):15-21. 
Ludlow A, Yee KO, Lipman R, et al. Characterization of integrin beta6 and thrombospondin-1 
double-null mice. J Cell Mol Med. 2005;9(2):421-37. 
Ma LJ, Yang H, Gaspert A, et al. Transforming growth factor-beta-dependent and -independent 
pathways of induction of tubulointerstitial fibrosis in beta6(-/-) mice. Am J Pathol. 
2003;163(4):1261-73. 
Morris DG, Huang X, Kaminski N, et al. Loss of integrin alpha(v)beta6-mediated TGF-beta 
activation causes Mmp12-dependent emphysema. Nature. 2003;422(6928):169-73. 
Mukae H, Iiboshi H, Nakazato M, et al. Raised plasma concentrations of alpha-defensins in 
patients with idiopathic pulmonary fibrosis. Thorax. 2002;57(7):623-8. 
Munger JS, Huang X, Kawakatsu H, et al. The integrin alpha v beta 6 binds and activates latent 
TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell. 
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Respir J. 2005;26(5):948-68. 
Pittet JF, Griffiths MJ, Geiser T, et al. TGF-beta is a critical mediator of acute lung injury. J Clin 
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of latent transforming growth factor-beta, prevents radiation-induced lung fibrosis. Am J Respir 
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Raghu G, Brown KK, Bradford WZ, et al. A placebo-controlled trial of interferon gamma-1b in 
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Raghu G, Collard HR, Egan JJ, 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(6):788-824. 
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biomarkers in idiopathic pulmonary fibrosis. PLoS Med. 2008;5(4):e93. 


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Sheppard D. Functions of pulmonary epithelial integrins: from development to disease. Physiol 
Rev. 2003;83(3):673-86. 
Shihab FS, Yamamoto T, Nast CC, et al. Transforming growth factor-beta and matrix protein 
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Trevillian P, Paul H, Millar E, et al. alpha(v)beta(6) Integrin expression in diseased and 
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Yamamoto T, Nakamura T, Noble NA, et al. Expression of transforming growth factor beta is 
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Yamamoto T, Noble NA, Cohen AH, et al. Expression of transforming growth factor-beta 
isoforms in human glomerular diseases. Kidney Int. 1996;49(2):461-9. 
Yokoyama A, Kohno N, Hamada H, et al. Circulating KL-6 predicts the outcome of rapidly 
progressive idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1998;158(5 Pt 1):1680-4. 
Zambruno G, Marchisio PC, Marconi A, et al. Transforming growth factor-beta 1 modulates beta 
1 and beta 5 integrin receptors and induces the de novo expression of the alpha v beta 6 
heterodimer in normal human keratinocytes: implications for wound healing. J Cell Biol. 
1995;129(3):853-65. 
 
 


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19. 
SIGNED AGREEMENT OF THE STUDY PROTOCOL 
I have read the foregoing protocol, “Randomized, Double-Blind, Placebo-Controlled, Multiple 
Dose, Dose-Escalation Study of BG00011 in Patients with Idiopathic Pulmonary Fibrosis (IPF)” 
and agree to conduct the study according to the protocol and the International Conference on 
Harmonisation (ICH) guidelines and Good Clinical Practice (GCP) regulations, and to inform all 
who assist me in the conduct of this study of their responsibilities and obligations. 
 
____________________________________________________ 
Investigator’s Signature 
 
 
 
Date 
 
 
____________________________________________________ 
Investigator’s Name (Print) 
 
 
____________________________________________________ 
Study Site (Print) 
 

SAP_000.pdf: 
 
Final V2.0: 23May2016                                                                        
             Page 1 of 22 
 
STATISTICAL ANALYSIS PLAN 
 
 
Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Dose-Escalation 
Study of STX-100 in Patients with Idiopathic Pulmonary Fibrosis (IPF) 
Statistical Analysis Plan Status: Final V2.0                                                                    
Statistical Analysis Plan Date:   23May2016 
Study Drug: BG00011  
Sponsor Reference:  203PF201(Formerly STX-003) 
Clinical Phase 2a 
 
 
 
Sponsor:                                        
Biogen MA Inc. 
14 Cambridge Center 
Cambridge, MA 021142 
United States                   
 
 
Sponsor Signatory:                             
, MD 
 
(SMT Physician) 
, PhD 
 
(CDT Statistician) 
 
, PhD  
 
(SMT Statistician) 
 


Statistical Analysis Plan  
 
CONFIDENTIAL 
 
 
Sponsor Reference 203PF201 
Final V2.0: 23May2016                                                                        
             Page 2 of 22 
 
1. STATISTICAL ANALYSIS PLAN APPROVAL SIGNATURES 
By signing this page when the Statistical Analysis Plan (SAP) is considered final, the signatories 
agree to the statistical analyses to be performed for this study, and to the basic format of the 
tables, figures, and listings (TFLs).         
 
 approval: 
 
 
 
 
 
, MS 
 
 
Date 
 
 
 
 
 
Sponsor approval: 
 
 
 
 
 
, MD 
 
(SMT Physician) 
 
 
Date 
 
 
 
 
 
, PhD 
 
(CDT Statistician)  
 
 
Date 
 
 
 
 
 
, PhD  
 
(SMT Statistician) 
 
Date 
 
 
 


