A Phase 2 Multicenter, Open-Label, Uncontrolled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of RA101495 in Subjects With Paroxysmal Nocturnal Hemoglobinuria Who Have an Inadequate Response to Eculizumab
Phase: PHASE2
Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
Sponsor: Ra Pharmaceuticals

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TITLE PAGE  
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RA PHARMACEUTICALS, INC. 
RA101495-01.203: A PHASE 2 MULTICENTER, OPEN-LABEL, UNCONTROLLED 
STUDY TO EVALUATE THE SAFETY, TOLERABILITY, EFFICACY, 
PHARMACOKINETICS, AND PHARMACODYNAMICS OF RA101495 IN SUBJECTS 
WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA WHO HAVE AN INADEQUATE 
RESPONSE TO ECULIZUMAB 
Protocol Number: 
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Indication Studied:
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Developmental Phase of Study:
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Company/Sponsor Signatory:
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Protocol Version:
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Release Date of Protocol:
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GHYLFHZLWKLQWKHGD\VSULRUWR6FUHHQLQJRUSDUWLFLSDWLRQLQDQRWKHU
FRQFXUUHQWFOLQLFDOWULDOLQYROYLQJDWKHUDSHXWLFLQWHUYHQWLRQ
SDUWLFLSDWLRQLQREVHUYDWLRQDOVWXGLHVDQGRUUHJLVWU\VWXGLHVLV
SHUPLWWHG
 8QDEOHRUXQZLOOLQJWRFRPSO\ZLWKWKHUHTXLUHPHQWVRIWKHVWXG\
Endpoints and 
Assessments
Safety and Tolerability
6DIHW\DVVHVVPHQWVZLOOLQFOXGHHYDOXDWLRQRI$(VDQG6$(VLQFOXGLQJ
PDMRUDGYHUVHYDVFXODUHYHQW0$9(FULWHULDFOLQLFDOODERUDWRU\WHVWV
(&*VYLWDOVLJQVDQGSK\VLFDOH[DPLQDWLRQV6DIHW\HYDOXDWLRQVZLOODOVR
LQFOXGHDGHWHUPLQDWLRQRIDQWLGUXJDQWLERGLHV$'$
Primary Efficacy:
x
7KHSULPDU\HYDOXDWLRQSHULRGLVIURP:HHNWR:HHN7KHSULPDU\
HIILFDF\HQGSRLQWLVWKHFKDQJHIURPEDVHOLQHLQVHUXP/'+OHYHOV
GXULQJWKLVSHULRGGHILQHGDVWKHPHDQ/'+YDOXHVRI:HHNV
DQGPLQXVWKHEDVHOLQHYDOXHRI/'+
Secondary Efficacy:
x
&KDQJHVIURPEDVHOLQHLQ/'+WRWDOELOLUXELQWRWDOKHPRJORELQIUHH
KHPRJORELQKDSWRJORELQUHWLFXORF\WHVDQGKHPRJORELQXULDDWHDFKRI
WKHVFKHGXOHGSRVWEDVHOLQHDVVHVVPHQWWLPHSRLQWV
Pharmacokinetic:
x
3ODVPDFRQFHQWUDWLRQVRI5$DQGLWVPDMRUPHWDEROLWHV
x
0D[LPXPSODVPDFRQFHQWUDWLRQ&PD[
x
7LPHFRUUHVSRQGLQJWR&PD[WPD[
x
$UHDXQGHUWKHGUXJFRQFHQWUDWLRQWLPHFXUYHV$8&W
x
3ODVPDFRQFHQWUDWLRQVRIHFXOL]XPDE
Pharmacodynamic:
x
&KDQJHVIURPEDVHOLQH&+
x
&KDQJHVIURPEDVHOLQHLQVKHHS5%&V5%&O\VLVIRUFODVVLFDO
FRPSOHPHQWSDWKZD\
x
&KDQJHVIURPEDVHOLQHLQ:LHVODEHQ]\PHOLQNHGLPPXQRVRUEHQWDVVD\
(/,6$IRUDOWHUQDWLYHFRPSOHPHQWSDWKZD\
x
&KDQJHVIURPEDVHOLQHLQ&OHYHOV
Exploratory:
x
&KDQJHVIURPEDVHOLQHLQTXDOLW\RIOLIH42/TXHVWLRQQDLUHVHJ
EORTC QLQ-C30, FACIT-Fatigue, and EQ-5D)
x
7UHDWPHQWVDWLVIDFWLRQTXHVWLRQQDLUH
x
0HFKDQLVWLFELRPDUNHUVHJFRPSOHPHQWIXQFWLRQFRPSOHPHQW

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3URWRFRO5$$PHQGPHQW''-DQXDU\
&21),'(17,$/

