A MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE LONG-TERM SAFETY, TOLERABILITY AND EFFICACY OF SUBCUTANEOUS PF-06741086 IN SUBJECTS WITH SEVERE HEMOPHILIA
Phase: PHASE2
Conditions: Hemophilia A or B
Sponsor: Pfizer

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A M U L TI C E N T E R, O P E N -L A B E L S T U D Y T O E V A L U A T E T H E L O N G - T E R M 
S A F E T Y, T O L E R A BI LI T Y A N D E F FI C A C Y O F S U B C U T A N E O U S P F - 0 6 7 4 1 0 8 6 I N 
S U B J E C T S WI T H S E V E R E H E M O P HI LI A
I n vesti g ati o n al Pr o d uct N u m ber:
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I n vesti g ati o n al Pr o d uct N a me:
N ot A p plica ble ( N/ A)
U nite d St ates ( U S) I n vesti g ati o n al Ne w 
Dr u g (I N D) N u m ber:
E ur o pe a n Cli nic al Tri als D at a b ase 
( E u dr a C T) N u m ber:
2 0 1 7- 0 0 1 2 5 5- 3 1
Pr ot oc ol N u m ber:
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P h ase:
2
T his d oc u me nt a n d acc o m pa n yi n g materials c o ntai n c o nfi de ntial i nf or mati o n bel o n gi n g t o Pfizer.  E xce pt as 
ot her wise a gree d t o i n writi n g, b y acce pti n g or re vie wi n g t hese d oc u me nts, y o u a gree t o h ol d t his i nf or mati o n i n 
c o nfi de nce a n d n ot c o p y or discl ose it t o ot hers (e xce pt w here re q uire d b y a p plica ble la w ) or use it f or 
u na ut h orize d p u r p oses.  I n t he e ve nt of a n y act ual or s us pecte d breac h of t his o bli gati o n, Pfizer m ust be 
pr o m ptl y n otifie d.
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PF-06741086
B7841003
Final Protocol Amendment 2, 08 November 2018
PFIZER CONFIDENTIAL
Page 2
Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 2
08 November 
2018
General Changes Throughout Protocol
•
Extension of treatment duration from 6 
months to up to 365 days.
•
Editorial changes to fix titles, headers, 
grammar and typographical errors.
Protocol Summary
•
Revised treatment duration from 6 months to 
up to 365 days.
•
Revised visit day numbers to correspond to
up to 365 days treatment duration.
Schedule of Activities
•
Added clinic visits on Day 225 (Month 8), 
Day 253 (Month 9), Day 281 (Month 10), 
Day 309 (Month 11), Day 337 (Month 12), 
and Day 365 (Month 13).
•
Revised Table 1 title and footnotes to 
correspond to additional clinic visits and 
extended treatment duration.
Section 1.2.4 B7841003 Study Rationale
•
Revised treatment duration from 6 months to 
up to 365 days.
Section 2 Study Objectives and Endpoints
•
Revised visit day numbers to correspond to 
up to 365 days treatment duration.
Section 3 Study Design
•
Revised treatment duration from 6 months to 
up to 365 days.
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B7841003
Final Protocol Amendment 2, 08 November 2018
PFIZER CONFIDENTIAL
Page 3
Section 3.2 Study Duration
•
Added clinic visits on Day 225 (Month 8), 
Day 253 (Month 9), Day 281 (Month 10), 
Day 309 (Month 11), Day 337 (Month 12), 
and Day 365 (Month 13).
•
Revised maximum study duration to 
15 months (365 days for subjects continuing 
from study B7841002).
Section 4.1 Inclusion Criterion
•
Revised Inclusion Criterion #2 for de novo 
subjects to add the requirement for episodic 
(on-demand) treatment prior to screening, as 
mandated by the FDA.
•
Added Inclusion Criterion #3 for de novo 
subjects to add the requirement for 6 or more 
breakthrough bleeding episodes in the 
6 month period prior to screening, as 
mandated by the FDA.
Section 5.2 Subject Compliance
•
Revised visit day numbers to correspond to 
up to 365 days treatment duration.
Section 5.3.2 Preparation and Dispensing
•
Revised visit day numbers to correspond to 
up to 365 days treatment duration.
Section 6.2.3 Day 29 [±2 days], Day 57 [±5 days], 
Day 85 [±5 days], Day 113 [±7 days], 
Day 141 [±7 days], Day 169 [±7 days], Day 225 
[±7 days], Day 253 [±7 days], Day 281 [±7 days], 
Day 309 [±7 days], Day 337 [±7 days], and Day 
365 [±7 days] Visits
•
Revised section to add clinic visits on Day 
225, Day 253, Day 281, Day 309, Day 337, 
and Day 365.
•
Added text to clarify that Day 57 hematology 
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a n d ser u m c he mistr y sa m ples are f or de n o v o 
s u bjects o nl y.

 

Re vise d visit da y  n u m bers t o c orres p o n d t o 
u p t o 3 6 5 da y s treat me nt d urati o n. 
Secti o n 6. 2. 4 D a y 3 9 3 [ 7 d a ys] – E n d of St u d y 
Visit

Re vise d secti o n t o a d d cli nic visit o n 
Da y 3 9 3.

Re vise d visit da y  n u m bers t o c orres p o n d t o 
u p t o 3 6 5 da y s treat me nt d uratio n. 
Secti o n 7. 8 Bl o o d V ol u me

Re vise d Ta ble 4 t o i ncl u de a d diti o nal 
sa m ples. 
A me n d me nt 1
1 1 J u ne 2 0 1 8
Title

Re m o ve d “ or I ntra ve n o us” as t his r o ute of 
a d mi nistrati o n will n ot be use d i n t his st u d y .
Ge ner al C h a n ges T hr o u g h o ut Pr ot oc ol

E dit orial c ha n ges t o fi x titles, hea ders, 
gra m mar a n d t y p o gra p hical err ors.
Pr ot oc ol S u m m ar y

I ncl u de d s u bjects wit h i n hi bit ors t o F VIII or 
FI X.

I ncl usi o n of a d olesce nt s u bjects 1 2 t o 
< 1 8 ye ars of a ge.
Sc he d ule of Acti vities

Scree ni n g: 
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B7841003
Final Protocol Amendment 2, 08 November 2018
PFIZER CONFIDENTIAL
Page 5
•
Added assent/parental consent.
•
Added CD4 cell count lab.
•
Added Factor VIII or Factor IX inhibitor 
labs.  Added footnote ‘o’ for instructions 
on inhibitor labs.
•
Added cardiac troponin I labs for de novo 
subjects from Day 1 to Day 29.
•
Updated footnote ‘m’ to add guidance on 
interim visits to perform IP administration or 
monitor self-administration.
Section 1.1 Mechanism of Action/Indication
•
Included subjects with inhibitors to FVIII or 
FIX.
Section 1.2.3 Clinical Experience with 
PF-06741086
•
Included subjects with inhibitors to FVIII or 
FIX.
•
Added text to indicate that interim clinical 
data from B7841002 may be found in the 
PF-06741086 Investigator’s Brochure.
Section 1.2.5 Dose Rationale
•
Added text to clarify dose assignments based 
on results from study B7841002. 
Section 1.2.6 Summary of Risk/Benefit
•
Included subjects with inhibitors to FVIII or 
FIX. 
Section 2 Study Objectives and Endpoints
•
Included subjects with inhibitors to FVIII or 
FIX. 
Section 3 Study Design
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PF-06741086
B7841003
Final Protocol Amendment 2, 08 November 2018
PFIZER CONFIDENTIAL
Page 6
•
Included subjects with inhibitors to FVIII or 
FIX. 
•
Figure 1 was updated to clarify dose 
assignments based on results from study 
B7841002.
Section 3.2 Study Duration
•
Editorial changes and clarifying text added 
regarding visit windows, visit requirements, 
and the use of unscheduled visits. 
Section 4.1 Inclusion Criteria
•
Included subjects with inhibitors to FVIII or 
FIX.
•
Inclusion of adolescent subjects ≥12 to 
<18 years of age.
•
Removal of requirements for episodic 
treatment and 6 or more breakthrough bleeds 
prior to study entry.
Section 4.2 Exclusion Criteria
•
Included subjects with inhibitors to FVIII or 
FIX.
•
An exclusion criterion regarding known 
severe hypercholesterolemia was added to 
comply with competent authority/ethics 
committee requests in France and 
Switzerland.
Section 4.3 Randomization Criteria
•
Included subjects with inhibitors to FVIII or 
FIX.
Section 5 Study Treatments
•
Removal of 100 mg/mL concentration from 
the study.
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PF-06741086
B7841003
Final Protocol Amendment 2, 08 November 2018
PFIZER CONFIDENTIAL
Page 7
Section 5.3.1 Dosage Form(s) and Packaging
•
Removal of 100 mg/mL concentration from 
the study.
Section 5.4 Administration
•
Editorial changes to clarify SC 
administrations.
Section 5.7.1 Prohibited Medications
•
Included subjects with inhibitors to FVIII or 
FIX.
•
Restrictions on rFVIIa dose level and 
prohibition of FEIBA conforms to study 
B7841002.
Section 5.7.2 Treatment(s) for Acute Bleeding 
Episodes
•
Included subjects with inhibitors to FVIII or 
FIX.
Section 6.1 Screening
•
Included subjects with inhibitors to FVIII or 
FIX.
•
Inclusion of adolescent subjects ≥12 to 
≤18 years of age.
•
Added assent/parental consent.
•
Added CD4 cell count.
•
Added Factor VIII or Factor IX inhibitor labs 
(for subjects with hemophilia. 
Section 6.2.1 Day 1 Visit
•
Included subjects with inhibitors to FVIII or 
FIX.
Section 7.1.1 Laboratory Tests
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
I ncl u de d s u bjects wit h i n hi bit ors t o F VIII or 
FI X.

E dit orial c ha n ge t o a d d C D 4 cell c o u nt t o 
ta ble.
Secti o n 7. 1. 3 Bl o o d Press ure a n d P ulse R ates

E dit orial c ha n ge t o re m o ve t he ter m 
“i ntra ve n o us” w hic h was n ot part of t he fi nal 
st u d y desi g n.
Secti o n 7. 2. 5 Bl o o d Press ure a n d P ulse R ates

I ncl usi o n of s u bjects wit h i n hi bit ors t o F VIII 
or FI X.
 
 
Secti o n 7. 8 Bl o o d V ol u me

U p date d ma xi m u m t otal bl o o d v ol u me i n 
Ta ble 4.
Secti o n 9 D at a A n al ysis/ St atistic al Met h o ds

E dit orial c ha n ges re gar di n g statistical h y p ot hesis 
testi n g a n d safet y a nal ysis.
Ori gi nal Versi o n
1 7 A pril 2 0 1 7
N/ A
T his a me n d me nt i nc or p orates all re visi o ns t o date, i ncl u di n g a me n d me nts ma de at t he 
re q uest of c o u ntr y healt h a ut h orities a n d i nstit uti o nal re vie w b oar ds (IR Bs)/et hics c o m mittees 
(E Cs).
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Final Protocol Amendment 2, 08 November 2018
PFIZER CONFIDENTIAL
Page 9
TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................13
LIST OF FIGURES .................................................................................................................13
APPENDICES .........................................................................................................................13
PROTOCOL SUMMARY.......................................................................................................14
SCHEDULE OF ACTIVITIES................................................................................................16
1. INTRODUCTION ...............................................................................................................22
1.1. Mechanism of Action/Indication.............................................................................22
1.2. Background and Rationale ......................................................................................22
1.2.1. Nonclinical Pharmacology and Pharmacokinetics .....................................23
1.2.2. Nonclinical Toxicology ..............................................................................24
1.2.3. Clinical Experience with PF-06741086......................................................25
1.2.4. B7841003 Study Rationale.........................................................................26
1.2.5. Dose Rationale............................................................................................26
1.2.6. Summary of Risk/Benefit ...........................................................................26
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................28
3. STUDY DESIGN.................................................................................................................29
3.1. Planned Number of Subjects...................................................................................30
3.2. Study Duration ........................................................................................................30
3.3. Dose Modification Rules for Adverse Events.........................................................31
3.3.1. Dose Modification Rules for Breakthrough Bleeding Episodes.................31
4. SUBJECT ELIGIBILITY CRITERIA.................................................................................32
4.1. Inclusion Criteria.....................................................................................................32
4.2. Exclusion Criteria....................................................................................................33
4.3. Randomization Criteria ...........................................................................................34
4.4. Lifestyle Requirements ...........................................................................................35
4.4.1. Contraception..............................................................................................35
4.5. Sponsor’s Qualified Medical Personnel..................................................................36
5. STUDY TREATMENTS.....................................................................................................36
5.1. Allocation to Treatment ..........................................................................................37
5.2. Subject Compliance.................................................................................................37
5.3. Investigational Product Supplies.............................................................................38
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5. 3. 1. D osa ge F or m(s) a n d Pac ka gi n g .................................................................. 3 8
5. 3. 2. Pre parati o n a n d Dis pe nsi n g ........................................................................ 3 8
5. 4. A d mi nistrati o n ......................................................................................................... 3 8
5. 5. I n vesti gati o nal Pr o d uct St ora ge .............................................................................. 3 9
5. 6. I n vesti gati o nal Pr o d uct Ac c o u nta bilit y ................................................................... 3 9
5. 6. 1. Destr ucti o n of I n vesti gati o nal Pr o d uct S u p plies ........................................ 4 0
5. 7. C o nc o mita nt Treat me nt(s) ....................................................................................... 4 0
5. 7. 1. Pr o hi bite d Me dicati o ns ............................................................................... 4 0
5. 7. 2. Treat me nt(s) f or Ac ute Blee di n g E pis o des ................................................. 4 1
6. S T U D Y P R O C E D U R E S..................................................................................................... 4 1
6. 1. Scree ni n g ................................................................................................................. 4 1
6. 2. St u d y  Peri o d............................................................................................................ 4 4
6. 2 . 1. Da y 1 Visit [ + 1 da y] ...................................................................................4 4
6. 2. 2. Da y  2 [1 da y ], Da y 4 [1 d a y ], Da y 8 [2 da y s], Da y 1 5 [2 d a y s], 
D a y 2 2 [ 2 da y s] a n d Da y 2 9 [2 d a y s] – 
 a n d Treat me nt Visits 
f or De N o v o S u bjects....................................................................................... 4 6
6. 2. 3. Da y  2 9 [2 da y s], Da y 5 7 [5 da y s], Da y 8 5 [5 da y s], Da y 
1 1 3 [ 7 da y s], Da y 1 4 1 [ 7 da y s], Da y 1 6 9 [7 da y s], Da y 2 2 5 [7 
da y s], Da y 2 5 3 [7 da y s], Da y 2 8 1 [ 7 da y s], Da y 3 0 9 [7 da y s], Da y 
3 3 7 [ 7 da y s], a n d Da y 3 6 5 [7 da y s] Visits .................................................. 4 7
6. 2. 4. Da y  3 9 3 [7 da y s] – E n d of St u d y  Visit..................................................... 4 9
6. 2. 5. F oll o w -u p C o ntact ...................................................................................... 4 9
6. 3. S u bject Wit h dra wal or Earl y Ter mi nati o n ..............................................................4 9
7. A S S E S S M E N T S .................................................................................................................. 5 1
7. 1. Safet y ....................................................................................................................... 5 1
7. 1. 1. L a b orat or y Tests......................................................................................... 5 1
7. 1. 2. P h y sical E xa mi nati o ns ................................................................................ 5 3
7. 1. 3. Bl o o d Press ure a n d P ulse Rate ...................................................................5 3
7. 1. 4. Res pirat or y  Rate .........................................................................................5 3
7. 1. 5. Te m perat ure ................................................................................................ 5 3
7. 1. 6. Electr ocar di o gra m ....................................................................................... 5 3
7. 1. 7. I njecti o n Site Reacti o ns ..............................................................................5 4
7. 2. Efficac y ................................................................................................................... 5 5
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7. 2. 1. He m o p hilic Blee di n g E pis o des ................................................................... 5 5
7. 2. 2. Blee di n g ...................................................................................................... 5 5
7. 2. 3. T y pes o f Blee di n g....................................................................................... 5 5
7. 2. 4. L ocati o n of Blee ds ...................................................................................... 5 6
7. 2. 5. Treat me nt of Blee di n g E pis o des ................................................................. 5 6
............................................................................................ 5 7
......................................................... 5 7
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..................... 5 8
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.................................................................................... 6 0
7. 8. Bl o o d V ol u me ......................................................................................................... 6 0
8. A D V E R S E E V E N T R E P O R TI N G ...................................................................................... 6 2
8. 1. Re q uire me nts ........................................................................................................... 6 2
8. 1. 1. A d diti o nal Detail s O n Rec or di n g A d verse E ve nts o n t he C R F ..................6 3
8. 1. 2. Eliciti n g A d verse E ve nt I nf or mati o n .......................................................... 6 4
8. 1. 3. Wit h dra wal Fr o m t he St u d y  D ue to A d verse E ve nts (see als o t he 
S u bject Wit h dra wal or Earl y  Ter mi nati o n secti o n)......................................... 6 4
8. 1. 4. Ti me Peri o d f or C ollecti n g A E/ S A E I nf or mati o n ...................................... 6 4
8. 1. 4. 1. Re p orti n g S A Es t o Pfizer Safet y ............................................... 6 4
8. 1. 4. 2. Rec or di n g N o n -seri o us A Es a n d S A Es o n t he C R F ................. 6 4
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8. 1. 5. Ca usalit y Assess me nt ................................................................................. 6 5
8. 1. 6. S p o ns or’s Re p orti n g Re q uire me nts t o Re g ulat or y  A ut h orities.................. 6 5
8. 2. Defi niti o ns ............................................................................................................... 6 5
8. 2. 1. A d verse E ve nts ........................................................................................... 6 5
8. 2. 2. A b n or mal Test Fi n di n gs ............................................................................. 6 6
8. 2. 3. He m o p hilia E ve nts ...................................................................................... 6 6
8. 2. 4. Seri o us A d verse E ve nts .............................................................................. 6 7
8. 2. 5. H os pitalizati o n ............................................................................................ 6 8
8. 3. S e verit y Assess me nt................................................................................................ 6 9
8. 4. S pecial Sit uati o ns .................................................................................................... 6 9
8. 4. 1. Pr ot oc ol - S pecifie d Seri o us A d verse E ve nts............................................... 6 9
8. 4. 2. P ote ntial Cases of Dr u g -I n d uce d Li ver I nj ur y............................................ 7 0
8. 4. 3. E x p os ure t o t he I n vesti gati o nal Pr o d uct D uri n g Pre g na nc y  or 
Breastfee di n g, a n d Occ u pati o nal E x p os ure .....................................................7 1
8. 4. 3. 1. E x p os ure D uri n g Pre g na nc y ...................................................... 7 1
8. 4. 3. 2. E x p os ure D uri n g Breastfee di n g ................................................ 7 3
8. 4. 3. 3. Occ u pati o nal E x p os ure ............................................................. 7 3
8. 4. 4. Me dicati o n Err ors ....................................................................................... 7 3
8. 4. 4. 1. Me dicati o n Err ors ...................................................................... 7 3
8. 5. Me dical De vice C o m plai nt Re p orti n g Re q uire me nts ............................................. 7 4
9. D A T A A N A L Y SI S/ S T A TI S TI C A L  M E T H O D S...............................................................7 4
9. 1. Sa m ple Size Deter mi nati o n ..................................................................................... 7 4
9. 2. Efficac y  A nalys is .................................................................................................... 7 5
9. 2. 1. A nal y sis of t he Efficac y E n d p oi nt..............................................................7 5
.................................................................7 5
...............................................................7 5
................................................................................... 7 5
9. 6. Safet y A nal ys is........................................................................................................ 7 5
9. 7. I nteri m A nal ys is...................................................................................................... 7 6
9. 8. Data M o nit ori n g C o m mittee ................................................................................... 7 6
1 0. Q U A LI T Y C O N T R O L  A N D Q U A LI T Y A S S U R A N C E .................................................7 6
1 1. D A T A H A N D LI N G A N D R E C O R D K E E PI N G ............................................................. 7 7
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1 1. 1. Case Re p ort F or ms/ Electr o nic Data Rec or d ......................................................... 7 7
1 1. 2. Rec or d Rete nti o n ................................................................................................... 7 7
1 2. E T HI C S ..............................................................................................................................7 8
1 2. 1. I nstit uti o nal Re vie w B oar d/ Et hics C o m mittee ...................................................... 7 8
1 2. 2. Et hi cal C o n d uct of t he St u d y ................................................................................ 7 8
1 2. 3. S u bject I nf or mati o n a n d C o nse nt .......................................................................... 7 8
1 2. 4. Re p orti n g of Safet y I ss ues a n d Seri o us Breac hes of t he Pr ot oc ol or I C H 
G C P ........................................................................................................................... 7 9
1 3. D E FI NI TI O N O F E N D O F T RI A L ................................................................................... 8 0
1 3. 1. E n d of Trial i n a Me m ber State ............................................................................. 8 0
1 3. 2. E n d of Trial i n All Ot her Partici pati n g C o u ntries ................................................. 8 0
1 4. S P O N S O R DI S C O N TI N U A TI O N C RI T E RI A ................................................................ 8 0
1 5. P U B LI C A TI O N O F S T U D Y R E S U L T S .......................................................................... 8 0
1 5. 1. C o m m u nicati o n of Res ults b y  Pfizer .................................................................... 8 0
1 5. 2. P u blicati o ns b y  In vesti gat ors ................................................................................ 8 1
1 6. R E F E R E N C E S .................................................................................................................. 8 3
LI S T O F T A B L E S
Ta ble 1.
Scree ni n g, Da y  1 t o Da y 3 9 3, All S u bjects.......................................................... 1 6
Ta ble 2.
D a y  2 t hr o u g h Da y 2 2: 
 a n d Treat me nt Visits f or De N o v o S u bjects....... 2 1
Ta ble 3.
La b orat or y  Tests................................................................................................... 5 2
Ta ble 4.
Bl o o d V ol u me ....................................................................................................... 6 1
Ta ble 5.
Tri g gere d Re q uire me nts ....................................................................................... 6 2
LI S T O F FI G U R E S
Fi g ure 1.
B 7 8 4 1 0 0 3 D ose Assi g n me nt ................................................................................2 9
A P P E N DI C E S
A p pe n di x 1. A b bre viati o ns ...................................................................................................... 8 4
A p pe n di x 2. T hr o m b otic A d verse E ve nts f or St o p pi n g Criteria ............................................. 8 7
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4
P R O T O C O L S U M M A R Y 
St u d y  B 7 8 4 1 0 0 3 is a P hase 2 , o pe n -la bel st u d y i n s u bjects wit h se vere he m o p hilia A or B, 
wit h or wit h o ut i n hi bit ors t o Fact or VIII ( F VIII) or Fact or I X ( FI X).  T his st u d y  is desi g ne d 
t o e val uate t he safety, t olera bilit y a n d efficac y of l o n g -ter m pr o p h yla xis wit h P F-0 6 7 4 1 0 8 6, a 
m o n ocl o nal a nti b o d y  t hat tar gets tiss ue fact or pat h wa y i n hi bit or ( T F PI).  T F PI is a n 
a nta g o nist of t he e xtri nsic c oa g ulati o n pat h wa y .  P F-0 6 7 4 1 0 8 6, t hr o u g h its ne utralizati o n of 
T F PI, is e x pecte d t o i ncrease c oa g ulati o n acti vit y i n s u bjects wit h he m o p hilia.
S u bjects t hat c o m plete st u d y  B 7 8 4 10 0 2, a 3 -m o nt h P hase 1 b/ 2 st u d y of pr o p h yla xis 
treat me nt wit h P F-0 6 7 4 1 0 8 6, are eli gi ble t o e nr oll i nt o t his st u d y  t o c o nti n ue pr o p h yla xis 
treat me nt.  St u d y B 7 8 4 1 0 0 3 will assess t he safet y, t olera bilit y  a n d efficac y of 
P F - 0 6 7 4 1 0 8 6 u p t o a 3 6 5- d a y  treat me nt peri o d at t he l o west d ose le vel deter mi ne d t o be safe 
a n d efficaci o us i n st u d y B 7 8 4 1 0 0 2. 
Se vere he m o p hilia A or B patie nts ( F VIII or FI X acti vit y  1 %), i ncl u di n g s u bjects wit h 
i n hi bit ors t o F VIII or FI X, w h o di d n ot partici pate i n st u d y B 7 8 4 1 0 0 2 will als o be eli gi ble f or 
e nr oll me nt i n B 7 8 4 1 0 0 3.  T w o c o h orts of s u bjects ( 6 s u bjects per c o h ort) will be e nr olle d t o 
pr o vi de s u p ple me ntal l o n g -ter m safet y, t olera bilit y, a n d efficac y data o n P F-0 6 7 4 1 0 8 6 i n a 
de n o v o p o p ulati o n.  De n o v o c o h orts will be o pe n t o t h e e nr oll me nt of a d olesce nt se vere 
he m o p hilia patie nts ( 1 2 t o < 1 8 ye ars of a ge) a n d se vere he m o p hilia patie nts wit h i n hi bit ors 
t o F VIII or FI X.  After all s u bc uta ne o us ( S C) c o h orts ha ve c o m plete d 3 m o nt hs of treat me nt 
i n st u d y B 7 8 4 1 0 0 2, t he de n o v o s u bjects will be c o nsi dere d f or e nr oll me nt i nt o B 7 8 4 1 0 0 3.  
All de n o v o s u bjects will be assi g ne d t o treat me nt wit h P F - 0 6 7 4 1 0 8 6 f or a treat me nt peri o d 
of u p t o 3 6 5 d a y s, at t he l o west d ose le vel deter mi ne d t o be safe a n d efficaci o us i n 
B 7 8 4 1 0 0 2. 
D uri n g t he 3 6 5- da y treat me nt peri o d, P F-0 6 7 4 1 0 8 6 will be a d mi nistere d s u bc uta ne o usl y.  All 
s u bjects will be re q uire d t o atte n d m o nt hl y cli nic visits d uri n g t he 3 6 5- d a y  treat me nt peri o d 
( Da y 1 t o Da y 3 6 5) a n d o ne m o nt h f oll o w -u p ( Da y 3 9 3). 
 