Statistical Analysis Plan  
 
CONFIDENTIAL 
 
Sponsor Reference 203PF201 
Final V2.0: 23May2016                                                                        
             Page 3 of 22 
 
2. TABLE OF CONTENTS 
1. 
STATISTICAL ANALYSIS PLAN APPROVAL SIGNATURES ................................... 2 
2. 
TABLE OF CONTENTS ................................................................................................... 3 
3. 
ABBREVIATIONS ............................................................................................................ 5 
4. 
INTRODUCTION .............................................................................................................. 8 
5. 
STUDY OBJECTIVES ...................................................................................................... 8 
6. 
STUDY DESIGN ............................................................................................................... 9 
6.1 NOMENCLATURE FOR STUDY PERIODS AND STUDY DAYS .............................. 10 
7. 
TREATMENT .................................................................................................................. 10 
8. 
SAMPLE SIZE JUSTIFICATION ................................................................................... 10 
9. 
DEFINITION OF ANALYSIS POPULATIONS ............................................................ 10 
10. STATISTICAL METHODOLOGY ................................................................................. 11 
10.1 General ....................................................................................................................... 11 
10.2 Definitions ................................................................................................................. 12 
10.3 Demographics and Baseline Characteristics .............................................................. 12 
10.4 Prior and Concomitant Medications .......................................................................... 12 
10.5 Protocol Deviations ................................................................................................... 12 
10.6 Study Medication Administration .............................................................................. 12 
10.7 Pharmacokinetic Assessment ..................................................................................... 12 
10.8 Safety and Tolerability Assessments ......................................................................... 12 
10.8.1 Adverse Events ................................................................................................. 13 
10.8.2 Clinical Laboratory Parameters ........................................................................ 14 
10.8.3 Vital Signs ........................................................................................................ 15 
10.8.4 Electrocardiogram (ECG) ................................................................................. 15 
10.8.5 Physical Examination ....................................................................................... 15 
10.8.6 Pulmonary Function Tests (PFT) ..................................................................... 15 
10.8.7 Bronchoalveolar Lavage (BAL) MMP-12 ....................................................... 16 
10.8.8 High Resolution Computed Tomography (HRCT) .......................................... 16 
10.8.9 Pulse Oximetry ................................................................................................. 17 
10.8.10 Immunogenicity (Anti-BG00011 Antibodies) ................................................. 17 
10.8.11 Investigator Assessment of Respiratory Status ................................................ 17 
10.8.12 Other Assessments ........................................................................................... 18 


Statistical Analysis Plan  
 
CONFIDENTIAL 
 
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Final V2.0: 23May2016                                                                        
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10.9 Data Safety Monitoring Board ................................................................................... 18 
10.10 Pharmacodynamic Analyses ...................................................................................... 18 
11. INTERIM ANALYSES .................................................................................................... 19 
12. CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES ....... 19 
13. CHANGES FROM THE PREVIOUS STATISTICAL ANALYSIS PLAN ................... 19 
14. REFERENCES ................................................................................................................. 21 
15. DATA PRESENTATION ................................................................................................ 21 
15.1 Missing Data .............................................................................................................. 22 
15.2 Presentation for Dates ................................................................................................ 22 
15.3 Unscheduled Assessments ......................................................................................... 22 
15.4 Insufficient Data for Presentation .............................................................................. 22 
 
LIST OF TABLES 
Table 1: 
Dosing Cohorts 
9 
Table 2: 
Pre-Specified Genes 
18 
 
 
 


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3. ABBREVIATIONS 
Abbreviations pertain to the SAP only (not the TFLs). 
αvβ6 
alpha v beta 6 
AE 
adverse event 
ALAT 
Latin American Thoracic Association 
ALOX5 
arachidonate 5-lipoxygenase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATS 
American Thoracic Society 
BAL 
bronchoalveolar lavage 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CSR 
clinical study report 
CV 
coefficient of variation 
DLco/Hb 
carbon monoxide diffusion capacity, corrected for hemoglobin 
DSMB 
Data Safety Monitoring Board 
ECG 
electrocardiogram 
ERS 
European Respiratory Society 
ETS1 
v-ets erythroblastosis virus E26 oncogene homolog 1 
FEV1 
a ratio of the forced expiratory volume in one second 
FN1 
fibronectin 
FU 
follow-up 
FVC 
forced vital capacity 
GGT 
gamma-glutamyl transpeptidase 
HCO3 
bicarbonate 
HRCT 
high resolution computed tomography 
ICH 
International Conference on Harmonization 
I/E 
inclusion/exclusion 


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IPF 
idiopathic pulmonary fibrosis 
JRS 
Japanese Respiratory Society 
LDH 
lactate dehydrogenase 
LDL 
low density lipoprotein 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MD  
multiple dose  
MedDRA 
Medical Dictionary for Regulatory Activities 
mRNA 
messenger ribonucleic acid 
NA 
not applicable 
OLR1 
oxidized low density lipoprotein receptor 1 
O2 
oxygen 
PAI-1 
plasminogen activator inhibitor-1 (SERPINE1) 
PFT 
pulmonary function test 
PK 
pharmacokinetic 
pSMAD2 
phosphorylated SMAD2 
PT 
preferred term 
RV 
residual volume 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous(ly) 
SD 
standard deviation 
SE 
standard error 
SLB 
surgical lung biopsy 
SOC 
system organ class 
SOP 
Standard Operating Procedure 
TEAE 
treatment emergent adverse event 
TESAE 
treatment emergent serious adverse event 
TFLs 
Tables, Figures, and Listings 
TGF-β 
transforming growth factor-beta 
TGM2 
transglutaminase 2 