SURWHLQVELRPDUNHUVRILQIODPPDWLRQELRPDUNHUVIRUWKURPERVLV
ELRPDUNHUVRIOLYHUIXQFWLRQ
x
3KDUPDFRJHQRPLFDQDO\VHVRSWLRQDO
Statistical 
considerations
Study Populations7KHIROORZLQJVWXG\SRSXODWLRQVDUHGHILQHG
x
Safety Population$OOVXEMHFWVZKRUHFHLYHDWOHDVWGRVHRI5$
x
Efficacy Evaluable Population$OOVXEMHFWVLQWKH6DIHW\3RSXODWLRQ
ZKRFRPSOHWHWKHZHHN7UHDWPHQW3HULRG
x
Per Protocol Population$OOVXEMHFWVLQWKH6DIHW\3RSXODWLRQZKR
FRPSOHWHWKHZHHN7UHDWPHQW3HULRGDQGKDYHQRPDMRUSURWRFRO
GHYLDWLRQV
x
PK Population$OOVXEMHFWVLQWKH6DIHW\3RSXODWLRQZKRKDYHDWOHDVW
SODVPDVDPSOHREWDLQHGIRU3.DVVHVVPHQW
x
PD Population$OOVXEMHFWVLQWKH6DIHW\3RSXODWLRQZKRKDYHDWOHDVW
SODVPDVDPSOHREWDLQHGIRU3'DVVHVVPHQW
General Considerations
$GLVSRVLWLRQRIDOOFRQVHQWHGVXEMHFWVZLOOEHSURYLGHGDQGZLOOLQFOXGHD
EUHDNGRZQRIVXEMHFWVZKRFRQVHQWHGZHUHWUHDWHGGLVFRQWLQXHGWUHDWPHQW
ZHUHORVWWRIROORZXSRUZLWKGUHZFRQVHQW
&RQWLQXRXVYDULDEOHVZLOOEHVXPPDUL]HGZLWKWKHPHDQVWDQGDUGGHYLDWLRQ
6'PHGLDQDQGUDQJH&DWHJRULFDOYDULDEOHVZLOOEHVXPPDUL]HGXVLQJ
FRXQWVDQGSURSRUWLRQV
Safety:$GYHUVHHYHQWVZLOOEHFRGHGXVLQJWKH0HGLFDO'LFWLRQDU\IRU
5HJXODWRU\$FWLYLWLHV0HG'5$YHUVLRQRUKLJKHU,QFLGHQFHUDWHV
IRUWUHDWPHQWHPHUJHQW$(V7($(VE\PD[LPXPVHYHULW\DQG6$(VZLOO
EHVXPPDUL]HG7KHVHVXPPDULHVZLOOEHSURYLGHGUHJDUGOHVVRIFDXVDOLW\
DQGIRUHYHQWVWKDWDUHFRQVLGHUHGUHODWHGWRWUHDWPHQWZLWK5$
4XDQWLWDWLYHODERUDWRU\HQGSRLQWVZLOOEHVXPPDUL]HGE\WLPHSRLQW
'HVFULSWLYHVWDWLVWLFVIRU(&*SDUDPHWHUVLHKHDUWUDWH>+5@35LQWHUYDO
55LQWHUYDO456LQWHUYDO47LQWHUYDO47F%LQWHUYDODQG47F)LQWHUYDODW
HDFKDVVHVVPHQWWLPHSRLQWZLOOEHSUHVHQWHG
'HVFULSWLYHVWDWLVWLFVIRUYLWDOVLJQVKHDUWUDWHERG\WHPSHUDWXUHDQGEORRG
SUHVVXUHZLOOEHSUHVHQWHG
7KHFRPSOHWHVHWRISK\VLFDOH[DPLQDWLRQILQGLQJVZLOOEHSURYLGHGLQ
OLVWLQJV&OLQLFDOO\VLJQLILFDQWSK\VLFDOH[DPLQDWLRQDEQRUPDOLWLHVZLOOEH
LQFOXGHGDQGVXPPDUL]HGDV$(VLIDSSURSULDWH
Efficacy:1RIRUPDOVWDWLVWLFDOFRPSDULVRQVZLOOEHSHUIRUPHG6XPPDU\
VWDWLVWLFVIRUWKHSULPDU\DQGRWKHUHIILFDF\HQGSRLQWVZLOOEHSURYLGHG
LQFOXGLQJWKHPHDQPHGLDQVWDQGDUGGHYLDWLRQDQGVWDQGDUG
Pharmacokinetics:'UXJH[SRVXUHZLOOEHHYDOXDWHGXVLQJ3.SDUDPHWHUV
GHULYHGIURPQRQFRPSDUWPHQWDOPHWKRGV$OOFDOFXODWLRQVIRUWKHILQDO
DQDO\VLVZLOOEHEDVHGRQDFWXDOVDPSOLQJWLPHV,QGLYLGXDO3.SDUDPHWHUV
ZLOOEHSUHVHQWHGLQOLVWLQJVDQGVXPPDUL]HGXVLQJGHVFULSWLYHVWDWLVWLFV
Pharmacodynamics1RIRUPDOVWDWLVWLFDOFRPSDULVRQVZLOOEHSHUIRUPHG
6XPPDU\VWDWLVWLFVZLOOEHSURYLGHGLQFOXGLQJWKHPHDQPHGLDQVWDQGDUG
GHYLDWLRQDQGVWDQGDUGHUURU