 S u bjects w h o c o m plete d st u d y 
B 7 8 4 1 0 0 2 will be all o we d t o self -a d mi nister treat me nt at h o me after trai ni n g b y t he site a n d 
de m o nstrati o n of a bilit y  t o self-a d mi nister b y t he s u bject.  De n o v o s u bjects will be all o we d 
t o self-a d mi nister f oll o wi n g t he Da y 2 9 visit, after trai ni n g b y t he site a n d de m o nstrati o n of 
a bilit y t o self-a d mi nister b y t he s u bject. 
T hr o u g h Da y 3 6 5 data will be re vie we d t o deter mi ne if P F - 0 6 7 4 1 0 8 6 is safe a n d well 
t olerate d at t he res pecti ve d ose le vels.  D osi n g of a n y s u bject ma y be st o p pe d if a vaila ble 
data i n dicate t hat t he treat me nt is n ot safe a n d well- t olerate d. 
U p t o 3 6 s u bjects are pla n ne d t o be treate d i n st u d y  B 7 8 4 1 0 0 3 ( 2 4 s u bjects fr o m 
B 7 8 4 1 0 0 2 a n d 1 2 a d diti o nal de n o v o s u bjects).  S u bjects will partici pate i n t he st u d y  f or u p 
t o 1 5 m o nt hs, i ncl u di n g scree ni n g a n d f oll o w - u p. 
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5
T here is n o f or mal statistical h y p ot hesis pla n ne d f or testi n g i n B 7 8 4 1 0 0 3.  T here is n o f or mal 
sa m ple size calc ulati o n i nf or mi n g c o h ort sa m ple size or o verall st u d y sa m ple size.  T he 
c o h ort sa m ple sizes a n d o verall st u d y  sa m ple size are base d o n t he n u m ber of s u bjects 
e nr olle d i n st u d y B 7 8 4 1 0 0 2, a n d o n cli nic al c o nsi derati o ns t o bala nce t he nee d t o mi ni mize 
e x p os ure of st u d y s u bjects t o t he i n vesti gati o nal pr o d uct wit h t he nee d t o pr o vi de a de q uate 
safety a n d t olera bilit y data f or cli nical de vel o p me nt.
Safet y  e n d p oi nts will i ncl u de treat me nt e mer ge nt a d verse e ve nts, i nf usi o n/i njecti o n site 
reacti o ns, safety 
 la b orat or y para meters.  Pr o p h yla xis efficac y will be 
assesse d b y c ollecti n g t he n u m ber of ac ute blee di n g e pis o des per s u bject d uri n g t he treat me nt 
peri o d of u p t o 3 6 5 da y s a n d deter mi ni n g the a n n ualize d blee d rate ( A B R).  F or s u bjects 
c o nti n ui n g fr o m st u d y B 7 8 4 1 0 0 2 o n t he sa me d ose, t hese data ma y  be c o m bi ne d bet wee n t he 
st u dies t o deter mi ne t he A B R.  All data will be s u m marize d descri pti vel y f or eac h c o h ort a n d 
t he o verall st u dy.
De m o nstrat i o n of safet y, t olera bilit y a n d efficac y t hat s u p p orts l o n g-ter m c hr o nic treat me nt 
o n a n acce pta ble d osi n g sc he d ule is i nte n de d t o s u p p ort pr o gressi o n of P F - 0 6 7 4 1 0 8 6 t o 
s u bse q ue nt i n vesti gati o ns i n patie nts wit h se vere he m o p hilia A or B.
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI

PF-06741086
B7841003
Final Protocol Amendment 2, 08 November 2018
PFIZER CONFIDENTIAL
Page 16
SCHEDULE OF ACTIVITIES
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the STUDY PROCEDURES and 
ASSESSMENTS sections of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed on the schedule of activities table, in order to 
conduct evaluations or assessments required to protect the well-being of the subject.
Table 1.
Screening, Day 1 to Day 393, All Subjects
Protocol 
Activity
Screening
Clinic Visits
End of 
Study 
Visitd
Visit 
Identifiera
Screen
ingb
Day 1c
Day 29
(Month 
1)
Day 57
(Month 2)
Day 85
(Month 3)
Day 113
(Month 
4)
Day 141
(Month 
5)
Day 169
(Month 6)
Day 197
(Month 7)
Day 225
(Month 8)
Day 253
(Month 
9)
Day 281
(Month 10)
Day 309
(Month 11)
Day 337
(Month 12)
Day 365
(Month 
13)
Day 393
(Month 
14)
Visit window 
Day 
-34 to 
Day -1
+ 1 day ±2 day
±5 days
±5 days
±7 days
±7 days
±7 days
±7 days
±7 days
±7 days
±7 days
±7 days
±7 days
±7 days
±7 days
Informed 
consent or 
Assent/
Parental 
consent
X
Xc
Medical history 
(including 
hemophilia 
history and 
inhibitor 
history, and 
bleeding 
episodes over 
past 6 months)e
X
X
Medication 
history
X
X
Demography, 
Height, Weight
X
X 
(weight)
Full physical 
examination
X
X
Limited 
physical 
examinationf
X
X
X
X
X
X
X
X
X
X
X
X
X
X
090177e196978055\0.1\Draft\Versioned On:23-Mar-2021 10:50 (GMT)

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7
T a ble 1.
Scree ni n g, D a y 1 t o D a y 39 3, All S u bjects
Pr ot oc ol 
Acti vit y
Scree ni n g
Cli nic Visits
E n d of 
St u d y 
Visit d
Visit 
I de ntifiera
Scree n
i n gb
D a y 1 c
D a y 2 9
( M o nt h 
1)
D a y 5 7
( M o nt h 2)
D a y 8 5
( M o nt h 3)
D a y 1 1 3
( M o nt h 
4)
D a y 1 4 1
( M o nt h 
5)
D a y 1 6 9
( M o nt h 6)
D a y 1 9 7
( M o nth 7)
D a y 2 2 5
( M o nt h 8)
D a y 2 5 3
( M o nt h 
9)
D a y 2 8 1
( M o nt h 1 0)
D a y 3 0 9
( M o nt h 1 1)
D a y 3 3 7
( M o nt h 1 2)
D a y 3 6 5
( M o nt h 
1 3)
D a y 3 9 3
( M o nt h 
1 4)
Visit wi n d o w 
D a y 
-3 4 t o 
D a y - 1
+ 1 d a y
2 d a y
5 d a ys
5 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
C o ntrace pti o n 
i nstr ucti o ns/
c hec k g
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
X
X
Vital Si g ns h
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Uri nal ysis i
X  
X
X
X
X
X
E C G
X b
X b
X b
Ser u m 
c he mi str yi
X  
X
X b
X b
X
X
X
X
He mat ol o g y i
X  
X
X b
X b
X
X
X
X
C D 4 cell c o u nt
X
Fi bri n o ge n
X
X b
X
X
X
X
 
 
Pr ot hr o m bi n 
ti me ( P T)
X
X b
X
X
X
X
Car diac 
tr o p o ni n I
X b
X b
Fact or VIII  a n d 
Fact or I X 
acti vit y
X  
X
X
X
X
X
Fact or VIII  or 
Fac t or IX 
i n hi bit or le vels 
(f or s u bjects 
wit h a 
he m o p hilia 
hist or y of 
i n hi bit or o nl y)
X b ,o
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8
T a ble 1.
Scree ni n g, D a y 1 t o D a y 39 3, All S u bjects
Pr ot oc ol 
Acti vit y
Scree ni n g
Cli nic Visits
E n d of 
St u d y 
Visit d
Visit 
I de ntifiera
Scree n
i n gb
D a y 1 c
D a y 2 9
( M o nt h 
1)
D a y 5 7
( M o nt h 2)
D a y 8 5
( M o nt h 3)
D a y 1 1 3
( M o nt h 
4)
D a y 1 4 1
( M o nt h 
5)
D a y 1 6 9
( M o nt h 6)
D a y 1 9 7
( M o nth 7)
D a y 2 2 5
( M o nt h 8)
D a y 2 5 3
( M o nt h 
9)
D a y 2 8 1
( M o nt h 1 0)
D a y 3 0 9
( M o nt h 1 1)
D a y 3 3 7
( M o nt h 1 2)
D a y 3 6 5
( M o nt h 
1 3)
D a y 3 9 3
( M o nt h 
1 4)
Visit wi n d o w 
D a y 
-3 4 t o 
D a y - 1
+ 1 d a y
2 d a y
5 d a ys
5 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
Pr ot hr o m bi n 
2 0 2 1 0 m utati o n 
testi n g
X
Fact or V 
Lei de n 
m utati o n 
testi n g
X
Li pi d pr ofile i
X
Pr otei n C 
acti vit y/ Pr otei n 
S le vel/ A TIII 
acti vit y
X
Ser ol o g y: H Bs 
A g, H Bc A b , 
H C V A b a n d 
HI V
X
 
 
I ncl usi o n/
e xcl usi o n 
criteria re vie w
X  
X
Treat me nt 
assi g n me nt
X
I n vesti g ati o n al 
Pr o d uct 
a d mi nistr ati o n 
( S C)
X
Wee kl y a d mi nistrati o n at h o me or i n cli nic m







m





m
S u bject diar y n
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9
T a ble 1.
Scree ni n g, D a y 1 t o D a y 39 3, All S u bjects
Pr ot oc ol 
Acti vit y
Scree ni n g
Cli nic Visits
E n d of 
St u d y 
Visit d
Visit 
I de ntifiera
Scree n
i n gb
D a y 1 c
D a y 2 9
( M o nt h 
1)
D a y 5 7
( M o nt h 2)
D a y 8 5
( M o nt h 3)
D a y 1 1 3
( M o nt h 
4)
D a y 1 4 1
( M o nt h 
5)
D a y 1 6 9
( M o nt h 6)
D a y 1 9 7
( M o nth 7)
D a y 2 2 5
( M o nt h 8)
D a y 2 5 3
( M o nt h 
9)
D a y 2 8 1
( M o nt h 1 0)
D a y 3 0 9
( M o nt h 1 1)
D a y 3 3 7
( M o nt h 1 2)
D a y 3 6 5
( M o nt h 
1 3)
D a y 3 9 3
( M o nt h 
1 4)
Visit wi n d o w 
D a y 
-3 4 t o 
D a y - 1
+ 1 d a y
2 d a y
5 d a ys
5 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
7 d a ys
C ollec t n u m ber 
of ne w 
blee di n g 
e pis o des 
X












X  
X
M o nit ori n g 
i njecti o n site 
reacti o ns
X












X  
X
Seri o us a n d 
n o n- seri o us 
a d verse e ve nt 
m o nit ori n g
X













X
C o nc o mita nt 
treat me nts
X













X
A b bre viati o ns: 
= o n g oi n g/c o nti n u o us e ve nt; 
; a P T T = acti vate d partial t hr o m b o plasti n ti me; E C G = electr ocar di o gra m; H Bc A b = he patitis B c ore 
a nti b o d y; H Bs A g = he patitis B s urface a nti ge n; H C V A b = he patitis C a n ti b o d y; HI V = h u ma n i m m u n o deficie nc y vir us; hr = h o urs; I P = i n vesti gati o nal pr o d uct; 
N/ A = n ot a p plica ble;
; P T /I N R = pr ot hr o m bi n ti me/i nter nati o nal n or malize d rati o;
.
a.
Da y relati ve t o start of st u d y treat me nt ( Da y 1).
b.
Scree ni n g a n d a d diti o nal acti vities n ote d a p pl y t o de n o v o s u bjects w h o di d n ot partici pate i n B 7 8 4 1 0 0 2.  Please see Secti o n 6 f or a d diti o nal details.
c.
F or s u bjects w h o c o m plete d st u d y B 7 8 4 1 0 0 2, i nf or me d c o nse nt pr oce d ures will occ ur at t he Da y 1 visit.  T he Da y 1 visit f or B 7 8 4 1 0 0 3 ma y occ ur o n t he sa me da y (sa me 
visit t o t he cli nic) as t he B 7 8 4 1 0 0 2 Da y 8 5 or Da y 1 1 3 visit. 
A ll Da y 1 ( or B 7 8 4 1 0 0 2 Da y 8 5 or Da y 1 1 3) bl o o d dra ws m ust be d o ne pri or t o a d mi nistrati o n of I P.
T he f oll o wi n g c o n diti o ns a p pl y t o all Da y 1 acti vities:

I ncl usi o n/e xcl usi o n criteria: Criteria s h o ul d be re vie we d (a n d eli gi bilit y c o nfir me d) at Da y 1 f or s u bjects w h o c o m plete d B 7 8 4 1 0 0 2 m ore t ha n 3 0 da ys pri or t o t he 
sc he d ule d Da y 1 visit.  Please see Secti o n 6. 1 f or re q uire d pr oce d ures.

Treat me nt assi g n me nt: All s u bjects will be re q uire d t o recei ve a ne w s u bject n u m ber f or t his st u d y.  Ot her pr oce d ures f or treat me nt assi g n me nt ma y n ot be necessar y f or 
s u bjects w h o c o m plete d st u d y B 7 8 4 1 0 0 2.
d.
See Secti o n 6. 2. 5 f or g ui da nce o n f oll o w-u p c o ntact, if necessar y.
e.
Me dical hist or y data f or s u bjects fr o m st u d y B 7 8 4 1 0 0 2 will als o be use d f or s u bjects e nr olli n g i nt o B 7 8 4 1 0 0 3.  Res ol ve d A Es fr o m B 7 8 4 1 0 0 2
ma y be e ntere d as a d diti o nal 
me dical hist or y, w here a p plica ble.
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI
C CI
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0
f.
At Da y 1 t hr o u g h Da y 3 6 5 , a n d at t he discreti o n of t he I n vesti gat or, li mite d e xa mi nati o ns base d o n si g ns a n d s y m pt o ms will be perf or me d, if cli nically i n dicate d t o assess 
c ha n ges fr o m baseli ne/ pre vi o us visits of a n y o n g oi n g s y m pt o ms.
g.
I nstr ucti o ns will be pr o vi de d at Scree ni n g a n d Da y 1 visit; c o ntrace pti o n c hec k will be perf or me d at ot her visits.
h.
Vital si g ns t o be assesse d i ncl u de p ulse rate, res pirat or y rate, oral te m perat ure, a n d bl o o d press ure (s u pi ne).
i.
See Secti o n 7. 1. 1 , Ta ble 3 , f or list of a nal ytes.  Differe ntial he mat ol o g y pa nel re q uire d at Da ys 1, 8 5, 1 6 9 a n d 3 3 7. 
 
m.
Pri or t o self -a d mi nistrati o n, sites m ust e ns ure s u bjects are trai ne d o n I P a d mi nistrati o n a n d st ora ge per t he I P ma n ual.  D osi n g bet wee n pl a n ne d cli nic visits ma y be 
a d mi nistere d b y i n vesti gati o nal site staff u nti l t he res pecti ve s u bject has bee n pr o perl y trai ne d i n self-a d mi nistrati o n.  Sites s h o ul d f oll o w -u p (e g, via p h o ne call) t o e ns ure 
c o m plia nce wit h a d mi nistrati o n i nstr ucti o ns, w here necessar y.  S u bjects w h o c o m plete d t he Da y 1 9 7 ( M o nt h 7) visit pri or t o A me n d me nt 2 (a n d e xte nsi o n of treat me nt 
d urati o n) are all o we d t o restart treat me nt, be gi n ni n g wit h Da y 2 2 5 ( M o nt h 8).  He mat ol o g y, c he mistr y, a n d uri nal ysis res ults fr o m Da y 1 6 9 ( M o nt h 6) s h o ul d be re vie we d 
a gai nst i ncl usi o n/e xcl usi o n criteria pri or t o t he re s u m pti o n of treat me nt t o e ns ure t here are n o e xcl usi o nar y la b orat or y a b n or malities. Da y 3 3 7 ( M o nt h 1 2) will be t he fi nal 
visit w here I P is dis pe nse d f or self- a d mi nistrati o n .  F or s u bjects bei n g d ose d i n t he cli nic, 7 da ys bef ore Da y 3 6 5 is t he fi nal da y for d osi n g.
n.
S u bject diar y dis pe nse d a n d/ or c ollecte d.  S u bject diar y is re vie we d, i ncl u di n g i nf or mati o n a b o ut st u d y c o m plia nce, blee di n g assess me nts (i ncl u di n g site a n d 
tra u matic/s p o nta ne o us) a n d i njecti o n site reacti o ns.  At Da y 1, s u bjects will be pr o vi d e d trai ni n g wit h res pect t o filli n g o ut t he diar y i ncl u di n g ti mi n g a n d nat ure of 
i nf or mati o n t o be e ntere d.
o.
F VIII a n d FI X i n hi bit or le vels m ust be deter mi ne d b y a l ocal la b orat or y.  A p ositi ve i n hi bit or test res ult will be a b o ve t he u p per li mit of n or mal f or t he assa y.  I n hi bit or test 
res ults fr o m u p t o 6 m o nt hs pri or t o Da y 1 ma y be use d t o meet t his re q uire me nt.
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 2 1
T a ble 2.
D a y 2 t hr o u g h D a y 2 2: 
a n d Tre at me nt Visits f or De N o v o S u bjects
Pr ot oc ol Acti vit y
Cli nic Visits
Visit I de ntifier a
D a y 2
D a y 4
D a y 8
D a y 1 5
D a y 2 2
Visit wi n d o w 
1 d a y
1 d a y
2 d a y
2 d a y
2 d a ys
Li mite d p h ysical e xa mi nati o n
X
X
X
X
X
C o ntrace pti o n i nstr ucti o ns/c hec k
X
X
X
X
X
Ser u m c he mistr y
X
X
X
H e m at ol o g y
X
X
X
Pr ot hr o m bi n ti me ( P T)
X
X
X
Car diac tr o p o ni n I
X
X
X
 