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TREM1 
triggering receptor expressed on myeloid cells 1 
tSMAD2 
total SMAD2 
UIP 
usual interstitial pneumonia  
 


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4. INTRODUCTION 
The intent of this document is to provide guidance for analyses of data for this Phase 2a study. 
This statistical analysis plan (SAP) has been developed after review of the Clinical Study Protocol 
203PF201 (version 4 dated 16 July 2015). 
This SAP describes the planned analyses to evaluate the safety, tolerability, pharmacokinetics 
(PK), immunogenicity, and impact on bronchoalveolar lavage (BAL) and peripheral blood 
biomarkers of multiple doses of STX-100 (BG00011) in subjects with idiopathic pulmonary 
fibrosis (IPF). Please note that study drug names STX-100 and BG00011 are equivalent, and the 
study drug will be referred to as BG00011 in the SAP and associated tables, figures, and listings 
(TFLs).  A detailed description of the planned TFLs to be presented in the clinical study report 
(CSR) is provided in the accompanying TFL shell document. This SAP must be finalised prior to 
the lock of the clinical database and unblinding for this study. When the SAP and TFL shells are 
agreed upon and finalized, they will serve as the template for this study’s CSR. 
This version 2.0 SAP supersedes the statistical considerations identified in the protocol and the 
statistical considerations identified in the version 1.0 SAP dated 06 March 2012; where 
considerations are substantially different, they will be so identified. If additional analyses are 
required to supplement the planned analyses described in this SAP, they will be identified in the 
CSR. Any substantial deviations from this SAP will be agreed upon between Biogen MA Inc. and 
 and identified in the CSR.  
This SAP is written with consideration of the recommendations outlined in the International 
Conference on Harmonization (ICH) E9 Guideline entitled Guidance for Industry: Statistical 
Principles for Clinical Trials1 and the ICH E3 Guideline entitled Guidance for Industry: Structure 
and Content of Clinical Study Reports2. 
 
5. STUDY OBJECTIVES  
Primary Objective: 
• To evaluate the safety and tolerability of subcutaneously (SC) administered, multiple 
escalating doses of BG00011 (humanized monoclonal antibody directed against the αvβ6 
integrin) in subjects with IPF 
Secondary Objectives: 
• To estimate the PK parameters after the first dose and after the last dose of multiple, 
escalating doses of BG00011 in subjects with IPF 
• To assess the immunogenicity of BG00011 in subjects with IPF 


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• To assess the effect of BG00011 on biomarkers isolated from BAL and peripheral blood 
in subjects with IPF 
 
6. STUDY DESIGN 
This is a multi-center, randomized, double-blind, placebo-controlled, multiple dose, dose-
escalation study designed to evaluate the safety, tolerability, PK, immunogenicity, and impact on 
BAL and peripheral blood biomarkers of BG00011 activity in subjects with IPF conducted at 
approximately 15 centers in North America.  
Approximately 40 subjects will be enrolled into 5 sequential ascending dose cohorts (Table 1). 
Cohorts will include 8 subjects randomized to receive either BG00011 (6 subjects) or placebo (2 
subjects). Additional subjects may be enrolled if deemed appropriate by the Data Safety 
Monitoring Board (DSMB).  Doses to be administered are as follows: 
Table 1: 
Dosing Cohorts  
Cohort 
                Dose 
Number of Subjects 
BG00011 
Placebo 
1 
0.015 mg/kg 
6 
2 
2 
0.1 mg/kg 
6 
2 
3 
0.3 mg/kg 
6 
2 
4 
1.0 mg/kg 
6 
2 
5 
3.0 mg/kg 
6 
2 
Total Number of Subjects 
30 
10 
 
Subjects with clinical symptoms and features consistent with IPF prior to screening; forced vital 
capacity (FVC) ≥ 50% of predicted value;  carbon monoxide diffusion capacity, corrected for 
hemoglobin (DLco/Hb) ≥ 30% of predicted value; oxygen (O2) saturation > 90% while breathing 
ambient air at rest or receiving ≤2 L/minute of supplemental oxygen; residual volume (RV) ≤ 
120% of predicted value; a ratio of the forced expiratory volume in one second (FEV1) to FVC ≥ 
0.65 after the use of a bronchodilator during screening pulmonary function tests (PFTs); high 
resolution computed tomography (HRCT) consistent with usual interstitial pneumonia (UIP) 
pattern; and who meet the other inclusion/exclusion (I/E) criteria are eligible to enroll in the 
study. Subjects who do not qualify for study eligibility may be rescreened at the discretion of the 
Principal Investigator. 
Each subject within a dose cohort will be randomized to receive either BG00011 or placebo and 
will participate in 2 consecutive study periods: 1) each subject will receive 8 consecutive weekly 
doses of BG00011 (or placebo) (Period 1; Multiple Dose [MD] phase); and, 2) each subject will 
be monitored for 12 weeks (8 weeks for Cohorts 4 and 5) following administration of the last dose 
of study drug (Period 2; Follow-Up [FU] Phase). 