5$
3URWRFRO5$$PHQGPHQW''-DQXDU\
&21),'(17,$/

Determination of Sample Size$VDPSOHVL]HRIVXEMHFWVZLOO\LHOGD
VWDQGDUGHUURURIDSSUR[LPDWHO\8/IRUDQ/'+PHDQFKDQJHIURP
EDVHOLQHHVWLPDWH7KLVDVVXPHVDVWDQGDUGGHYLDWLRQRI8/IRUWKH
EDVHOLQHDQGSRVWEDVHOLQHHQGSRLQWVDQGDZLWKLQVXEMHFWFRUUHODWLRQ
HVWLPDWHRI
Interim Analysis'XULQJWKLVRSHQODEHOVWXG\WKH6SRQVRUZLOOUHYLHZ
VDIHW\DQGHIILFDF\GDWDDVLWEHFRPHVDYDLODEOHGXULQJWKH7UHDWPHQW3HULRG
)ROORZLQJFRPSOHWLRQRIWKHZHHN7UHDWPHQW3HULRGGDWDZLOOEHFOHDQHG
DQGORFNHGDWWKHLQGLYLGXDOVXEMHFWOHYHODQGZLOOEHDYDLODEOHIRUILQDO
DQDO\VLVE\WKH6SRQVRURQDUROOLQJEDVLV

5$
3URWRFRO5$$PHQGPHQW''-DQXDU\
&21),'(17,$/

3
TABLE OF CONTENTS 
1 
TITLE PAGE ...............................................................................................................1 
2 
SYNOPSIS ....................................................................................................................4 
3 
TABLE OF CONTENTS ..........................................................................................10 
4 
LIST OF ABBREVIATIONS AND DEFINITIONS ..............................................15 
5 
TIME AND EVENTS TABLE ..................................................................................18 
6 
INTRODUCTION......................................................................................................22 
 
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 
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 
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 
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 
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 
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 
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 
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7 
STUDY OBJECTIVES AND ENDPOINTS ............................................................33 
 
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 
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 
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 
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8 
STUDY DESIGN ........................................................................................................35 
 
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 
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9 
SELECTION OF STUDY POPULATION .............................................................43 
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10 
INVESTIGATIONAL MEDICINAL PRODUCTS AND 
TREATMENTS..........................................................................................................46 
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11 
STUDY ASSESSMENTS ..........................................................................................49 
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12 
SAFETY REPORTING.............................................................................................56 
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13 
STATISTICAL AND ANALYTICAL PLANS .......................................................64 
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ETHICAL CONSIDERATIONS ..............................................................................68 
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REGULATORY AND ADMINISTRATIVE CONSIDERATIONS .....................71 
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16 
REFERENCES ...........................................................................................................74 

LIST OF TABLES 
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RA101495  
Protocol RA101495-01.203                                                                                  Amendment 1 DD 17 January 2017
CONFIDENTIAL 
14
LIST OF FIGURES 
Figure 1 
Mechanism of Action of RA101495 in Complement System .....................................23 
Figure 2 
Inhibition of C5a (left) and C5b-9 (MAC; right) Formation by 
RA101495 ....................................................................................................................23 
Figure 3 
Mean (SD) Plasma RA101495 Concentrations Over Time by Dose 
Group Following Single-Dose SC Administration in Healthy 
Volunteers (Study RA101495-1001) ...........................................................................25 
Figure 4 
Mean (SD) Plasma RA101495 Concentrations Over Time by Dose 
Group Following Multiple-Dose SC Administration of 0.2 mg/kg for 7 
Days in Healthy Volunteers (Study RA101495-1001) ................................................25 
Figure 5 Mean (SD) Red Blood Cell Lysis Over Time by Dose Group Following 
Single-Dose SC Administration in Healthy Volunteers (Study 
RA101495-1001) .........................................................................................................26 
Figure 6 Mean (SD) Red Blood Cell Lysis Over Time by Dose Group in the 
Multiple-Dose Cohort Once Daily for 7-Days in Healthy Volunteers in 
(Study RA101495-1001) ..............................................................................................27 
Figure 7 Predicted PK and PD Effects Resulting From Weight-Bracketed Dosing 
of RA101495 (0.1mg/kg daily) ....................................................................................30 
Figure 8 RA101495 Loading Dose (0.3mg/kg) and Predicted Control of 
Hemolysis After the First Dose....................................................................................31 
Figure 9 
Simulation of PK (blue) and PD (red) of RA101495 with a Loading 
Dose of 0.3mg/kg on Day 1 Followed by 0.1mg/kg Daily Thereafter. .......................32 
Figure 10 RA101495-01.203 Study Design .................................................................................35 
Figure 11 Kaplan-Meier survival of PNH patients stratified by LDH level (LDH 
dichotomized at 1.5xULN compared with age- and gender- matched 
controls) .......................................................................................................................38 
Figure 12 Patient-reported symptoms in the International PNH registry, stratified 
by LDH level (dichotomized at 1.5xULN). .................................................................39 
Figure 13 Inhibition of Hemolysis in vitro Lysis of PNH RBCs Without and With 
the Presence of RA101348 (identical peptide sequence to RA101495) ......................40 

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Abbreviation
Definitions
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5
TIME AND EVENTS TABLE 
$VVHVVPHQWVWREHSHUIRUPHGGXULQJWKHVWXG\DUHVKRZQLQ7DEOH