I n vesti g ati o n al Pr o d uct 
a d mi nistr ati o n ( S C)
X b
X b
X b
S u bject diar y c
X
X
X
C ollect n u m ber of ne w blee di n g 
e pis o des 





M o nit ori n g i njecti o n site reacti o ns





A d verse e ve nt m o nit ori n g





C o nc o mita nt treat me nts





A b bre viati o ns: 
= o n g oi n g/c o nti n u o us e ve nt; 
a.
Da y relati ve t o start of st u d y treat me nt ( D a y 1).
b.
I P a d mi nistrati o n o n Da y 8, Da y 1 5, a n d Da y 2 2 t o occ ur at t he cli nic wit h trai ni n g o n I P self-a d mi nistrati o n f or de n o v o s u bjects.
c.
S u bject diar y dis pe nse d a n d/ or c ollecte d.  S u bject diar y is re vie we d, i ncl u di n g i nf or mati o n a b o ut st u d y c o m plia nce, i n vesti gati o nal pr o d uct i nf usi o ns, blee di n g assess me nts 
(i ncl u di n g site a n d tra u matic/s p o nta ne o us) a n d i njecti o n site reacti o ns.  At Da y 1, s u bjects will be pr o vi de d trai ni n g wit h res pect t o filli n g o ut t he diar y i ncl u di n g ti mi n g a n d 
nat ure of i nf or mati o n t o be e ntere d.
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI
C CI
C CI
C CI

PF-06741086
B7841003
Final Protocol Amendment 2, 08 November 2018
PFIZER CONFIDENTIAL
Page 22
1. INTRODUCTION
1.1. Mechanism of Action/Indication
PF-06741086 is a human monoclonal immunoglobulin of the G isotype, subclass 1 (IgG1) 
that targets the Kunitz-2 domain of tissue factor pathway inhibitor (TFPI).  PF-06741086 is 
in development as a prophylactic treatment to prevent or reduce the frequency of bleeding 
episodes in individuals with severe hemophilia A or B with or without inhibitors.
Protocol B7841003 is a long-term study on the safety, tolerability and efficacy of 
PF-06741086 during up to 365 days of treatment.  Satisfactory safety, tolerability, and 
efficacy data from this study are intended to support the development of PF-06741086 as a 
treatment in hemophilia.
1.2. Background and Rationale
The current standard of care for treatment of individuals with hemophilia A or B is 
replacement of their deficient clotting factor using Factor VIII (FVIII) or Factor IX (FIX) 
clotting factor concentrate, respectively.1 This replacement therapy is administered to treat 
or prevent acute bleeding episodes, to provide hemostasis during surgery, invasive 
procedures and the subsequent wound healing period, or to provide routine prophylaxis to 
prevent bleeding episodes.  However, a subset of patients with hemophilia develop 
neutralizing antibodies (inhibitors) directed against FVIII or FIX, reducing the effectiveness 
of factor replacement therapy as a first-in-line therapy for prophylaxis against or treatment of 
hemophilia bleeding episodes.2 For patients who respond to clotting factor replacement, the 
intravenous (IV) administration route and frequency of infusion required for effective 
prophylaxis treatment remains burdensome, and may result in reduced adherence to the 
treatment schedule and compromised prophylactic efficacy.  As well, venous access for IV 
administration of clotting factor concentrates is limited in the youngest pediatric patients with 
hemophilia.  In these patients, indwelling central venous catheters are frequently required to 
assure venous access with the attendant infectious and thrombotic complications.  Thus, an 
unmet medical need exists for a standalone SC or low frequency IV intervention to promote 
hemostasis and coagulation in patients with hemophilia in lieu of coagulation factor 
replacement therapy.
TFPI is a protease inhibitor which acts as an antagonist of the extrinsic coagulation pathway 
via inhibition of tissue factor-activated coagulation Factor VII (FVIIa) and activated 
Factor X (FXa).3 TFPI has two isoforms, TFPIα and TFPIβ.  The two isoforms share two of 
the same Kunitz-type domains (K1 and K2), but TFPIβ lacks the K3 domain.  Isoforms are 
distributed in plasma and on vascular endothelial cell surfaces through 
glycosylphosphatidylinositol anchors.  TFPIα is also located in platelets.  Available data 
indicates that a reduced quantity of TFPI in plasma is associated with faster coagulation 
times and increased thrombin generation.4 Individuals with TFPI free antigen at the 5th
percentile and 2nd percentile have an odds ratio for deep vein thrombosis that is 2.1- and 
2.2-fold that of the general population, respectively, indicating a wide therapeutic index is 
associated with modulation of TFPI activity.5 Additionally, single doses of 
PF-06741086 have been evaluated in a Phase 1 first-in-human study without significant 
adverse effects.  These results suggest that TFPI may serve as an acceptable target for a 
090177e196978055\0.1\Draft\Versioned On:23-Mar-2021 10:50 (GMT)

PF-06741086
B7841003
Final Protocol Amendment 2, 08 November 2018
PFIZER CONFIDENTIAL
Page 23
pharmaceutical treatment to reduce inhibition of the extrinsic coagulation pathway and 
thereby increase clotting activity in patients with bleeding disorders, such as hemophilia. 
1.2.1. Nonclinical Pharmacology and Pharmacokinetics
Analysis at the molecular level demonstrated that PF-06741086 targets an epitope in the 
K2 domain.  Surface Plasmon Resonance (SPR) was used to characterize 
PF-06741086 binding affinity and kinetics of binding to human, cynomolgus monkey, rabbit, 
mouse, and rat TFPI and was in the low-nanomolar to sub-nanomolar range.  The 
neutralization of TFPI by PF-06741086 was measured using a number of in vitro functional 
assays.  The analysis included FXa chromogenic activity assays which measure reversal of 
TFPI inhibition of Factor Xa or FXa/FVIIa/TF complex in purified systems.  
PF-06741086 promoted hemostasis in hemophilic plasma from hemophilia A, B, and 
hemophilia inhibitor plasma and in non-hemophilic plasma as measured in thrombin 
generation assays (TGA), and dilute prothrombin time (dPT) assays.  
PF-06741086 inhibitory activity was also demonstrated using thromboelastography (TEG) 
performed on whole non-hemophilic blood.  PF-06741086 also improved the thrombin 
generation response of severe hemophilia plasma dosed with rFVIIa.  The efficacy of 
PF-06741086 was demonstrated in injury models of hemostasis using Factor VIII deficient 
mice (model of hemophilia A) and Factor IX deficient mice (model of hemophilia B).  
PF-06741086 restored hemostasis in hemophilia mouse injury models when administered 
before and after the onset of a bleeding injury.  The pharmacodynamic profile of 
PF-06741086 is consistent with its TFPI inhibitory activity.
The cumulative pharmacodynamic and potential additive effects of the combined, repeated 
dose administration of PF-06741086 and NovoSeven®RT (rFVIIa) was evaluated in rats in a 
10-day IV investigative study.  Combined, repeated dose administration of PF-06741086 at
50 mg/kg and NovoSeven RT at 3 mg/kg to rats was associated microscopically with an 
increased incidence and/or severity of minimal to mild, acute thrombi/emboli in the lung and 
injection site (tail) without any microscopic evidence of secondary tissue injury or effects on 
the animals’ clinical condition in the main study animals.  These findings were not observed 
with the same incidence/severity with either test article administration at the same doses 
alone or in combination when administered as PF-06741086 at 50 mg/kg and NovoSeven RT 
at 0.8 (0.4 BID) mg/kg indicating a greater effect of combined administration of 
PF-06741086 and NovoSeven RT at 50 and 3 mg/kg, respectively.  Administration of 
Novoseven RT at any dose alone or in combination with PF-06741086 resulted in test 
article-, non-dose-related lower group means for PT.  The magnitude of the change was not 
significantly altered by co-administration of PF-06741086.  Thrombi/emboli formation and 
shortening of PT are consistent with the pharmacology of both test articles.  There was 1 test 
article-related unscheduled moribund euthanasia of an animal in the 
PF-06741086 (50 mg/kg)/NovoSeven RT (3 mg/kg)-dose pharmacokinetic group on 
Day 8 within 2 hours of the first Novoseven RT dose because of bilateral hindlimb paralysis 
related to acute thrombi/emboli in the iliac arteries; acute thrombi/emboli were also observed
in other tissues.  This animal also had ileal and cecal erosions of uncertain etiology, which
may have contributed to the animal’s hypercoagulable state.  The systemic exposure of 
NovoSeven RT observed in rats at 0.4, 1, and 3 mg/kg was equivalent or greater than the 
090177e196978055\0.1\Draft\Versioned On:23-Mar-2021 10:50 (GMT)

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 2 4
pre dicte d cli nical e x p os ure of N o v o Se ve n R T at 3 0, 9 0, a n d 2 7 0 g/ k g res pecti vel y.  I n 
a d diti o n, t he o bser ve d dail y  t otal e x p os ure of N o v o Se ve n R T at 0. 8 ( 0. 4 BI D) m g/ k g i n rats 
was a p p r o xi matel y e q ui vale nt t o t he pre dicte d t otal dail y cli nical e x p os ure after 3 d oses of 
N o v o Se ve n R T at 9 0 g/ k g.  S y ste mic e x p os ures c haracterize d b y C ma x a n d A U C t f or 
P F - 0 6 7 4 1 0 8 6 a n d N o v o Se ve n R T wer e n ot affected b y c o m bi ne d test article a d mi nistrati o n.
S e parate safet y p har mac ol o g y st u dies were n ot c o n d ucte d wit h P F -0 6 7 4 1 0 8 6, b ut safet y 
p har mac ol o g y  e n d p oi nts e val uati n g t he p ote ntial effects of P F-0 6 7 4 1 0 8 6 o n t he res pirat or y , 
car di o vasc ular ( C V), a n d ce ntral ner v o us s ys te ms ( C N S) were i ncl u de d i n t he 1 3-we e k 
t o xicit y st u d y i n m o n ke ys.
1. 2. 2. N o ncli nic al T o xic ol o g y
T he t o xicit y  of i ntra ve n o usl y or s u bc uta ne o usly a d mi nistere d P F -0 6 7 4 1 0 8 6 was e val uate d i n 
n o n pi v otal 
8 -d a y , re peat-d ose st u dies i n rats a n d m o n ke y s a n d pi v otal ( G LP) 
st u dies i n rats a n d m o nke y s of u p t o 6 or 3 m o nt hs i n d urati o n, res pecti vel y.   T he I V a n d S C 
r o utes of a d mi nistrati o n were selecte d f or t hese st u dies si nce t he y are t he i nte n de d r o utes of 
cli nical e x p os ure.  Rats a n d m o n ke y s were c h ose n as t he n o ncli nical s pecies beca use 
P F - 0 6 7 4 1 0 8 6 bi n ds t o T F PI i n t hese s pecies.  T he use of rats a n d m o n ke y s i n n o ncli nical 
t o xic ol o g y st u dies is f urt her j ustifie d b y e vi de nce of p har mac ol o gical acti vit y, s uc h as 
decreases i n fi bri n o ge n ( FI B) a n d i ncreases i n D -di mer, i n b ot h s pecies i n re peat -d ose
t o xicit y st u dies.  B ot h s pecies de m o nstrate d dr u g e x p os ure f oll o wi n g I V or S C 
a d mi nistrati o ns a n d tar get or ga n t o xicit y ; t heref ore t he rat was s uita ble f or use as t he o nly 
s pecies f or e val uati n g c hr o nic t o xicit y.  Ot her t o xicit y st u dies i ncl u de d tiss ue cr oss reacti vity 
assa y, Fc R a n d C 1 q bi n di n g assa ys, a n d a c yt o ki ne release assa y.  Ge netic t o xicit y st u dies 
were n ot c o n d ucte d beca use t he y  are ge nerally n ot a p pr o priate f or bi otec h n ol o g y- deri ve d 
pr o d ucts.  T his n o ncli nical pr o gra m is i nte n de d t o s u p p ort cli nical trials of u p t o 3 m o nt hs i n 
d urati o n.
P F - 0 6 7 4 1 0 8 6 was a d mi nistere d t o rats a n d m o n ke ys b y i ntra ve n o us (I V) a n d s u bc uta ne o us 
( S C) i njecti o n, i n st u dies u p t o 2 6 wee ks i n d urati o n.  W he n a d mi nistere d wee kly t o rats f or 
2 6 wee ks at d oses u p t o 1 0 0 0 m g/ k g/ d ose, t he n o o bser ve d a d verse effect le vel ( N O A E L) 
was 1 0 0 0 m g/ k g/ d ose, c orres p o n di n g t o a C ma x of 2 9, 8 0 0, 0 0 0 n g/ m L a n d a n A U C 1 6 8 of 
1, 8 4 0, 0 0 0, 0 0 0 n g· h/ m L.  I n rats, at 1 0 0 0 m g / k g/ d ose I V, Cma x ( 2 9, 8 0 0, 0 0 0 n g/ m L) a n d 
A U C 1 6 8 ( 1, 8 4 0, 0 0 0, 0 0 0 n g• h/ m L) o n Da y 1 7 6 were 9 5 x a n d 6 9 x t he pre dicte d h u ma n 
e x p os ure at t he hi g hest i nte n de d I V d ose of 1 0 0 0 m g o nce m o nt hl y  ( Q M) 
( Cma x = 3 1 3, 0 0 0 n g/ m L a n d A U C 1 6 8 = 2 6, 6 0 0, 0 0 0 n g• h/ m L).  W he n a d mi nistere d o nce 
wee kl y f or 1 3 wee ks, t he n o o bser ve d a d verse effect le vels ( N O A E Ls) were 
1 0 0 0 m g/ k g/ d ose I V a n d 1 8 0 m g/ k g/ d ose S C i n rats a n d 5 0 0 m g/ k g/ d ose I V a n d 
9 0 m g/ k g/ d ose S C i n m o n ke y s.  I n rats, at 1 0 0 0 m g / k g/ d ose I V, Cma x ( 2 7, 8 0 0, 0 0 0 n g/ m L) 
a n d A U C 1 6 8 ( 1, 9 4 0, 0 0 0, 0 0 0 n g• h/ m L) o n Da y 8 5 were 8 9 x a n d 7 3 x t he pre dicte d h u ma n 
e x p os ure at t he hi g hest i nte n de d I V d ose a n d at 1 8 0 m g/ k g/ d ose S C, C ma x ( 4 1 6, 0 0 0 n g/ m L) 
a n d A U C 1 6 8 ( 4 5, 3 0 0, 0 0 0 n g• h/ m L) o n Da y 8 5 were 3 x a n d 2 x t he pre dicte d h u ma n e x p os ure 
at t he hi g hest i nte n de d S C d ose of 4 5 0 m g o nce wee kl y ( Q W) ( C ma x = 1 3 4, 0 0 0 n g/ m L a n d 
A U C 1 6 8 = 2 1, 5 0 0, 0 0 0 n g• h/ m L ).  I n m o n ke ys, at 5 0 0 m g/ k g/ d ose I V, 
C ma x ( 1 8, 4 0 0, 0 0 0 n g/ m L) a n d A U C 1 6 8 ( 2, 0 0 0, 0 0 0, 0 0 0 n g• h/ m L) o n Da y 8 5 were 5 9 x a n d 
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI

PF-06741086
B7841003
Final Protocol Amendment 2, 08 November 2018
PFIZER CONFIDENTIAL
Page 25
75x the predicted human exposure at the highest intended IV dose and at 90 mg/kg/dose SC, 
Cmax (2,480,000 ng/mL) and AUC168 (364,000,000 ng•h/mL) on Day 85 were 19x and 17x 
the predicted human exposure at the highest intended SC dose.  Anticipated staining in the 
endothelium and placental decidual cells and trophoblasts was observed in the tissue cross 
reactivity assay.  In the C1q binding and FcR binding assays, PF-06741086 did not bind to 
C1q, suggesting an inability to activate the classical complement pathway and induce CDC, 
and FcR binding assays showed that PF-06741086 had low potential to elicit ADCC activity.  
In the cytokine release assay, PF-06741086 did not elicit a test article-related release of 
TNF α, IL-6, or IFN-γ.  When administered to rats as a single SC dose of 300 mg/kg, the 
NOAEL in the 1-day local toleration study with a 1-week recovery was 300 mg/kg SC, 
corresponding to a Cmax (1,390,000 ng/mL) and AUC168 (139,000,000 ng•h/mL) with 
10x and 7x the predicted human exposure at the highest intended SC dose.  The potential 
target organs identified in these studies was the coagulation cascade based on changes in 
D-dimer, PT, APTT and fibrinogen, with no clinical signs or microscopic evidence of 
bleeding or adverse thrombi/emboli formation.  However, there were other effects on ALB, 
GLOB, ALB:GLOB and total protein values of rats and monkeys, the SC injection site of 
rats, and ADA’s were observed in rats.  Consistent with ICH S6 guidance, PF-06741086 was 
not evaluated in genotoxicity studies because it is not expected that this large molecule would 
interact directly with DNA or other chromosomal material.
1.2.3. Clinical Experience with PF-06741086
To date, a single clinical study has been completed with PF-06741086.  The clinical 
development of PF-06741086 began with study B7841001: a Phase 1, first-in-human (FIH) 
single ascending dose (SAD) study in healthy subjects.  Male subjects between the ages of 
18 and 55 with no known risk factors for thrombosis were eligible for this study.  Subjects 
were enrolled sequentially into cohorts ordered by PF-06741086 maximum single-dose 
concentration and randomized to receive a single SC or IV dose of PF-06741086 or placebo.  
Data on safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and 
immunogenicity were collected during clinic confinement (7 days) and outpatient follow-up 
(up to 84 days). 
In study B7841001, there were no significant adverse effects following single dose 
administration with PF-06741086.  There were no serious adverse events (SAEs).  There 
were no severe adverse events (AEs).  There were no clinically significant changes in 
laboratory parameters.  Additional clinical information regarding PF-06741086 including 
data from study B7841001 may be found in the Investigator Brochure.
The second clinical investigation of PF-06741086 is ongoing with study B7841002, an 
open-label, Phase 1b/2, multiple ascending dose (MAD) study in severe hemophilia A or B, 
with or without inhibitors to FVIII or FIX.  The clinical risk/benefit profile for this 
population is considered appropriate for the evaluation of safety, tolerability, PK, PD, and 
efficacy of multiple doses of PF-06741086. 
090177e196978055\0.1\Draft\Versioned On:23-Mar-2021 10:50 (GMT)

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 2 6
T he pri mar y  o bjecti ve of st u d y B 7 8 4 1 0 0 2 is t o e val uate t he safet y a n d t olera bilit y of m ulti ple 
asce n di n g d oses of P F- 0 6 7 4 1 0 8 6 a d mi nistere d b y t he S C.  Sec o n dar y  o bjecti ves i ncl u de 
e val uati n g t he P K a n d P D pr o perties of P F -0 6 7 4 1 0 8 6 , as well as assessi n g cli nical efficac y 
base d o n t he fre q ue nc y  of blee di n g e pis o des.  It is e x pecte d t hat at least o ne d ose le vel i n 
st u d y B 7 8 4 1 0 0 2 will ac hie ve pr o p h yl a xis efficac y o utc o mes s ufficie nt t o s u p p ort f urt her 
cli nical de vel o p me nt, i ncl u di n g st u d y  B 7 8 4 1 0 0 3.
I nteri m cli nical data fr o m st u d y B 7 8 4 1 0 0 2 m a y  be f o u n d i n t he P F-0 6 7 4 1 0 8 6 I nvesti gat or 
Br oc h ure.
1. 2. 4. B 7 8 4 1 0 0 3 St u d y R ati o n ale 
T he cli nical i n vesti gati o n of P F - 0 6 7 4 1 0 8 6 will c o nti n ue wit h st u d y  B 7 8 4 1 0 0 3, a l o n g-ter m 
st u d y o n t he safety, t olera bil it y a n d efficac y of P F- 0 6 7 4 1 0 8 6 u p t o 3 6 5 da ys of treat me nt.  
T he pri mar y  o bjecti ve of st u d y B 7 8 4 1 0 0 3 is t o e val uate t he safet y a n d t olera bilit y of 
l o n g-ter m ( u p t o 3 6 5 da ys ) pr o p hyl a xis wit h P F- 0 6 7 4 1 0 8 6 a d mi nistere d b y t he S C r o ute.  
T he sec o n dar y  o bjective is t he assess me nt of cli nical efficac y  base d o n t he fre q ue nc y of 
blee di n g e pis o des. 
 