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6.1 NOMENCLATURE FOR STUDY PERIODS AND STUDY DAYS 
Days for the MD period are designated with an “MD” and days for the FU period are designated 
with an “FU.” 
• Day 1-MD is the day the subject receives the first dose during the MD period of the study. 
• Day 1-FU is first day of the follow-up period, which should coincide with the day of last 
dose during the MD period (Day 50-MD).   
 
7. TREATMENT 
BG00011 will be administered as an SC injection. Doses will be 0.015 mg/kg, 0.1 mg/kg, 0.3 
mg/kg, 1.0 mg/kg, and 3.0 mg/kg. Weight obtained at initial screening will be used to calculate 
dose throughout the study. At the end of a screening period, eligible subjects will return for 
dosing on Day 1-MD. Study drug will be administered once weekly for 8 doses (7 weeks), i.e., on 
Days 1-MD, 8-MD, 15-MD, 22-MD, 29-MD, 36-MD, 43-MD, and 50-MD of the multiple-
doseperiod.  
In cohorts 1 to 3, each subject’s participation in the study will be for approximately 24 weeks 
(~5.5 months), i.e., up to 5 weeks to perform screening/entry evaluations, followed by 7 weeks of 
double-blind study dosing (8 doses) and a Follow-up period of 12 weeks.  For Cohorts 4 and 5,  
the subject’s participation in the study will be for approximately 23 weeks (~5.5 months), i.e., up 
to 8 weeks to perform screening/entry evaluations, followed by 7 weeks of double-blind study 
dosing (8 doses) and Follow-up period of 8 weeks. 
 
8. SAMPLE SIZE JUSTIFICATION 
No formal statistical justification for the sample size was performed for this Phase 2a study. 
Cohort size was determined based on requirements for PK analyses and safety assessments. With 
6 subjects per cohort administered BG00011 the probability of observing an event is 82% if the 
actual probability of such an event is 25%. 
 
9. DEFINITION OF ANALYSIS POPULATIONS 
The “Safety” population will consist of all subjects who received at least one dose of BG00011 or 
placebo. 


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The “Pharmacodynamic” population will consist of all subjects who received at least 1 multiple 
dose injection of BG00011 and have a corresponding sample collected for BAL and/or blood 
biomarkers (e.g., Visit 16 Day 8-FU).  
All protocol deviations that occur during the study will be considered for their severity/impact 
prior to treatment assignment unblinding and will be taken into consideration when subjects are 
assigned to analysis populations. Details of subject assignment to the analysis populations will be 
listed. 
 
10. 
STATISTICAL METHODOLOGY 
10.1 
General 
Data listings will be provided by treatment group, subject and visit, if applicable. Summary 
statistics and statistical analyses will only be presented for data where detailed in this SAP. For 
continuous data, summary statistics will include the arithmetic mean, arithmetic standard 
deviation (SD), median, minimum (Min), maximum (Max) and n; for log-normal data the 
geometric mean and geometric coefficient of variation (CV) will also be presented. For 
categorical data, frequency count and percentages will be presented. Data listings will be provided 
for all subjects up to the point of withdrawal, with any subjects excluded from the relevant 
population highlighted. Summary statistics and statistical analyses will generally only be 
performed for subjects included in the relevant analysis population. For the calculation of 
summary statistics and statistical analysis, unrounded data will be used.  
Due to the small number of subjects expected to enroll at each participating center, all summaries 
and analyses will be performed using data pooled across centers. Data for BG00011 treated 
subjects will be grouped by treatment group. Data for all placebo subjects, regardless of treatment 
group, will be treated as one group. Data will be summarized and presented by treatment group, 
defined as each of the BG00011 dose groups and the combined placebo group. Data will be listed 
by treatment group. Exposure to study medication will be tabulated by treatment group.  
Mean change from baseline is the mean of all individual subject’s change from their baseline 
value. Each individual change from baseline will be calculated by subtracting the individual 
subject’s baseline value from the value at their subsequent visit(s). The individual subject’s 
change from baseline values will be used to calculate the mean change from baseline using a 
SAS® procedure such as Proc Univariate. 
Data analyses will be performed using SAS® Version 9.1.3 or greater. 
As previously stated (Section 4), this document describes the planned analyses for this Phase 2a 
study evaluating the safety, tolerability, PK, immunogenicity, and impact on BAL and peripheral 
blood biomarker of multiple doses of BG00011 in subjects with IPF. Some of the analyses 
described in this SAP will be performed by outside vendors. These data will be imported to the 
Biometrics database for study 203PF201 or, alternatively, provided as separate reports. 