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Table 1 
Time and Events Table    
Phase 
Screening 
Period 
Treatment Period 
Study Week o 
-8 to 1 
0 
1 
2 
3 
4 
6 
8 
10 
12  
Study Daya o 
-56 to -1 
1 ± 2b 
8 ± 2 
15 ± 2 
22 ± 2 
29 ± 2 
43 ± 4 
57 ± 4 
71 ± 4 
84 ± 4 
(End of Study) 
Study Procedure p 
 
 
 
 
 
 
 
 
 
 
ICF process and signed ICF 
X 
 
 
 
 
 
 
 
 
 
Review eligibility criteria 
X 
X 
 
 
 
 
 
 
 
 
Medical history and demographics 
X 
 
 
 
 
 
 
 
 
 
Prior and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
X 
 
 
 
X 
 
 
 
X 
Height and weightc 
X 
X 
 
 
 
X 
 
 
 
X 
Vital signs 
X 
X 
 
 
 
X 
 
 
 
X 
Electrocardiogram 
X 
X 
 
 
 
X 
 
 
 
X 
Neisseria throat swabd 
X 
 
 
 
 
 
 
 
 
 
Documentation of Neisseria vaccinationd 
X 
 
 
 
 
 
 
 
 
 
Blood chemistrye 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulationf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PNH clone size 
X 
 
 
 
 
X 
 
X 
 
X 
Pregnancy testg 
X 
X 
 
 
 
X 
 
X 
 
X 
Adverse eventsh 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment of injection site reactionsi 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Phase 
Screening 
Period 
Treatment Period 
Study Week o 
-8 to 1 
0 
1 
2 
3 
4 
6 
8 
10 
12  
Study Daya o 
-56 to -1 
1 ± 2b 
8 ± 2 
15 ± 2 
22 ± 2 
29 ± 2 
43 ± 4 
57 ± 4 
71 ± 4 
84 ± 4 
(End of Study) 
Pharmacokinetics RA101495ij 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetics eculizumabk 
X 
X 
 
X 
 
X 
X 
 
 
 
Pharmacodynamics RA101495j 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-drug antibodyl 
 
Xk 
 
 
 
X 
 
X 
 
X 
Quality of life questionnaires  
 
 
 
 
 
 
 
 
 
 
EORTC-QLQ-C30 
 
X 
 
 
 
X 
 
X 
 
X 
FACIT-Fatigue  
 
X 
 
 
 
X 
 
X 
 
X 
EQ-5D 
 
X 
 
 
 
X 
 
X 
 
X 
Treatment satisfaction assessment 
 
 
 
 
 
 
 
 
 
X 
Additional biomarker samplesj 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacogenomic analysis (optional)m 
 
Xl 
 
 
 
 
 
 
 
 
Electronic diary training, dispensation, 
and collection 
 
X 
 
 
 
 
 
 
 
X 
RA101495 administrationn 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study drug dispensing and returno 
 
X 
 
X 
 
X 
X 
X 
X 
X 
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6
INTRODUCTION 
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6.1
OVERVIEW OF PAROXYSMAL NOCTURNAL HEMOGLOBINURIA 
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6.2
MECHANISM OF ACTION OF RA101495 
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Figure 1 
Mechanism of Action of RA101495 in Complement System 
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DQWLERGLHVVSHFLILFIRU&DDQG&E
Figure 2 
Inhibition of C5a (left) and C5b-9 (MAC; right) Formation by RA101495 
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1RWH,QKLELWRULV5$
$EEUHYLDWLRQV& FRPSOHPHQWFRPSRQHQW0$& PHPEUDQHDWWDFNFRPSOH[
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Confiden al
Alterna vePathway
ClassicalPathway
MBLPathway
APC5Convertase
(C3bC3bBb)
C5
C5a
C5b
C6
C5b6
C7,C8,C9
MAC
CPC5Convertase
(C3bC4bC2a)
RA101495
Lysis
Log [Inhibitor] M
% Inhibition, C5a Production
-8
-6
-4
-2
0
2
4
0
50
100
Confi
Confiden
den alll

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6.3
CLINICAL TRIAL EXPERIENCE WITH RA101495 
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Figure 3 
Mean (SD) Plasma RA101495 Concentrations Over Time by Dose Group Following 
Single-Dose SC Administration in Healthy Volunteers (Study RA101495-1001) 
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Figure 4 
Mean (SD) Plasma RA101495 Concentrations Over Time by Dose Group Following 
Multiple-Dose SC Administration of 0.2 mg/kg for 7 Days in Healthy Volunteers 
(Study RA101495-1001) 
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0 .0 5  m g /kg
0 .1  m g /kg
0 .2  m g /kg
0 .4  m g /kg

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Figure 5 
Mean (SD) Red Blood Cell Lysis Over Time by Dose Group Following Single-Dose 
SC Administration in Healthy Volunteers (Study RA101495-1001) 
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0 .0 5  m g /kg
0 .1  m g /kg
0 .2  m g /kg
0 .4  m g /kg

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Mean (SD) Red Blood Cell Lysis Over Time by Dose Group inthe Multiple-Dose 
Cohort Once Daily for 7-Days in Healthy Volunteers in(Study RA101495-1001)
 