 
Safet y  data i ncl u di n g treat me nt-e mer ge nt A Es a n d la b orat or y a b n or malities will be re vie we d 
t hr o u g h o ut t he st u dy t o m o nit or a n y  u na ntici pate d ris ks ass ociate d wit h 
P F - 0 6 7 4 1 0 8 6 treat me nt.  De m o nstrati o n of safet y, t olera bilit y a n d efficac y t hat is s u p p orti ve 
f or l o n g-ter m c hr o nic treat me nt o n a n acce pta ble d osi n g sc he d ule is i nte n de d t o s u p p ort 
pr o gressi o n of P F -0 6 7 4 1 0 8 6 t o s u bse q ue nt i n vesti gati o ns i n patie nts wit h se vere 
he m o p hilia A or B.
1. 2. 5. D ose R ati o n ale
S u bjects e nr olli n g i n B 7 8 4 1 0 0 3 fr o m C o h ort 1 ( 3 0 0 m g S C) of B 7 8 4 1 0 0 2 will c o nti n ue wit h 
t heir assi g ne d d ose le vel at t he c o m pleti o n of B 7 8 4 1 0 0 2.  All ot her s u bjects e nr olli n g i n 
st u d y B 7 8 4 1 0 0 3 (f oll o wi n g partici pati o n i n B 7 8 4 1 0 0 2) will recei ve t he l o west S C d ose le vel 
deter mi ne d t o be safe a n d efficaci o us i n st u d y  B 7 8 4 1 0 0 2 f or t he respecti ve he m o p hil ia 
p o p ulati o n: 3 0 0 m g S C l oa di n g d ose o n Da y 1, f oll o we d b y 1 5 0 m g  S C Q W f or n o n-i n hi bit or 
s u bjects; 3 0 0 m g S C Q W f or i n hi bit or s u bjects.  De n o v o s u bjects i n C o h ort 5 (a d olesce nts 
wit h or wit h o ut i n hi bit ors) a n d C o h ort 6 (a d ults wit h i n hi bit ors) will recei ve a 3 0 0 m g S C 
l oa di n g d ose o n Da y 1, f oll o we d b y 1 5 0 m g  S C Q W.
All d oses will be a d mi nistere d b y t he S C r o ute.
1. 2. 6. S u m m ar y of Ris k/ Be nefit
Base d o n t he p ote ntial ris ks, s u bjects will be m o nit ore d f or treat me nt e mer ge nt e ve nts usi n g 
para meters t hat i ncl u de: s er u m c he mistr y, he mat ol o g y, uri nalys is; vital si g ns; p h ysical 
e xa mi nati o ns; a n d a d verse e ve nts.  M o nit ori n g f or a nti b o d y  i m m u ne res p o nse will use a 
tiere d testi n g strate g y i ncl u di n g meas ure me nt of A D A t o P F- 0 6 7 4 1 0 8 6 a n d f urt her 
c haracterizati o n of a n y p osi ti ve a nti b o d y i m m u ne res p o nses s uc h as testi n g f or ne utralizi n g 
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 2 7
a nti b o d y.  A d diti o nally, s u bjects will be m o nit ore d f or brea kt hr o u g h blee di n g e ve nts a n d a n y 
cli nicall y-rele va nt effects t hat ma y i m pact he m ostasis.
Safet y  has bee n de m o nstrate d at all teste d si n gle d ose le vels i n t he B 7 8 4 1 0 0 1 FI H st u d y.  
F urt her safet y a n d t olera bilit y testi n g is o n g oi n g i n t he 3-m o nt h B 7 8 4 1 0 0 2 st u d y i n s u bjects 
wit h he m o p hilia.  S u bjects c o nti n ui n g o n t o st u d y  B 7 8 4 1 0 0 3 fr o m B 7 8 4 1 0 0 2 will o nl y be 
all o we d t o d o s o at a d ose le v el a n d r o ute of a d mi nistrati o n t hat was deter mi ne d t o be safe 
a n d well-t olerate d i n st u d y B 7 8 4 1 0 0 2.  De n o v o s u bjects e nr olli n g i n st u d y B 7 8 4 1 0 0 3 will 
o nl y  be assi g ne d t o P F-0 6 7 4 1 0 8 6 treat me nt at t he l o west S C d ose le vel deter mi ne d t o be safe 
a n d efficaci o us f or t he res pecti ve he m o p hilia p o p ulati o n ( n o n -i n hi bit or or i n hi bit or) i n st u d y 
B 7 8 4 1 0 0 2.  F urt her, de n o v o s u bjects will o nl y  be eli gi ble f or e nr oll me nt f oll o wi n g 
c o m pleti o n of all S C c o h orts t hr o u g h 3 m o nt hs of treat me nt i n B 7 8 4 1 0 0 2.
P ossi ble ris ks fr o m l o n g -ter m treat me nt wit h P F-0 6 7 4 1 0 8 6 i ncl u de t he p ote ntial f or 
t hr o m b oe m b olic a n d isc he mic e ve nts, hy perse nsiti vit y  reacti o ns (i ncl u di n g l ocal 
i njecti o n/i nf usi o n site reacti o ns), a n d a nti b o dy i m m u ne res p o nse wit h f or mati o n of a nti -dr u g 
a nti b o dies.  H o we v er, it is e x pecte d t hat t he p ote ntial ris k of a t hr o m b oe m b olic or isc he mic 
e ve nt i n s u bjects wit h he m o p hilia will be l o w d ue t o t he effects of F VIII or FI X deficie nc y . 
T he p ote ntial t hera pe utic efficac y  of pr o p h yla xis wit h P F- 0 6 7 4 1 0 8 6 m a y  be reflecte d i n a 
re d uce d fre q ue nc y of blee di n g e pis o des vers us t he nat ural hist or y of blee di n g e pis o des f or 
s u bjects usi n g F VIII or FI X re place me nt t hera py, or b y pass a ge nt t hera p y, f or o n -de ma n d 
treat me nt of blee di n g e pis o des.  F urt her, it is ass u me d t hat a ny occ urre nce of ne utralizi n g 
a nti b o dies a gai nst P F -0 6 7 4 1 0 8 6 will ha ve n o i m pact o n pr o p h yl actic treat me nt wit h F VIII or 
FI X re place me nt.  T hese a ntici pate d be nefits ma y  j ustif y t he p ote ntial ris ks of treat me nt wit h 
P F - 0 6 7 4 1 0 8 6 f or s u bjects wit h he m o p hilia A or B wit h o ut i n hi bit ors c urre ntl y  recei vi n g 
fact or re place me nt t hera p y, a n d s u bjects wit h i n hi bit ors c urre ntly recei vi n g b y pass a ge nt 
t hera py.
A d diti o nal i nf or mati o n f or t his c o m p o u n d ma y  be f o u n d i n t he si n gle refere nce safety 
d oc u me nt ( S R S D), w hic h f or t his st u d y  is t he I n vesti gat ors Br oc h ure.
 
 
 
 
 
 
 
 
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P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 2 8
2. S T U D Y O B J E C TI V E S A N D E N D P OI N T S
Pri m ar y O bjecti ve(s):
Pri m ar y E n d p oi nt(s):

T o deter mi ne t he safet y  a n d t olera bilit y of 
l o n g-ter m treat me nt ( u p t o 3 6 5 d a y s) wit h 
P F -0 6 7 4 1 0 8 6 i n se vere he m o p hilia A a n d B 
s u bjects wit h or wit h o ut i n hi bit ors t o FVIII or FI X.

Fre q ue nc y , se verit y a n d ca usal relati o ns hi p of 
treat me nt e mer ge nt a d verse e ve nts ( T E A Es); 
Da y 1 u p t o Da y 3 9 3.

Fre q ue nc y  a n d ma g nit u de of a b n or mal la b orat or y 
fi n di n gs (i ncl u di n g he mat ol o g y, c he mistr y, 
uri nal y sis); Da y 1 u p t o Da y 3 9 3.

C ha n ges fr o m baseli ne i n vital si g n ( bl o o d 
press ure, p ulse rate, te m perat ure a n d res pirati o n 
rate) meas ure me nts a n d p h ysical e xa mi nati o ns; 
Da y 1 u p t o Da y 3 9 3 a n d E C G Da y 1 t o Da y 2 9 i n 
de n o v o s u bjects o nl y .

Fre q ue nc y , se verit y a n d cas ual relati o ns hi p of 
i nf usi o n a n d i njecti o n site reacti o ns; Da y 1 u p t o 
Da y 3 9 3.
Sec o n d ar y O bjecti ve(s):
Sec o n d ar y E n d p oi nt(s):

T o deter mi ne t he efficac y  of l o n g-ter m treat me nt 
wit h P F -0 6 7 4 1 0 8 6 i n severe he m o p hilia A a n d B 
s u bjects wit h or wit h o ut i n hi bit ors t o FVIII or FI X. 

Fre q ue nc y  a n d a n n ualize d rate of blee di n g 
e pis o des; Da y 1 u p t o Da y 3 9 3.

Fre q ue nc y  of resc ue ( FVIII, or FI X) t hera p y f or 
treat me nt of brea kt hr o u g h blee di n g e pis o des.
Terti ar y/ E x pl or at or y O bjecti ve(s):
Terti ar y/ E x pl or at or y E n d p oi nt(s):
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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3. STUDY DESIGN
B7841003 is an open-label long-term (treatment of up to 365 days) evaluation of 
PF-06741086 as a prophylactic treatment regimen in subjects with hemophilia A or B, with 
or without inhibitors to FVIII or FIX.  Investigators, subjects, site staff and sponsor study 
team members will not be blinded to treatment assignment.  Subjects will be assigned to 
treatment cohorts as indicated in Figure 1 below. 
Figure 1.
B7841003 Dose Assignment
Subjects enrolling in B7841003 from Cohort 1 (300 mg SC) of B7841002 will continue with 
their assigned dose level at the completion of study B7841002.  All other subjects enrolling 
in B7841003 will receive the lowest dose level determined to be safe and efficacious for the 
respective hemophilia population in study B7841002. 
Subjects who complete study B7841002 may enroll immediately into study B7841003 at the 
B7841002 Day 85 or Day 113 visit.  This visit will be Day 1 for the B7841003 Schedule of 
Activities.  Procedures that are required at the B7841002 Day 85 or Day 113 visit do not 
need to be repeated for B7841003 Day 1.
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All subjects who complete study B7841002 are eligible for study B7841003, unless a specific 
exclusion criterion in Section 4.2 is noted at the Day 1 visit.  It is expected that some subjects 
who complete B7841002 may not be able to immediately enroll in B7841003.  These 
subjects do not require a complete re-screening, however if there is a 30-day or longer gap 
between the B7841002 last study visit and the B7841003 Day 1 visit, the investigator must 
review the criteria in Section 4.1 and Section 4.2, perform the limited set of procedures listed 
in Section 6.1 and confirm that the subject still meets eligibility criteria.
Subjects who completed the Day 197 (Month 7) visit prior to Amendment 2 (and extension 
of treatment duration) are allowed to restart treatment, beginning with Day 225 (Month 8).  
Hematology, chemistry, and urinalysis results from Day 169 (Month 6) should be reviewed 
against inclusion/exclusion criteria prior to the resumption of treatment to ensure there are no 
exclusionary laboratory abnormalities.
De novo subjects will be eligible for enrollment following completion of all subcutaneous 
cohorts (ie, after Cohort 3) through 3 months of treatment in B7841002.
Dosing of any subject may be stopped if available data indicate that the treatment is not safe 
and well-tolerated.
3.1. Planned Number of Subjects
Approximately 36 subjects (24 subjects from B7841002 and 12 additional de novo subjects) 
are planned for enrollment at approximately 20 study sites. 
3.2. Study Duration
Subjects who completed B7841002 within 30 days of B7841003 Day 1 will begin this study 
at Day 1 (no Screening visit).  A limited Screening visit and eligibility criteria review is 
required prior to Day 1 for subjects who completed study B7841002 more than 30 days prior 
to the scheduled Day 1 visit.
All Screening activities apply to de novo subjects who did not participate in B7841002.  
Screening procedures may be completed up to 35 days prior to the Day 1 visit for these 
subjects (ie, Day -34). 
All subjects that meet inclusion/exclusion criteria at Day 1 will be assigned to a treatment 
regimen and dosed.  All subjects will return for clinic visits on Day 29, Day 57, Day 85, 
Day 113, Day 141, Day 169, Day 197, Day 225, Day 253, Day 281, Day 309, Day 337, 
Day 365 with follow-up and end-of-study procedures on Day 393.  De novo subjects will 
undergo additional visits, as per Table 2 during the interval between Day 1 and Day 29.  The 
total duration of the treatment period will be up to 365 days. 
Subjects not yet proficient in SC self-administration may have scheduled doses of 
PF-06741086 administered by investigational site staff or their properly trained designees 
during the interval(s) between planned study visits.
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P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 3 1
 
S u bjects w h o e x perie nce a treat me n t-relate d a d verse e ve nt (i ncl u di n g la b a b n or malities) at 
a n y ti me p oi nt will c o nti n ue t o be f oll o we d t hr o u g h res ol uti o n or sta bilizati o n of t he e ve nt as 
a gree d u p o n b y t he i n vesti gat or a n d s p o ns or. 
T he ma xi m u m t otal d urati o n of t he st u d y  f or a s u bject w h o c o m plete d B 7 8 4 1 0 0 2 will be 
a p pr o xi matel y 1 4 m o nt hs (e xcl u di n g scree ni n g a n d a n y  i nterr u pti o n i n treat me nt pri or t o 
a p pr o val of A me n d me nt 2).  T he ma xi m u m t otal d urati o n of t he st u d y  f or de n o v o s u bjects, 
fr o m i nitial scree ni n g t o fi nal f oll o w- u p, will be a p pr o xi matel y 1 5 m o nt hs. 
3. 3. D ose M o dific ati o n R ules f or A d verse E ve nts
D osi n g ma y  be st o p pe d, pa use d, or m o difie d base d o n t he f oll o wi n g criteria:

D osi n g at t he c urre nt d ose le vel ( or hi g her d ose le vels) will be pa use d f or a n y  
treat me nt e mer ge nt t hr o m b otic eve nt (see A p pe n di x 2 f or q ualif yi n g A Es) i n a s u bject 
recei vi n g P F-0 6 7 4 1 0 8 6, t o per mit c haracterizati o n of t he res pecti ve e ve nt a n d 
c o m m u nicati o n t o re g ulat or y  a ge ncies w here re q uire d. 

Vessel occl usi o n relate d t o t he i nserti o n or prese nce of a ce ntral ve n o us cat heter 
ma y  be e xcl u de d fr o m t his criteri o n after re vie w of t he A E wit h t he res pecti ve 
i n vesti gat or t o assess ca usalit y a n d/ or cli nical si g nifica nce. 

D osi n g will be pa use d (a n d ma y res u me at a l o wer d ose after s p o ns or re v ie w of safet y 
data) if a s u bject e x perie nces a treat me nt e mer ge nt se vere or Gra de 3 a d verse e ve nt 
wit h o ut res ol uti o n after re peat a d mi nistrati o n wit h P F- 0 6 7 4 1 0 8 6, u nless 
i nc o ntr o verti bl y d ue t o e xtra ne o us ca uses.
A n y  s u bject w h o meets t he a b o ve criteria d uri n g treat me nt wit h P F -0 6 7 4 1 0 8 6 will be 
re m o ve d fr o m t he c urre nt d ose le vel a n d dr o p pe d t o t he ne xt l o west e x p os ure le vel, u nless 
t he e ve nt(s) are i nc o ntr o verti bl y d ue t o e xtra ne o us ca uses or are i nc o ntr o verti bl y 
c o m plicati o ns of he m o p hilia (see Secti o n 8. 2. 3 f or q ualif yi n g e ve nts).
3. 3. 1. D ose M o dific ati o n R ules f or Bre a kt hr o u g h Blee di n g E pis o des
D osi n g ma y  be m o difie d t o t he ne xt hi g her per mitte d d ose le vel ( base d o n st u d y 
B 7 8 4 1 0 0 2 safety res ults) if a s u bject e x perie nces i ncrease d brea kt hr o u g h blee di n g fre q ue nc y 
t hat meets t he f oll o wi n g criteria:

T w o s p o nta ne o us (atra u matic) blee di n g e pis o des i nt o maj or j oi nts s uc h as el b o w, 
a n kle or k nee j oi nt(s) a n d/ or ot her tar get j oi nts o ver a 4 wee k ( 2 8 d a y ) peri o d.
O R

