Clinical trial NCT03000673
Conditions: Antithrombotic
Sponsor: Bristol-Myers Squibb
Start date: 2017-05-23; Completion date: 2017-10-23
Enrollment: 32 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
To investigate safety of Single Doses of BMS-986177 in Patients with End Stage Renal Disease treated with hemodialysis

Detailed description:

Arms: arm 1: UFH, BMS-986177 - dose 1, BMS-986177 - dose 2, Enoxaparin arm 2: BMS-986177 - dose 1, Enoxaparin, UFH, BMS-986177 - dose 2 arm 3: BMS-986177 - dose 2, UFH, Enoxaparin, BMS-986177 - dose 1 arm 4: Enoxaparin, BMS-986177 - dose 2, BMS-986177 - dose 1, UFH
Interventions: intervention 1: Enoxaparin intervention 2: unfractionated heparin (UFH) intervention 3: BMS-986177
Intervention descriptions: intervention 1: Specified dose of Enoxaparin on specified days intervention 2: Specified dose of UFH on specified days intervention 3: Specified dose of BMS-986177 on specified day

Protocol documents:
Prot_002.pdf: 


Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
2
574
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v












88
90
Clinical Protocol
BMS 986177
CV010010
FXIa
Revised Protocol No.: 03
Date: 06 Sep 2017
8
580
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
N/A
Revised Protocol No.: 03
Date: 06-Sep-2017
9
581
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Informed Consent
x
A participant is considered enrolled only when a 
protocol specific informed consent is signed.
Inclusion/Exclusion Criteria
x
Medical History
x
Include any toxicities or allergy related to previous
treatments.
Concomitant Medications
x
Physical Examination (PE)
x
If the screening PE is performed within 24 hours prior to 
dosing on Day 1 then a single exam may count as both 
the screening and pre-dose evaluation.
Physical Measurements
x 
Includes height, weight, and BMI.
Vital Signs
x
Includes body temperature, respiratory rate, and seated 
blood pressure and heart rate. Blood pressure and heart 
rate should be measured after the participant has been 
resting quietly for at least 5 minutes.  
Electrocardiogram (ECGs)
x
ECGs should be recorded after the participant has been 
supine for at least 5 minutes. 
Drug Screen (urine or saliva) 
x
Alcohol Screen
x 
Breathalyzer
Clinical Labs
x
Chemistry, CBC, Coagulation and urine dipstick for 
blood (if participant is able to produce urine).
Serology
x 
HIV 
Pregnancy test
x 
WOCBP only. See Section 9.4.4.
Stool sample for occult blood
x 
Subjects may bring sample to the unit on or prior to D1.
Monitor for Serious Adverse 
Events
x
All SAEs must be collected from the date of 
participant’s written consent until 30 days post 
discontinuation of dosing or participant’s participation in 
the study if the last scheduled visit occurs at a later time.
a
Screening and Day -1 to -3 activities can be combined if performed on the same day
Revised Protocol No.: 03
Date: 06-Sep-2017
10
582
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Physical Examination (PE) 
x
Targeted PE
x 
x 
x 
x 
x 
Targeted physical based on subject complaint.
Concomitant Medications 
x 
x 
x 
x 
x 
x
Physical Measurements 
x 
x 
x 
x 
x
Weight only. Collect prior to Day 1 visit and collect 
pre and post dialysis (SoC can be used).
Vital Signs
x 
x 
x 
x 
x 
x
Includes body temperature, respiratory rate, seated 
blood pressure (BP), and heart rate (HR) on Day -1 
to -3 and for those that discontinue prematurely. 
BP and HR(pre-dose & 3h post HD for all 
treatments on Days 1, 5, 8, and 12, at 24h post-dose 
only when BMS-986177 is administered).
BP and HR should be measured after the participant 
has been resting quietly for at least 5 minutes.  
Electrocardiogram (ECGs) 
x 
x 
x 
x 
x
ECGs should be performed prior to Day 1 and 
conducted 3-6 hours post dialysis.
(See note in screening procedures, Section 2)  
Laboratory Tests
x 
x 
x 
x 
x 
x
Labs should be obtained prior to Day 1 and obtained
3-6 h post dialysis.
(See note in screening procedures,Section 9.4.4.)  
Stool, occult blood
x 
x 
x 
x 
x
Anytime 2-20 h post-HD. Can bring sample to next 
HD session.
Pregnancy Test
x
x 
WOCBP only. See Section 9.4.4.
Urine dipstick
x 
x 
x 
x
For blood if urine is produced by the participant. 
Revised Protocol No.: 03
Date: 06-Sep-2017
11
583
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
____________________________________________
________________________________________ 
--
________________________________________________
2.0
Approved
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Obtain Pre-dose if possible; anytime up to 2- 20 h 
post HD if possible.
Drug Test (urine or saliva or 
plasma)
x
Alcohol screen
x 
x 
x 
x
Breathalyzer; Pre-dose  
Monitor for Non-Serious 
Adverse Events
x
x
 
x
 
x
 
x
AE collection to begin 3 hours prior to dialysis start 
on Day 1 regardless of study drug administered
Monitor for Serious Adverse 
Events
x 
x 
x 
x 
x 
x 
See note in screening procedures.
Serial Blood PK Sampling
x 
x 
x 
x
See Section 9.5. PK only being collected on days 
when BMS-986177 is administered depending on 
randomization.
Single PK Sampling
Obtained 24-72 hours after each dose
Serial Blood PD Sampling
x 
x 
x 
x
See Section 9.6andTable  9.6-1(for  BMS-986177 
and enoxaparin) and Table 9.6-2(for UFH).
Single PD Sampling
Obtained 24-72 hours after each dose of BMS-986177 
only.
Only after BMS-986177 dosing. See Section 9.6 and
Table 9.6-1.
D-dimer, F1,2 and 
exploratory plasma sample
x
x
 
x
 
x
See Section 9.8and Table 9.8-1and Table 9.8-2.
Revised Protocol No.: 03
Date: 06-Sep-2017
12
584
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
____________________________________________
________________________________________ 
--
________________________________________________
2.0
Approved
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
FXI antigen
x
See Section 9.8andTable 9.8-1and Table 9.8-2.
Clotting assessment for 
dialysis filter, drip chamber
dialysis circuit pressure; 
number and volume of saline 
flushes; Kt/V, Time to 
hemostasis at puncture site 
x
x
 
x
 
x
See Section 9.8 and Table 9.8-1 and Table 9.8-2.
Clotting Assessment to be conducted by a blinded 
staff member.
Retain dialysis filter
x 
x 
x 
x
See Section 9.8.
Whole Blood Collection for 
Analysis of DNA Variants in 
ADME-related Genes and 
thrombosis and hemostasis 
related genes 
x
See Section 9.7.
Only one sample required per subject for the study.  
Maybe obtained any time on or after randomization
Additional Research 
Sampling 
x
x
 
x
x (24-72 h post dose 
D12)
Residual samples from biomarkers and PD blood. 
See Section 9.8.1.
Randomize
x
Visit can be conducted with scheduled HD session.
Study Drug Administration
x 
x 
x 
x
Administration of study drugs (i.e., BMS-986177, 
enoxaparin, and UFH) will be depending on the 
randomized sequence the subject is assigned to.
a Visit can be performed between D13-15 based on last PK sample obtained between 24-72 hours post D12 dose. End of study procedures should be performed 
for subjects that discontinue prematurely
.
In the event of  multiple procedures are required at a single time point, the  
following  
is  a  
list of procedures from  highest priority to 
low:
Revised Protocol No.: 03
Date: 06-Sep-2017
13
585
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
____________________________________________
________________________________________ 
--
________________________________________________
2.0
Approved
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Safety
Pharmacokinetic Sampling
Pharmacodynamic Sampling
Biomarker sampling 
Revised Protocol No.: 03
Date: 06-Sep-2017
14
586
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
____________________________________________
________________________________________ 
--
________________________________________________
2.0
Approved
930125554
1.0
v




Clinical Protocol
CV010010
BMS-986177
FXIa
weight heparin  such as enoxaparin,  
is administered during the HD session. However, UFH and 
LMWH  can  potentially  increase  the  hemorrhagic  risk  in  patients with  ESRD  who  frequently 
exhibit  a  uraemia-associated  platelet  dysfunction.  Furthermore,  some  patients  treated  with 
heparins develop anti-heparin antibodies causing an autoimmune disorder called heparin-induced 
thrombocytopenia  (HIT)  that  prevents  further  use  of  heparin.  In  this  regard,  FXIa  inhibition 
might represent an alternative and safer anticoagulant option in patients undergoing HD in whom 
heparin administration is not indicated. Anti-coagulant agents are utilized in clinical practice to 
reduce  the  incidence  of  thrombotic agents  in  several  conditions,  and  although  effective  in 
preventing  thrombus  formation,  they  are  also  associated  with  dose-related  bleeding 
complications.  Observations  from  patients  with  genetic  deficit of  FXI  and  from  clinical  and 
preclinical studies that investigated this mechanism of action suggest that inhibition of FXIa may 
be safer in terms of bleeding risk compared to other anti-coagulants. If this is confirmed, BMS-
986177 may in the future be also used to prevent or treat thrombotic events. Thus, this study will 
also provide relevant information on the anticoagulant activity of BMS-986177 compared to two 
different  comparators  (UFH  and  enoxaparin)  that  are  routinely  used  in  several  thrombotic 
conditions.
The purpose of this study is to evaluate the safety profile, tolerability, and pharmacokinetics of 
single  oral  doses  of  BMS-986177  in  ESRD  patients  undergoing  chronic  stable  hemodialysis 
treatment. Although there is no primary research hypothesis to be formally tested, it is expected 
that  administration of  BMS-986177  will prolong  the  plasma  activated  partial  thromboplastin 
time (aPTT), reduce plasma  Factor XI clotting activity,  and  have  no effect on the prothrombin 
time and international normalized ratio (PT and INR).
It  is  expected  that  the  administration  of  BMS-986177  will  prevent  clot  formation  in  the 
extracorporeal  HD  circuit,  hence  clotting  in  the  HD  filter,  lines,  and drip  chambers  will  be 
assessed, additional clotting-related pharmacodynamic (PD) endpoints will be also explored.
 
 
 
 
 
 
 
 
 
 
 
 
Revised Protocol No.: 03
Date: 06-Sep-2017
16
588
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v










Clinical Protocol
CV010010
BMS-986177
FXIa
Study  patients  will  be admitted  
to  
the  study  
facility  
the  same  day  of  HD  
treatment  day or  
the 
night before. Assessment of vital signs and clinical biochemistry will be performed pre-dose. 
Study treatments will be administered:
BMS-986177: one single oral dose 3 hours prior beginning the HD session
UFH:  
I.V.  
infusion  
to  start  within  10  minutes  prior  beginning  
the  HD  session.  The  dosage 
and duration of UFH use are at the discretion of the physicians and are per their institutional 
practice.
Enoxaparin: one single dose (40 mg) by subcutaneous injection 3 hours prior beginning the 
HD session
The HD session will last approximately 4 hours. However, the duration could range from 3 to 4 
hours  but  should  be  consistent  on  the  days  when  study  drug  is  administered.  After the HD, 
patients will remain in the study facility for at least:
Approximately 3 hours post-HD on UFH and Enoxaparin treatment days
Approximately 24 hours post-dose on BMS-986177 days
Site staff members blinded to treatment will perform an assessment of clot formation according 
to criteria set forth in the Clot Formation Assessment Manual which will be provided to the site 
in a separate document. 
Physical examinations, vital sign measurements, 12-lead electrocardiograms (ECG), and clinical 
laboratory  evaluations  will  be  performed  at  selected  times  throughout  the  dosing  interval. 
Participants  will  be  closely  monitored  
for  adverse  events  
throughout the  study. Blood samples 
will  be  collected  for  up  
to  72 hours  after  study  drug  administration  for  pharmacokinetic  
(PK) 
analysis and  pharmacodynamic  
(PD)  analysis.  Approximately  365 mL of  blood  will  be  drawn 
from each participant during the study.
The study design schematic is presented in Figure 5.1-1.
Revised Protocol No.: 03
Date: 06-Sep-2017
21
593
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Note: Per amendment/revised protocol 01, the BMS-986177 doses will be 100 mg (BMS dose 1) and 300 mg (BMS 
dose 2).
Not Applicable
Target  sample  size  is  32 participants to  achieve 24 participants  who  completed  the 4  study 
treatments.
The  start  of  the  trial  is  defined  as  the  first  visit  for  first participant  screened.  End  of  trial  is 
defined as the last visit or scheduled procedure shown in the Schedule of Activities for the last 
participant. Study completion is defined as the final date on which data for the primary endpoint 
was or is expected to be collected. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Revised Protocol No.: 03
Date: 06-Sep-2017
22
594
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v