 
 
 
 
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P la c e b o
R A 1 0 1 4 9 5
Direct Hemolysis 
Direct Hemolysis 

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6.4
DEVELOPMENT RATIONALE 
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6.5
DOSE JUSTIFICATION FOR STUDY  
6.5.1
RATIONALE FOR STARTING DOSE (0.1 MG/KG)  
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Table 2 
Experimental and Predicted PK Values for RA101495 in Humans 
Pharmacokinetic 
Parameter
Statistic
RA101495 
(2 mg/kg) 
NOAEL 
NHP
RA101495 
(0.2 mg/kg) 
QDx7; Day 
7 Human 
(SD)
RA101495 (0.1 mg/kg) 
Steady State Prediction in
Human
1RPLQDO
0LQLPDO
PJNJ
4'
0D[LPXP
GRVH
PJNJ
4'
Cmax (μg/mL)
0HDQ




AUC0-24(h·μg/mL)
0HDQ




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Figure 7 
Predicted PK and PD Effects Resulting From Weight-Bracketed Dosing of 
RA101495 (0.1mg/kg daily) 
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6.5.2
RATIONALE FOR USE OF LOADING DOSE 
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Figure 8 
RA101495 Loading Dose (0.3mg/kg) and Predicted Control of Hemolysis After the 
First Dose 
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6.5.3
RATIONALE FOR DOSE ESCALATION TO 0.3MG/KG DAILY AFTER WEEK 2 
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Figure 9 
Simulation of PK (blue) and PD (red) of RA101495 with a Loading Dose of 0.3mg/kg 
on Day 1 Followed by 0.1mg/kg Daily Thereafter.  
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0
500
1000
1500
0
2
4
6
8
ss trough
0
50
100
90
Time (hours)
Plasma concentration (g/mL)
0.3 loading + 0.1 mpk QD
plasma level
%inh
% Inhibition of hemolysis

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7
STUDY OBJECTIVES AND ENDPOINTS 
7.1
OBJECTIVES 
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7.2
ENDPOINTS 
7.2.1
SAFETY AND TOLERABILITY 
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7.2.2
EFFICACY  
Primary efficacy
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Secondary efficacy:  
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7.2.3
PHARMACOKINETIC  
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7.2.4
PHARMACODYNAMIC  
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7.2.5
EXPLORATORY  
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8
STUDY DESIGN 
8.1
OVERVIEW OF STUDY DESIGN  
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Figure 10 
RA101495-01.203 Study Design 
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8.1.1
RATIONALE FOR STUDY DESIGN   
No Comparator 
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Figure 11 
Kaplan-Meier survival of PNH patients stratified by LDH level (LDH dichotomized 
at 1.5xULN compared with age- and gender- matched controls) 
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Figure 12 
Patient-reported symptoms in the International PNH registry, stratified by LDH 
level (dichotomized at 1.5xULN).
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Figure 13 
Inhibition of Hemolysis in vitro Lysis of PNH RBCs Without and With the Presence 
of RA101348 (identical peptide sequence to RA101495)
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8.2
STUDY PERIODS 
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8.2.1
SCREENING PERIOD 
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8.2.2
TREATMENT 
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8.3
SUBJECT REGISTRATION PROCEDURES 
8.3.1
SCREENING AND ENROLLMENT 
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8.3.2
TREATMENT GROUP ASSIGNMENT 
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8.3.3
BLINDING 
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8.4
DISCONTINUATION CRITERIA 
8.4.1
DISCONTINUATION OF INVESTIGATIONAL MEDICINAL PRODUCT 
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8.4.2
WITHDRAWAL FROM THE STUDY 
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8.5
EARLY STUDY TERMINATION  
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8.6
END OF STUDY 
7KHHQGRIVWXG\LVGHILQHGDVWKHGDWHRIWKHODVWVXEMHFW¶VODVWYLVLW6XEMHFWVZKRFRPSOHWHWKH
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9
SELECTION OF STUDY POPULATION 
9.1
INCLUSION CRITERIA  
7REHHOLJLEOHIRUWKLVVWXG\VXEMHFWVPXVWPHHWALL RIWKHIROORZLQJLQFOXVLRQFULWHULD

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
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IRUP,&)

'LDJQRVLVRI31+E\IORZF\WRPHWU\
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PRQWKVSOXVRQHRUPRUHRIWKHIROORZLQJFULWHULD
o
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WR6FUHHQLQJ
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DQGZLWKLQKRXUVSULRUWRWKHILUVWGRVHRI5$
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6H[XDOO\DFWLYHIHPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOLHZRPHQZKRDUHQRWSRVW
PHQRSDXVDORUZKRKDYHQRWKDGDELODWHUDORRSKRUHFWRP\K\VWHUHFWRP\RUWXEDOOLJDWLRQ
DQGDOOPDOHVXEMHFWVZKRKDYHQRWEHHQVXUJLFDOO\VWHULOL]HGE\YDVHFWRP\PXVWDJUHHWR
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DGPLQLVWUDWLRQWKURXJKRXWWKHVWXG\DQGIRUZHHNVDIWHUWKHODVWGRVHRIVWXG\GUXJ
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6FUHHQLQJ9LVLWWKURXJKRXWWKHVWXG\DQGIRUZHHNVDIWHUWKHODVWGRVHRIVWXG\GUXJ
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DQGIRUZHHNVDIWHUWKHODVWGRVHRIVWXG\GUXJ
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7RWDODEVWLQHQFHIURPVH[XDOLQWHUFRXUVHIRUDWOHDVWRQHFRPSOHWHPHQVWUXDOF\FOHSULRU
WRWKH6FUHHQLQJ9LVLWWKURXJKRXWWKHVWXG\DQGIRUZHHNVDIWHUWKHODVWGRVHRIVWXG\
GUXJ
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9.2
EXCLUSION CRITERIA 
6XEMHFWVZKRPHHWANY RIWKHIROORZLQJH[FOXVLRQFULWHULDPXVWEHH[FOXGHGIURPWKHVWXG\