T hree or m ore s p o nta ne o us (atra u matic) blee di n g e pis o des (e g, 1 j oi nt a n d 2 s oft 
tiss ue or ot her site) o ver a 4 wee k ( 2 8 d a y ) peri o d.
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4. SUBJECT ELIGIBILITY CRITERIA
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate.  All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular subject is suitable for this protocol. 
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study. 
4.1. Inclusion Criteria
All subjects must meet the following inclusion criteria to be eligible for enrollment into the 
study.  Subjects continuing from B7841002 within 30 days of the B7841003 - Day 1 visit do 
not require screening procedures to confirm eligibility:
1. Evidence of a personally signed and dated informed consent document indicating that 
the subject (or a legally acceptable representative/parent(s)/legal guardian) has been 
informed of all pertinent aspects of the study.
2. Males ≥18 and <75 years of age.
3. Body Mass Index (BMI) ≥17.5 and ≤30.5 kg/m2 and total body weight ≥50 and 
≤100 kg. 
a.
For adolescents, the BMI must be ≥14 kg/m2 and total body weight must be 
≥30 kg.
4. Diagnosis of severe hemophilia A or B (FVIII or FIX activity ≤1%).
5. If receiving therapy for human immunodeficiency virus (HIV) or active hepatitis 
infection, have stable disease and be on a stable regimen at the time of study entry 
(ie, stable dosing for at least 3 months before consent).
6. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other study procedures.
The following inclusion criteria only apply to de novo subjects (Cohorts 5 and 6) only:
1. Adolescent males ≥12 to <18 years of age are eligible.
2. Patients with an episodic (on-demand) treatment regimen who are willing and able to 
washout from Factor VIII (for at least 72 hours) or Factor IX (for at least 96 hours) 
replacement therapy, or bypass agent therapy (for rFVIIa and activated prothrombin 
complex concentrate [APCC]: at least 72 hours; for other products: at least 
5 half-lives) prior to Screening laboratory assessments of factor activity and have no 
plans to institute prophylactic factor or bypass agent treatment during the study 
period.
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3. Had at least 6 acute bleeding episodes (spontaneous/traumatic) during the 6 month 
period prior to Screening.  Surgical bleeding episodes do not apply to this criterion.
4. Subjects enrolled as Factor VIII or Factor IX inhibitor patients must have a positive 
inhibitor test result (above the upper limit of normal) at the local laboratory and must 
receive a bypass agent as primary treatment for bleeding episodes.  A positive 
inhibitor test result will be above the upper limit of normal for the assay.  Inhibitor 
test results from up to 6 months prior to Day 1 may be used to meet this requirement.
4.2. Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the 
study:
1. Females.
2. Known coronary artery, thrombotic, or ischemic disease, or known severe, 
uncontrolled hypercholesterolemia.
3. Known hemostatic defect other than hemophilia A or B.
4. ATIII, Protein C, or Protein S deficiency, Factor V Leiden, 
Prothrombin 20210 mutation, or other known pro-thrombotic condition.
5. Regular, concomitant therapy with immunomodulating drugs (eg, intravenous 
immunoglobulin [IVIG], and routine systemic corticosteroids).
6. Currently receiving treatment for acute bleeding episodes with APCC (eg, Factor 
Eight Inhibitor Bypass Agent [FEIBA]) and cannot substitute treatment with rFVIIa 
at a dose level of approximately 90 μg/kg for the duration of the study. 
7. Abnormal renal or hepatic function as defined by the following laboratory results at 
any time prior to Day 1:
•
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels 
>3 times the upper limit of normal (ULN).
•
Total bilirubin level >2 mg/dL (>35 μmol/L).
•
Serum albumin < the lower limit of normal (LLN).
•
Serum creatinine level >1.25 times the ULN.
8. Abnormal hematology values as defined by the following laboratory results at any 
time prior to Day 1: 
•
Platelet count <100,000/μL.
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•
Fibrinogen level < LLN.
•
Hemoglobin level <10 gm/dL.
9. Abnormal coagulation activity as defined by the following laboratory results at any 
time prior to Day 1:
•
Prothrombin time (PT) >1.25 times the ULN.
10. CD4 cell count ≤200/μL.
11. Known hypersensitivity (eg, latex allergy) or allergic reaction to hamster protein.
12. Known sensitivity to heparin or heparin induced thrombocytopenia.
13. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or 
subjects who are Pfizer employees, including their family members, directly involved 
in the conduct of the study.
14. Participation in other studies involving investigational drug(s) (excluding 
PF-06741086) within 30 days prior to study entry and/or during study participation.
15. Other acute or chronic medical or psychiatric condition including recent (within the 
past year) or active suicidal ideation or behavior or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the subject inappropriate for entry into this 
study.
16. Fertile male subjects who are unwilling or unable to use a highly effective method of 
contraception as outlined in this protocol for the duration of the study and for at least 
28 days after the last dose of investigational product. 
17. Had major surgery, as judged by the investigator, within 3 months prior to the study
or have elective surgery planned during the study (applies only to de novo subjects).
4.3. Randomization Criteria
This study is not a randomized trial, but allocation to treatment will follow procedures 
similar to randomization (which may be referred to as enrollment).
All subjects will be given PF-06741086.  All subjects will be required to receive a new 
subject number for this study.  Other procedures for treatment assignment may not be 
necessary for subjects who completed study B7841002.
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Subjects will be assigned a randomization number provided they have satisfied all eligibility 
criteria and the following enrollment criteria:
1. De novo subjects in B7841003 must washout from FVIII (for at least 72 hours) or 
FIX (for at least 96 hours) replacement therapy prior to the Day 1 visit laboratory 
testing for clotting factor activity level.  Subjects cannot be enrolled or treated with 
investigational product if they have received treatment for an acute bleeding episode 
with FVIII or FIX replacement therapy within 72 hours or 96 hours, respectively, or 
rFVIIa or APCC (eg, FEIBA) bypass agent therapy within 72 hours (or for other 
products: 5 half-lives) of the Day 1 visit.  If factor replacement or bypass agent 
therapy is required to treat a bleeding episode during the Screening period, then the 
subject may return for the Day 1 visit after completing the required washout period 
and remain eligible for study participation.  See Section 6.1 for further Screening 
procedure guidance.
4.4. Lifestyle Requirements 
4.4.1. Contraception
All fertile male subjects who are, in the opinion of the investigator, sexually active and at risk 
for pregnancy with their partner(s) must agree to use a highly effective method of 
contraception consistently and correctly for the duration of the active treatment period and 
for at least 28 days after the last dose of investigational product.  A longer duration of 
contraception usage may be required if data warrant this change.  The investigator or his or 
her designee, in consultation with the subject, will confirm that the subject has selected an 
appropriate method of contraception for the individual subject and his partner from the 
permitted list of contraception methods (see below) and will confirm that the subject has 
been instructed in its consistent and correct use.  At time points indicated in the Schedule of 
Activities, the investigator or designee will inform the subject of the need to use highly 
effective contraception consistently and correctly and document the conversation and the 
subject’s affirmation in the subject’s chart (subjects need to affirm their consistent and 
correct use of at least 1 of the selected methods of contraception).  In addition, the 
investigator or designee will instruct the subject to call immediately if the selected 
contraception method is discontinued or if pregnancy is known or suspected in the subject or 
the partner. 
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include the following:
1. Established use of hormonal methods of contraception associated with inhibition of 
ovulation (eg, oral, inserted, injected, implanted, transdermal) provided the subject or 
male subject’s female partner plans to remain on the same treatment throughout the 
entire study and has been using that hormonal contraceptive for an adequate period of 
time to ensure effectiveness. 
2. Correctly placed copper-containing intrauterine device (IUD). 
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3. Male condom or female condom used WITH a separate spermicide product (ie, foam, 
gel, film, cream, or suppository).  For countries where spermicide is not available or 
condom plus spermicide is not accepted as highly effective contraception, this option 
is not appropriate.
4. Male sterilization with absence of sperm in the postvasectomy ejaculate.
5. Bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label).
NOTE: Sexual abstinence, defined as completely and persistently refraining from all 
heterosexual intercourse (including during the entire period of risk associated with the study 
treatments) may obviate the need for contraception ONLY if this is the preferred and usual 
lifestyle of the subject. 
All sexually active male subjects must agree to prevent potential transfer to and exposure of 
partner(s) to drug through ejaculate by using a condom consistently and correctly, beginning 
with the first dose of investigational product and continuing for at least 28 days after the last 
dose of investigational product.
4.5. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card.  The contact card contains, 
at a minimum, protocol and investigational product identifiers, subject study numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study.  The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the subject directly, and if a subject calls that number, he 
or she will be directed back to the investigator site.
5. STUDY TREATMENTS
For the purposes of this study, and per International Conference on Harmonisation (ICH) 
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator in a clinical trial, 
including a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33). 
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For this study, the investigational product(s) is PF-06741086.
Study Treatment
Route of Administration
Protocol Term
PF-06741086, Solution for 
Injection, 150 mg/mL
subcutaneous (SC)
investigational product (IP)
5.1. Allocation to Treatment
The investigator’s knowledge of the treatment should not influence the decision to enroll a 
particular subject or affect the order in which subjects are enrolled.
Allocation of subjects to treatment groups will proceed through the use of an interactive 
response technology (IRT) system (interactive Web-based response [IWR]).  The site 
personnel (study coordinator or specified designee) will be required to enter or select 
information including but not limited to the user’s identification (ID) and password, the 
protocol number, and the subject number.  The site personnel will then be provided with a 
treatment assignment, randomization number, and dispensable unit (DU) or container number 
when investigational product is being supplied via the IRT system.  The IRT system will 
provide a confirmation report containing the subject number, randomization number, and DU 
or container number assigned.  The confirmation report must be stored in the site’s files. 
The study-specific IRT reference manual will provide the contact information and further 
details on the use of the IRT system. 
5.2. Subject Compliance
Subjects will be permitted to self-administer PF-0674106 once they have demonstrated an 
understanding of the preparation and administration process at the site.  Confirmation of a 
subject’s ability to perform preparation and administration must be documented in the site 
file.  For self-administration of PF-06741086 at home, compliance will be captured and 
completed by the subject by completing the subject diary.
Subjects will self-administer treatment weekly from the point of which they have 
demonstrated the capability to do so (as stated above) until Day 365 (see Section 3.2).  Prior 
to self-administration, sites must ensure subjects are trained on IP administration and storage 
per the IP manual.  Dosing between planned clinic visits may be administered by 
investigational site staff until the respective subject has been properly trained in 
self-administration.  Sites should follow-up (eg, via phone call) to ensure compliance with 
administration instructions, where necessary.  Day 337 (Month 12) will be the final visit 
where IP is dispensed for self-administration.  For subjects being treated in the clinic, 7 days 
before Day 365 is the final date that IP is administered in the clinic.
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P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 3 8
5. 3. I n vesti g ati o n al Pr o d uct S u p plies
5. 3. 1. D os a ge F or m(s) a n d P ac k a gi n g
P F - 0 6 7 4 1 0 8 6 S ol uti o n f or I njecti o n ( 1 5 0 m g / m L) will be s u p plie d b y Pfizer as a g o o d 
ma n ufact uri n g practice ( G M P) ma n ufact ure d, sterile li q ui d s ol uti o n f or i njecti o n pac ka ge d i n 
a 6 m L  glass vial seale d wit h a st o p per a n d a n al u mi n u m seal ( n o mi nal fill v ol u me of 
1. 0 m L ).
T hese pr o d ucts will be s u p plie d t o sites as o pe n la bel pac ka ge d s u p plies f or s u bse q ue nt u nit 
d osi n g.
5. 3. 2. Pre p ar ati o n a n d Dis pe nsi n g
T he i n vesti gati o nal pr o d uct will be dis pe nse d usi n g a n I RT dr u g ma na ge me nt s y ste m at eac h 
visit fr o m Da y 1 t o Da y 3 3 7.  A q ualifie d staff me m ber will dis pe nse t he i n vesti gati o nal 
pr o d uct via u ni q ue c o ntai ner n u m bers i n t he cart o ns pr o vi de d, a n d i n q ua ntities a p pr o priate 
s o t hat s u bjects self-a d mi nisteri n g treat me nts at h o me will recei ve e n o u g h i n vesti gati o nal 
pr o d uct t o c o ver t he n u m ber of d oses u ntil t he ne xt sc he d ule d cli nic visit.  T he 
s u bject/care gi ver s h o ul d be i nstr ucte d t o mai ntai n t he pr o d uct i n t he cart o ns pr o vi de d, a n d 
t he cart o ns s h o ul d n ot be o pe ne d u ntil t he i n vesti gati o nal pr o d uct is t o be a dmi nistere d.
See t he I n vesti gati o nal Pr o d uct Ma n ual (I P M) f or i nstr ucti o ns o n h o w t o pre pare t he 
i n vesti gati o nal pr o d uct f or a d mi nistrati o n.  In vesti gati o nal pr o d uct s h o ul d be pre pare d, w he n 
necessar y , a n d dis pe nse d b y a n a p pr o priately q ualifie d a n d e x perie nce d me m ber of t he st u d y  
staff (e g, p hys icia n, n urse, p h ysicia n’s assista nt, n urse practiti o ner, p har mac y 
assista nt/tec h nicia n, or p har macist) as all o we d b y l ocal, state, a n d i nstit uti o nal g ui da nce.  
T hese re q uire me nts will n ot a p pl y  f or self-a d mi nistrati o n b y  s u bjects. 
5. 4. A d mi nistr ati o n
I n vesti gat or site pers o n nel, t he s u bject a n d/ or t he s u bject’s care gi ver will a d mi nister 
i n vesti gati o nal pr o d uct acc or di n g t o t he s u bject diar y.  Site pers o n nel will i nstr uct t he s u bject 
or desi g nate d pers o n o n t he pr o per ster ile tec h ni q ue t o pre pare a n d a d mi nister a S C i njecti o n 
at h o me.  D uri n g t he Da y 1 visit, t he i nitial d ose of i n vesti gati o nal pr o d uct m ust be 
a d mi nistere d i n t he office b y st u d y pers o n nel, w hile t he s u bject a n d/ or t he s u bject’s care gi ver 
o bser ves.
F or all S C treat me nts, t he n u m ber of i njecti o ns a n d i njecti o n sites will be rec or de d.  T he 
preferre d b o d y l ocati o ns of t he S C i njecti o n(s) are t he fr o nt of t he mi d dle of t he t hi g h, 
i ncl u di n g a nter olateral, or o uter area of t he u p per ar m.  Ot her l ocati o ns (e g, a b d o me n) are 
acce pta ble if re q uire d. 
 
  M ulti ple i njecti o ns s h o ul d use a 
u ni q ue site f or eac h i njecti o n w here p ossi ble, t o li mit t he i nje cti o n site v ol u me t o 1 m L  
(ie, 1 m L  i n ar m, 1 m L  i n t hi g h f or a 2 m L , 2 i njecti o n d ose).  W he n feasi ble, if m ulti ple 
i njecti o ns are re q uire d, t he si m ulta ne o us use of b ot h ar ms (e g, 1 m L  i n left ar m a n d 1 m L  i n 
ri g ht ar m) s h o ul d be a v oi de d. 
All self -a d mi nistrati o n i nf or mati o n will be d oc u me nte d i n t he s u bject diar y. 
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5.5. Investigational Product Storage 
The investigator or an approved representative, eg, pharmacist, will ensure that all 
investigational products at the clinical site are stored in a secured area with controlled access 
under required storage conditions and in accordance with applicable regulatory requirements.  
Investigational products should be stored in their original containers and in accordance with 
the labels. 
Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as
applicable, including frozen, refrigerated, and/or room-temperature products).  This should 
be captured from the time of investigational product receipt throughout the study.  Even for 
continuous-monitoring systems, a log or site procedure that ensures active evaluation for 
excursions should be available.  The intent is to ensure that the minimum and maximum 
temperature is checked each business day to confirm that no excursion occurred since the last 
evaluation and to provide the site with the capability to store or view the minimum/maximum 
temperature for all non-working days upon return to normal operations.  The operation of the 
temperature monitoring device and storage unit (for example, refrigerator), as applicable, 
should be regularly inspected to ensure they are maintained in working order. 
Any excursions from the product label storage conditions should be reported to Pfizer upon 
discovery.  The site should actively pursue options for returning the product to the storage 
conditions described in the labeling, as soon as possible.  Deviations from the storage 
requirements, including any actions taken, must be documented and reported to Pfizer. 
Once an excursion is identified, the investigational product must be quarantined and not used 
until Pfizer provides permission to use the investigational product.  It will not be considered a 
protocol deviation if Pfizer approves the use of the investigational product after the 
temperature excursion.  Use of the investigational product prior to Pfizer approval will be 
considered a protocol deviation.  Specific details regarding information that the site should 
report for each excursion will be provided to the site.
Site staff will instruct subjects on the storage requirements for take home medications,
including how to report temperature excursions.
5.6. Investigational Product Accountability 
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.  All investigational products will be 
accounted for using a drug accountability form/record. 
All unused study drug must be returned to the investigator by the subject at every visit and at 
the end of the trial.
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5.6.1. Destruction of Investigational Product Supplies 
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site).  If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.
5.7. Concomitant Treatment(s)
•
Subjects will abstain from all prohibited concomitant medications, except for the 
treatment of adverse events or acute bleeding episodes as described in 
Section 5.7.1 of this protocol. 
•
All concomitant treatments taken during the study must be recorded with indication, 
and start and stop dates of administration.  All subjects will be questioned about 
concomitant treatments at each clinic visit.
•
For emergency or unplanned surgical interventions, investigators must contact the 
sponsor’s medical monitor as soon as possible to review concomitant treatments and 
any impact on subject participation. 
•
Treatments taken within 28 days prior to informed consent being signed will be 
documented as a prior treatment.  Treatments taken from date of signed informed 
consent will be documented as concomitant treatments.
5.7.1. Prohibited Medications
Routine prophylaxis with FVIII or FIX replacement therapy, or bypass agent therapy 
(rFVIIa, APCC or emicizumab), is prohibited throughout the study for all subjects.
FVIII (within 72 hours) or FIX replacement therapy (within 96 hours), or bypass agent 
therapy (rFVIIa or APCC: within 72 hours; for other products:  5 half-lives) before Screening 
is prohibited.  Depending on the coagulation factor product in use, additional wash out time 
may be required prior to the screening assessments to achieve a factor activity level ≤1%.  If 
a subject experiences an acute bleeding episode during this washout period requiring 
treatment with a FVIII or FIX replacement therapy, or bypass agent therapy, the subject is to 
be stabilized utilizing this regimen and a new washout period should be initiated.  The 
regimen used to treat the episode should be recorded as a prior medication.
FVIII (within 72 hours) or FIX replacement therapy (within 96 hours), or bypass agent 
therapy (for rFVIIa or APCC: at least 72 hours; for other products:  5 half-lives), before 
Day 1 treatment is also prohibited.  If a subject experiences an acute bleeding episode during 
this washout period requiring treatment with a Factor VIII or IX replacement therapy, or 
bypass agent therapy, the subject is to be stabilized utilizing this regimen and a new washout 
period should be initiated.  The regimen used to treat the episode should be recorded as a 
concomitant medication.  All acute bleeding episodes between Screening and Day 1 must be 
recorded.
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Subjects who received treatment with extended half-life (EHL) FVIII or FIX products may 
require longer washout periods than those noted above; careful consideration by investigators 
should be given to the dose and half-life of these treatments prior to planning the duration of 
washout.
Treatment with rFVIIa at a dose level greater than approximately 90 μg/kg, or 
administered at intervals more frequent than every 2 hours, is prohibited throughout 
the study.  If a subject receiving investigational product is subsequently administered a 
rFVIIa dose greater than approximately 90 μg/kg, or requires dosing more frequently than 
every 2 hours the investigator must immediately contact the Sponsor’s medical monitor to 
discuss the case to determine if the respective subject should continue to receive IP, remain 
in the study, or be withdrawn immediately.
Treatment with activated prothrombin complex concentrate (APCC, eg, FEIBA) is prohibited 
throughout the study.  Subjects receiving such therapy who cannot substitute treatment with 
rFVIIa at the 90 μg/kg per dose are not to be enrolled into this study.  Subjects who are 
treated with investigational product who are subsequently administered APCC therapy must 
be withdrawn from treatment with investigational product immediately.  These subjects 
should be followed at all remaining clinic visits up to Day 393 to monitor for adverse events 
and any additional safety concerns.
The use of immunomodulatory medications (eg, Intravenous Immunoglobulin (IVIG), 
routine systemic corticosteroids) is prohibited during the study.
The use of antifibrinolytic agents or medications known to influence platelet function 
(eg, aspirin or certain non-steroidal anti-inflammatory drugs) within 5 days before initial
study drug administration through Day 365 is prohibited. 
5.7.2. Treatment(s) for Acute Bleeding Episodes
If a subject experiences an acute bleeding episode at any point throughout the study, the 
subject is to be stabilized utilizing the subject’s standard hemostatic treatment regimen 
(which may include FVIII or FIX replacement therapy, or rFVIIa bypass agent therapy at 
approximately 90 μg/kg per dose).  Pausing or withdrawal of treatment with investigational 
product is not required in the event of a breakthrough bleed, but may be considered at the 
discretion of the investigator.  See Section 7.2.5 for additional information.
6. STUDY PROCEDURES 
6.1. Screening
All subjects participating in this study must sign the B7841003 informed consent or assent 
document (and parental consent must be completed, where required).  The investigator (or an 
appropriate delegate at the investigator site) will obtain informed consent or assent from each 
subject in accordance with the procedures described in the Subject Information and Consent
section (Section 12.3). 
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P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 4 2
F or s u bjects w h o c o m plete d st u d y  B 7 8 4 1 0 0 2 wit hi n 3 0 da y s of t he Da y 1 visit o f st u d y 
B 7 8 4 1 0 0 3, i nf or me d c o nse nt pr oce d ures will occ ur at t he Da y 1 visit.  Scree ni n g acti vities 
f or t hese s u bjects, f oll o wi n g i nf or me d c o nse nt, will c o nsist of usi n g res ults fr o m t he fi nal 
visit of st u d y  B 7 8 4 1 0 0 2 t o c o nfir m t hat n o ne of t he B 7 8 4 1 0 0 3 st ud y  e xcl usi o n criteria 
(Secti o n 4. 2 ) ha ve bee n met. 
Me dical hist or y  data f or s u bjects fr o m st u d y B 7 8 4 1 0 0 2 will als o be use d f or s u bjects 
e nr olli n g i nt o B 7 8 4 1 0 0 3.  Res ol ve d A Es fr o m B 7 8 4 1 0 0 2 ma y be e ntere d as a d diti o nal 
me dical hist or y , w here a p plica ble. 
F or s u bjects w h o ha ve c o m plete d partici pati o n i n st u d y  B 7 8 4 1 0 0 2 m ore t ha n 3 0 da y s pri or t o 
t he Da y 1 visit i n st u d y  B 7 8 4 1 0 0 3, a n d f or s u bjects e nr olle d de n o v o i nt o st u d y B 7 8 4 1 0 0 3, 
t he f oll o wi n g scree ni n g acti vities will a p pl y: 
T he f oll o wi n g pr oce d ures will be c o m plete d d uri n g Scree ni n g:

O btai n writte n i nf or me d c o nse nt.

Re vie w I ncl usi o n a n d E xcl usi o n criteria.

O btai n c o m plete me dicati o n hist or y  of all prescri pti o n or n o n prescri pti o n dr u gs, a n d 
d ietar y a n d her bal s u p ple me nts ta ke n si nce t he start of Scree ni n g.

C ollect wei g ht. 

Pr o vi de i nstr ucti o ns re gar di n g st u d y c o ntrace pti o n re q uire me nts.

O btai n p ulse rate, res pirat or y  rate, oral te m perat ure, a n d s u pi ne bl o o d press ure.

C o n d uct f ull p h y sical e xa mi nati o n ( P E).  O n a n d after Da y 1 a n d at t he discreti o n of 
t he i n vesti gat or, li mite d p h ysical e xa mi nati o ns base d o n si g ns a n d sy m pt o ms will be 
perf or me d, if cli nicall y i n dicate d, t o assess c ha n ges fr o m baseli ne/ pre vi o us visits of 
a n y o n g oi n g sy m pt o ms.

 

F oll o wi n g at least a 4 -h o ur fast c ollect bl o o d a n d uri ne s peci me ns f or t he f oll o wi n g 
f or s hi p me nt t o t he st u d y ce ntral la b orat or y :

Uri nal y sis; 

Ser u m c he mistr y ;

He mat ol o g y .
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The following additional screening procedures apply to de novo subjects who did not 
participate in study B7841002.
•
For adolescent subjects, obtain assent (and parental consent, where required).
•
Collect demography, height and weight. 
•
Obtain medical history, including hemophilia history and inhibitor history, and collect 
the number of bleeding episodes over the past 6 months.
•
Review use of FVIII or FIX replacement therapy, or bypass agent therapy, to ensure 
subject meets washout criteria prior to Screening.
•
Collect blood specimens for the following for analysis at a local laboratory, if 
necessary:
•
Factor VIII or Factor IX inhibitor (this test is only required for subjects with a 
hemophilia history of inhibitors).  Inhibitor test results from up to 6 months prior 
to Day 1 may be used to meet this requirement.
•
Following at least a 4-hour fast (and at least a 12-hour fast prior to lipid panel, collect 
blood and urine specimens for the following for shipment to the study central 
laboratory:
•
FVIII and FIX activity;
•
CD4 cell count;
•
Prothrombin 20210 mutation testing;
•
Factor V Leiden mutation testing; 
•
Lipid panel;
•
Protein C activity/Protein S level;
•
Fibrinogen;
•
Serology (HBs Ag, HBc Ab, HCV Ab, and HIV).
•
Collect single 12-lead electrocardiogram (ECG).  If ECG is abnormal, collect 
triplicate ECG.
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B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 4 4
All scree ni n g pr oce d ures m ust be re peate d f or a n y s u bject w h o faile d i nitial scree ni n g 
pr oce d ures a n d is re- scree ni n g i nt o t he st u d y, wit h t he e xcepti o n of t he f oll o wi n g la bs relate d 
t o ge netic m utati o n scree ni n g 
 sa m ples:

Pr ot hr o m bi n 2 0 2 1 0 m utati o n testi n g.

Fact or V Lei de n m utati o n testi n g.

F VIII a n d FI X acti vit y .
T o pre pare f or st u d y partici pati o n, s u bjects w ill be i nstr ucte d o n t he use of t he Li festyl e 
Re q uire me nts a n d C o nc o mita nt Treat me nt(s) secti o ns of t he pr ot oc ol.
6. 2. St u d y Peri o d
F or t he st u d y peri o d descri be d bel o w, w he n m ulti ple pr oce d ures are sc he d ule d at t he sa me 
ti me p oi nt(s) relati ve t o d osi n g, t he f oll o wi n g c hr o n ol o g y of e ve nts s h o ul d be a d here d t o, 
w here p ossi ble.

Bl o o d press ure/ p ulse rate: pri or t o bl o o d s peci me n c ollecti o n.
 

Ot her pr oce d ures (e g, trai ni n g s u bject o n self -a d mi nistrati o n, diar y c o m plia nce).
W he n a n I V cat heter is utilize d f or bl o o d sa m ple c ollecti o ns, E C Gs a n d vital si g ns ( p ulse 
rate, res pirat or y rate, bl o o d press ure a n d oral te m perat ure) assess me nts s h o ul d be c ollecte d 
pri or t o t he i nserti o n of t he cat heter.
6. 2. 1. D a y 1 Visit [ + 1 d a y] 
T he Da y 1 visit f or B 7 8 4 1 0 0 3 ma y  occ ur o n t he sa me da y (sa me visit t o t he cli nic) as t he 
B 7 8 4 1 0 0 2 D a y 8 5 or Da y  1 1 3 visit.  All Da y 1 ( or B 7 8 4 1 0 0 2 D a y 8 5 or Da y  1 1 3) bl o o d 
dra ws m ust be d o ne pri or t o a d mi nistrati o n of I P.
Pri or t o d osi n g o n Da y 1 t he f oll o wi n g pr oce d ures will be c o m plete d:

F or s u bjects w h o c o m plete d st u d y B 7 8 4 1 0 0 2, o bt ai n writte n i nf or me d c o nse nt.

Assess baseli ne s y m pt o ms/ A Es.

Re vie w c ha n ges i n s u bject’s c o nc o mita nt treat me nt i nf or mati o n. 