Clinical Protocol
CV010010
BMS-986177
FXIa
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
For entry into the study, the following criteria MUST be met.
a) The signed informed consent form.
a) Subjects with ESRD treated with  hemodialysis prescribed 3 times  a week  
for at  
least 3 
months  prior  enrollment. For  at  least  2  weeks  prior  to  study  drug  administration, 
participants should undergo all 3 hemodialysis sessions per week.
b) Subjects  with  severe  renal  impairment  may  include  
those  with a  variety  of  underlying 
stable renal disease such as nephrosclerosis and chronic glomerulonephritis
Revised Protocol No.: 03
Date: 06-Sep-2017
24
596
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
a) Males and Females, ages 18 or age of majority to  75 years, inclusive
b) Women  of  childbearing  potential  (WOCBP)  must  have  a  negative serum  or  urine 
pregnancy  test  (minimum  sensitivity  25  IU/L  or  equivalent  units  of  HCG)  within 
24 hours prior to the start of study treatment.
c) Women must not be breastfeeding
d) Women  of  childbearing  potential  (WOCBP)  must  agree  to  follow instructions  for 
method(s) of contraception (Appendix 4) for the duration of the study plus 5 half-lives of 
study  
treatment BMS-986177 (2 days) plus  30  days  
(duration  of  ovulatory  cycle)  
for  a 
total of 32 days post-treatment completion.
e) Males  who  are  sexually  active  with  WOCBP  must  agree  to  follow  instructions  for 
method(s)  of  contraception  (Appendix  4)  for  the  duration  of  treatment  with  study 
treatment(s) BMS-986177 plus 5 half-lives of the study treatment (2 days) plus 90 days 
(duration of sperm turnover) for a total of 92 days post-treatment completion. In addition, 
male participants must be willing to refrain from sperm donation during this time. 
i) With amendment/revised  protocol  02,  males  who  are  sexually  active  with  WOCBP 
must agree to follow  
instructions  
for  methods of contraception (Appendix 4)  
for the 
duration  of  
treatment  with  BMS-996177  plus  5  half-lives  of  
the study  
treatment  
(2 
days) for a total of 2 days post-treatment completion.
f) Azoospermic  males  are  exempt from  contraceptive  requirements.  WOCBP  who  are 
continuously not heterosexually active are also exempt from contraceptive requirements, 
and still must undergo pregnancy testing as described in this section.
Investigators  shall  counsel  WOCBP,  and  male  participants  who  are  sexually  active  with 
WOCBP,  on  the  importance  of  pregnancy  prevention  and  the  implications  of  an  unexpected 
pregnancy.  
Investigators  shall  advise  on  
the  use  of  highly  effective  methods  of  contraception, 
(Appendix 4) which have a failure rate of < 1% when used consistently and correctly.
a) Subjects  receiving  dialysis  through  central  venous  catheters.  After  amendment/revised 
protocol 01,  this  exclusion  criteria  will  not  be  applicable and  will  not  be  needed  for 
eligibility. 
b) History of uncontrolled or unstable cardiovascular, respiratory,  hepatic, gastrointestinal, 
endocrine, hematopoietic, psychiatric and/or neurological disease in the past 3 months
c) Evidence  or  history  of  coagulopathy,  prolonged  or  unexplained  clinically  significant 
bleeding, or frequent unexplained bruising.
d) Current or recent (within 3 months of study drug administration) gastrointestinal disease 
or  surgery,  which  by  
the  
judgment  of  
the  
Investigator,  may  
increase  a  subject’s  
risk  of 
gastrointestinal bleeding or interfere with absorption of study drug (eg, peptic or gastric 
ulcer  disease,  severe  gastritis,  history  of  gastrointestinal  surgery with  
the  exception  of 
history of cholecystectomy).
Revised Protocol No.: 03
Date: 06-Sep-2017
25
597
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
e) Any  condition  requiring  chronic  systemic  anticoagulation  such  as,  but  not  limited  to, 
atrial  fibrillation, mechanical  prosthetic  valve,  deep  venous  thrombosis,  or  pulmonary 
embolism
f) Not  considered  by  the  study  principal  investigator  to  be  candidates  for  oral 
anticoagulation (for example, history of  
intracranial  hemorrhage, active bleeding, recent 
gastrointestinal bleed or retroperitoneal bleed, severe hepatic impairment)
g) Any major surgery within 12 weeks of study drug administration
h) History of significant head injury within the last 2 years, including subjects with base of 
skull fractures
i) Donation of blood to a blood bank within 4 weeks of study drug administration (within 2 
weeks for plasma only)
j) Blood transfusion within 2 weeks of study drug administration
k) Inability to tolerate oral medication
l) Inability to be venipunctured and/or tolerate venous access
m) Smoking more than 10 cigarettes per day
n) Recent (within 6 months of study drug administration) drug or alcohol abuse as defined 
in DSM IV, Diagnostic Criteria for Drug and Alcohol Abuse (Appendix 6)
o) Any  other  sound  medical,  psychiatric  and/or  social  reason  as determined  by  the 
investigator
a) Chronic therapy  with  aspirin,  dipyridamole,  or  P2Y12  antagonists  (for  example 
clopidogrel, prasugrel, or ticagrelor). Prior aspirin use is allowed after a washout period 
of at least 1 week before dosing.
b) Inability to comply with prohibited/restricted treatments as listed in Section 7.7
a) Evidence  of  organ  dysfunction  or  any  clinically  significant  deviation  in  physical 
examination,  vital  signs,  ECG  or  clinical  laboratory determinations  beyond  what  is 
consistent  with  their  degree  of  renal  dysfunction  and  other  underlying  conditions  as 
determined  by  medical  history,  physical  examination,  ECG,  and  clinical  laboratory 
determinations.
b) Subjects with macro-hematuria and/or fecal occult blood detected during screening, 
baseline, or documented during other recent medical assessment, unless deemed not 
clinically significant by the Investigator.
c) Subjects at screening with the following abnormal laboratory values upon repeat testing
are excluded:
i) Hemoglobin <9 g/dL
ii) Hematocrit < 30%
iii) Platelet count < 80,000/mm
3
iv) ALT or AST > ULN
v) Total bilirubin > 1.5X ULN
vi) aPTT or PT/INR > 1.2X ULN
Revised Protocol No.: 03
Date: 06-Sep-2017
26
598
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
d) Positive  urine  or  saliva  or  plasma  screen  for  drugs  of  abuse with  exception  for 
prescription medications
e) Positive blood screen for HIV-1 and HIV-2 antibody 
a) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity)
a) Prisoners or participants who are involuntarily incarcerated. (Note: under certain specific 
circumstances  a  person  who  has  been  imprisoned  may  be  included or  permitted  to 
continue  as  a  participant.  Strict  conditions  apply  and  Bristol-Myers  Squibb  approval  
is 
required.)
b) Participants who  are  compulsorily  detained  for  treatment  of  either  a  psychiatric  or 
physical (eg, infectious disease) illness
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
participants and that the results of the study can  be used. It is  
imperative that participants  
fully 
meet all eligibility criteria.
Subjects  are  to  refrain  from  strenuous  exercise,  contact  sports,  and  sunbathing  from  at  least 
5 day(s) prior to the first dose until study discharge.
1) Unless restricted by the clinical facility, subjects are permitted to smoke while residing at the 
clinical facility and on dialysis days.
2) Participants are not permitted to consume alcohol-containing beverages from 3 days prior to 
the first dose until study discharge.
3) Participants are not permitted to consume grapefruit-containing products from 3 days prior to 
the first dose until study discharge.
4) Participants are  not permitted to consume  more than two caffeine-containing  beverages per 
day for the whole study duration.
5) On  each  study treatment day,  patients  are  required  
to  fast  (nothing  
to  eat  or  drink  except 
water)  for  4  hours  prior  to  a  standard  meal,  which  will  be  consumed  approximately 
30 minutes prior to study drug administration. Patients may not drink water one hour before 
and  after  study  drug  administration  except  with  dosing  and  
the beverage  provided  with  
the 
pre-dose standard meal. Water may be consumed 
at other times.
Screen failures are defined as participants who consent to participate in the clinical study but are 
not  subsequently  [randomized/entered  in  the  study/included  in  the  analysis  population].  A 
minimal  set  of  screen  failure  
information  
is  
required  
to  ensure  
transparent  
reporting  of  screen 
failure  participants,  to  meet  the  Consolidated  Standards  of  Reporting  Trials  (CONSORT) 
publishing  requirements,  and  to  respond  to  queries  from  regulatory  authorities.  Minimal 
Revised Protocol No.: 03
Date: 06-Sep-2017
27
599
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
information includes date of consent, demography, screen failure details, eligibility criteria, and 
any serious AEs.
Participant  Re-enrollment:  This  study  permits  the  re-enrollment  of  a  participant that  has 
discontinued the study as a pre-treatment failure (i.e., participant has not been randomized / has 
not been treated). If re-enrolled, the participant must be re-consented.
Laboratory parameters and/or assessments that are included in Table 2.-1, Screening Procedural 
Outline may be repeated in an effort to find all possible well-qualified participants. Consultation 
with  
the  Medical  Monitor  may  be  needed  
to  
identify  whether  repeat  
testing  of  any  particular 
parameter is clinically relevant.
Study  
treatment  
is  defined  as  any  
investigational  
treatment(s),  marketed  product(s),  placebo  or 
medical  device  intended  to  be  administered  to  a  study  participant  according  to  the  study 
randomization or treatment allocation.
Study  treatment includes  both  Investigational  [Medicinal]  Product  (IP/IMP)  and 
Non-investigational [Medicinal] Product (Non-IP/Non-IMP) and can consist of the following:
BMS-986177, unfractionated heparin (UFH) and Enoxaparin as IP/IMP.
An investigational product, also known as investigational medicinal product in some regions, is 
defined  a  pharmaceutical  form  of  an  active  substance  or  placebo  being  tested  or  used  as  a 
reference in a clinical study, including products already with a marketing authorization but used 
or  assembled  (formulated  or  packaged)  differently  than  the  authorized  form,  or  used  for  an 
unauthorized indication, or when used to gain further information about the authorized form.
Other  medications  used  as  support  or  escape medication  for  preventative,  diagnostic,  or 
therapeutic  reasons,  as  components  of  the  standard  of  care  for a  given  diagnosis,  may  be 
considered as non-investigational products.  Not Applicable for this study.
Revised Protocol No.: 03
Date: 06-Sep-2017
28
600
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
BMS 986177/SDD 
75% as the basea
100 mg or 300 mg
IP
Open label
Labeled bulk product in 
glass vials / white to 
off-white powder which 
may appear as lumps
Store at 2 C to 8 C, 
protected from light and 
moisture
UFH  
Per Standard of Care
IP
Open label
Sourced by Site
Per Label
  Enoxaparin
40 mg
IP
Open label
Sourced by Site
Per Label
a Compounding instructions will be provided separately to the site
Revised Protocol No.: 03
Date: 06-Sep-2017
29
601
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
____________________________________________
________________________________________ 
--
________________________________________________
2.0
Approved
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Dose 1 
BMS 986177/SDD 
75% as the base
a
100 mg
Single dose
PO
Dose 2 
BMS 986177/SDD 
75% as the base
a
300 mg
Single dose
PO
UFH
Per SoC
(Standard of Care)
IV  
Enoxaparin
40 mg
Single Dose
(Standard of Care)
SC
a
Compounding instructions will be provided separately to the site
Note: Per amendment/revised protocol 01, the BMS-986177 doses will be 100 mg (BMS dose 1) and 300 mg (BMS 
dose 2).
Study treatments will be dosed:
BMS-986177: one single oral dose 3 hours prior beginning the HD session
UFH:  
I.V.  
infusion  
to  start  within  10  minutes  prior  beginning  
the  HD  session.  The  dosage 
and duration of UFH use are at the discretion of the physicians and are per their institutional 
practice.
Enoxaparin: one single dose (40 mg) by subcutaneous injection 3 hours prior beginning the 
HD session
At  
the  
time  of  dosing,BMS-986177, 240  mL  of  water  will  be  administered  
to  
the  participant 
along with his/her dose of study drug. The time of dose administration will be called “0” hour.
Restrictions related to food and fluid intake are described in Section 6.3.
Study  treatment  will  be  dispensed  at  the  study  visits as  listed in  Schedule  of  Activities 
(Section 2). 
Enrolled participants, including those not dosed, will be assigned sequential participant numbers 
starting  with  00001,  
(eg,  00001,  00002,  00003....  00010).  Sequential  numbering  may  
restart  at 
00001  for  each  participating  site  as  the  distinct  patient  identification  number  (PID)  will 
ultimately  be  comprised  of  
the  site  number  and  participant number,  (eg,  0002  00001).  Those 
enrolled participants meeting inclusion and exclusion criteria will be eligible to be randomized. 
Randomization numbers will be assigned prior to dosing. 
Revised Protocol No.: 03
Date: 06-Sep-2017
30
602