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UHFXUUHQFHDUHDOORZHG
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9.3
REMOVAL AND REPLACEMENT OF SUBJECTS IN THE STUDY 
9.3.1
PREMATURE DISCONTINUATION 
(YHU\UHDVRQDEOHHIIRUWVKRXOGEHPDGHWRHQFRXUDJHUHWHQWLRQRIVXEMHFWVLQWKHVWXG\
PD[LPL]HFRPSOLDQFHZLWKVWXG\GUXJDQGIDFLOLWDWHDWWHQGDQFHDWDOOVFKHGXOHGVWXG\YLVLWV
$OOVXEMHFWVKDYHWKHULJKWWRUHIXVHIXUWKHUSDUWLFLSDWLRQLQWKHVWXG\DWDQ\WLPHDQGIRUDQ\
UHDVRQ$VXEMHFW¶VSDUWLFLSDWLRQPXVWWKHUHIRUHEHWHUPLQDWHGLPPHGLDWHO\XSRQKLVKHU
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7KHLQYHVWLJDWRUZLOOPDNHHYHU\DWWHPSWWRDVFHUWDLQWKHUHDVRQVIRUGLVFRQWLQXDWLRQDQGWR
GRFXPHQWWKLVLQGHWDLOLQWKHVRXUFHGRFXPHQWDWLRQDQGWKHDSSURSULDWHVHFWLRQVRIWKHHOHFWURQLF
FDVHUHSRUWIRUPH&5)6XEMHFWVPD\EHZLWKGUDZQIURPWKHVWXG\GXHWRDQ\RIWKHIROORZLQJ
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9.3.2
REPLACEMENT OF SUBJECTS 
(QUROOHGVXEMHFWVZKRSUHPDWXUHO\GLVFRQWLQXHVWXG\WUHDWPHQWIRUDQ\UHDVRQSULRUWRWKH'D\
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10
INVESTIGATIONAL MEDICINAL PRODUCTS AND TREATMENTS 
10.1
STUDY TREATMENT ADMINISTRATION 
10.1.1
IDENTITY OF INVESTIGATIONAL MEDICINAL PRODUCT AND TREATMENT 
7KHLQYHVWLJDWLRQDOPHGLFLQDOSURGXFW,035$ZLOOEHVXSSOLHGDVDVWHULOH
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10.1.2
TREATMENT GROUPS  
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VWXG\GUXJDWPJNJ6&RQFHGDLO\
10.1.2.1
DOSE ESCALATION  
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7DEOH7DEOH
10.1.3
DOSING SCHEDULE 
7KH'D\9LVLWVKRXOGEHVFKHGXOHGWRFRLQFLGHZLWKWKHQH[WVFKHGXOHGGRVHRIHFXOL]XPDELH
rGD\VDIWHUIURPWKHODVWHFXOL]XPDEGRVH(FXOL]XPDEVKRXOG127EHDGPLQLVWHUHGRQ
WKH'D\9LVLWRUDWDQ\WLPHWKHUHDIWHUGXULQJWKHVWXG\
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DGPLQLVWHUHGGXULQJWKHVWXG\YLVLWE\WKHVLWHVWDII'XULQJWKHUHPDLQGHURIWKH7UHDWPHQW
3HULRGVXEMHFWVZLOOVHOIDGPLQLVWHUWKHGDLO\GRVHPJNJRUPJNJHYHU\KRXUVDW
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VLWHWKHGRVHPXVWEHDGPLQLVWHUHGDIWHUWKHEORRGZRUNLVFRPSOHWHGDWWKHLQYHVWLJDWRUVLWH
10.1.4
DOSE PRESENTATION  
'RVHVRI5$ZLOOEHGHWHUPLQHGE\DWDUJHWGRVHDQGZHLJKWDFFRPSOLVKHGXVLQJDIL[HG
GRVHE\ZHLJKWEUDFNHWV7KHVHEUDFNHWVDUHJURXSHGE\ERG\ZHLJKWFDWHJRU\VXFKWKDWHDFK
VXEMHFWZLOOUHFHLYHWKHQROHVVWKDQWKHWDUJHWPLQLPXPGRVHWRDYRLGVXEWKHUDSHXWLFGRVLQJ
)RUWKHPJNJGRVHVXEMHFWVZLOOUHFHLYHDWDPLQLPXPDIL[HGGRVHRIPJNJUDQJH