Re vie w use of F VIII or FI X re place me nt t hera p y, or b y pass a ge nt t hera p y, t o e ns ure 
a n y de n o v o s u bject meets was h o ut criteria pri or t o D a y 1 .
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI
C CI
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 4 5

Re vie w c ha n ges i n t he s u bject’s me dical hi st or y i ncl u di n g me dicati o n.

C ollect i nf or mati o n o n ne w blee di n g e pis o des.

Re vie w I ncl usi o n a n d E xcl usi o n criteria f or a n y de n o v o s u bject.

C o n d uct a li mite d p h y sical e xa mi nati o n at t he discreti o n of t he i n vesti gat or, if 
cli nicall y i n dicate d, t o assess c ha nges of a n y o n g oi n g s y m pt o ms.

C o nfir m pr o per c o ntrace pti o n is bei n g use d.

O btai n p ulse rate, res pirat or y  rate, oral te m perat ure, a n d s u pi ne bl o o d press ure.

C ollect bl o o d a n d uri ne s peci me ns f or t he f oll o wi n g f or s hi p me nt t o t he st u d y  ce ntral 
la b orat or y:

Uri nal y sis;

Ser u m c he mistr y ;

He mat ol o g y  wit h differe ntial pa nel;

F VIII a n d FI X acti vit y ;

P T;
 

F or de n o v o s u bjects, t he f oll o wi n g acti vities are als o re q uire d pri or t o d osi n g:

C ollect bl o o d a n d uri ne s peci me ns f or t he f oll o wi n g f or s hi p me nt t o t he st u d y  
central la b orat or y :

Fi bri n o ge n;
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 4 6

Car diac tr o p o ni n I.

C ollect tri plicate 1 2 -lea d E C G.

Treat me nt assi g n me nt a n y ti me pri or t o d osi n g o nce s u bject has met all eli gi bilit y  
criteria.

After all pre -d ose pr oce d ures ha ve bee n c o m plete d, a d mi nister t he i n vesti gati o nal
pr o d uct (see S T U D Y T R E A T M E N T S a n d A d mi nistrati o n Secti o ns).
After d osi n g , t he f oll o wi n g pr oce d ures will be c o m plete d:

M o nit or i nf usi o n/i njecti o n site reacti o ns.

Assess s y m pt o ms b y  s p o nta ne o us re p orti n g of a d verse e ve nts a n d b y as ki n g t he 
s u bjects t o res p o n d t o a n o n-lea di n g q uesti o n s uc h as “ H o w d o y o u feel?”

Iss ue s u bject diar y a n d pr o vi de trai ni n g wit h res pect t o c o m pleti n g t he diar y i ncl u di n g 
ti mi n g a n d nat ure of i nf or mati o n t o be e ntere d.
6. 2. 2. D a y 2 [1 d a y], D a y 4 [1 d a y], D a y 8 [2 d a ys], D a y 1 5 [2 d a ys], 
D a y 2 2 [ 2 d a ys] a n d D a y 2 9 [2 d a ys] –
 Tre at me nt Visits f or De N o v o 
S u bjects 
T he f oll o wi n g pr oce d ures will be c o m plete d at t he visits a b o ve f or de n o v o s u bjects o nl y :

O btai n i nf or mati o n re gar di n g t he use of c o nc o mita nt treat me nt a n d t he occ urre nce of 
a d verse e ve nts.

C ollect i nf or mati o n o n ne w blee di n g e pis o des.

C o n d uct a li mite d p h y sical e xa mi nati o n at t he discreti o n of t he i n vesti gat or, if 
cli nicall y i n dicate d, t o assess c ha n ges fr o m baseline/ pre vi o us visits of a n y  o n g oi n g 
s ym pt o ms.

C o nfir m pr o per c o ntrace pti o n is bei n g use d.

C ollect bl o o d s peci me ns f or t he f oll o wi n g f or s hi p me nt t o t he st u d y  ce ntral la b orat or y 
( n ote t hat Da y 2 9 bl o o d s peci me ns are i n a d diti o n t o Da y 2 9 acti vities perf or me d o n 
all st u d y s u bjects per Secti o n 6. 2. 3 ):

Ser u m c he mistr y  ( Da y 8, 1 5, 2 2, 2 9);

He mat ol o g y  wit h differe ntial pa nel ( Da y 8, 1 5, 2 2, 2 9);
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 4 7

P T ( Da y 8, 1 5, 2 2, 2 9);

Car diac tr o p o ni n I ( Da y 8, 1 5, 2 2, 2 9).

O btai n p ulse rate, res pirat or y  rate, oral te m perat ure, a n d s u pi ne bl o o d press ure. 
( Da y 2 9).

C ollect si n gle 1 2 -lea d E C G.  If E C G is a b n or mal, c ollect tri plicate E C G ( Da y 2 9).

D a y 8, D a y 1 5 a n d D a y 2 2 - After all pre -d ose pr oce d ures ha ve bee n c o m plete d, 
a d mi nister t he i n vesti gati o nal pr o d uct (see S T U D Y T R E A T M E N T S a n d 
A d mi nistrati o n Secti o ns).

M o nit or i njecti o n site reacti o ns.

C ollect t he s u bject’s diar y a n d re vie w wit h t he s u bject/care gi ver, i ncl u di n g 
i nf or mati o n a b o ut st u d y c o m plia nce, i n vesti gati o nal pr o d uct i nf usi o ns, blee di n g 
assess me nts (i ncl u di n g site a n d tra u matic/s p o nta ne o us) a n d i njecti o n site 
reacti o ns.  Dis pe nse ne w s u bject diar y.
6. 2. 3. D a y 2 9 [2 d a ys], D a y 5 7 [ 5 d a ys], D a y 8 5 [ 5 d a ys], D a y 1 1 3 [ 7 d a ys], 
D a y 1 4 1 [ 7 d a ys], D a y 1 6 9 [ 7 d a ys], D a y 2 2 5 [ 7 d a ys], D a y 2 5 3 [ 7 d a ys], D a y 2 8 1 
[7 d a ys], D a y 3 0 9 [ 7 d a ys], D a y 3 3 7 [ 7 d a ys], a n d D a y 3 6 5 [ 7 d a ys] Visits
T he f oll o wi n g pr oce d ures will be c o m plete d:

O btai n i nf or mati o n re gar di n g t he use of c o nc o mita nt treat me nt a n d t he occ urre nce of 
a d verse e ve nts.

C ollect i nf or mati o n o n ne w blee di n g e pis o des.

C o n d uct a li mite d p h y sical e xa mi nati o n at t he discreti o n of t he i n vesti gat or, if 
cli nicall y i n dicate d, t o assess c ha n ges fr o m baseli ne/ pre vi o us visits of a n y o n g oi n g 
s ym pt o ms.

C o nfir m pr o per c o ntrace p ti o n is bei n g use d.

O btai n p ulse rate, res pirat or y  rate, oral te m perat ure, a n d s u pi ne bl o o d press ure.
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 4 8

C ollect bl o o d s peci me ns f or t he f oll o wi n g f or s hi p me nt t o t he st u d y ce ntral 
la b orat or y.

De n o v o s u bjects o nl y :

Ser u m c he mistr y  ( Da y 5 7);

He mat ol o g y  ( Da y 5 7).

C ollect t he s u bject’s diar y a n d re vie w wit h t he s u bject/care gi ver, i ncl u di n g 
i nf or mati o n a b o ut st u d y c o m plia nce, i n vesti gati o nal pr o d uct i nf usi o ns, blee di n g 
assess me nts (i ncl u di n g site a n d tra u matic/s p o nta ne o us) a n d i njecti o n site reacti o ns.  
Dis pe nse ne w s u bject diar y .

M o nit or i nf usi o n/i njecti o n site reacti o ns. 

D a y 8 5 [ 7 d a ys ], D a y 1 6 9 [ 7 d a ys], D a y 2 5 3 [ 7 d a ys], a n d D a y 3 6 5 [ 7 d a ys] -
C ollect bl o o d a n d uri ne s peci me ns f or t he f oll o wi n g f or s hi p me nt t o t he st u d y  ce ntral 
la b orat or y:

Uri nal y sis;

Se r u m c he mistr y;

He mat ol o g y  wit h differe ntial pa nel;

F VIII a n d FI X acti vit y ;

P T;

After all pre -d ose pr oce d ures ha ve bee n c o m plete d, a d mi nister t he i n vesti gati o nal 
pr o d uct (see S T U D Y T R E A T M E N T S a n d A d mi nistrati o n Secti o ns).

Dis pe nse i n vesti gati o nal pr o d uct t o self -a d mi nistrati o n at h o me (if a p plica ble). 

D a y 3 3 7 is t he fi nal visit f or dis pe nsi n g i n vesti gati o nal pr o d uct t o t he s u bject f or 
self-a d mi nistrati o n.
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI
C CI

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•
No IP will be administered or dispensed on Day 365.
6.2.4. Day 393 [±7 days] – End of Study Visit
The following procedures will be completed:
•
Obtain information regarding the use of concomitant treatment and the occurrence of 
adverse events.
•
Collect information on new bleeding episodes. 
•
Monitor infusion/injection site reactions.
•
Assess symptoms by spontaneous reporting of adverse events and by asking the 
subjects to respond to a non-leading question such as “How do you feel?”
•
Conduct a full physical examination.
•
Collect the subject’s diary and review with the subject/caregiver, including 
information about study compliance, investigational product infusions, bleeding 
assessments (including site and traumatic/spontaneous) and injection site reactions.
•
Confirm proper contraception is being used. 
•
Collect weight.
•
Obtain pulse rate, respiratory rate, oral temperature, and supine blood pressure.
6.2.5. Follow-up Contact
Follow-up contact will be completed at least 28 calendar days, and up to 35 calendar days
after the last administration of the investigational product to capture any potential adverse 
events (see the Time Period for Collecting AE/SAE Information section) and to confirm 
appropriate contraception usage (see the Contraception section).  Contact with the subject 
may be done via a phone call.
6.3. Subject Withdrawal or Early Termination
Withdrawal of consent:
Subjects who request to discontinue receipt of study treatment will remain in the study and 
must continue to be followed for protocol specified follow-up procedures.  The only 
exception to this is when a subject specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the subject to provide this information.  
Subjects should notify the investigator in writing of the decision to withdraw consent from 
future follow-up, whenever possible.  The withdrawal of consent should be explained in 
detail in the medical records by the investigator, as to whether the withdrawal is only from 
further receipt of investigational product or also from study procedures and/or post-treatment 
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study follow-up, and entered on the appropriate case report form (CRF) page.  In the event 
that vital status (whether the subject is alive or dead) is being measured, publicly available 
information should be used to determine vital status only as appropriately directed in 
accordance with local law.
Lost to follow-up: 
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status.  This includes follow-up with persons authorized by the subject as noted above.  Lost 
to follow-up is defined by the inability to reach the subject after a minimum of 2 documented 
phone calls, faxes, or e-mails as well as lack of response by the subject to 1 registered mail 
letter.  All attempts should be documented in the subject’s medical records.  If it is 
determined that the subject has died, the site will use locally permissible methods to obtain 
the date and cause of death.  If the investigator’s use of a third-party representative to assist 
in the follow-up portion of the study has been included in the subject’s informed consent, 
then the investigator may use a sponsor-retained third-party representative to assist site staff 
with obtaining the subject’s contact information or other public vital status data necessary to 
complete the follow-up portion of the study.  The site staff and representative will consult 
publicly available sources, such as public health registries and databases, in order to obtain 
updated contact information.  If, after all attempts, the subject remains lost to follow-up, then 
the last-known-alive date as determined by the investigator should be reported and 
documented in the subject’s medical records.
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety (see also the 
Withdrawal From the Study Due to Adverse Events section) or behavioral reasons, or the 
inability of the subject to comply with the protocol-required schedule of study visits or 
procedures at a given study site. 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  In any circumstance, every effort should be made to document subject outcome, if 
possible.  The investigator should inquire about the reason for withdrawal, request that the 
subject return all unused investigational product, request that the subject return for a final 
visit, if applicable, and follow up with the subject regarding any unresolved adverse events 
(AEs).
If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent.
Subjects who withdraw from the study for reasons other than safety may be replaced at the 
discretion of the sponsor. 
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7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test.  In these cases the investigator will take all steps necessary to ensure the 
safety and well-being of the subject.  When a protocol-required test cannot be performed, the 
investigator will document the reason for this and any corrective and preventive actions that 
he or she has taken to ensure that normal processes are adhered to as soon as possible.  The 
study team will be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
7.1. Safety
7.1.1. Laboratory Tests
The following safety laboratory tests will be performed at times defined in the Schedule of 
Activities section of this protocol.  Additional laboratory results may be reported on these 
samples as a result of the method of analysis or the type of analyzer used by the clinical 
laboratory; or as derived from calculated values.  These additional tests would not require 
additional collection of blood.  Unscheduled clinical labs may be obtained at any time during 
the study to assess any perceived safety concerns.
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P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 5 2
T a ble 3.
L a b or at or y Tests
H e m at ol o g y d
C he mistr y
Uri n al ysis
Ot her
H e m o gl o bi n
H e m at ocrit
R B C c o u nt
Platelet c o u nt
W B C c o u nt
T otal ne utr o p hils 
( A bs)
E osi n o p hils ( A bs)
M o n oc ytes ( A bs)
Bas o p hils ( A bs)
L y m p h oc ytes ( A bs)
B U N/ urea a n d Creati ni ne
Gl uc ose (fasti n g)
Calci u m
S o di u m
P otassi u m
C hl ori de
T otal C O 2 ( Bicar b o nate)
A S T, A L T
T otal bilir u bi n
Al kali ne p h os p hatase
Uric aci d
Al b u mi n
T otal pr otei n
p H
Gl uc ose ( q ual)
Pr otei n ( q ual)
Bl o o d ( q ual)
Ket o nes
Nitrites
Le u k oc yte esterase
Ur o bil i n o ge n
Uri ne bilir u bi n
Micr osc o p y
a
Fact or V Lei de n m utati o n b
Pr ot hr o m bi n 2 0 2 1 0 M utati o n
b
H Bs A g b
T otal H Bc A b b
H C V A b b
HI V b
A nti -t hr o mbi n III
Pr otei n C acti vit y b
Pr otei n S le vel b
P T/I N R
Fi bri n o ge n
Car diac Tr o p o ni n I (f or de 
n o v o s u bjects o nl y) 
F act or VIII c
Fact or I X c
Fact or VIII a n d Fact or I X 
i n hi bit ore
Li pi d pr ofile b
C D 4 cell c o u nt b
A d diti o nal Tests ( Nee de d 
f or H y’s la w)
A S T, A L T (re peat)
T otal bilir u bi n (re peat)
Al b u mi n (re peat)
Al kali ne p h os p hatase 
(re peat)
Direct bilir u bi n
I n direct bilir u bi n
Creati ne ki nase
G G T
P T/I N R
a.
O nl y if uri ne di pstic k is p ositi ve f or bl o o d, pr otei n, nitrites or le u k oc yte esterase.
b.
F or de n o v o s u bjects at Scree ni n g o nl y.
c.
F or de n o v o s u bjects at At Scree ni n g a n d Da y 1 o nl y.
d.
Differe ntial he mat ol o g y pa nel re q uire d a t Da ys 1, 8 5, 1 6 9, 2 5 3 a n d 3 6 5 .
e.
O nl y At Scree ni n g a n d o nl y f or s u bjects w it h he m o p hilia hist or y of i n hi bit ors, if necessar y.  I n hi bit or 
test res ults fr o m u p t o 6 m o nt hs pri or t o Da y 1 ma y be use d t o meet re q uire me nt.  F VIII a n d FI X 
i n hi bit or le vels m ust be deter mi ne d b y a l ocal la b orat or y.  A p ositi ve i n hi bit or test res ult will be a b o ve 
t he u p per li mit of n or mal f or t he assa y.
 
 
 
 
 
 
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI
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7.1.2. Physical Examinations
Physical examinations may be conducted by a physician, trained physician’s assistant, or 
nurse practitioner as acceptable according to local regulation.  A full physical examination 
will include head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, 
gastrointestinal, musculoskeletal, and neurological systems.  The limited or abbreviated 
physical examination will be focused on general appearance, the respiratory and 
cardiovascular systems, as well as towards subject reported symptoms.
For measuring weight, a scale with appropriate range and resolution is used and must be 
placed on a stable, flat surface.  Subjects must remove shoes, bulky layers of clothing, and 
jackets so that only light clothing remains.  They must also remove the contents of their 
pockets and remain still during measurement of weight.
7.1.3. Blood Pressure and Pulse Rate
Blood pressure and pulse rate will be measured at times specified in the Schedule of 
Activities.  Additional collection times, or changes to collection times of blood pressure and 
pulse rate will be permitted, as necessary, to ensure appropriate collection of safety data.
Supine blood pressure will be measured with the subject’s arm supported at the level of the 
heart, and recorded to the nearest mm Hg after approximately 5 minutes of rest.  The same
arm (preferably the dominant arm) should be used throughout the study.  Subjects should be 
instructed not to speak during measurements. 
Where possible, the same properly sized and calibrated blood pressure cuff will be used to 
measure blood pressure each time.  The use of an automated device for measuring blood 
pressure (BP) and pulse rate is acceptable, although, when done manually, pulse rate will be 
measured in the brachial/radial artery for at least 30 seconds.  When the timing of these 
measurements coincides with a blood collection, blood pressure and pulse rate should be 
obtained prior to the nominal time of the blood collection.
7.1.4. Respiratory Rate
Respiratory rate should be measured after approximately 5 minutes rest in supine position by 
observing and counting the respirations of the subject for 30 seconds and multiplied by 2.  
When blood pressure is to be taken at the same time, measurement should be done during the 
5 minutes of rest and before blood pressure measurement.
7.1.5. Temperature
Temperature will be measured orally.  No eating, drinking or smoking is allowed for 
15 minutes prior to the measurement.
7.1.6. Electrocardiogram 
ECGs should be collected at times specified in the Schedule of Activities.
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All scheduled ECGs should be performed after the subject has rested quietly for at least 
10 minutes in a supine position. 
Triplicate 12-lead ECGs (Day 1 only) will be obtained approximately 2-4 minutes apart; the 
average of the triplicate ECG measurements collected at each nominal time point on 
Day 1 will serve as each subject’s baseline QTcF value.  To ensure safety of the subjects, a 
qualified individual at the investigator site will make comparisons to baseline measurements.  
If the QTcF interval is increased by ≥45 msec from the baseline, or an absolute QTcF value 
is ≥500 msec for any scheduled ECG, then 2 additional ECGs will be collected, 
approximately 2-4 minutes apart, to confirm the original measurement.  If either of the QTcF 
values from these repeated ECGs remains above the threshold value (≥45 msec from the 
baseline; or is ≥500 msec), then a single ECG must be repeated at least hourly until QTcF 
values from 2 successive ECGs fall below the threshold value that triggered the repeat 
measurement. 
If the average of QTcF values from the triplicate measurements remains above the threshold 
value (≥45 msec from the baseline; or is ≥500 msec), then a single ECG must be repeated at 
least hourly until QTcF values from 2 successive ECGs fall below the threshold value that 
triggered the repeat measurement.
If QTcF values remain ≥500 msec (or ≥45 msec from the baseline) for greater than 4 hours 
(or sooner at the discretion of the investigator); or QTcF intervals get progressively longer, 
the subject should undergo continuous ECG monitoring.  A cardiologist should be consulted 
if QTcF intervals do not return to less than 500 msec (or to <45 msec above the baseline) 
after 8 hours of monitoring (or sooner at the discretion of the investigator).
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality.  It is important that leads are placed in the 
same positions each time in order to achieve precise ECG recordings.  If a machine-read 
QTcF value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified physician’s interpretation determines that the QTcF values are in the acceptable 
range.
7.1.7. Injection Site Reactions
Injection site reactions will be assessed according to the Schedule of Activities.  Injection site 
reactions may include but are not limited to: erythema, induration, ecchymosis, pain and 
pruritus.  The size and severity of injection site reactions will be assessed and documented.  
If deemed appropriate by the investigator, a consultation with a dermatologist will be 
performed.  Documentation may include a dermatologist report, clinic notes and 
photographs.
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7.2. Efficacy
7.2.1. Hemophilic Bleeding Episodes
During this study, the investigator (or qualified designee) will review the subject diary with 
the subject, and inquire about and record AEs, concomitant treatments, bleeding episodes 
(including location and etiology – traumatic or spontaneous) and any hemostatic treatments 
(including intravenous treatments with coagulation factor products).  Hemostatic therapy that 
is administered to treat bleeding episodes during the Screening period and during the study 
through the final study visit will be documented as concomitant treatment.  Subject diary 
review will include any bleeding episodes treated with hemostatic agents.  Bleeding episodes 
requiring treatment with intravenous coagulation factor products will count toward the 
determination of bleeding episode frequency during the period of treatment with 
PF-06741086.  Subject assessment(s) will be captured on the subject diary and reviewed by 
the investigator at study visits.  One assessment per infusion will be required.
7.2.2. Bleeding
Occurrences of bleeding episodes treated with hemostatic agent(s) will be obtained from 
subject diaries and medical records.  Where relevant, investigators (or designee) and 
monitors will ensure that there is consistency between the subject’s medical record and/or 
subject diaries and the CRFs.  Bleeding episodes will not be reported as AEs unless 
associated with a serious adverse event, although the concomitant events associated with a 
bleed may be reported as an AE if appropriate (eg, a fracture, pain - see Section 8.2.3 below 
for guidance on hemophilia related events).  Both spontaneous bleeding episodes and 
traumatic bleeding episodes will be collected.  Only bleeding episodes that are considered 
serious and meet the SAE criteria should be listed on the AE CRF page.  When bleeding 
episodes that meet the SAE criteria are recorded on the AE CRF, the location (site) of the 
bleed and the etiologic classification as spontaneous or traumatic should be included (as 
described in Section 7.2.1 and Section 7.2.3).  The subject diary or medical record will serve 
as the source document for bleeding episodes during the study.  Investigators (or designee) 
and/or monitors will review the subject’s diary/medical records to assist in classification if 
necessary.
7.2.3. Types of Bleeding
For the purposes of this study, a bleed treated with a hemostatic agent will be classified as 
either spontaneous or traumatic.  The criteria for spontaneous and traumatic bleeds are 
described below.
•
Spontaneous Bleeding Episodes: Bleeding episodes should be classified as 
spontaneous if a subject records a bleeding event when there is no known
contributing factor such as definite trauma, antecedent “strenuous” activity, or 
“overuse”.  The determination of “strenuous” or “overuse” is at the discretion of the 
subject/caregiver/investigator.  For example, if a subject were to wake up in the 
morning and note he was bleeding, a “spontaneous” bleed would be recorded.  Target 
joints can have spontaneous bleeding episodes. 
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P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 5 6