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Participants will not be replaced if they are discontinued from the study secondary to an adverse 
event unless the adverse event can be determined to be unrelated to treatment. If a participant is 
replaced after dosing then the replacement participant will be assigned the original participant’s 
number plus 100. The replacement participant will receive the same treatment as the participant
being  
replaced  but  a  new  
randomization  number  will  be  assigned  
to  him  or  her.  For  example, 
participant 4 would be replaced by Participant 104.
This is an open-label study. Blinding procedures are not applicable. 
Not Applicable
The investigational product should be stored in a secure area according to local regulations. It is 
the  
responsibility  of  
the  
investigator to  ensure  
that  
investigational  product  
is only  dispensed  
to 
study Participants. The investigational product must be dispensed only  
from official study sites 
by authorized personnel according to local regulations.
The product storage manager should ensure that the study treatment is stored in accordance with 
the  environmental  conditions  (temperature,  light,  and  humidity)  as  determined  by  BMS.  If 
concerns  
regarding  
the  quality  or  appearance  of  
the  study  
treatment arise,  
the  study  
treatment
should not be dispensed and contact BMS immediately.
Study treatment not supplied by BMS will be stored in accordance with the package insert.
Investigational product  documentation  
(whether  supplied by  BMS  or  not)  must  be maintained 
that  includes  all  processes  required  to  ensure  drug  is  accurately  administered.  This  includes 
documentation  of  drug  storage,  administration  and,  as  applicable,  storage  temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets).
For study drugs not provided by BMS (enoxaparin and UFH) and obtained commercially by the 
site, storage should in accordance with the product label.
Compounding instructions for BMS-986177 will be provided separately to the site.
Further guidance and information for final disposition of unused study treatment are provided 
in Appendix 2.
Not Applicable
Study drug will be administered in the clinical facility. After administration of BMS-986177 an 
examination of the oral cavity is required to verify that a participant has swallowed the solution.
The participant should drink the entire aliquot of water given to swallow the solution. 
Revised Protocol No.: 03
Date: 06-Sep-2017
31
603
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
UFH and Enoxaparin will be administered by the healthcare staff at the clinical facility according 
to protocol and standard of care. 
Prohibited and/or restricted medications taken prior to study drug administration in the study are 
described  below. Medications taken within 4  weeks prior to study drug administration  must be 
recorded on the CRF.
1) Use  of  any  agent,  including  but  not  limited  to  anti-platelet agents (except  aspirin), 
anticoagulants (except heparin for routine hemodialysis use), fish oil capsules, and ginko that 
is  known  to  increase  the  potential  for  bleeding  within  2  weeks prior  to  study drug 
administration. Use  of  non-steroidal  anti-inflammatory  compounds  (NSAIDs)  or  aspirin 
within 1 week prior to study drug administration.
2) Exposure to any investigational drug or placebo within 4 weeks of study drug administration.
3) Use of acid  controllers  within  
two  days  of BMS-986177  study  drug  administration  except 
those  medications  cleared  by  
the  BMS  medical  monitor. The  use  of  acid  controllers  after 
BMS-986177 administration and after hemodialysis is allowed. The use of acid controllers is 
also allowed when enoxaparin or UFH are administered.
a) Sodium bicarbonate is allowed during the study.
4) Use  of  strong  and  moderate  CYP3A  inhibitors  within  1  week  of enrollment  including  
the 
following:  the  antifungals  and  antibiotics  ketoconazole,  fluconazole,  itraconazole, 
miconazole,  clotrimazole,  erythromycin  and  clarithromycin;  the calcium  channel  blockers 
diltiazem and verapamil; the HIV anti-virals delaviridine, indinavir, nelfinavir, ritonavir, and 
saquinavir; and the serotonin reuptake inhibitor fluoxetine. Use of CYP3A inducers such as 
carbamazapine, dexamethasone, phenobarbitol, phenytoin, rifampin, St John
's Wort within 4 
weeks of enrollment. Topical antifungal use is allowed.
Study  patients  may  receive  treatment  with  medications  necessary  for  maintaining  the  clinical 
status of their condition as described in Inclusion Criteria.
Any concomitant therapies must be recorded on the CRF.
Not Applicable
At  
the  end  of  
the  study,  BMS  will  not  continue  
to  provide  BMS  supplied  study  
treatment to 
participants/investigators  unless  BMS  chooses  to  extend  the  study.  The  investigator  should 
ensure  that  the  participant receives  appropriate  standard  of  care  to  treat  the  condition  under 
study.
Revised Protocol No.: 03
Date: 06-Sep-2017
32
604
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Participants  MUST  discontinue  
investigational  product  
(and  non-investigational  product  at  
the 
discretion of the investigator) for any of the following reasons:
Participant’s  
request  
to  stop  study  
treatment. Participants  who request  
to  discontinue  study 
treatment  will  
remain  
in  
the  study  and  must  continue  
to  be  
followed  for  protocol  specified 
follow-up procedures. The only exception to this is when a participant specifically withdraws 
consent for any further contact with him/her or persons previously authorized by participant 
to provide this information
Any clinical adverse event (AE), laboratory abnormality or intercurrent illness which, in the 
opinion  of  
the  
investigator,  
indicates  
that  continued  participation in the study is not in the 
best interest of the participant
Termination of the study by Bristol-Myers Squibb (BMS)
Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness
Pregnancy
Overt bleeding producing a Hb decrease 2 g/dL in 24 hours
Need for blood transfusion
Overt bleeding which is retroperitoneal, intracranial, intra-spinal, intraocular, or intraarticular
Any  overt  bleeding  deemed  by  the  investigator  to  necessitate  discontinuation  of  trial 
medication
Medical  or  surgical  treatment  for  bleeding  beyond  the  application  of  pressure  or  cold 
compress
Need for surgery during the study period
Need  
for treatment with an anticoagulant or antiplatelet agent during the study period, with 
the exception of heparin and enoxaparin use during HD
Need for treatment with a strong CYP3A4 inhibitor or any CYP3A4 inducers
Inability to continue on the hemodialysis treatment for the duration of the study
Inability to comply with the protocol
Occurrence in one of the BMS-986177 treatment arm or in the enoxaparin treatment arm of 5 
or  more  patients with  events  of  complete  clotting  of  HD  circuit causing  premature 
interruption of the HD procedure. This will result in a discontinuation of that treatment arm. 
The  randomized  sequence  for  the  following  patients  will  not  be changed,  and  the 
discontinued  treatment  arm  will  be  replaced  by  standard  of  care  (UFH) in  the  treatment 
sequence.
In  case  a  subject  experiences  complete  clotting  
leading  
to  premature  
interruption  of  HD  
in  
the 
BMS-986177 arms, the HD session can be restarted using standard of care at the discretion of the 
study Investigator.
Refer  to  the Schedule  of  Activities  for  data  to  be  collected  at  the  time  of  treatment 
discontinuation and follow-up and for any further evaluations that can be completed
Revised Protocol No.: 03
Date: 06-Sep-2017
33
605
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
All participants who discontinue study treatment should comply with protocol specified follow-
up  procedures  as  outlined  in Section  2.  The  only  exception  to  this  requirement  is  when  a 
participant withdraws consent for all study procedures including post-treatment study follow-up 
or  loses  the  ability  to  consent  freely  (i.e.,  is  imprisoned  or involuntarily  incarcerated  for  the 
treatment of either a psychiatric or physical illness).
If study treatment is discontinued prior to the participant’s completion of the study, the reason 
for the discontinuation must be documented in the participant’s medical records and entered on 
the appropriate case report form (CRF) page.
Participants who discontinue study treatment may continue to be followed.
Participants  who  request  to  discontinue  study  treatment will  remain  in  the  study  and  must 
continue to be followed for protocol specified follow-up procedures. The only exception to this 
is  when  a  participant  specifically  withdraws  consent  for  any  further  contact  with  him/her  or 
persons previously authorized by participant to provide this information. 
Participants  should  notify  
the  
investigator  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 from further treatment with study treatment only 
or  also  from  study  procedures  and/or  post  treatment  study  follow-up,  and  entered  on  the 
appropriate CRF page.
In  
the  event  
that  vital  status  (whether  
the  participant  is  alive  or  dead)  is  being  measured, 
publicly available information should be used to determine vital status only as appropriately 
directed in accordance with local law.
If  
the  participant  withdraws  consent  for  disclosure  of  future  
information,  
the  sponsor  may 
retain and continue to use any data collected before such a withdrawal of consent.
All  reasonable  efforts  must  be  made  to  locate  participants  to  determine  and  report  their 
ongoing status. This includes follow-up with persons authorized by the participant.
Lost to follow-up is defined by the inability to reach the participant after a minimum of 
documented  phone  calls,  
faxes,  or  emails  as  well  as  
lack  of  
response  by  participant to one 
registered  mail  letter.  All  attempts should  be  documented  in  the  participant’s  medical 
records.
If it is determined that the participant has died, the site will use permissible local methods to 
obtain date and cause of death.
If  investigator’s  use  of  third-party  representative  to  assist  in the  follow-up  portion  of  the 
study has been included in the participant’s informed consent, then the investigator may use a 
Sponsor  retained  third-party  representative  to  assist  site  staff  with  obtaining  participant’s 
contact  information  or  other  public  vital  status  data  necessary  to  complete  the  follow-up 
portion of the study. 
Revised Protocol No.: 03
Date: 06-Sep-2017
34
606
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
The site staff and representative will consult publicly available sources, such as public health 
registries and databases, in order to obtain updated contact information.
If after all attempts, the participant remains lost to follow-up, then the last known alive date 
as  determined  by  the  investigator  should  be  reported  and  documented  in  the  participant’s 
medical records.
Study procedures and timing are summarized in the Schedule of Activities. 
Protocol waivers or exemptions are not allowed.
All immediate  safety  concerns  must  be discussed  with  the  Sponsor immediately  upon 
occurrence  or  awareness  to  determine  if  the  participant  should continue  or  discontinue 
treatment.
Adherence  to  
the  study  design  requirements,  including  those  specified  in  the Schedule  of 
Activities, is essential and required for study conduct.
All  screening  evaluations  must  be  completed  and  reviewed  to  confirm  that  potential 
participants meet all eligibility criteria before randomization. The investigator will maintain a 
screening log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable.
Procedures  conducted  as  part  of  the  participant’s  routine  clinical  management  (eg,  blood 
count)  and  obtained  before  signing  of  informed  consent  may  be  utilized  for  screening  or 
baseline  purposes  provided  
the  procedure meets  
the protocol-defined  criteria  and  has  been 
performed within the timeframe defined in the Schedule of Activities.
Not Applicable
Not Applicable
The definitions of an AE or serious adverse event (SAE) can be found in Appendix 3.
AEs will  be reported by the participant (or, when appropriate, by  a caregiver, surrogate, or the 
participant
's legally authorized representative). 
The  investigator  and  any  designees  are  responsible  for  detecting,  documenting, and  reporting 
events that  meet the definition of an  AE or SAE and remain responsible  
for  
following up  AEs 
that  are  serious,  considered  related  to  the study  treatment  or the  study,  or  that  caused  the 
participant to discontinue before completing the study. 
The collection of  nonserious  AE  
information  should  begin at  
initiation of study treatment until 
[the  follow-up  contact],  at  
the  timepoints  specified  in  the  Schedule  of  Activities  (Section  2). 
Revised Protocol No.: 03
Date: 06-Sep-2017
35
607
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Nonserious AE information should also be collected from the start of a placebo lead-in period or 
other observational period intended to establish a baseline status for the participants.
Sections  5.6.1  and  5.6.2  in  the  Investigator  Brochure  (IB)  represent  the  Reference  Safety 
Information  to  determine  expectedness  of  serious  adverse  events  for  expedited  reporting. 