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10.2 
Definitions 
The following definitions apply: 
Baseline - last observation collected prior to the date/time of study drug administration, unless 
otherwise noted. 
Treatment group - each of the five BG00011 dose groups and the combined placebo group. 
10.3 
Demographics and Baseline Characteristics 
Subject disposition will be summarized for the safety and efficacy populations. Reasons for 
discontinuation will be summarized by treatment group. The demographic variables age, sex, 
race, ethnicity, body weight, height, and body mass index will be summarized. By-subject listings 
of these variables will be provided. 
Listings will also be created for subject eligibility, smoking history, and general/IPF-specific 
medical history. 
10.4 
Prior and Concomitant Medications 
Prior and concomitant medications will be listed in the by-subject data listings. WHODRUG 
Version March 2011 or higher will be used to encode these medications. 
10.5 
Protocol Deviations 
Protocol deviations will be listed. 
10.6 
Study Medication Administration 
Study medication administration will be listed and the frequency of subjects who were 
administered treatment at each of the 8 visits will be summarized. 
10.7 
Pharmacokinetic Assessment 
The date and time of pharmacokinetic (PK) blood sample collections by treatment group and by 
subject will be listed. The analysis of PK data will be described in a separate PK analysis plan and 
provided in a separate report.  
10.8 
Safety and Tolerability Assessments 
Data will be summarized and presented by treatment group, defined as each of the BG00011 dose 
groups, the combined BG00011 group, and the combined placebo group. Data will be listed by 
treatment group. The safety population will be used for the following safety analyses. No 
inferential statistical analyses are planned. 


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10.8.1 Adverse Events 
Adverse events (AEs) will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA Version 14.0 or later). Summary tables will be based on treatment emergent AEs 
(TEAE). A TEAE is defined as an AE that occurs during or after first dose or which is present 
prior to study drug administration and becomes more severe during or after first dose. Any event 
occurring prior to the first dose of study medication will be recorded as medical history.  Related 
events are those classified as Possible, Probable, or Definite by the investigator.  All AE analyses 
will be performed on TEAEs. All TEAEs will be listed by subject. 
The following will be summarized and presented for each treatment group: 
• The total number of TEAEs for each treatment group overall, by highest severity, by 
strongest causal relationship to study medication, the frequency of adverse events, the 
number of subjects with treatment emergent serious adverse events (TESAEs), and the 
number of subjects with TEAEs leading to study discontinuation;  
• The number and percentage of subjects experiencing a TEAE for each system organ class 
(SOC) and each preferred term (PT) within each SOC;  
• The number and percentage of subjects experiencing a TEAE for each preferred term (PT) 
in descending frequency; 
 
• The number and percentage of subjects experiencing a TEAE by greatest severity for each 
system organ class (SOC) and each preferred term (PT) within each SOC;  
• The number and percentage of subjects experiencing a related TEAE for each system organ 
class (SOC) and each preferred term (PT) within each SOC;  
• A listing of subjects experiencing a TESAE;  
• A listing of subjects experiencing a TEAE leading to withdrawal; and 
• A listing of subject deaths occurring on study and relatedness to TEAE. 
The incidence of TEAEs will be calculated by dividing the number of subjects who have 
experienced the event by the number of subjects in the treatment group. Thus, the incidence of 
TEAEs counts only the first occurrence of an event for each subject in that treatment group that 
experiences the event, and does not represent the total number of episodes of the particular event 
in the treatment group. If a subject has repeated episodes of a particular TEAE, only the most 
severe episode or the episode with the strongest causal relationship to study medication, as 
appropriate, will be counted. 
A subject with more than one TEAE for a particular PT will be counted only once in the total of 
subjects experiencing TEAEs in that particular PT.  Likewise, a subject with more than one type 
of TEAE in a particular SOC will be counted only once in the total of subjects experiencing 


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TEAEs in that particular SOC. Similarly, a subject who has experienced a TEAE in more than 
one SOC will be counted only once in the total number of subjects experiencing TEAEs in all 
SOCs.  
All occurrences of all TEAEs will be listed for each subject. In the listing of individual subjects 
who have TEAEs, the following information on each episode will be provided: verbatim term, 
PT, SOC, severity of the event, relationship to study medication, onset date, resolution date, 
treatment given to treat the adverse event, the outcome, and whether the event was a TESAE.  
A listing of any subject deaths occurring on study will be provided. Deaths on study are those 
which occur after randomization but prior to early discontinuation or completion of study.  
10.8.2 Clinical Laboratory Parameters 
Serum chemistry and hematology data will be summarized by treatment group and visit. 
Descriptive statistics will be presented at each visit by treatment group for the parameters listed 
below. Shift tables of the baseline value compared to each post baseline value will be presented 
for the following selected laboratory parameters: a) alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), blood urea nitrogen (BUN), creatinine, direct bilirubin, glucose, and 
cholesterol for chemistry; and b) hemoglobin, hematocrit, white blood cell (WBC) count, 
neutrophil count, lymphocyte count, and platelet count for hematology. Urinalysis data and 
pregnancy data will be listed only. In addition, all serum chemistry, hematology and urinalysis 
data outside the central laboratory standard reference ranges will be listed by parameter and 
treatment group. 
Individual subject listings of clinical laboratory parameters at each visit will be provided. Values 
for any serum chemistry, hematology, and urinalysis values outside the central laboratory 
reference ranges will be flagged on the individual subject data listings. 
The following laboratory safety assessments will be included in the subject listings: 
• 
Hematology: complete blood count (CBC) with differential and platelet counts. CBC includes 
red blood cells (RBCs), WBCs, hemoglobin, hematocrit, mean corpuscular volume (MCV), 
mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration 
(MCHC) 
• 
Serum chemistry: albumin, alkaline phosphatase, ALT, AST, BUN, calcium, chloride, 
bicarbonate (HCO3), creatinine, direct bilirubin, gamma-glutamyl transpeptidase (GGT), 
glucose, lactate dehydrogenase (LDH), magnesium, phosphorus, potassium, sodium, total 
cholesterol, total protein, and uric acid  
• 
Urinalysis: including determination of the presence of protein, glucose, ketones, occult blood, 
and WBCs by dipstick, with microscopic examination, if indicated  