Tr a u m atic Blee di n g E pis o des: Blee di n g e pis o des s h o ul d be classifie d as tra u matic 
if a s u bject rec or ds a blee di n g e ve nt w he n t here is a k n o w n or pres u me d c o ntri b uti n g 
fact or/reas o n f or t he blee d.  F or e xa m ple, if a s u bject were t o e xercise “stre n u o usl y ” 
a n d t he n ha ve a blee d i n t he a bse nce of a n y o b vi o us i nj ur y, t he blee d w o ul d be 
rec or de d as a tra u matic blee d.  Tar get j oi nt blee di n g e pis o des ca n be tra u matic if a 
k n o w n acti o n le d t o blee di n g i nt o t he j oi nt.
7. 2. 4. L oc ati o n of Blee ds
F or t he p ur p oses of t his st u d y , w he n s u bjects re p ort a blee d treate d wit h he m ostatic t hera py, 
t he l ocati o n of t he blee d s h o ul d be rec or de d i n t he s u bject diar y or me dical rec or d.  Blee ds 
will be re p orte d as occ urri n g i n 1 of t he f oll o wi n g l ocati o ns: j oi nt, m uscle/s oft tiss ue, or 
ot her.  Eac h i n di vi d ual l ocati o n of m ulti ple -site blee ds will be re p orte d.  F or j oi nt blee ds, t he 
s pecific j oi nt will be re p orte d.  Para meters t o i de ntif y j oi nt blee ds i ncl u de: pai n o n j oi nt 
m oti o n, li mitati o n of m oti o n, a n d visi ble s welli n g of j oi nt.
7. 2. 5. Tre at me nt of Blee di n g E pis o des 
Blee di n g e pis o des t hat occ ur d uri n g t his st u d y  ma y be treate d ( o n-de ma n d) wit h he m ostatic 
t hera py (e g, i ntra ve n o us c oa g ulati o n fact or pr o d ucts or r F VIIa b y pass a ge nt t hera p y at 
a p pr o xi matel y 9 0 µ g/ k g, a d mi nistere d at i nter vals 2 h o urs ) as dee me d a p pr o priate by t he 
i n vesti gat or.  T he s pecific treat me nt wit h he m ostatic t hera py is at t he discreti o n of t he 
s u bject/care gi ver/i n vesti gat or, b ut all d oses of he m ostatic t hera py ta ke n after si g ni n g of 
i nf or me d c o nse nt will be d oc u me nte d as c o nc o mita nt me dicati o ns or c o nc o mita nt treat me nts. 
If a s u bject e x perie nces a blee di n g e pis o de d uri n g t he was h o ut peri o d prece di n g scree ni n g 
la b orat or y assess me nts, t he s u bject is t o be sta bilize d utilizi n g t he s u bject’s us ual he m ostatic 
treat me nt re gi me n.  O nce t he blee di n g e pis o de has bee n s uccessf ully treate d a ne w was h o ut 
peri o d s h o ul d be c o m plete d pri or t o o btai ni n g t he scree ni n g la b orat or y  tests. 
If a s u bject e x perie nces a blee di n g e pis o de d uri n g t he was h o ut peri o d prece di n g t he i nitial 
a d mi nistrati o n of P F -0 6 7 4 1 0 8 6 t he s u bject is t o be sta bilize d utilizi n g t he s u bject’s us ual 
he m ostatic treat me nt re gi me n a n d a ne w was h o ut peri o d s h o ul d be i m ple me nte d.  O nce 
treat me nt of t he blee di n g e pis o de wit h he m ostatic a ge nts has bee n c o m plete d a ne w was h o ut 
peri o d s h o ul d be i nitiate d i n a ntici pati o n of t he i nitial treat me nt wit h P F -0 6 7 4 1 0 8 6.
 
 
 
  
 
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 5 7
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 5 8
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 5 9
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 6 0
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
7. 8. Bl o o d V ol u me
T he t otal bl o o d sa m pli n g v ol u me f or de n o v o s u bjects i n t his st u d y  is a ma xi m u m of 
a p pr o xi matel y 2 5 4 m L ( base d o n Scree ni n g t hr o u g h Da y 1 9 7 ).  S u bjects c o nti n ui n g fr o m 
B 7 8 4 1 0 0 2 will ha ve a n a p pr o xi mate ma xi m u m of 1 2 5 m L dra w n d uri n g t he st u d y .  T he ta ble 
bel o w reflects a p pr o xi mate sa m ple v ol u mes nee de d f or eac h meas ure d e n d p oi nt.  T he act ual 
c ollecti o n ti mes of bl o o d sa m pli n g ma y  c ha n ge, b ut t he a p pr o xi mate t otal bl o o d v ol u me 
c ollecte d s h o ul d n ot i ncrease.  A d diti o nal bl o o d sa m ples ma y  be ta ke n f or safety assess me nts 
at ti mes s pecifie d b y Pfizer, pr o vi de d t he t otal v ol u me ta ke n d uri n g t he st u d y  d oes n ot e xcee d 
5 5 0 m L  d uri n g a ny peri o d of 3 0 co nsec uti ve da y s.
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 6 1
T a ble 4. 
Bl o o d V ol u me
S a m ple T y pe
S a m ple 
V ol u me 
( mL)
N u m ber of S a m pli n g Ti m es c
T ot al 
V ol u me 
( mL)
Scree ni n g
St u d y 
Peri o d
F oll o w -U p
S afet y L a bs 
Ser u m c he mistr y ( wit h Li pi d pr ofile a) 
5 
1 
7 
0
4 5
H e m at ol o g y d
3 
1 
7 
0
2 7
Pr ot hr o m bi n 2 0 2 1 0 m utati o n
3 
1 
0 
0
3
Fact or V Lei de n m utati o n testi n g
3. 5
1 
0 
0
3. 5
P T/I N R, Fact or VIII a n d Fact or I X 
acti vit y, b Fi bri n o ge n, Pr otei n C, a Pr otei n 
S, a
[ Si n gle 
c o m bi ne d sa m ple] 
4. 5
1 
9 
0
4 9. 5
Fact or VIII a n d Fact or I X i n hi bit or a
4. 5
1 
0 
0
4. 5
C D 4 cell c o u nt a bs ol ute ( C D 4) a
5 
1 
0 
0
5
Ser ol o g y ( H Bs A g, H Bc A b, H C V A b, 
a n d HI V) 
5 
1 
0 
0
5
C ar di ac Tr o p o ni n I e
3
5
1 5
a de n o v o s u bjects at Scree ni n g o nl y.
b de n o v o s u bjects at Scree ni n g a n d Da y 1 o nl y.
c t otal sa mples reflects a m o u nt re q uire d f or de n o v o s u bjects ( w it h Scree ni n g a n d a d diti o nal visits d uri n g 
first m o nt h of treat me nt); s u bjects c o nti n ui n g fr o m B 7 8 4 1 0 0 2 will ha ve less sa m ples dra w n a n d t h us less 
ma xi m u m bl o o d v ol u me .
d scree ni n g s peci me n o nl y f or no v o s u bjects a n d f or s u bjects e nr olli n g > 3 0 da ys f oll o wi n g da y 8 5 or da y 
1 1 3 visit i n st u d y B 7 8 4 1 0 0 2, 
e at da ys 1, 8, 1 5, 2 2 a n d 2 9 f or de n o v o s u bjects o nl y.
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 6 2
T a ble 5.
Tri g gere d Re q uire me nts
C o n diti o n
Acti o n

Platelet c o u nt < 7 5, 0 0 0/ L

Fi bri n o ge n le vel < L L N

He m o gl o bi n le vel < 1 0 g m/ d L

P T/I N R 1. 2 5 ti mes t he U L N
S u bjects w h o are f o u n d t o ha ve o ne of t he 
c oa g ulati o n pat h wa y a b n or malities 
defi ne d b y t hese c orres p o n di n g la b val ue 
criteria s h o ul d be br o u g ht i nt o t he cli nic 
i m me diatel y f or a n u nsc he d ule d visit a n d 
t he res pecti ve la b orat or y test s h o ul d be 
re peate d.
  
 
8. A D V E R S E E V E N T R E P O R T I N G
8. 1. Re q uire me nts
T he ta ble bel o w s u m marizes t he re q uire me nts f or rec or di n g safet y e ve nts o n t he C R F a n d f or 
re p orti n g safet y e ve nts o n t he Cli nical Trial (C T) Seri o us A d verse E ve nt ( S A E) Re p ort F or m 
t o Pfizer Safet y.  T hese re q uire me nts are deli neate d f or 3 t ypes of e ve nts: ( 1) S A Es; 
( 2) n o n-seri o us a d verse e ve nts ( A Es); a n d ( 3) e x p os ure t o t he i n vesti gati o nal pr o d uct u n der 
st u d y d uri n g pre g na nc y or breastfee di n g, a n d occ u pati o nal e x p os ure. 
S afet y E ve nt
Rec or de d o n t he C R F
Re p orte d o n t he C T S A E 
Re p ort F or m t o Pfizer 
S afet y Wit hi n 2 4 H o urs of 
A w are ness
S A E
All
All
N o n -seri o us A E
All
N o ne
E x p os ure t o t he 
i n vesti gati o nal pr o d uct 
u n der st u d y  d uri n g 
pre g na nc y or 
breastfee di n g, a n d 
occ u pati o nal e x p os ure
All (re gar dless of w het her 
ass ociate d wit h a n A E), 
e xce pt occ u p ati o n al 
e x p os ure
E x p os ure d uri n g pre g na nc y , 
e x p os ure via breastfee di n g, 
occ u pati o nal e x p os ure 
(re gar dless of w het her 
ass ociate d wit h a n A E)
All o bs er ve d or v ol u nteere d e ve nts re gar dless of treat me nt gr o u p or s us pecte d ca usal 
relati o ns hi p t o t he i n vesti gati o nal pr o d uct(s) will be re p orte d as descri be d i n t he f oll o wi n g 
para gra p hs.
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI

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Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening, 
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information.  This time frame also applies to additional new (follow-up) information on 
previously forwarded reports.  In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the 
event.
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see the Serious Adverse Events section below).  In addition, the investigator may be 
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion.  
This information is more detailed than that recorded on the CRF.  In general, this will include 
a description of the event in sufficient detail to allow for a complete medical assessment of 
the case and independent determination of possible causality.  Any information relevant to 
the event, such as concomitant medications and illnesses, must be provided.  In the case of a 
subject death, a summary of available autopsy findings must be submitted as soon as possible 
to Pfizer Safety.  Any pertinent additional information must be reported on the CT SAE 
Report Form; additional source documents (eg, medical records, CRF, laboratory data) are to 
be sent to Pfizer Safety ONLY upon request.
As part of ongoing safety reviews conducted by the sponsor, any non-serious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
As noted in the Protocol-Specified Serious Adverse Events section, should an investigator 
judge one of the identified protocol-specified SAEs to have a causal relationship with the 
investigational product, the investigator must report the SAE to Pfizer Safety within 24 hours 
of investigator awareness.
8.1.1. Additional Details On Recording Adverse Events on the CRF
All events detailed in the table above will be recorded on the AE page(s) of the CRF.  It 
should be noted that the CT SAE Report Form for reporting of SAE information is not the 
same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE Report 
Form for reporting of SAE information.
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8.1.2. Eliciting Adverse Event Information
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously 
reported by the study subject/parent(s)/legal guardian/legally acceptable representative.  In 
addition, each study subject/parent(s)/legal guardian/legally acceptable representative will be 
questioned about the occurrence of AEs in a non-leading manner.
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the Subject 
Withdrawal or Early Termination section)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF. 
When a subject withdraws from the study because of an SAE, the SAE must be recorded on 
the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with the 
Requirements section above.
8.1.4. Time Period for Collecting AE/SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection
period”) for each subject begins from the time the subject provides informed consent, which 
is obtained before the subject’s participation in the study (ie, before undergoing any 
study-related procedure and/or receiving investigational product), through and including a 
minimum of 28 calendar days; except as indicated below after the last administration of the 
investigational product.
For subjects who are screen failures, the active collection period ends when screen failure 
status is determined.
8.1.4.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a subject during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form.
SAEs occurring in a subject after the active collection period has ended are reported to Pfizer 
Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
Follow up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF
During the active collection period, both non-serious AEs and SAEs are recorded on the 
CRF.
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
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8.1.5. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious); the investigator must record the causal relationship on the CRF, and report such 
an assessment in accordance with the SAE reporting requirements, if applicable.  An 
investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that the investigational product caused or contributed to an AE; generally the facts 
(evidence) or arguments to suggest a causal relationship should be provided.  If the 
investigator does not know whether or not the investigational product caused the event, then 
the event will be handled as “related to investigational product” for reporting purposes, as 
defined by the sponsor.  If the investigator's causality assessment is “unknown but not 
related” to investigational product, this should be clearly documented on study records. 
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, and 
report such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements.
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.
8.2. Definitions
8.2.1. Adverse Events
An AE is any untoward medical occurrence in a study subject administered a product or 
medical device; the event need not necessarily have a causal relationship with the treatment 
or usage.  Examples of AEs include, but are not limited to: 
•
Abnormal test findings;
•
Clinically significant signs and symptoms;
•
Changes in physical examination findings;
•
Hypersensitivity;
•
Progression/worsening of underlying disease;
•
Drug abuse;
•
Drug dependency.
Additionally, AEs may include signs and symptoms resulting from:
•
Drug overdose;
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•
Drug withdrawal;
•
Drug misuse; 
•
Drug interactions;
•
Extravasation;
•
Exposure during pregnancy (EDP);
•
Exposure via breastfeeding;
•
Medication error;
•
Occupational exposure.
8.2.2. Abnormal Test Findings
Abnormal objective test findings should be recorded as AEs when any of the following 
conditions are met: 
•
Test result is associated with accompanying symptoms; and/or
•
Test result requires additional diagnostic testing or medical/surgical intervention; 
and/or
•
Test result leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy; and/or
•
Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
recording as an AE.
8.2.3. Hemophilia Events
Hemophilia events are certain AEs that are likely to occur due to the subject’s hemophilia.  
For example, pain, swelling, or decreased range of motion due to a bleed may be an expected 
consequence of hemophilia (the bleeding episode itself is not reported as an AE, unless the 
bleeding episode meets the criteria for a Serious Adverse Event, see Section 8.2.4).  
Investigators should determine if an AE is expected because of the subject’s hemophilia.  
Bleeding or bruising, not due to the subject’s hemophilia, will be recorded as an AE, and not 
a hemophilia event.  Hemophilia events that require hospitalization or meet other SAE 
criteria should be reported as SAEs. 
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8.2.4. Serious Adverse Events
A serious adverse event is any untoward medical occurrence at any dose that:
•
Results in death;
•
Is life-threatening (immediate risk of death);
•
Requires inpatient hospitalization or prolongation of existing hospitalization;
•
Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);
•
Results in congenital anomaly/birth defect.
Or that is considered to be:
•
An important medical event.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
Medical device complaints may meet the SAE reporting requirement criteria (see the Medical 
Device Complaint Reporting Requirements section).  An incident is any malfunction (ie, the 
failure of a device to meet its performance specifications or to perform as intended; 
performance specifications include all claims made in the labeling for the device) that, 
directly or indirectly, might lead to or might have led to the death of a subject, or user, or of 
other persons, or to a serious deterioration in their state of health. 
A serious injury that can cause a serious deterioration in state of health can include:
•
A life-threatening illness, even if temporary in nature;
•
A permanent impairment of a body function or permanent damage to a body 
structure; 
•
A condition necessitating medical or surgical intervention to prevent the above 
2 bulleted items:
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•
Examples: clinically relevant increase in the duration of a surgical procedure; a 
condition that requires hospitalization or significant prolongation of existing 
hospitalization.
•
Any indirect harm as a consequence of an incorrect diagnostic or in vitro diagnostic 
device test results when used within the manufacturer’s instructions for use;
•
Fetal distress, fetal death, or any congenital abnormality or birth defects.
8.2.5. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility, or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is assessed for medical importance.
Hospitalization does not include the following:
•
Rehabilitation facilities;
•
Hospice facilities;
•
Respite care (eg, caregiver relief);
•
Skilled nursing facilities;
•
Nursing homes;
•
Same-day surgeries (as outpatient/same-day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical 
AE is not in itself an SAE.  Examples include:
•
Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of a persistent pretreatment laboratory abnormality);
•
Social admission (eg, subject has no place to sleep);
•
Administrative admission (eg, for yearly physical examination);
•
Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);
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•
Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);
•
Hospitalization for observation without a medical AE;
•
Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE.  For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
AE.
8.3. Severity Assessment
If required on the AE page of the CRF, the investigator will use the adjectives MILD, MODERATE, 
SEVERE, or Life threatening to describe the maximum intensity of the AE. For purposes of consistency, 
these intensity grades are defined as follows:
Corresponding numerical 
toxicity grade
Severity
1
MILD
Does not interfere with subject's usual 
function.
2
MODERATE
Interferes to some extent with subject's usual 
function.
3
SEVERE
Interferes significantly with subject's usual 
function.
4
Life threatening
Extreme limitation in activity, significant 
assistance required; significant medical 
intervention/therapy required, 
hospitalization or hospice care required.
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.4. Special Situations
8.4.1. Protocol-Specified Serious Adverse Events
Thromboembolic or ischemic events are considered important medical events.  As important 
medical events, Pfizer is to be notified within 24 hours of awareness of any thromboembolic 
or ischemic event.  Data entry and additional reporting requirements will follow the same 
instructions for all other SAEs as listed in Section 8.1. 
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8.4.2. Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some subjects, transaminase elevations are a harbinger of a more 
serious potential outcome.  These subjects fail to adapt and therefore are "susceptible" to 
progressive and serious liver injury, commonly referred to as drug-induced liver injury 
(DILI).  Subjects who experience a transaminase elevation above 3 times the upper limit of 
normal (× ULN) should be monitored more frequently to determine if they are an “adaptor” 
or are “susceptible.”
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same lab sample).  
In rare instances, by the time TBili elevations are detected, AST/ALT values might have 
decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the subject’s 
individual baseline values and underlying conditions.  Subjects who present with the 
following laboratory abnormalities should be evaluated further as potential DILI (Hy’s law) 
cases to definitively determine the etiology of the abnormal laboratory values:
•
Subjects with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available;
•
For subjects with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:
•
Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).
•
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor. 
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The subject should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment. 
In addition to repeating measurements of AST and ALT and TBili, laboratory tests should 
include albumin, creatine kinase (CK), direct and indirect bilirubin, gamma-glutamyl 
transferase (GGT), prothrombin time (PT)/international normalized ratio (INR), total bile 
acids, alkaline phosphatase and acetaminophen drug and/or protein adduct levels.  
Consideration should also be given to drawing a separate tube of clotted blood and an 
anticoagulated tube of blood for further testing, as needed, for further contemporaneous 
analyses at the time of the recognized initial abnormalities to determine etiology.  A detailed 
history, including relevant information, such as review of ethanol, acetaminophen (either by 
itself or as a coformulated product in prescription or over-the-counter medications), 
recreational drug, supplement (herbal) use and consumption, family history, sexual history, 
travel history, history of contact with a jaundiced person, surgery, blood transfusion, history 
of liver or allergic disease, and potential occupational exposure to chemicals, should be 
collected.  Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging 
(eg, biliary tract) may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the liver function test (LFT) abnormalities has yet been found.  Such 
potential DILI (Hy’s law) cases are to be reported as SAEs, irrespective of availability 
of all the results of the investigations performed to determine etiology of the LFT 
abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
8.4.3. Exposure to the Investigational Product During Pregnancy or Breastfeeding, and 
Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.4.3.1. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy (EDP) occurs if:
•
A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product:
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•
An example of environmental exposure would be a case involving direct contact 
with a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant 
and has been exposed to chemotherapeutic products).
•
A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy.
If a subject or subject’s partner becomes or is found to be pregnant during the subject’s 
treatment with the investigational product, the investigator must report this information to 
Pfizer Safety on the CT SAE Report Form and an EDP supplemental form, regardless of
whether an SAE has occurred.  In addition, the investigator must submit information 
regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a subject 
reports that she is pregnant and has been exposed to a cytotoxic product by inhalation or 
spillage) to Pfizer Safety using the EDP supplemental form.  This must be done irrespective 
of whether an AE has occurred and within 24 hours of awareness of the exposure.  The 
information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
pre-procedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
follows: 
•
Spontaneous abortion includes miscarriage and missed abortion;
•
Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the investigational product.
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Additional information regarding the EDP may be requested by the sponsor.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the subject with the Pregnant Partner Release of Information Form 
to deliver to his partner.  The investigator must document in the source documents that the 
subject was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.4.3.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  An exposure during breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.
8.4.3.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE.  Since the information does not pertain to a subject enrolled in the study, the 
information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.
8.4.4. Medication Errors
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
Medication errors
All (regardless of whether 
associated with an AE)
Only if associated with an 
SAE
8.4.4.1. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong subject, or at the wrong time, or at the wrong dosage strength. 
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Medication errors include:
•
Medication errors involving subject exposure to the investigational product;
•
Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating subject.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and non-serious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.5. Medical Device Complaint Reporting Requirements 
All medical device complaints, regardless of whether the medical device complaint is 
associated with an AE, will be recorded on the applicable pages within the CRF.  This 
includes potential incidents or malfunctions associated with the use of a medical device 
product.  An incident or malfunction is an event that might have led to death or serious 
deterioration in health, or if it occurred again might lead to death or serious deterioration in 
health.
Pfizer is to be notified of all medical device complaints within 24 hours of the investigator’s 
awareness of the event. 
9. DATA ANALYSIS/STATISTICAL METHODS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.  The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.
9.1. Sample Size Determination
No formal statistical hypothesis will be tested.  The total sample size of approximately 
36 subjects (24 subjects from B7841002 and 12 additional de novo subjects) is based on the 
number of subjects enrolled in study B7841002, and on clinical considerations to balance the 
need to minimize exposure of study subjects to the test article with the need to provide 
adequate safety and tolerability data for clinical development.
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9. 2. Effic ac y A n al ysis
9. 2. 1. A n al ysis of t he Effic ac y E n d p oi nt
A B R will be calc ulate d a n d s u m marize d descri pti vel y.  T he A B R is calc ulate d as ( n u m ber of 
blee di n g e ve nts/ o bser ve d treat me nt peri o d i n da y s) * 3 6 5. 2 5. 
 