Following the participant’s written consent to participate in the study, all SAEs, whether related 
or  not  
related  
to  study  drug,  must  be  collected,  
including  
those  
thought  
to  be  associated  with 
protocol-specified procedures.
ll  SAEs  must  be  collected  that  occur  during  the  screening  period  and  within  30  days  of 
discontinuation of dosing.
Medical  occurrences  that  begin  before  the  start  of  study  treatment  but  after  obtaining 
informed consent will be recorded on the appropriate section of the eCRF section.
All SAEs will be recorded and reported to Sponsor or designee within 24 hours, as indicated 
in Appendix 3. 
The  
investigator  will  submit  any  updated  SAE  data  
to  
the  sponsor  within  24  hours  of  
this 
being available.
Investigators  are  not  obligated  to  actively  seek  AEs  or  SAEs  in  former study  participants. 
However, if the investigator learns of any SAE, including a death, at any time after a participant 
has  been  discharged  from  
the  study,  and  he/she  considers  
the  event  reasonably  related  
to  
the 
study treatment or study participation, the investigator must promptly notify the sponsor.
The  method  of  evaluating,  and  assessing  causality  of  AEs  and  SAEs  and  the  procedures  for 
completing and reporting/transmitting SAE reports are provided in Appendix 3.
Adverse  events  can  be  spontaneously  reported  or  elicited  during  open-ended  questioning, 
examination, or evaluation of a subject. (In order to prevent reporting bias, subjects should not be 
questioned regarding the specific occurrence of one or more AEs.)
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Appendix 3).
Follow-up  
is  also  
required  
for  nonserious  AEs  
that  cause  
interruption  or  discontinuation  of 
study treatment and for those present at the end of study treatment as appropriate.
All identified nonserious AEs must be recorded and described on the nonserious AE page of 
the CRF (paper or electronic). Completion of supplemental CRFs may be requested for AEs 
and/or laboratory abnormalities that are reported/identified during the course of the study.
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at  subsequent  visits/contacts.  All  SAEs,  and  non-serious  AEs  of  special  
interest  
(as  defined  
in 
Section  9.2will  be  followed  until  resolution,  until  the  condition  stabilizes,  until  the  event  is 
otherwise explained, or until the participant is lost to follow-up (as defined in Section 8.3).
Revised Protocol No.: 03
Date: 06-Sep-2017
36
608
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Further information on follow-up procedures is given in Appendix 3.
Prompt  notification  by  the  investigator  to  the  Sponsor  of  SAEs is  essential  so  that  legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
product under clinical investigation are met.
An investigator who receives an investigator safety report describing SAEs or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor will file it along with 
the  Investigator’s  Brochure  and  will  notify  
the  IRB/IEC,  if  appropriate  according  
to  
local 
requirements.
Sponsor  or  designee will  be  reporting  adverse  events  to  regulatory  authorities  and  ethics 
committees  according  to  local  applicable  laws  including  European  Directive  2001/20/EC  and 
FDA  Code  of  Federal  Regulations  21  CFR  Parts  312  and  320.  A  SUSAR  (Suspected, 
Unexpected  Serious  Adverse  Reaction)  is  a  subset  of  SAEs  and  will  be  reported  to  the 
appropriate  regulatory  authorities  and  investigators  following local  and  global  guidelines  and 
requirements.
If,  
following  
initiation of the study treatment, it is subsequently discovered that a participant is 
pregnant  or  may  have  been  pregnant  at  
the  
time  of  study  exposure,  including  during  at  least 
5 half-lives after  product  administration,  the  investigator  must immediately  notify  the  BMS 
Medical  Monitor/designee  of  this  event  and  complete  and  forward  a  Pregnancy  Surveillance 
Form to BMS Designee within 24 hours of awareness of the event and in accordance with SAE 
reporting procedures described in Appendix 3
In  most  cases,  
the  study  
treatment will  be  permanently  discontinued  
in  an  appropriate  manner 
(eg,  dose  tapering  if  necessary  for  participant safety).  Please call  the  BMS  Medical  Monitor 
within 24 hours of awareness of the pregnancy.
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
participant.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
Sponsor  or  designee.  In  order  for  Sponsor  or  designee  to  collect  any  pregnancy  surveillance 
information from the female partner, the female partner must sign an informed consent form for 
disclosure of this information. Information on this pregnancy will be collected on the Pregnancy 
Surveillance Form.
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form electronic, as appropriate. Paper forms are only intended as a back-up 
option when the electronic system is not functioning.
Any laboratory test result that is clinically significant or meets the definition of an SAE 
Revised Protocol No.: 03
Date: 06-Sep-2017
37
609
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Any  
laboratory  
test  
result  abnormality  
that  
required  
the  participant to  have  study  
treatment
discontinued or interrupted
Any  laboratory  test  result  abnormality  that  required  the  participant to  receive  specific 
corrective therapy
It is expected that wherever possible, the clinical  
rather than  
laboratory term would  be used  by 
the reporting investigator (eg, anemia versus low hemoglobin value).
Some coagulation tests (eg, aPTT,) are affected by the investigational drug and therefore changes 
in such tests are not to be considered as AEs but as PD biomarkers.
Wherever  possible,  
timely  confirmation  of  initial  liver-related  
laboratory  abnormalities  should 
occur  prior  to  the  reporting  of  a  potential  DILI  event.  All  occurrences  of  potential  DILIs, 
meeting  the  defined  criteria,  must  be  reported  as  SAEs  (see Section  9.2and Appendix  3 for 
reporting details).
Potential drug induced liver injury is defined as: 
Wherever  possible,  
timely  confirmation  of  initial  liver-related  
laboratory  abnormalities  should 
occur  prior  to  the  reporting  of  a  potential  DILI  event.  All  occurrences  of  potential  DILIs, 
meeting the defined criteria, must be reported as SAEs (see Appendix 3 for reporting details).
Potential drug induced liver injury is defined as: 
1) AT (ALT or AST) elevation > 3 times ULN
AND
2) Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase),
AND
3) No  other  immediately  apparent  possible  causes  of  AT  elevation  and  hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic.
Any  significant  worsening  noted  during  interim  or  final  physical  examinations, 
electrocardiogram, x-ray filming, any other potential safety assessment required or not required 
by protocol should also be recorded as a non-serious or serious AE, as appropriate, and reported 
accordingly.
An overdose  
is defined  as the accidental or  
intentional administration of any dose of a product 
that is considered both excessive and medically important. All occurrences of overdose must be 
reported as an SAE (see Section 9.2).
Revised Protocol No.: 03
Date: 06-Sep-2017
38
610
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Planned timepoints for all safety assessments are listed in the Schedule of Activities.
Refer to Schedule of Activities.
Refer to Schedule of Activities.
Refer to Schedule of Activities.
Investigators must document their review of each laboratory safety report.
A local laboratory will perform the analyses and will provide reference ranges for these tests.
Results of clinical laboratory tests performed on Day -1 to -3 must be available prior to first dose 
of study drug.
Hemoglobin
Hematocrit
Total leukocyte count, including differential
Platelet count
PT
aPTT
INR
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Total bilirubin
Direct bilirubin
Alkaline phosphatase
Lactate dehydrogenase (LDH)
Creatinine
Blood Urea Nitrogen (BUN)
Uric acid
Fasting glucose (if possible)
Total Protein
Albumin
Sodium
Potassium
Chloride
Calcium
Phosphorus
Magnesium
Creatine kinase
Revised Protocol No.: 03
Date: 06-Sep-2017
39
611
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Blood (only if the participant is able to produce urine)
HIV-1 and -2 antibody (screening only)
Test for drugs of abuse (urine or salivaor plasma)
Alcohol breathalyzer 
Fecal occult blood (screening and after each treatment period if sample can be obtained)
Pregnancy test (urine or blood)- WOCBP only
Not Applicable
Not Applicable
Pharmacokinetics of  BMS-986177 will  be derived from  plasma  concentration  versus  
time.  The 
pharmacokinetic parameters to be assessed include:
Cmax
Maximum observed plasma concentration
Tmax
Time of maximum observed plasma concentration
AUC(0-T) 
Area under the plasma concentration-time curve from time zero to time 
of last quantifiable concentration
AUC(INF) 
Area under the plasma concentration-time curve from time zero 
extrapolated to infinite time
AUC(0-48) 
Area under the plasma concentration-time curve from time zero to 
48 hours
T-HALF
Terminal plasma half-life
fu
Fraction of unbound drug
Cmaxfu
Maximum observed plasma concentration of free drug
AUC(0-T)fu 
Area under the plasma concentration-time curve from time zero to time 
of last quantifiable concentration of free drug
AUC(INF)fu 
Area under the plasma concentration-time curve from time zero 
extrapolated to infinite time of free drug
AUC(3-7) 
Area under the plasma concentration-time curve from 3 to 7 hours. (ie, 
during dialysis. Determined from blood samples entering and exiting the 
dialyzer)
%DR
Percent dose of BMS-986177 recovered in dialysate (%)
CLD
Dialysate clearance of drug from plasma
Cumulative amount in dialysate over 3 to 7 hours postdose divided by 
plasma AUC(3-7)
Revised Protocol No.: 03
Date: 06-Sep-2017
40
612
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Individual participant pharmacokinetic parameter values will  be derived  by  non-compartmental 
methods  by  a  validated  pharmacokinetic  analysis  program.  Actual  times  will  be  used  for  the 
analyses.
BMS-986177 dosing 
day (depending on 
randomization 
sequence it may be 
study day 1, 5, 8, or 
12)
predose
00:00
Xa
postdose
1:00
X
hemodialysis 
startc
3:00
Xb
X (3-7)e
3:30
Xb
4:00
Xb
5:00
Xb
X
6:00
Xb
hemodialysis 
stopc
7:00
Xb
8:00
X
9:00
X
24 to 72 hours after 
BMS-986177 dosing
24:00 - 72:00 d
X
Note: Day 1, 5, 8, and 12 is the start of Period 1, 2, 3, and 4, respectively. Hemodialysis duration could range from 3 
to 4 hours but should be consistent on the days when study drug is administered.
a Sample to be obtained prior to study drug administration.
b Two  blood  samples  are  obtained  at  each  of  these time  points (one  sample  is  collected  prior  to  entering  the 
dialyzer and the second sample is collected after exiting the dialyzer) for Periods for BMS-986177 only 
c Sample to be collected from the blood prior to entering the dialyzer.
d Single sample between days 2-4, days 6-8, days 9-11, and days 13-15.
e Dialysate sample to be collected hourly between 3 to 7 hr during the hemodialysis session.
Revised Protocol No.: 03
Date: 06-Sep-2017
41
613
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
The  plasma  samples  will  be  analyzed  for  BMS-986177  by  a  validated  LC/MS/MS  assay.  In 
addition, plasma samples will be archived for potential metabolite analysis, if the need arises and 
to the extent possible.
Detailed instructions for the PK blood collection, labeling, processing, storage, and shipping will 
be provided to the site in the procedure manual.
After  the  scheduled  PK  analyses  are  completed,  residual  plasma may  be  used  for  metabolite 
profiling. If these analyses are conducted, they will be reported separately from the CSR.
Blood will be drawn at the times indicated inTable 9.6-1andTable 9.6-2, for the measurement 
of  pharmacodynamic  markers  (PD): aPTT,  and  Factor  XI  clotting  activity (FXIc) for 
BMS-986177, aPTT and Anti-Xa for heparin and Enoxaparin. Further details of blood collection 
and processing will be provided to the site in the procedure manual. 
predose
00:00
X
X
01:00
X
X
Hemodialysis start
03:00
Xa
Xa
04:00
Xa
Xa
05:00
Xa
Xa
06:00
Xa
Xa
Hemodialysis stop
07:00
Xa
Xa
08:00
X
X
09:00
X
X
24 to 72 hours after 
BMS-986177 dosing
24:00 - 72:00
X
Note: Hemodialysis duration could range from 3 to 4 hours but should be consistent on the days when study drug is 
administered.
Blood sample is collected prior to entering the dialyzer.
Single sample between days 2-4, days 6-8, days 9-11, and days 13-15.
Revised Protocol No.: 03
Date: 06-Sep-2017
42
614
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Predose/ Hemodialysis start
00:00
Xa
01:00
Xa
02:00
Xa
03:00
Xa
Hemodialysis stop
04:00
Xa
05:00
X
06:00
X
Note: Hemodialysis duration could range from 3 to 4 hours but should be consistent on the days when study drug is 
administered.
a Blood sample is collected prior to entering the dialyzer.
A  6-mL  whole  blood sample  will  be  drawn  at  baseline  for  dosed  participants as  indicated  in 
Section 2Schedule of Activities) for potential analysis of DNA variants in ADME-related genes 
(see Appendix 5) which contains the lists of ADME-related genes from http://pharmaadme.org), 
and/or  hemostasis and  thrombosis  related  genes.  Further  details of  blood  collection  and 
processing will be provided to the site in the procedure manual.
 