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10.8.3 Vital Signs 
Descriptive statistics will be used to summarize and present vital sign measurements at each 
nominal timepoint for each treatment group. Individual subject listings of vital signs at each 
timepoint will also be provided by treatment group.  
10.8.4 Electrocardiogram (ECG) 
The ECG data will be obtained directly from the 12-lead ECG traces. These data include the PR 
interval, QTcB interval, QRS duration, and heart rate. The ECG data will be listed by subject. 
Descriptive statistics will be used to summarize ECG measurements at each visit for each 
treatment group. In addition, a shift table of ECG interpretation results will be presented at each 
visit by treatment group. Individual subject listings of ECG parameters at each timepoint will also 
be provided by treatment group. 
10.8.5 Physical Examination 
Individual subject listings of physical examination results will be provided by treatment group.  
10.8.6 Pulmonary Function Tests (PFT) 
Under Protocol Version 1, for screening and baseline PFTs, 3 PFTs will be performed on separate 
days during the screening period (within 5 weeks prior to dosing). The first of these tests will be 
performed before and after bronchodilator administration to determine if the subject qualifies for 
the study, whereas the other 2 will be averaged to serve as the subject’s baseline value.  
Under Protocol Version 2 and later, for screening and baseline PFTs, 2 PFTs will be performed 
on separate days during the screening period (within 5 weeks prior to dosing). The first of these 
tests will be performed before and after bronchodilator administration to determine if the subject 
qualifies for the study, whereas the other PFT (performed without bronchodilator administration) 
will serve as the subject’s baseline value. If the baseline PFT does not meet quality criteria, the 
pre-bronchodilator screening PFT (or repeat pre-bronchodilator screening PFT, if appropriate) 
will be substituted as the baseline value.  
PFT parameters include: 
FVC:  
forced (expiratory) vital capacity 
FEV1:  
forced expiratory volume over one second 
TLC:  
total lung capacity 
DLco/Hb:carbon monoxide diffusion capacity, corrected for hemoglobin 
RV: 
 
residual volume 
The assessment of changes in lung function during this study will be performed by comparing the 
subject’s follow-up PFT parameters (i.e., Visit 9 Day 29-MD and Visit 16 Day 8-FU visits) to 


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their baseline value. Each subject’s percent change from baseline will be calculated by subtracting 
the individual subject’s baseline value from the value at the desired time point and then dividing 
this calculated value by the individual subject’s baseline value and multiplying by 100. The 
individual subject’s percent change from the baseline value will be used to calculate the mean 
percent change from baseline for the treatment group using a SAS procedure such as Proc 
Univariate. 
The following decreases in PFT parameters have been prospectively defined as significant and 
may be clinically important: TLC ≥ 8%, FEV1 ≥ 12%, FVC ≥ 12%, and/or DLco/Hb ≥ 15% 
change from the baseline value. PFTs demonstrating a potentially clinically significant decline 
from baseline must be confirmed by repeating the abnormal parameter. A confirmed decline in a 
PFT parameter will be reported as an adverse event and will be used for analysis purposes.  
Listings of individual subject data by study visit and treatment assignment will be provided for 
each of the PFT parameters as well as the percent change from baseline. Summary statistics of the 
PFT parameters will be provided by treatment group for the actual PFT value and the percent 
predicted for each of the PFT parameters specified above (reference populations are NHANES III 
for Spirometry and Crapo 1982 for DLco/Hb 3,4).  
10.8.7 Bronchoalveolar Lavage (BAL) MMP-12 
A BAL will be performed during the screening period and after receiving the last dose of study 
medication (i.e., from Visit 14 Day 3-FU to Visit 16 Day 8-FU). Analysis of the BAL 
macrophage MMP-12 mRNA levels (which are increased when macrophages are activated) will 
be measured.  
Subject listings of the screening and Visit 16 Day 8-FU MMP-12 levels, as well as the % change 
from screening, will be provided. Summary statistics of the relative expression of MMP-12 levels 
at screening and following the last dose of study medication, as well as the percent change from 
Screening, will also be provided for each treatment group.  
10.8.8 High Resolution Computed Tomography (HRCT) 
The diagnostic criteria for IPF in study 203PF201 are based on the recently updated evidence-
based guidelines developed by the ATS/ERS/JRS/ALAT joint task force for the diagnosis and 
management of IPF5. An HRCT scan will be performed during screening to establish subject 
eligibility as well as the pre-dosing pattern and extent of disease. Each subject will have a repeat 
HRCT performed within 21 days after receiving the last dose of study medication to assess for 
changes in the extent of IPF. The details of the independent HRCT and surgical lung biopsy 
(SLB) assessments are described in the Perceptive Informatics ‘Independent Review Manual’. 
For the eligibility review, a minimum of 2 and a maximum of 3 independent radiologists will 
evaluate the screening HRCT images to determine whether they fulfill the radiographic criteria 
for UIP pattern. If a SLB is available at screening (lung biopsy performed prior to screening is 
acceptable), a minimum of 2 and a maximum of 3 independent pathologists will assess the SLB 
for UIP pattern. For all subjects that have a SLB available at the time of screening, the combined 
results of radiology and pathology assessments will be used to determine subject eligibility. If a 