 
 
 
 
 
 
9. 6. S afet y A n al ysis
A d verse e ve nts, E C Gs, vital si g ns ( bl o o d press ure, p ulse rate, te m perat ure a n d res pirat or y  
rate), p h ys ical e xa mi nati o ns a n d safety la b orat or y data (i ncl u di n g he mat ol o g y , P T/I N R, 
a P T T, c he mistr y, uri nalysis, fi bri n o ge n, a nti -t hr o m bi n III acti vit y a n d car diac tr o p o ni n I) will 
be re vie we d a n d s u m marize d o n a n o n g oi n g basis d uri n g t he st u d y t o e val ua te t he safety of 
s u bjects.  Safety data will be prese nte d i n ta b ular a n d/ or gra p hical f or mat a n d s u m marize d 
descri pti vel y, w here a p pr o priate.  I nci de nce a n d se verit y of treat me nt -e mer ge nt A Es 
( T E A Es), wit h dra wals d ue t o T E A Es, a n d i nf usi o n a n d i njecti o n site reacti o ns will be 
s u m marize d b y d ose le vel.  A b n or mal safet y fi n di n gs will als o be prese nte d se paratel y f or 
i n hi bit or s u bjects b y d ose le vel.
A b n or mal a n d cli nicall y rele va nt c ha n ges i n vital si g ns a n d E C G para meters will be 
s u m marize d b y d ose le vel a n d st u d y da y.  I nci de nce a n d ma g nit u de of a b n or mal la b orat or y 
fi n di n gs will be s u m marize d b y d ose le vel.  
 
 
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Me dical hist or y , me dicati o n hist or y a n d p hys ical e xa mi nati o n i nf or mati o n, as a p plica ble, 
c ollecte d d uri n g t he c o urse of t he st u d y will be ca pt ure d f or i ncl usi o n i nt o t he st u d y data base, 
u nless ot her wise n ote d.  A n y u nt o war d fi n di n gs i de ntifie d o n p h y sical e xa mi nati o n 
c o n d ucte d after t he a d mi nistrati o n of t he first d ose of i n vesti gati o nal pr o d uct will be ca pt ure d 
as a n a d verse e ve nt, if t h ose fi n di n gs meet t he defi niti o n of a n a d verse e ve nt. 
9. 7. I nteri m A n al ysis
N o f or mal i nteri m a nal ys is will be c o n d ucte d f or t his st u d y.  H o we ver, as t his is a n 
o pe n -la bel st u dy, t he s p o ns or ma y c o n d uct u n bli n de d re vie ws of t he data d uri n g t he c o urse of 
t he st u d y f or t he p ur p ose of safety assess me nt, facilitati n g d ose -escalati o n decisi o ns, 
 a n d/ or t o s u p p ort cli nical de vel o p me nt. 
9. 8. D at a M o nit ori n g C o m mittee 
T his st u d y  will n ot use a data m o nit ori n g c o m mittee. 
1 0. Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E
Pfizer or its a ge nt will c o n d uct peri o dic m o nit ori n g visits d ur i n g st u dy c o n d uct t o e ns ure t hat 
t he pr ot oc ol a n d G o o d Cli nical Practices ( G C Ps) are bei n g f oll o we d.  T he m o nit ors ma y 
re vie w s o urce d oc u me nts t o c o nfir m t hat t he data rec or de d o n C R Fs are acc urate.  T he 
i n vesti gat or a n d i nstit uti o n will all o w Pfizer m o nitors/a u dit ors or its a ge nts a n d a p pr o priate 
re g ulat or y a ut h orities direct access t o s o urce d oc u me nts t o perf or m t his verificati o n.  T his 
verificati o n ma y  als o occ ur after st u d y c o m pleti o n.
D uri n g st u d y c o n d uct a n d/ or after st u d y c o m pleti o n, t he i n vesti gat or site ma y be s u bject t o 
re vie w by t he I RB/ E C, a n d/ or t o q ualit y  ass ura nce a u dits perf or me d b y Pfizer, or c o m pa nies 
w or ki n g wit h or o n be half of Pfizer, a n d/ or t o i ns pecti o n b y  a p pr o priate re g ulat or y 
a ut h orities.
T he i n vesti gat or(s) will n otif y  Pfizer or its a ge nts i m me diatel y of a n y re g ulat or y i ns pecti o n 
n otificati o n i n relati o n t o t he st u d y .  F urt her m ore, t he i n vesti gat or will c o o perate wit h Pfizer 
or its a ge nts t o pre pare t he i n vesti gat or site f or t he i ns pecti o n a n d will all o w Pfizer or its 
a ge nt, w he ne ver feasi ble, t o be prese nt d uri n g t he i ns pecti o n.  T he i n vesti gat or site a n d 
i n vesti gat or will pr o m ptl y res ol ve a ny discre pa ncies t hat are i de ntifie d bet wee n t he st u d y 
data a n d t he s u bject's me dical rec or ds.  T he i n vesti gat or will pr o m ptl y pr o vi de c o pies of t he 
i ns pecti o n fi n di n gs t o Pfizer or its a ge nt.  Bef ore res p o nse s u b missi o n t o t he re g ulat or y 
a ut h orities, t he i n vesti gat or will pr o vi de Pfizer or its a ge nts wit h a n o p p ort u nit y  t o re vie w 
a n d c o m me nt o n res p o nses t o a n y  s uc h fi n di n gs.
It is i m p orta nt t hat t he i n vesti gat or(s) a n d t heir rele va nt pers o n nel are a vaila ble d uri n g t he 
m o nit ori n g visits a n d p ossi ble a u dits or i ns pecti o ns a n d t hat s ufficie nt ti me is de v ote d t o t he 
pr ocess.
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11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included subject.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true.  Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry. 
In most cases, the source documents are the hospital or the physician subject chart.  In these 
cases, data collected on the CRFs must match the data in those charts. 
In some cases, the CRF may also serve as the source document.  In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document.
11.2. Record Retention
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the 
investigator agrees to keep records, including the identity of all participating subjects 
(sufficient information to link records, eg, CRFs and hospital records), all original signed 
informed consent/assent documents, copies of all CRFs, safety reporting forms, source 
documents, and detailed records of treatment disposition, and adequate documentation of 
relevant correspondence (eg, letters, meeting minutes, and telephone call reports).  The 
records should be retained by the investigator according to the ICH guidelines, according to 
local regulations, or as specified in the clinical study agreement (CSA), whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or an independent third party arranged by Pfizer. 
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.
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The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board/Ethics Committee
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent/assent documents, and other relevant documents, 
eg, recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the 
IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements, and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of 
Helsinki.
12.3. Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where 
required by law. 
When study data are compiled for transfer to Pfizer and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by Pfizer in order to de-identify study subjects.  The investigator 
site will maintain a confidential list of subjects who participated in the study, linking each 
subject’s numerical code to his or her actual identity.  In case of data transfer, Pfizer will 
maintain high standards of confidentiality and protection of subjects’ personal data consistent 
with applicable privacy laws.
The informed consent/assent documents and any subject recruitment materials must be in 
compliance with ICH GCP, local regulatory requirements, and legal requirements, including 
applicable privacy laws.
The informed consent/assent documents used during the informed consent process and any 
subject recruitment materials must be reviewed and approved by Pfizer, approved by the 
IRB/EC before use, and available for inspection.
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The investigator must ensure that each study subject, or his or her legally acceptable 
representative, or parent(s) or legal guardian if a minor, is fully informed about the nature 
and objectives of the study and possible risks associated with participation.
Whenever consent is obtained from a subject’s legally acceptable representative/parent(s) or 
legal guardian, the subject’s assent (affirmative agreement) must subsequently be obtained 
when the subject has the capacity to provide assent, as determined by the IRB/EC.  If the 
investigator determines that a subject’s decisional capacity is so limited he/she cannot 
reasonably be consulted, then, as permitted by the IRB/EC and consistent with local 
regulatory and legal requirements, the subject’s assent may be waived with source 
documentation of the reason assent was not obtained.  If the study subject does not provide 
his or her own consent, the source documents must record why the subject did not provide 
consent (eg, minor, decisionally impaired adult), how the investigator determined that the 
person signing the consent was the subject’s legally acceptable representative, the consent 
signer’s relationship to the study subject (eg, parent, spouse), and that the subject’s assent 
was obtained or waived.  If assent is obtained verbally, it must be documented in the source 
documents.
If the study includes minor subjects who reach the age of majority during the study, as 
recognized under local law, they must re-consent as adults to remain in the study.  If the 
enrollment of emancipated minors is permitted by the study age criteria, the IRB/EC, and 
local law, they must provide documentation of legal status to give consent without the 
permission of a parent or legal guardian. 
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject or the subject's legally acceptable representative, parent(s) or legal 
guardian and the subject’s assent, when applicable, before any study-specific activity is 
performed, unless a waiver of informed consent has been granted by an IRB/EC.  The 
investigator will retain the original of each subject's signed consent/assent document.
Where required, provisions for post-trial investigational product availability will be made in 
accordance with local CA/EC rules and regulations.
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
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13. DEFINITION OF END OF TRIAL
13.1. End of Trial in a Member State 
End of trial in a Member State of the European Union is defined as the time at which it is 
deemed that a sufficient number of subjects have been recruited and completed the study as 
stated in the regulatory application (ie, clinical trial application [CTA]) and ethics application 
in the Member State.  Poor recruitment (recruiting less than the anticipated number in the 
CTA) by a Member State is not a reason for premature termination but is considered a 
normal conclusion to the study in that Member State.
13.2. End of Trial in All Other Participating Countries 
End of trial in all other participating countries is defined as last subject last visit (LSLV). 
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or investigational product safety problems, or at the 
discretion of Pfizer.  In addition, Pfizer retains the right to discontinue development of 
PF-06741086 at any time.
If a study is prematurely terminated, Pfizer will promptly notify the investigator.  After 
notification, the investigator must contact all participating subjects and the hospital pharmacy 
(if applicable) within 7 days.  As directed by Pfizer, all study materials must be collected and 
all CRFs completed to the greatest extent possible.
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations. 
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted.  US 
Basic Results are submitted for posting within 1 year of the primary completion date (PCD) 
for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
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PCD is defined as the date that the final subject was examined or received an intervention for 
the purposes of final collection of data for the primary outcome, whether the clinical study 
concluded according to the pre-specified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by the 
principal investigator (PI) of the results of the study based on information collected or 
generated by the PI, whether or not the results are favorable to the Pfizer product.  However, 
to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “publication”) 
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before it is submitted 
for publication or otherwise disclosed.  If any patent action is required to protect intellectual 
property rights, the investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.
If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites, and that any subsequent publications 
by the PI will reference that primary publication.  However, if a joint manuscript has not 
been submitted for publication within 12 months of completion or termination of the study at 
all participating sites, the investigator is free to publish separately, subject to the other 
requirements of this section.
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For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CSA will control as to all other 
issues.
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16. REFERENCES
1.
Berntorp E, Shapiro AD. Modern haemophilia care. Lancet. 2012;379(9824):1447-56.
2.
Astermark J.  Overview of inhibitors. Semin Hematol. 2006; 43(suppl 4): S3-S7.
3.
Maroney SA, Ellery PE, Wood JP, Ferrel JP, et al. Comparison of the inhibitory activity 
of human TFPIα and TFPIβ. Thromb Haemost 2013; 11:911-918.
4.
Knappe S, Gorczyca ME, Jilma B, et al. Plasmatic tissue factor pathway inhibitor is a 
major determinant of clotting in factor VIII inhibited plasma or blood. Thromb 
Haemost. 2013; 109:450-7.
5.
Dahm A, Vlieg AVH, Bendz B et al.  Low levels of tissue factor pathway inhibitor 
(TFPI) increase the risk of venous thrombosis.  Blood. 2003;101:4387-4392.
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P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
Fi nal Pr ot oc ol A me n d me nt 2, 0 8 N o ve m ber 2 0 1 8
P FI Z E R C O N FI D E N TI A L
Pa ge 8 4
A p pe n di x 1. A b bre vi ati o ns 
T his f oll o wi n g is a list of a b bre viati o ns t hat ma y  be use d i n t he pr ot oc ol. 
A b bre vi ati o n
Ter m
A B R
a n n ualize d blee di n g rate
A D C C
a nti b o d y-de pe n de nt cell -me diate d c y t ot o xicit y
A E
a d verse e ve nt
A L B
al b u mi n
A L T
ala ni ne a mi n otra nsferase
A P C C
acti vate d pr ot hr o m bi n c o m ple x c o nce ntrate
A P T T
acti vate d partial t hr o m b o plasti n ti me
A S T
as partate a mi n otra nsferase
A U C
area u n der t he c ur ve
BI D
bis i n die (“t wice a da y ’)
B MI
b o d y  mass i n de x
B P
bl o o d press ure
C D 4
C D 4 c o u nt a bs ol ute
C D C
c o m ple me nt de pe n de nt c yt ot o xicit y
C K
creati ne ki nase
C ma x
ma xi m u m c o nce ntrati o n
C N S
ce ntral ner v o us s ys te m
C R F
case re p ort f or m
C S A
cli nical st u d y a gree me nt
C S F
cere br os pi nal fl ui d
C S R
cli nical st u d y re p ort
C T A
cli nical trial a p plicati o n
C V
car di o vasc ular
DI LI
dr u g -i n d uce d li ver i nj ur y
D M C
data m o nit ori n g c o m mittee
D N A
de o x yri b o n ucleic aci d
d P T
dil ute Pr ot hr o m bi n Ti me
D U
dis pe nsa ble u nit
E C
et hics c o m mittee
E C G
electr ocar di o gram
E- D M C
e xter nal data m o nit ori n g c o m mittee 
E D P
e x p os ure d uri n g pre g na nc y
E H L
e xte n de d half-life
E U
E ur o pea n U ni o n
E u dra C T
E ur o pea n Cli nical Trials Data base
Fc R
Fc (fra g me nt cr y stalliza ble) rece pt or
F EI B A
A nti- i n hi bit or C oa g ula nt C o m ple x ( pr o prietary na me)]
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C CI
C CI

P F -0 6 7 4 1 0 8 6
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P FI Z E R C O N FI D E N TI A L
Pa ge 8 5
A b bre vi ati o n
Ter m
FI B
fi bri n o ge n
FI H
first-i n-h u ma n
F S H
f ollicle-sti m ulati n g h or m o ne
F VIIa
acti vate d c oa g ulati o n fact or VII
F VIII
fact or VIII
FI X
fact or I X
F Xa
fact or Xa
G C P
G o o d Cli nical Practice
G G T
Ga m ma -gl uta m yl  tra nsferase
G L O B
gl o b uli n
G L P
G o o d La b orat or y  Practice
G M P
G o o d Ma n ufact uri n g Practice
H Bc A b
he patitis B c ore a nti b o d y
H Bs A g
he patitis B s urface a nti ge n
H C V A b
he patitis C vir us a nti b o d y
HI V
h u ma n i m m u n o deficie nc y vir us
H R Q L
healt h -relate d q ualit y of life
I C H
I nter nati o nal C o nfere nce o n Har m o nisati o n
I D
i de ntificati o n
I g G
i m m u n o gl o b uli n G
I ND
i n vesti gati o nal ne w dr u g a p plicati o n
I N R
i nter nati o nal n or malize d rati o
I P
i n vesti gati o nal pr o d uct
I P M
i n vesti gati o nal pr o d uct ma n ual
I RB
i nstit uti o nal re vie w b oar d
I R C
i nter nal re vie w c o mmittee
I R T
i nteracti ve res p o nse tec h n ol o g y
I UD
i ntra uteri ne de vice
I V
i ntra ve n o us
I VI G
i ntra ve n o us i m m u n o gl o b uli n
I W R
i nteracti ve we b res p o nse
K 2E D T A
di p otassi u m et h y le ne dia mi netetraacetic aci d
L F T
li ver f u ncti o n test
L L N
l o wer li mit of n or mal
L S L V
last s u bject last visit 
M A D
m ulti ple asce n di n g d ose
N/ A
n ot a p plica ble
N O A E L
n o o bser ve d a d verse effect li mit
P C D
pri mar y  c o m pleti o n date
P D
P har mac o d y na mics(s)
P F S
prefille d s yri n ge
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI
C CI

P F -0 6 7 4 1 0 8 6
B 7 8 4 1 0 0 3
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P FI Z E R C O N FI D E N TI A L
Pa ge 8 6
A b bre vi ati o n
Ter m
P E
p h y sical e xa m
PI
pri nci pal i n vesti gat or
P K
p har mac o ki netic
P T
pr ot hr o m bi n ti me
Q M
q ua q ue m o nt hl y  (“ o nce m o nt hl y”)
Q W
q ua q ue wee kl y (“ o nce wee kl y”)
R N A
ri b o n ucleic aci d
S A D
si n gle asce n di n g d ose
S A E
seri o us a d verse e ve nt
S A P
statistical a nal ysis pla n
S C
s u bc uta ne o us
S O P
sta n dar d o perati n g pr oce d ure
S P R
s urface plas m o n res o na nce
S R S D
si n gle refere nce safety d oc u me nt
S U S A R
s us pecte d u ne x pecte d seri o us a d verse reacti o n
T bili
t otal bilir u bi n
T E G
t hr o m b oelast o gra p hy
T F PI
tiss ue fact or pat h wa y i n hi bit or
T G A
t hr o m bi n ge nerati o n assa y
T N F
t u m or necr osis fact or
U L N
u p per li mit of n or mal
U S
U nite d States
0 9 0 1 7 7 e 1 9 6 9 7 8 0 5 5\ 0. 1\ Dr aft\ V er si o n e d O n: 2 3- M ar- 2 0 2 1 1 0: 5 0 ( G M T)
C CI

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Appendix 2. Thrombotic Adverse Events for Stopping Criteria
Acute coronary syndrome
Hepatic artery thrombosis 
Retinal artery embolism 
Acute myocardial infarction
Hepatic vascular thrombosis
Retinal artery occlusion 
Aortic embolus 
Hepatic vein thrombosis 
Retinal artery thrombosis 
Aortic thrombosis 
Iliac artery embolism
Retinal vascular thrombosis 
Arterial thrombosis 
Intracardiac mass
Retinal vein occlusion 
Atrial thrombosis
Intracardiac thrombus
Retinal vein thrombosis 
Axillary vein thrombosis 
Intracranial venous sinus 
thrombosis 
Silent myocardial infarction
Basilar artery thrombosis 
Intrapericardial thrombosis
Spinal artery embolism 
Blue toe syndrome 
Jugular vein thrombosis 
Spinal artery thrombosis 
Budd-Chiari syndrome 
Mesenteric artery embolism 
Splenic vein thrombosis 
Carotid arterial embolus 
Mesenteric artery thrombosis Subclavian artery embolism 
Carotid artery thrombosis 
Mesenteric vein thrombosis 
Subclavian artery thrombosis 
Cavernous sinus thrombosis 
Microembolism
Subclavian vein thrombosis 
Cerebellar artery thrombosis 
Myocardial infarction
Subendocardial ischaemia
Cerebellar embolism 
Pelvic venous thrombosis 
Superior sagital sinus 
thrombosis
Cerebral artery embolism 
Penile vein thrombosis 
Myocardial ischaemia
Cerebral artery thrombosis 
Peripheral artery thrombosis 
Thrombosis corpora cavernosa 
Cerebral thrombosis 
Peripheral embolism 
Thrombosis mesenteric vessel 
Cerebral venous thrombosis 
Precerebral artery thrombosis Thrombotic cerebral infarction 
Cerebrospinal thrombotic 
tamponade 
Portosplenomesenteric 
thrombosis
Thrombotic microangiopathy 
Coronary artery embolism
Portal vein thrombosis 
Thrombotic stroke 
Coronary artery thrombosis
Pulmonary artery thrombosis Transverse sinus thrombosis 
Deep vein thrombosis 
Pulmonary embolism 
Truncus coeliacus thrombosis 
Disseminated intravascular 
coagulation 
Pulmonary microemboli 
Vena cava embolism 
Embolia cutis medicamentosa 
Pulmonary thrombosis 
Vena cava thrombosis 
Embolic cerebral infarction 
Pulmonary venous thrombosis Vena caval embolism and 
thrombosis
Embolic stroke 
Purpura fulminans
Venous thrombosis 
Embolism 
Renal artery thrombosis 
Venous thrombosis limb 
Embolism arterial 
Renal embolism 
Vertebral artery thrombosis
Embolism venous 
Renal vascular thrombosis 
Femoral artery embolism 
Renal vein embolism 
Hepatic artery embolism 
Renal vein thrombosis 
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