 
 
 
 
 
 
 
 
 
 
Revised Protocol No.: 03
Date: 06-Sep-2017
43
615
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
 
 
 
 
 
 
 
 
Revised Protocol No.: 03
Date: 06-Sep-2017
44
616
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v






Clinical Protocol
CV010010
BMS-986177
FXIa
Additional  research  collections  and  retention  are  mandatory  for all subjects,  except  where 
prohibited by local laws or regulations.
This protocol will include residual sample storage for additional research (AR).
This collection for additional research is intended to expand the translational R&D capability at 
Bristol-Myers  Squibb,  and  will  support  as  yet  undefined  research  aims  that  will  advance our 
understanding  of  disease  and  options  for  treatment.  It  may  also  be  used  to support  health 
authority  
requests  
for  analysis,  and  advancement  of  pharmacodiagnostic  development  
to  better 
target  drugs  
to  
the  
right  patients.  This  may  also  
include  genetic/genomic  exploration  aimed  at 
exploring disease pathways, progression and response to treatment etc. 
All requests for access to samples or data for additional research will be vetted through a diverse 
committee  of  the  study  sponsor’s  senior  leaders  in  Research  and  Development  to  ensure  the 
research supports appropriate and well-defined scientific research activities.
Residual plasma from PD and biomarker collections (seeTable 9.6-1, Table 9.6-2, Table 9.8-1, 
and Table 9.8-2) will also be retained for additional research purposes.
Samples  will  be  securely  stored by  
the  BMS  Biorepository  
in  NJ  or  at  a  BMS  approved  
third 
party storage management facility.
Samples will be stored in a coded fashion, and no researcher will have access to the key. The key 
is securely held by the Investigator at the clinical site, so there is no direct ability for a researcher 
to connect a sample to a specific individual
Additional research samples will be retained for 15 years or the maximum allowed by applicable 
law. No additional sampling is required for residual collections. 
Further details of sample collection and processing will be provided to the site in the procedure 
manual
D-dimer, F1.2 and 
exploratory sample
All timepoints as in Table 9.8-1and Table 9.8-2
aPTT, FXIc, anti-Xa
All timepoints as inTable 9.6-1and Table 9.6-2
Not Applicable
Revised Protocol No.: 03
Date: 06-Sep-2017
47
619
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Health  Economics/Medical  Resource  Utilization  and  Health  Economics  parameters  will  not  be 
evaluated in this study.
Although the number of patients is not based on statistical power considerations, administration 
of BMS-986177 to 32 subjects with ESRD would provide over 80% probability of observing at 
least  one  occurrence  of  any adverse  event  that  would  occur with  incidence  of  5%  in  the 
population from which the sample is drawn 
For purposes of analysis, the following populations are defined:
Enrolled 
All subjects who sign informed consent
Randomized
All  subjects  who  are randomized  to  the  study  including the 
subjects who replace  the discontinuing randomized subjects
Evaluable
All  randomized  subjects  who  take  at  least  1  dose  of  study 
treatment. 
Safety
All  randomized  subjects  who  take  at  least  1  dose  of  study 
treatment.
Pharmacokinetic
All  participants  who  receive  BMS-986177 from  whom  PK 
parameter data were obtained before and after HD. 
Pharmacodynamic  
Is a subset of the Safety Population and includes all subjects who 
received  at  least  1  dose  of  study  medication  and had  any 
available PD or biomarker data.
The  statistical  analysis  plan  will  be  developed  and  finalized  before  database lock  and  will 
describe  the  selection  of  participants  to  be  included  in  the  analyses,  and  procedures  for 
accounting for  missing,  unused,  and  spurious  data.  Below  
is  a  summary  of  planned  statistical 
analyses of the primary and secondary endpoints.
Revised Protocol No.: 03
Date: 06-Sep-2017
48
620
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Primary 
NA
Safety analyses will be performed on all safety assessments. 
Primary 
Descriptive summaries will be presented for continuous variables using 
number of subjects (N), mean, standard deviation (SD), median, minimum 
and maximum. Descriptive summaries for categorical variables will utilize 
counts and percentages.
All recorded AEs will be listed and tabulated by system organ class and 
preferred term, and treatment. Changes from baseline in vital signs, ECG, and 
clinical laboratory test results will be listed and summarized by treatment and 
time point. Any significant physical examination findings and any marked 
abnormal clinical laboratory test results will be listed. Electrocardiogram 
readings will be summarized by time point, and investigator-identified 
abnormalities, if present, will be listed.
See 
section 
9.5for  all  PK 
parameters 
Descriptive  summaries  will  be  presented  for  continuous  variables  using 
number  of  subjects  (N),  mean,  standard  deviation  (SD),  median, minimum 
and maximum. Geometric mean and coefficient of variation (%CV) will also 
be presented for sample plasma concentration-time data and PK parameters. 
 
 
 
 
 
 
 
 
 
Revised Protocol No.: 03
Date: 06-Sep-2017
49
621
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Results of DNA variants and other exploratory measures may not be reported in the CSR.
Not Applicable
Revised Protocol No.: 03
Date: 06-Sep-2017
50
622
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v






Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
53
625
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
ADME
Absorption, distribution, metabolism, excretion
AE
adverse event
ACLS
advanced cardiac life support
ALT
alanine aminotransferase
ANC
absolute neutrophil count
aPTT
activated partial thromboplastin time
ARIC
Atherosclerosis Risk in Communities
AST
aspartate aminotransferase
AT
aminotransaminases
AUC
area under the concentration-time curve
AUC(INF) 
area under the concentration-time curve from time zero extrapolated to 
infinite time
AUC(0-T) 
area under the concentration-time curve from time zero to the time of the 
last quantifiable concentration
AUC(TAU) 
area under the concentration-time curve in one dosing interval
-HCG
beta-human chorionic gonadotrophin
BID, bid
bis in die, twice daily
BLQ
below limit of quantification 
BMI
body mass index
BMS
Bristol-Myers Squibb
BP
blood pressure
BUN
blood urea nitrogen
C
Celsius
Ca++
calcium
CBC
complete blood count
CFR
Code of Federal Regulations 
CI
confidence interval
C1-
chloride
CLcr
creatinine clearance
CLD
Dialysate clearance of drug from plasma/serum
Revised Protocol No.: 03
Date: 06-Sep-2017
54
626
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
cm
centimeter
Cmax, CMAX 
maximum observed concentration
Cmin, CMIN 
minimum observed concentration
CNS
Central nervous system
CONSORT 
Consolidated Standards of Reporting Trials
CRC
Clinical Research Center
CRF
Case Report Form, paper or electronic
CV
coefficient of variation
CYP
cytochrome p-450
D/C
discontinue
dL
deciliter
DMC
Data monitoring committee
DRt, DR 
Total amount recovered in dialysate
%DRt, %DR 
Total percent of administered dose recovered in dialysate
DSM IV
Diagnostic and Statistical Manual of Mental Disorders (4
thEdition)
DVT
deep vein thrombosis
EC20, EC50, 
EC80
Effective concentration at 20%, 50%, 80%
ECG
electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
eg, e.g. 
exempli gratia (for example)
ESR
Expedited Safety Report
ESRD
end-stage renal disease
F
bioavailability
FIH
First in human
FDA
Food and Drug Administration
FSH
follicle stimulating hormone
fu
fraction of unbound drug
FXI
Factor XI
FXIa
Factor XIa
Revised Protocol No.: 03
Date: 06-Sep-2017
55
627
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
FXIc
Factor XI clotting activity
g
gram
GC
gas chromatography
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
h
hour
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HCO3-
bicarbonate
HD
hemodialysis
HIT
heparin-induced thrombocytopenia
HIV
Human Immunodeficiency Virus
HR
heart rate
HRT
hormone replacement therapy
IB
investigator brochure
ICD
International Classification of Diseases
ICH
International Conference on Harmonisation 
ie, i.e.
id est (that is)
IEC
Independent Ethics Committee
IMP
investigational medicinal products
IND
Investigational New Drug Exemption
INR
international normalized ratio
IRB
Institutional Review Board
IU
International Unit
IUD
intrauterine devices
IV, I.V.
intravenous
K
slope of the terminal phase of the log concentration-time curve
K3EDTA
potassium ethylenediaminetetraacetic acid
K+
potassium
Revised Protocol No.: 03
Date: 06-Sep-2017
56
628
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Ki
inhibition constant
kg
kilogram
Kt/V
Number used to quantify hemodialysis and peritoneal dialysis treatment
adequacy. Assessment includes: pre-dialysis blood BUN, post-dialysis 
blood BUN, ultrafiltration volume, post-dialysis body weight, duration of 
dialysis session.
L
liter
LAM
lactation amenorrhea method
LC
liquid chromatography
LDH
lactate dehydrogenase
LFTs
liver function tests
LMWH
low molecular weight heparin
MAD
multiple ascending dose
mg
milligram
Mg++
magnesium
min
minute
mL
milliliter
mmHg
millimeters of mercury
MR
medical research
MS
mass spectrometry
g
microgram
N
number of subjects or observations
Na+
sodium
N/A, NA 
not applicable
ng
nanogram
NIMP
non-investigational medicinal products 
NOAEL
no-observed-adverse-effect-level
NSAID
nonsteroidal anti-inflammatory drug
P2Y12
Gi class of a group of G protein-coupled (GPCR) purinergic receptors 
and is a chemoreceptor for adenosine diphosphate (ADP)
PD
pharmacodynamics
Revised Protocol No.: 03
Date: 06-Sep-2017
57
629
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
PID
patient identification number
PK
pharmacokinetics
PO
per os (by mouth route of administration)
PT
prothrombin time
PTT
partial thromboplastin time
QC
quality control
QD, qd
quaque die, once daily
RATIO
Risk of Arterial Thrombosis In relation to Oral contraceptives
RBC
red blood cell
SAD
single ascending dose
SAE
serious adverse event
SC
subcutaneous
SD
standard deviation
SDD
spray dry dispersion
SOA
schedule of activities
SOC
standard of care
SOP
Standard Operating Procedures
t
temperature
T
time
TAO
Trial Access Online, the BMS implementation of an EDC capability
T-HALF 
Half life
TID, tid
ter in die, three times a day
Tmax, TMAX 
time of maximum observed concentration
UFH
unfractionated heparin
ULN
upper limit of normal
WBC
white blood cell
WHO
World Health Organization
WOCBP
women of childbearing potential
WNOCBP 
women 
of childbearing potential
x g
times gravity
Revised Protocol No.: 03
Date: 06-Sep-2017
58
630
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
The  term  ‘Participant’  is  used  in  the  protocol  to  refer  to  a  person  who  has  consented  to 
participate  
in  
the  clinical  
research  study.  
  The  
term  
‘Subject’  used  
in  
the  eCRF  
is  
intended  
to 
refer to a person (Participant) who has consented to participate in the clinical research study.
This study will be conducted in accordance with:
Good Clinical Practice (GCP), 
as defined by the International Council on Harmonisation (ICH)
in  accordance  with  the  ethical  principles  underlying  European  Union  Directive 
2001/20/EC
United States Code of Federal Regulations, Title 21, Part 50 (21CFR50) 
applicable local requirements.
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and  the  participant informed  consent  will  receive  approval/favorable  opinion  by  Institutional 
Review Board/Independent Ethics Committee (IRB/IEC), and regulatory authorities according to 
applicable local regulations prior to initiation of the study.
All potential  serious  breaches  must be reported to Sponsor or designee  
immediately.  A  serious
breach  
is a  breach of the conditions and principles of GCP  
in connection with the study or the 
protocol,  which  is  likely  to  affect,  to  a  significant  degree,  the  safety  or  physical  or  mental 
integrity of the subjects of the study or the scientific value of the study.
Personnel  involved  in  conducting  this  study  will  be  qualified  by  education,  training,  and 
experience to perform their respective tasks.
This  study  will  not  use  
the  services  of  study  personnel  where  sanctions  have  been  
invoked  or 
where there has been scientific misconduct or fraud (e.g., loss of medical licensure, debarment). 
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from  the  IRB/IEC  for  the  protocol,  consent  form,  participant recruitment  materials  (e.g., 
advertisements), and any other written information to be provided to subjects. The investigator or 
BMS  should  also  provide  the  IRB/IEC  with  a  copy  of  the  Investigator  Brochure  or  product 
labeling information to be provided to subjects and any updates. 
The  investigator,  Sponsor  or  designee  should  provide  the  IRB/IEC  with  reports,  updates  and 
other  information  (e.g.,  expedited  safety  reports,  amendments,  and  administrative  letters) 
according to regulatory requirements or institution procedures.
Revised Protocol No.: 03
Date: 06-Sep-2017
59
631
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
The  investigator  should  not  implement  any  deviation  or  change  to  
the  protocol  without  prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and if 
applicable,  also  by  local  health  authority) except  where  necessary  to eliminate  an  immediate 
hazard(s) to study subjects. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior 
to obtaining relevant  approval/favorable opinion(s) the deviation or change will be submitted, as 
soon as possible to:
IRB/IEC for 
Regulatory Authority(ies), if applicable by local regulations (per national requirements)
Documentation  of  approval/favorable  opinion  signed  by  the  chairperson  or  designee  of  the 
IRB(s)/IEC(s) and if applicable, also by local health authority must be sent to BMS.
If  an  amendment  substantially  alters  the  study  design  or  increases  the  potential  risk  to  the 
participant: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review 
and  approval/favorable  opinion;  (2)  the  revised  form  must  be  used  to  obtain  consent  from 
subjects currently enrolled  
in the study  
if they  are affected by the amendment; and (3) the new 
form must be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
Investigators  and  sub-Investigators  will provide  
the  Sponsor  with  sufficient,  accurate  
financial 
information  
in  accordance with  
local  
regulations  
to allow  
the  Sponsor  
to  submit  complete  and 
accurate  financial  certification  or  disclosure  statements  to  the  appropriate  health  authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study.
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate. 
In situations where consent cannot be given to subjects, their legally acceptable representatives 
(as per country guidelines) are clearly and fully informed about the purpose, potential risks, and 
other critical issues regarding clinical studies in which the participant volunteers to participate. 
Sponsor  or  designee  will  provide  the  investigator  with  an  appropriate  (i.e.,  Global  or  Local) 
sample informed  consent  form  which  will  include  all  elements  required  by  ICH,  GCP  and 
applicable regulatory requirements. The sample informed consent form will adhere to the ethical 
principles that have their origin in the Declaration of Helsinki.
Investigators must:
Revised Protocol No.: 03
Date: 06-Sep-2017
60
632
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Provide  a  copy  of  the  consent  form  and  written  information  about  the  study  in  the 
language  
in which the participant is  most proficient prior to clinical  study participation. 
The language must be non-technical and easily understood. 
Allow time  necessary  
for participant or participant's  
legally acceptable representative to 
inquire about the details of the study.
Obtain  an  informed  consent  signed  and  personally  dated  by  the  participant or  the 
participant's  legally  acceptable  representative  and  by  the  person  who  conducted  the 
informed consent discussion. 
Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent 
form and any other information to be provided to the subjects, prior to the beginning of 
the study, and after any revisions are completed for new information.
If informed consent is initially given by a participant’s legally acceptable representative or legal 
guardian, and the participant subsequently becomes capable of making and communicating his or 
her  informed  consent  during  the  study,  consent  must  additionally  be  obtained  from  the 
participant.
Revise  the  informed  consent  whenever  important  new  information becomes  available  that  is 
relevant to the participant's consent. The investigator, or a person designated by the investigator, 
should  
fully  
inform the participant or the participant's  
legally acceptable representative or legal 
guardian,  of  all  pertinent  aspects  of  the  study  and  of  any  new information  relevant  to  the 
participant's  willingness  
to  continue  participation  
in  
the  study.  This  communication  should  be 
documented. 
The  confidentiality  of  records  that  could  identify  subjects  must  be  protected,  respecting  the 
privacy and confidentiality rules applicable to regulatory requirements, the subjects
' signed ICF 
and, in the US, the subjects’ signed HIPAA Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to participant records. 
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
The  Investigator  is  responsible  for  ensuring  that  the  source  data  are  accurate,  legible, 
contemporaneous,  original  and  attributable,  whether  the  data  are  hand-written  on  paper  or 
entered electronically. If source data are created (first entered), modified, maintained, archived, 
retrieved,  or  transmitted  electronically  via  computerized  systems  (and/or  any  other  kind  of 
electronic devices) as part of regulated clinical trial  activities, such  systems  must be compliant 
with  all  applicable  laws  and  regulations  governing  use  of  electronic  records  and/or  electronic 
signatures.  Such  systems  may  
include,  but  are  not  
limited  
to,  electronic  medical/health  
records 
Revised Protocol No.: 03
Date: 06-Sep-2017
61
633
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
(EMRs/EHRs),  adverse  event  tracking/reporting,  protocol  required  assessments,  and/or  drug 
accountability records).
When  paper  records  from  such  systems  are  used  in  place  of  electronic  format  to  perform 
regulated activities, such paper records should be certified copies. A certified copy consists of a 
copy of original information that has been verified, as indicated by a dated signature, as an exact 
copy having all of the same attributes and information as the original. 
Records  for  study  treatments (whether  supplied  by  BMS,  its  vendors,  or  the  site)  must 
substantiate  study  
treatment integrity  and  
traceability  
from  
receipt,  preparation,  administration, 
and through destruction or return. Records must be  made available  
for review at the request of 
BMS/designee or a Health Authority.
Supplied by BMS (or its vendors):
Records or logs must comply with applicable 
regulations  and  guidelines  and  should 
include:
amount received and placed in storage 
area
amount currently in storage area
label identification number or batch 
number
amount dispensed to and returned by each 
participant, including unique participant
identifiers
amount transferred to another area/site for 
dispensing or storage
nonstudy disposition (e.g., lost, wasted) 
amount destroyed at study site, if 
applicable
amount returned to BMS
retain samples for 
bioavailability/bioequivalence, if 
applicable 
dates and initials of person responsible for 
Investigational Product 
dispensing/accountability, as per the 
Delegation of Authority Form.
Sourced by site, and not supplied by BMS or 
its  vendors  (examples  include  IP  sourced 
from the sites stock or commercial supply, or 
The  investigator  or  designee  accepts 
responsibility  for  documenting  traceability 
and  study  drug  integrity  in  accordance  with 
requirements  applicable  under  law  and  the 
Revised Protocol No.: 03
Date: 06-Sep-2017
62
634
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
a specialty pharmacy)
SOPs/standards of the sourcing pharmacy.   
These records should include:
label identification number or batch 
number 
amount dispensed to and returned by each 
participant, including unique participant
identifiers
dates and initials of person responsible for 
Investigational Product 
dispensing/accountability, as per the 
Delegation of Authority Form.
BMS  or  designee  will  provide forms  to  facilitate inventory  control  if  the  investigational  site  does not  have  an 
established system that meets these requirements.
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or  entered  as  a  control  
in  
the  
investigation.  Data  
that  are  derived  from  source  documents  and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities
that are reported or identified during the course of the study.
For  sites  using  the  Sponsor  or  designee electronic  data  capture tool,  electronic  CRFs  will  be 
prepared  
for  all  data  collection  
fields  except  
for fields  specific  
to  SAEs  and  pregnancy,  which 
will  be reported on the electronic SAE form and Pregnancy Surveillance form, respectively.  If 
electronic SAE form is not available, a paper SAE form can be used. Spaces may be left blank 
only in those circumstances permitted by study-specific CRF completion guidelines provided by 
Sponsor or designee.
The  confidentiality  of  records  that  could  identify  subjects  must  be  protected,  respecting  the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The  completed  CRF,  SAE/pregnancy CRFs,  must  be promptly  
reviewed,  signed,  and  dated  by 
the investigator or qualified physician who is a subinvestigator and who is delegated this task on 
the  Delegation  of  Authority  Form.  Subinvestigators  in  Japan  may  not  be  delegated  the  CRF 
approval  For  electronic  CRFs,  review  and  approval/signature  is completed  electronically 
through the BMS electronic data capture tool. The investigator must retain a copy of the CRFs 
including records of the changes and corrections.
Revised Protocol No.: 03
Date: 06-Sep-2017
63
635
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Each  
individual electronically signing electronic  CRFs  must  meet Sponsor or designee training 
requirements and  must only  access the BMS electronic data capture tool using the unique user 
account  provided  by  Sponsor or  designee.  User  accounts  are  not to  be  shared  or  
reassigned  
to 
other individuals
Sponsor  or  designee representatives  will  review  data  centrally  to  identify  potential  issues  to 
determine a schedule of on-site visits for targeted review of study records. 
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data  quality  and  study  integrity.  On  site  
they  will  review  study  records  and  directly  compare 
them with source documents, discuss the conduct of the study with the  
investigator, and verify 
that the  
facilities remain acceptable Certain CRF pages and/or electronic  
files  may  serve as the 
source documents:
In addition, the study may be evaluated by Sponsor or designee internal auditors and government 
inspectors who must be allowed access to CRFs, source documents, other study files, and study 
facilities. BMS audit reports will be kept confidential.
The  investigator  must  notify  BMS  promptly  of  any  inspections  scheduled  by  regulatory 
authorities, and promptly forward copies of inspection reports to Sponsor or designee.
The  investigator  (or  head  of  
the  study  site  in  Japan)  must  retain  all  study  records  and  source 
documents  for  the  maximum  period  required  by  applicable  regulations  and  guidelines,  or 
institution procedures, or for the period specified by BMS or designee, whichever is longer. The 
investigator  (or  head  of  the  study  site  in  Japan)  must  contact BMS  prior  to  destroying  any 
records associated with the study.
BMS or designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed.
If  
the  
investigator  withdraws  from  
the  study  
(e.g.,  
relocation,  
retirement),  
the  
records  shall  be 
transferred  to  a  mutually  agreed  upon designee  (e.g.,  another investigator,  study  site,  IRB). 
Notice of such transfer will be given in writing to BMS or designee. 
For this study, study treatments (those supplied by BMS, a vendor or sourced by the investigator) 
such as partially used study treatment containers, vials and syringes may be destroyed on site. 
If..
Then
Study treatments supplied by BMS (including 
its vendors
Any  unused  study  treatments  supplied  by 
BMS  can  only  be  destroyed  after  being 
inspected  and  reconciled  by  the  responsible 
Study  Monitor  unless  study  treatments 
containers  must  be  
immediately  destroyed  as 
Revised Protocol No.: 03
Date: 06-Sep-2017
64
636
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
required  for  safety,  or  to  meet  local 
regulations (e.g., cytotoxics or biologics).
If study treatments will be returned, the return 
will  be  arranged  by  the  responsible  Study 