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subject does not have a SLB available at the time of screening, eligibility will be determined by 
radiology assessment alone. A consensus panel will be convened if subject eligibility is not clear 
based upon the initial independent review of the HRCT and SLB.  
For the safety review, the independent radiologists will also compare each subject’s screening and 
follow-up HRCT images to determine whether a change in IPF by HRCT has occurred. A 
qualitative and semi-quantitative assessment will be performed. The qualitative assessment will 
summarize the change in the combination of honeycombing and reticulation (i.e., same, better, 
much better, worse, much worse, unknown). For the semi-quantitative assessment, the extent of 
fibrosis including the extent of reticular abnormalities and honeycombing together will be scored 
for each lung separately as well as for both lungs combined using the following categories: 
absent, 1-25%, 26-50%, 51-75%, 76-100%, or unknown. At the time of review the radiologists 
will also assess the HRCT images for technical adequacy and quality (i.e., noting anatomy that is 
not complete, motion artifacts present, crucial anatomy is out of the field of view, other, etc.). 
Shift tables of the semi-quantitative HRCT assessments will be presented by treatment group. 
Individual subject listings of all HRCT and SLB eligibility assessments, as well as the qualitative 
and semi-quantitative HRCT safety assessments, will also be provided (including reviewer 
comments and consensus panel assessments). 
10.8.9 Pulse Oximetry 
Descriptive statistics will be used to summarize and present O2 saturation at each visit, and 
change from baseline, for each treatment group. Individual subject listings of O2 saturation at 
each visit will be provided.  
10.8.10 Immunogenicity (Anti-BG00011 Antibodies) 
Blood samples for potential antibodies to BG00011 will be collected during screening and prior to 
dosing on Visit 2 Day 1-MD. Post-dose samples will be obtained on Visit 19 Day 29-FU and 
Visit 85 Day 85-FU. 
Each blood sample will initially be tested for the presence of anti-BG00011 antibodies using a 
validated electrochemiluminescence (ECL) method. Confirmed positive samples using the 
screening assay will be titered and subsequently tested using a validated neutralization assay. 
Antibody results will be presented by treatment group and subject in listings. The incidence of 
antibodies to BG00011 (both binding as well as neutralizing) will be tabulated over time by 
treatment group using descriptive statistics. The antibody titer and natural log transformed results 
will be summarized and presented using descriptive statistics. If antibodies are present, their 
effect on PK parameters will be explored.  
10.8.11  Investigator Assessment of Respiratory Status 
For subjects in Cohorts 4 & 5, a listing will be created of the investigator’s assessment of the 
subject’s respiratory status relative to baseline (better, worse, or the same) at Day 57-FU. 


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10.8.12  Other Assessments 
All other safety assessments not detailed in this section will be listed but not summarized or 
statistically analyzed. 
10.9 
Data Safety Monitoring Board 
An independent DSMB experienced in the oversight and monitoring of the conduct of clinical 
trials will determine whether dose escalation should proceed. The DSMB will be comprised of a 
biostatistician and two pulmonologists with expertise in interstitial lung diseases. The DSMB 
members’ responsibilities and the process for data reviews and dose-escalation are described in 
the DSMB Charter. 
Dose escalation will be based on the DSMB’s review of unblinded PK and safety data through 
Day 15 from the initial 4 (of 8) subjects administered BG00011 or placebo (3:1, respectively) in 
each cohort. Safety assessments will include a review of AEs, vital signs, physical examination, 
clinical laboratory tests, and pulse oximetry from these visits. In order to allow for compilation 
and evaluation of the data, it is anticipated that the DSMB will convene approximately 9-10 
weeks after the first 4 subjects in the previous cohort are initially dosed.  
Serious adverse events will be provided to the DSMB on an ongoing basis throughout the study. 
Updated safety (including BAL, PFTs, and HRCT results) and PK information on all participants 
will be provided in each subsequent DSMB data package. For example, at the DSMB meetings 
for Cohorts 2 and 3, updated safety and PK data will be available through at least week 8 of the 
follow-up period (i.e., complete PK data through the dosing phase and follow-up BAL, PFT, and 
HRCT) for all participants in Cohorts 1 and 2, respectively.  
10.10 Pharmacodynamic Analyses 
Secondary objectives of this study are to assess the effect of BG00011 on biomarkers isolated 
from BAL and peripheral blood in subjects with IPF. Listings and summary tables of expression 
level of 7 prespecified genes (Table 2) will be provided by treatment group and visit. A listing 
and summary table of ratio of pSMAD2 to tSMAD2 levels will be provided by treatment group 
and visit. Additional analyses of gene expression data from serum or BAL may be provided in a 
separate report. 
Table 2: 
Pre-Specified Genes 
Gene 
Gene Description 
ALOX5 (Arachidonate 5-lipoxygenase) 
A member of the lipoxygenase family of enzymes 
that transforms arachidonic acid into pro-
inflammatory leukotrienes. Associated with fibrotic 
lesions in IPF lung tissue. 
ETS1 (v-ets erythroblastosis virus E26 
oncogene homolog 1) 
A transcription factor that negatively regulates 
TGF-β induced collagen expression and inhibits 
IL-1b induced lung inflammation and MUC5AC 