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WRPJNJ)RUWKHPJNJGRVHOHYHOVXEMHFWVZLOOUHFHLYHDPLQLPXPGRVHRI
PJNJUDQJHPJNJWRPJNJ7DEOHVXPPDUL]HVGRVHSUHVHQWDWLRQVIRU5$
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EHDFFRPPRGDWHGRQDFDVHE\FDVHEDVLVLQFRQVXOWDWLRQZLWKWKHPHGLFDOPRQLWRU
Table 3 
Dose Presentations by Weight Brackets 
Target 
Dose 
(mg/kg) 
Dose Presentation 
Weight Range 
(kg) 
Dose Range 
(mg/kg) 
Fill Volume 
Dose  
Number 
mL 
mg 
0.1 
1 
0.150 
6 
43 to <61 
0.10 to 0.14 
0.1 
2 
0.220 
8.8 
61 to <88 
0.10 to 0.14 
0.1 
3 
0.310 
12.4 
88 to <109
0.11 to 0.14 
0.3 
4 
0.416 
16.6 
43 to <56
0.30 to 0.39 
0.3 
5 
0.574 
23 
56 to <77
0.30 to 0.41 
0.3 
6 
0.810 
32.4 
77 to <109
0.30 to 0.42 

10.1.4.1
MISSED DOSES 
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GRVHLQKLVKHUVXEMHFWHGLDU\DQGWDNHWKHQH[WSODQQHGGRVHDVVFKHGXOHG7KHVXEMHFWVKRXOG
FRQWDFWWKHLQYHVWLJDWRUDVVRRQDVSRVVLEOH,IDVXEMHFWPLVVHVRUPRUHGRVHVWKHVXEMHFWPXVW
QRWLI\WKHLQYHVWLJDWRULPPHGLDWHO\
10.2
STUDY TREATMENT MANAGEMENT 
10.2.1
PREPARATION AND DISPENSING 
3UHILOOHGV\ULQJHVZLOOEHGLVSHQVHGWRHDFKVXEMHFWHYHU\ZHHNVEHJLQQLQJRQ'D\RIWKH
7UHDWPHQW3HULRG
6XEMHFWVZLOOEHSURYLGHGWUDLQLQJDQGGHWDLOHGLQVWUXFWLRQVUHJDUGLQJDGPLQLVWUDWLRQRI
5$XVLQJWKHSUHILOOHGV\ULQJHVDQGWKHLQMHFWLRQGHYLFHZLOOEHVXSSOLHGLQDVHSDUDWH
PDQXDO
10.2.2
STUDY DRUG SUPPLY, STORAGE, AND HANDLING 
5$ZLOOEHSURYLGHGDVDVWHULOHSUHVHUYDWLYHIUHHDTXHRXVVROXWLRQIRULQMHFWLRQ
FRQWDLQLQJPJP/RIDFWLYHLQJUHGLHQW5$LQDIRUPXODWLRQRIP0VRGLXP
SKRVSKDWHDQGP0VRGLXPFKORULGHDWDS+RISUHILOOHGLQWRDP/JODVVV\ULQJHZLWKD
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10.2.3
DISPOSAL, RETURN, OR RETENTION OF UNUSED DRUG 
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10.2.4
DRUG ACCOUNTABILITY 
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10.3
COMPLIANCE 
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GLDU\7KHHGLDU\HQWULHVZLOOEHHYDOXDWHGWRGHWHUPLQHFRPSOLDQFHZLWKVWXG\GUXJ
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11
STUDY ASSESSMENTS 
3OHDVHUHIHUWR7DEOHIRUWKHWLPLQJRIVWXG\DVVHVVPHQWV
11.1
SUBJECT AND BASELINE DISEASE CHARACTERISTICS 
11.1.1
DEMOGRAPHIC DATA 
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11.1.2
DISEASE AND PRIOR TREATMENT HISTORY  
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11.1.3
PRIOR AND CONCOMITANT MEDICATIONS 
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11.2
SAFETY ASSESSMENTS 
11.2.1
MEDICAL AND SURGICAL HISTORY  
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11.2.2
PHYSICAL EXAMINATION  
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11.2.3
VITAL SIGNS 
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11.2.4
ELECTROCARDIOGRAM  
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11.2.5
NEISSERIA MENINGITIDIS TESTING 
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11.2.6
ADVERSE EVENT RECORDING  
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11.2.7
LABORATORY SAFETY ASSESSMENTS 
11.2.7.1
BLOOD CHEMISTRY AND HEMATOLOGY  
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EHSHUIRUPHGDVVSHFLILHGLQWKH7LPHDQG(YHQWV7DEOH$OOFRDJXODWLRQWHVWVVKRXOGEH
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Table 4 
Clinical Chemistry, Hematology, and Coagulation Analytes 
Clinical Chemistry
Hematology
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11.2.7.2
URINALYSIS 
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11.2.7.3
PREGNANCY TEST 
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11.2.8
PNH CLONE  
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EORRGIORZF\WRPHWU\DQDO\VLV5%&VDQGJUDQXORF\WHV
11.2.9
IMMUNOGENICITY 
$PXOWLWLHUHG$'$WHVWLQJDSSURDFKKDVEHHQLPSOHPHQWHGDFFRUGLQJWR)'$*XLGDQFHIRU
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11.3
EFFICACY ASSESSMENTS  
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11.4
PHARMACOKINETIC AND PHARMACODYNAMIC ASSESSMENTS 
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11.5
ELECTRONIC DIARY CARD 
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11.6
EXPLORATORY ASSESSMENTS  
11.6.1
QUALITY OF LIFE ASSESSMENTS 
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11.6.1.1
EORTC-QLQ-C30 
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11.6.1.2
FACIT-FATIGUE 
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11.6.1.3
EQ-5D 
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11.6.2
TREATMENT SATISFACTION QUESTIONNAIRE 
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11.6.3
BIOMARKERS 
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11.6.4
PHARMACOGENOMIC ASSESSMENTS 
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SAFETY REPORTING 
12.1
DEFINITIONS 
12.1.1
ADVERSE EVENT 
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12.1.2
SERIOUS ADVERSE EVENT 
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12.1.3
ADVERSE EVENTS OF SPECIAL INTEREST 
12.1.3.1
THROMBOTIC ADVERSE EVENTS  
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12.1.3.2
HEPATIC ADVERSE EVENTS 
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12.1.3.3
PANCREATIC ENZYME ELEVATIONS  
6XEMHFWVVKRXOGEHPRQLWRUHGGXULQJWKHVWXG\IRUV\PSWRPVRISDQFUHDWLWLVRUFKROHF\VWLWLV
3DQFUHDWLFHQ]\PHVDP\ODVHDQGOLSDVHDUHPRQLWRUHGZHHNO\IRUWKHILUVWZHHNVIROORZHGE\
HYHU\ZHHNVGXULQJWKHVWXG\
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GLVFRQWLQXHGLIDWWKHPJNJGDLO\GRVH7KHVXEMHFWVKRXOGEHPRQLWRUHGXQWLODP\ODVH
DQGRUOLSDVHUHWXUQVWR*UDGHRUORZHU7KHPHGLFDOPRQLWRUVKRXOGEHFRQWDFWHGWR
UHYLHZWKHFDVH