Monitor.
Study treatments sourced by site, not supplied 
by  BMS  (or  its  vendors)  (examples  include 
study treatments sourced from the  sites  stock 
or  commercial  supply,  or  a  specialty 
pharmacy)
It  is  the  investigator’s  or  designee’s 
responsibility  to  dispose  of  all  containers 
according  to  the  institutional  guidelines  and 
procedures.
It  is  the  investigator’s  or  designee’s  responsibility  to  arrange  for  disposal,  provided  that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept. The following minimal standards must be met:
On-site disposal practices must not expose humans to risks from the drug.
On-site  disposal  practices  and  procedures  are  in  agreement  with  applicable  laws  and 
regulations, including any special requirements for controlled or hazardous substances.
Written procedures for on-site disposal are available and followed. The procedures must 
be filed with the site’s SOPs and a copy provided to BMS upon request.
Records  are  maintained  
that  allow  
for  
traceability  of  each  container,  
including  
the  date 
disposed of, quantity disposed, and identification of the person disposing the containers. 
The  method  of  disposal,  i.e.,  incinerator,  licensed  sanitary  landfill,  or  licensed  waste 
disposal vendor must be documented.
Accountability  and  disposal  records  are  complete,  up-to-date,  and  available  for  the 
Monitor to review throughout the clinical trial period.
It is the investigator’s or designee’s responsibility to arrange for disposal of all empty containers.
If  conditions  for  destruction  cannot  be  met  the  responsible  Study  Monitor  will  make 
arrangements  for  
return  of  study  
treatments  provided  by  BMS  
(or  
its  vendors).  Destruction  of 
non- study treatments sourced by the site, not supplied by BMS, is solely the responsibility of the 
investigator or designee.
It is however, the investigator’s or designee’s responsibility to arrange for disposal of all empty 
study  
treatment  containers, provided  
that procedures  
for  proper  disposal  have  been  established 
according  to  applicable  federal, state,  local,  and  institutional  guidelines  and  procedures,  and 
provided that appropriate records of disposal are kept. The return of full or partially used study 
treatments supplied by BMS or its vendors will be arranged by the responsible Study Monitor.
Revised Protocol No.: 03
Date: 06-Sep-2017
65
637
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
A Signatory Investigator must be selected to sign the clinical study report. 
For  this  protocol,  the  Signatory  Investigator  will  be  selected as  appropriate  based  on  the 
following criteria:
External Principal Investigator designated at protocol development
Participant recruitment (e.g., among the top quartile of enrollers)
Involvement in trial design
Other criteria (as determined by the study team)
The data collected during this study are confidential and proprietary to Sponsor or designee. Any 
publications or abstracts arising from this study must adhere to the publication requirements set 
forth in the clinical trial agreement (CTA) governing [Study site or Investigator] participation in 
the study. These requirements include, but are not limited to, submitting proposed publications to 
Sponsor  or  designee  at  the  earliest  practicable  time  prior  to  submission  or  presentation  and 
otherwise within the time period set forth in the CTA.
Revised Protocol No.: 03
Date: 06-Sep-2017
66
638
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting  medical  condition  in  a  clinical  investigation  participant administered  study  drug 
and that does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of study drug, whether or not 
considered related to the study drug.
Revised Protocol No.: 03
Date: 06-Sep-2017
67
639
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Results in death
Is life-threatening (defined as an event in which the participant was at risk of death at the time 
of the event;  
it does not refer to an event which  hypothetically  might have caused death  
if  
it 
were more severe)
Requires  inpatient  hospitalization  or  causes  prolongation  of  existing  hospitalization  (see 
NOTE below)
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies: 
a  visit  
to  
the  emergency  room  or  other  hospital  department  <  24  hours,  
that 
does  not  
result  
in  admission  
(unless  considered  an  
important  medical  or  
life-
threatening event)
elective surgery, planned prior to signing consent
admissions as per protocol for a planned medical/surgical procedure
routine  health  assessment  requiring  admission  for  baseline/trending  of  health 
status (e.g., routine colonoscopy)
medical/surgical admission other than to remedy ill health and planned prior to 
entry into the study. Appropriate documentation is required in these cases
admission encountered for another life circumstance that carries no bearing on 
health  status  and  requires  no medical/surgical  intervention  (e.g.,  lack  of 
housing,  economic  inadequacy,  caregiver  respite,  family  circumstances, 
administrative reason)
admission for administration of anticancer therapy in the absence of any other 
SAEs (applies to oncology protocols)
Results in persistent or significant disability/incapacity
Is a congenital anomaly/birth defect
Revised Protocol No.: 03
Date: 06-Sep-2017
68
640
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
is an important medical event (defined as a medical event(s) that may not be immediately life-
threatening  or  result  in  death  or  hospitalization  but,  based  upon  appropriate  medical  and 
scientific judgment, may jeopardize the participantor may require intervention [e.g., medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above.) Examples 
of such events include, but are not limited to, intensive treatment in an emergency room or at 
home  for  allergic  bronchospasm;  blood  dyscrasias  or  convulsions  that  do  not  result  in 
hospitalization.)  Potential  drug  induced  liver  injury  (DILI)  is  also  considered  an  important 
medical event. (See Section 8.1.1 for the definition of potential DILI.) 
Suspected transmission of an infectious agent (e.g., pathogenic or nonpathogenic) via the study 
treatment is an SAE. 
Although  pregnancy,  overdose,  cancer,  and  potential  drug  induced  liver  injury  (DILI)  are  not 
always  serious  by  regulatory  definition,  these  events  must  be  handled  as  SAEs.  (See Section 
9.2.5for reporting pregnancies).
Any component of a study endpoint that is considered related to study therapy should be reported 
as  SAE  
(e.g.,  death  
is  an  endpoint,  
if  death  occurred  due  
to  anaphylaxis,  anaphylaxis  must  be 
reported).
The causal relationship to study drug is determined by a physician and should be used to 
assess all adverse events (AE). The causal relationship can be one of the following:
Related:  There  is  a  reasonable causal  relationship  between  study  drug 
administration and the AE.
Not  related:  There  is  not  a  reasonable  causal  relationship  between  study  drug 
administration and the AE. 
The  
term  "reasonable  causal  relationship"  means  
there  is  evidence  
to  suggest  a  causal 
relationship. 
If  only  
limited  
information  
is  
initially  available,  follow-up  
reports  are  
required.  
(Note: 
Follow-up SAE reports must include the same investigator term(s) initially reported.) 
If  an  ongoing  SAE  changes  in  its  intensity  or  relationship  to  study  drug  or  if  new 
information becomes available, the SAE report must be updated and submitted within 24 
hours  
to  BMS (or  designee)  using  
the  same  procedure  used  for  
transmitting  
the  
initial 
SAE report.
Revised Protocol No.: 03
Date: 06-Sep-2017
69
641
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
All SAEs must be followed to resolution or stabilization.
SAEs,  whether  related  or  not  related  to  study drug,  and  pregnancies  must  be 
reported to BMS (or designee) within 24 hours of awareness of the event.
SAEs  must  be  
recorded  on  
the  SAE  Report  Form;  pregnancies  on  a Pregnancy 
Surveillance Form (electronic or paper forms).
The preferred method for SAE data reporting collection is through the eCRF.
The  paper  SAE/pregnancy  surveillance  forms  are  only  intended  as  a  back-up 
option when the eCRF system is not functioning.
In this case, the paper forms are to be transmitted via email or confirmed 
facsimile (fax) transmission to:
For studies capturing SAEs through electronic data capture (EDC), electronic submission 
is the required method for reporting. In the event the electronic system is unavailable for 
transmission, paper forms must be used and submitted immediately.  When paper  
forms 
are used, the original paper forms are to remain on site.
(required for SAE and pregnancy reporting): Refer to Contact 
Information list
Revised Protocol No.: 03
Date: 06-Sep-2017
70
642
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
A woman  
is considered  
fertile  
following  menarche and until  becoming post-menopausal unless 
permanently  sterile.  Permanent  sterilization  methods  include  hysterectomy,  bilateral 
salpingectomy, and bilateral oophorectomy.
Premenarchal
Premenopausal female with 1 of the following:
Documented hysterectomy
Documented bilateral salpingectomy
Documented bilateral oophorectomy
Note: Documentation  can  come  from  
the  site  personnel’s  
review  of  
the  participant’s  medical 
records, medical examination, or medical history interview.
Postmenopausal female
A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 45 
years  in  the  absence  of  other  biological or  physiological  causes.  In  addition,  females 
under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level > 
40 mIU/mL to confirm menopause.
Note: Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed  FSH  
levels and  may require a washout period  
in order to obtain a physiologic  FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the  washout  period  below  are  suggested  guidelines  and  the  investigators  should  use  their 
judgement in checking serum FSH levels. 
1 week minimum for vaginal hormonal products (rings, creams, gels)
4 week minimum for transdermal products
8 week minimum for oral products
Other parenteral products may require washout periods as  
long as 6  months. If the serum  FSH 
level  is  >  40  mIU/ml  at  any  time  during  the  washout  period,  the  woman  can  be  considered 
postmenopausal.
Any  one  of  the  approved  methods  of  contraception  (highly  effective  and/or  less  than  highly 
effective)  listed  below  is  required  during  study  duration  plus 5 half-lives of study treatment
Revised Protocol No.: 03
Date: 06-Sep-2017
71
643
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
BMS-986177 (2  days)  plus  30  days  
(duration  of  ovulatory  cycle)  for  a  
total  of  32  days  post-
treatment completion or after treatment has been discontinued.
Local  laws  and  regulations  may  require  use  of  alternative  and/or  additional  contraception 
methods.
a
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of 
ovulationb 
− oral 
− intravaginal 
− transdermal 
Progestogen-only hormonal contraception associated with inhibition of ovulation
b 
− oral 
− injectable 
Implantable progestogen-only hormonal contraception associated with inhibition of ovulation b
Intrauterine device (IUD)
c
Intrauterine hormone-releasing system (IUS)
c
Bilateral tubal occlusion
Vasectomized partner 
Sexual abstinence 
It is not necessary to use any other method of contraception when complete abstinence is elected. 
WOCBP participants who choose complete abstinence must continue to have pregnancy tests, as specified in 
Section 2. 
Acceptable alternate methods of highly effective contraception must be discussed in the event that the 
WOCBP participants chooses to forego complete abstinence 
Male  or  female  condom  with  or  without  spermicide.    Male  and  female  condoms  cannot  be  used 
simultaneously
Diaphragm with spermicide
Cervical cap with spermicide
Vaginal Sponge with spermicide
Revised Protocol No.: 03
Date: 06-Sep-2017
72
644
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Progestogen-only oral hormonal contraception, where inhibition of  ovulation is not the primary mechanism 
of action
Periodic abstinence (calendar, symptothermal, post-ovulation methods)
Withdrawal(coitus interruptus).
Spermicide only
Lactation amenorrhea method (LAM)
NOTES: 
a
Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for participants participating in 
clinical studies. 
b
Hormonal contraception may be susceptible to interaction with the study treatment, which may reduce the 
efficacy of the contraceptive method.  Hormonal contraception is permissible only when there is sufficient 
evidence that the IMP and other study medications will not alter hormonal exposures such that contraception 
would be ineffective or result in increased exposures that could be potentially hazardous.  In this case, hormonal
methods of contraception can be utilized. 
c
Intrauterine devices and intrauterine hormone releasing systems are acceptable methods of contraception in 
the absence of definitive drug interaction studies when hormone exposures from intrauterine devices do not alter 
contraception effectiveness
Male participants with female partners of childbearing potential are eligible to participate if they 
agree to the following during the treatment and until the end of relevant systemic exposure.
Inform  any  and  all  partner(s)  of  
their  participation  
in  a  clinical  drug  study  and  
the  need  
to 
comply with contraception instructions as directed by the investigator.
Male  participants  are  required  to  use  a  condom  for  study  duration  and  until  the  end  of 
relevant  systemic  exposure  defined  as  2  days after  the  end  of  treatment  in  the  male 
participant with amendment/revised protocol 02 (See Section 6.1 Inclusion Criteria).
Female partners of  males participating  
in the  study to consider use of effective  methods of 
contraception (see Table 1-1) until the end of relevant systemic exposure, defined as 2 days
after the end of treatment in the male participant.
Male  participants  with  a  pregnant  or  breastfeeding  partner  must  agree  
to  
remain  abstinent 
from  penile  vaginal  intercourse  or  use  a  male  condom  during  each  episode  of  penile 
penetration during the treatment and until 2 days after the end of treatment. 
Refrain from donating sperm for the duration of the study treatment and for 2 days after the 
end of treatment with amendment/revised protocol 02 (See Section 6.1 Inclusion Criteria).
Revised Protocol No.: 03
Date: 06-Sep-2017
73
645
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Guidance for collection of Pregnancy Information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 9.2.5 and the Appendix for Adverse Events and Serious 
Adverse Events Definitions and procedures for Evaluating, Follow-up and Reporting.
Revised Protocol No.: 03
Date: 06-Sep-2017
74
646
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
75
647
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
76
648
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
77
649
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
78
650
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
79
651
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
80
652
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
81
653
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
82
654
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
83
655
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
84
656
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
85
657
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
86
658
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Revised Protocol No.: 03
Date: 06-Sep-2017
87
659
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
The following is taken from DSM-IV:
Diagnostic Criteria for Psychoactive Substance Dependence
A maladaptive pattern of substance use, leading to clinically significant impairment or distress as 
manifested  by  
three  (or  more)  of  
the  following,  occurring  at  any  
time  in  
the  same  12-month 
period:
1. Tolerance, as defined by either of the following:
a) A  need  for  markedly  increased  amounts  of  the  substance  to  achieve  intoxication  or 
desired effect,
b) Markedly diminished effect with continued use of the same amount of the substance.
2. Withdrawal, as manifested by either of the following:
a) The characteristic withdrawal syndrome for the substance,
b) The  same  (or  closely  related)  substance  is  taken  to  relieve  or  avoid  withdrawal 
symptoms.
3. The substance is often taken in larger amounts or over a longer period than was intended.
4. There is a persistent desire or unsuccessful efforts to cut down or control substance use.
5. A  great  deal  of  time  is  spent  in  activities  necessary  to  obtain  the  substance  (eg, visiting 
multiple doctors or driving long distances), use the substance (eg, chain-smoking) or recover 
from its effects.
6. Important  social,  occupational  or  
recreational  activities  are  given  up  or  
reduced  because  of 
substance use.
7. The  substance  use  is  continued  despite  knowledge  of  having  a persistent  or  recurring 
physical  or  psychological  problem  
that  
is  
likely  
to  have  been  caused  or  exacerbated  by  
the 
substance  (eg, current  cocaine  use  despite  recognition  of  cocaine-induce  depression,  or 
continued  drinking  despite  recognition  that  an  ulcer  was  made  worse  by  alcohol 
consumption.)
Criteria for Severity of Psychoactive Substance Dependence:
Mild:    Few,  if  any,  symptoms  in  excess  of  those  required  to  make  the  diagnosis,  and  the 
symptoms result in no more than mild impairment in occupational functioning or in usual social 
activities or relationships with others.
Moderate:  Symptoms or functional impairment between “mild” and “severe”.
Severe:  Many symptoms in excess of those required to make the diagnosis, and the symptoms 
markedly  
interfere with occupational  
functioning  or with usual social activities or relationships 
with others.
In  Partial  Remission:    During  the  past  six  months,  some  use  of the  substance  and  some 
symptoms of dependence.
Revised Protocol No.: 03
Date: 06-Sep-2017
88
660
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
In  Full  Remission:  
  During  
the  past  six  months,  either  no  use  of  
the  substance,  or  use  of  
the 
substance and no symptoms of dependence.
Diagnostic Criteria for Psychoactive Substance Abuse
A. A  maladaptive  pattern  of  psychoactive  substance  use,  leading to  clinically  significant 
impairment or distress as manifested by one (or more) of the following, occurring at any time 
in the same 12-month period:
1. Recurrent  substance  use  resulting  in  a  failure  
to  
fulfill  major  role  obligations  at  work, 
school, or home (e.g., repeated absences or poor work performance related to substance 
use;  substance-related  absences,  suspensions,  or  expulsions  from  school,  neglect  of 
children or household).
2. Recurrent substance use  
in  situations  
in which  
it  
is physically  hazardous (eg, driving an 
automobile or operating a machine when impaired by substance use).
3. Recurrent  substance-related  legal  problems  (eg, arrests  for  substance-related  disorderly 
conduct).
4. Continued  substance  use  despite  having  persistent  or  recurrent  social  or  interpersonal 
problems  caused  or exacerbated  by  the  effects  of  the  substance (eg, arguments  with 
spouse about consequences of intoxication, physical fights).
B. The  symptoms  have  never  met  the  criteria  for  substance  dependence  for  this  class  of 
substance.
Revised Protocol No.: 03
Date: 06-Sep-2017
89
661
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
 