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production. 
FN1 (fibronectin) 
An extracellular matrix protein that plays a major 
role in cell adhesion, growth, migration, and 
differentiation. Altered fibronectin expression is 
associated with fibrosis. 
OLR1 (oxidized low density lipoprotein 
[LDL] receptor 1) 
A LDL receptor belonging to the C-type lectin 
superfamily. Internalizes and degrades oxidized 
LDL. Upregulates angiotensin II activity and 
knockout protected against renal injury and 
fibrosis. Knockout also decreases TGF-β induced 
collagen production from cardiac fibroblasts. 
PAI-1 (plasminogen activator inhibitor-
1; also known as SERPINE1) 
A serine protease inhibitor and the principal 
inhibitor of tissue plasminogen activator and 
urokinase, the activators of plasminogen and hence 
fibrinolysis. PAI-1 inhibits the activity of matrix 
metalloproteinases and plays a significant role in 
the progression to fibrosis. 
TGM2 (transglutaminase 2) 
Catalyzes the crosslinking of extracellular matrix 
proteins including fibronectin and collagen. Acts as 
a co-receptor with beta integrins for binding to 
fibronectin enhancing cell adhesion and migration. 
Can enhance expression and maturation of fibrillar 
fibronectin.  
TREM1 (triggering receptor expressed 
on myeloid cells 1) 
Amplifies monocyte/macrophage- and neutrophil- 
mediated toll-like receptor inflammatory responses 
by stimulating release of pro-inflammatory 
chemokines and cytokines. Elevated soluble serum 
TREM1 levels are negatively correlated with 
pulmonary function in scleroderma subjects. 
 
11. 
INTERIM ANALYSES 
No formal interim statistical analyses are planned. An administrative interim analysis of data 
collected on Cohorts 1-4 may be used for internal (Biogen) decision making. 
12. 
CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES  
There were no changes from the protocol specified statistical analyses. 
13. 
CHANGES FROM THE PREVIOUS STATISTICAL ANALYSIS PLAN 
Several changes were made to SAP version 2.0 that differed from the SAP version 1.0.  All 
changes to the SAP were finalized prior to database lock and unblinding. In addition to editorial 
updates, the following changes were made: 


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• A test for trend analysis will not be performed to assess the relationship between dose level 
and incidence of antibodies due to small sample sizes. 
• Many of the efficacy analyses described in Section 10.8 of SAP version 1.0 will not be 
performed under this SAP.  Additional analyses of gene expression data from serum or 
BAL will be provided in a separate report.  ETS1 and tSMAD2 were added as biomarkers 
to analyze. 
• The “Efficacy” analysis population was renamed to the “Pharmacodynamic” population to 
more accurately reflect its purpose.  Also, only 1 injection of BG00011 will be necessary 
for part of the requirement to be included in this population, rather than the 5 injections 
noted in SAP version 1.0. 
• The PK methods and analysis will be described in a separate PK analysis plan. 


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14. 
REFERENCES 
1. International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline, Statistical Principles 
for Clinical Trials (E9), 5 February 1998. 
2. International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline, Structure and 
Content of Clinical Study Reports (E3), 30 November 1995. 
3. Spirometic Reference Values from a Sample of the General U.S. Population. Hankinson JL, 
Odencrantz JR, Fedan KB. Am J Respir Crit Care Med 159:179-187, 1999. 
4. Lung Volumes in Healthy Nonsmoking Adults. Crapo RO, Morris AH, Clayton PD, Nixon 
CR. Bull Europ Physiopath Respir 18:419-425, 1982. 
5. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based 
Guidelines for Diagnosis and Management. Am J Respir Crit Care Med 183:788-824, 2011. 
 
15. 
DATA PRESENTATION 
Values will be presented as indicated below. 
For safety data analysis:  
• 
Report mean values to the same decimal place as the individual data to which they 
refer. 
• 
Report SD and standard error (SE) of the mean to one more decimal place than the 
mean.  
• 
Report Med, Min, and Max values to the same number of decimal places as the 
individual data to which they refer.  
• 
Report CV, defined as the ratio of the standard deviation over the mean, as a 
percentage to one decimal point. 
• 
Report n to whole numbers. 
For example: 
Individual Values 
n  
Mean 
SD 
SE 
Min Med Max CV 
136, 123, 135  
    12  
131  
7.2 
4.2 
123 135 136 5.5% 
2.3, 3.1, 2.7, 3.0     12  
2.8 
 
0.36 0.18 2.3 
2.9 
3.1 
13.0% 
 


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15.1 
Missing Data 
Missing data will not be displayed in listings; the data inputs for the relevant timepoint will be 
left blank if the data are missing. 
15.2 
Presentation for Dates  
Dates will be presented in format (ddmonyyyy). Dates that are missing because they are not 
applicable will be presented as “NA,” unless otherwise specified. 
15.3 
Unscheduled Assessments 
Unscheduled assessments in the listings will be labeled as “Unscheduled.”  Values obtained 
during unscheduled visits will not be presented in summary tables, unless requested by the 
Sponsor. 
15.4 
Insufficient Data for Presentation 
Some of the TFLs may not have any data for presentation. If this occurs, the blank TFL shell will 
be presented with a message printed in the center of the table, such as, “No serious adverse 
events occurred during this study.”