 
 
 
 
 
Title Page
Updated study director/medical 
monitor.
2 Schedule of 
Activities (SOA)
Duplicate row for pregnancy 
test was deleted and the Day 8 
pregnancy test was moved to 
Day 13 to 15/Study Discharge 
column and clarified for 
WOCBP only. Clarified vital 
signs, stool occult blood, whole 
blood for genotyping/ADME, 
and SAEs.
2 SOA and 9.4.4 
Clinical Safety 
Laboratory 
Assessments
Clarified urine dipstick for 
blood only if the participant is 
able to produce urine. Clarified 
that the pregnancy test is for 
WOCBP only.
2 Schedule of 
Activities (SOA)
5.1 Overall 
Design
Updated the screening window 
from 21 days to 28 days.
5.2 Number of 
Participants
Clarified the target sample size 
of 32 participants is to achieve 
24 participants who complete 
the 4 study treatments.
Revised Protocol No.: 03
Date: 06-Sep-2017
90
662
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
6.2 Exclusion 
Criteria
Clarify prior aspirin use to at 
least 1 week before dosing in 
exclusion criteria 2a. Updated 
duration contraceptive methods 
to be used for men in exclusion 
criteria 3e.
7.7.1 Prohibited 
and/or Restricted 
Treatments
Clarify concomitant use of 
NSAIDS or aspirin to within 1 
week prior to study drug 
administration. Also allow the 
use of topical antifungals.
9.5 
Pharmacokinetics Extraction ratio was deleted
9.7.1 Genotyping 
and ADME 
Sampling
Clarify that whole blood 
sample to be drawn at baseline 
for dosed participants.
Appendix 4 
WOCBP 
Definitions and 
Methods of 
Contraception
Requirements for WOCBP 
participants to use one highly 
effective and/or one less 
effective method of 
contraceptive has been added. 
Duration of contraceptive 
methods for males has been 
updated to align with updating 
exclusion criteria 3e.
Title Page
Updated study director/medical 
monitor.
2 Schedule of 
Activities (SOA)
Duplicate row for pregnancy 
test was deleted and the Day 8 
pregnancy test was moved to 
Day 13 to 15/Study Discharge 
column and clarified for 
WOCBP only. Clarified vital 
signs, stool occult blood, whole 
blood for genotyping/ADME, 
and SAEs.
Revised Protocol No.: 03
Date: 06-Sep-2017
91
663
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
2 SOA and 9.4.4 
Clinical Safety 
Laboratory 
Assessments
Clarified urine dipstick for 
blood only if the participant is 
able to produce urine. Clarified 
that the pregnancy test is for 
WOCBP only.
Clarification added based on feedback 
from a site that many of the end stage 
renal disease patients (ESRD) are 
unable to produce urine.
2 Schedule of 
Activities (SOA)
5.1 Overall 
Design
Updated the screening window 
from 21 days to 28 days.
Being a hemodialysis patient study, 
flexible in the screening period is 
needed to schedule the study with the 
participant’s hemodialysis schedule.
5.2 Number of 
Participants
Clarified the target sample size 
of 32 participants is to achieve 
24 participants who complete 
the 4 study treatments.
It was not intended to achieve 24 
evaluable participants as previously 
written which would be those who 
received 1 dose of study drug.
6.2 Exclusion 
Criteria
Clarify prior aspirin use to at 
least 1 week before dosing in 
exclusion criteria 2a. Updated 
duration contraceptive methods 
to be used for men in exclusion 
criteria 3e.
Updated based on review of screen 
failures and the change will not likely 
impact the study assessment or patient 
safety. Definitive embryo-fetal 
development (EFD) studies have been 
completed and findings from these 
studies indicate that BMS-986177 is 
non-terogenic and non-genotoxic.
7.7.1 Prohibited 
and/or Restricted 
Treatments
Clarify concomitant use of 
NSAIDS or aspirin to within 1 
week prior to study drug 
administration. Also allow the 
use of topical antifungals.
Updated based on review of screen 
failures. These changes will not likely 
impact the study assessment or patient 
safety.
9.5 
Pharmacokinetics Extraction ratio was deleted
It was a duplication to %DR (Percent 
dose of BMS-986177 recovered in 
dialysate %).
9.7.1 Genotyping 
and ADME 
Sampling
Clarify that whole blood 
sample to be drawn at baseline 
for dosed participants.
To make this consistent with Section 2 
Schedule of Activities (SOA).
Appendix 4 
WOCBP 
Definitions and 
Methods of 
Contraception
Requirements for WOCBP 
participants to use one highly 
effective and/or one less 
effective method of 
contraceptive has been added. 
Duration of contraceptive 
Appendix has been updated to reflect 
the latest protocol model template. 
Definitive embryo-fetal development 
(EFD) studies have been completed and 
findings from these studies indicate that 
BMS-986177 is non-terogenic and non-
Revised Protocol No.: 03
Date: 06-Sep-2017
92
664
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
methods for males has been 
updated to align with updating 
exclusion criteria 3e.
genotoxic.
Revised Protocol No.: 03
Date: 06-Sep-2017
93
665
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
 
 
 
 
 
Section 3.3: 
Benefit/Risk 
Assessment
Safety data was updated from 
FIH SAD/MAD study 
(CV010001). Also, the safety 
data from the HD PK study 
(CV010012) was added.
Section 5.1: 
Overall Design
BMS dose 1 and BMS dose 2 
were updated to be BMS-
986177 100 mg and BMS-
986177 300 mg, respectively.
Other minor changes made in 
this section.
Section 5.5: 
Justification for 
Dose
Updated targeted exposures 
based on hemodialysis PK 
study to support the BMS 
dose 1 (100 mg) and BMS 
dose 2 (300 mg)
Section 6.2: 
Exclusion Criteria
and Section 6.3: 
Lifestyle 
Restrictions
Exclusion criteria 1a, 1d, 1i, 
1n, 3b, and 3e were clarified. 
Exclusion criterion 2b was 
added. Restrictions were 
updated.
Section 7: 
Treatment
BMS-986177 100 mg and 300 
mg (to replace BMS dose 1 
and dose 2) were added to 
Table 7.-1 and Table 7.1-1.
Section 7.2: 
Method of 
Treatment 
Reference to IRT was 
removed.
Revised Protocol No.: 03
Date: 06-Sep-2017
94
666
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


Clinical Protocol
CV010010
BMS-986177
FXIa
Assignment and 
Section 7.3: 
Blinding
Section 7.7.1: 
Prohibited and/or 
Restricted 
Treatments
Prohibited/restricted 
treatments were updated.
Section 8.1: 
Discontinuation 
from Study 
Treatment
Updated the discontinuation 
criteria on events of complete 
clotting of hemodialysis 
circuit to include enoxaparin 
treatment arm and 5 or more 
patients.
Section 9.5: 
Pharmacokinetics
Updates to further clarify 
Table 9.5-1 were made.
Section 9.6: 
Pharmacodynami
cs
Updates to further clarify 
Table 9.6-1 and Table 9.6-2 
were made.
Section 9.8: 
Biomarker
Updates to further clarify 
Table 9.8-1 and Table 9.8-2 
were made. Also, to remove 
clotting assessment from the 
blood line and URR. Kt/V 
assessment was further 
clarified.
All
Minor formatting and 
typographical corrections. 
One additional reference was 
added. Additional 
abbreviations were added to 
Appendix 1.
Revised Protocol No.: 03
Date: 06-Sep-2017
95
667
Final Clinical Study Report
MS- 86177
CV010010
Factor XIa In
________________________
____
________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v



SAP_003.pdf: 
Official Title of Study: 
A Study to Assess Safety and Tolerability of Single Oral Doses of BMS-986177 in Patients with 
ESRD treated with chronic hemodialysis 
 
NCT Number: NCT03000673 
 
Document Date (Date in which document was last revised): 02-Nov-2017  






1138
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v




 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1140
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1141
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v






1144
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


1145
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


1146
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


1147
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


1148
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


1149
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


1150
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


1151
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


1152
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


1153
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v




1155
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


1156
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


1157
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v


1158
Final Clinical Study Report
BMS-986177
CV010010
Factor XIa Inhibitor
_________________
____________________________
__________________________________________________
2.0
Approved 
930125554
1.0
v