5$
3URWRFRO5$$PHQGPHQW''-DQXDU\
&21),'(17,$/
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XQWLODP\ODVHDQGRUOLSDVHUHWXUQVWR*UDGHRUORZHU7KHPHGLFDOPRQLWRUVKRXOGEH
FRQWDFWHGWRUHYLHZWKHFDVH
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12.1.3.4
INJECTION SITE REACTIONS  
7KHLQYHVWLJDWRUVKRXOGDVVHVVWKHLQMHFWLRQVLWHDWHDFKVFKHGXOHGYLVLWIRU
x
3DLQWHQGHUQHVVHU\WKHPDDQGLQGXUDWLRQVHYHULW\7DEOH
x
(U\WKHPDDQGLQGXUDWLRQUHFRUGWKHPD[LPXPOLQHDUGLDPHWHU
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%OLVWHUVXOFHUDWLRQQHFURVLVUHFRUGWKHPD[LPXPOLQHDUGLDPHWHUDQGVHYHULW\
x
/\PSKDGHQRSDWK\
,QDGGLWLRQWKHLQYHVWLJDWRUZLOOZKHQHYHUSRVVLEOHWDNHGHLGHQWLILHGSKRWRVRIWKHLQMHFWLRQ
VLWHUHDFWLRQ,65
,QMHFWLRQVLWHUHDFWLRQVVKRXOGEHUHFRUGHGDV$(VSHU6HFWLRQDQG6HFWLRQDQG
UHFRUGHGRQWKH,65VSHFLILFH&5)DQG$(H&5)DVDSSURSULDWH
Table 5 
Grading the Severity of Local Injection Site Reactions 
Local Reaction 
to Injectable 
Product
Grade 1
(Mild)
Grade 2
(Moderate)
Grade 3
(Severe)
Grade 4
(Potentially Life 
Threatening)
3DLQ
'RHVQRWLQWHUIHUH
ZLWKDFWLYLW\
5HSHDWHGXVHRI
QRQQDUFRWLFSDLQ
UHOLHYHU!KRXUVRU
LQWHUIHUHVZLWK
DFWLYLW\
$Q\XVHRIQDUFRWLF
SDLQUHOLHYHURU
SUHYHQWVGDLO\
DFWLYLW\
(PHUJHQF\URRP
YLVLWRU
KRVSLWDOL]DWLRQ
7HQGHUQHVV
0LOGGLVFRPIRUW
WRWRXFK
'LVFRPIRUWZLWK
PRYHPHQW
6LJQLILFDQW
GLVFRPIRUWDWUHVW
(PHUJHQF\URRP
YLVLWRU
KRVSLWDOL]DWLRQ
(U\WKHPD
UHGQHVV
WRFP
WRFP
!FP
1HFURVLVRU
H[IROLDWLYH
GHUPDWLWLV
,QGXUDWLRQ
VZHOOLQJ
WRFPDQG
GRHVQRWLQWHUIHUH
ZLWKDFWLYLW\
WRFPRU
LQWHUIHUHVZLWK
DFWLYLW\
!FPRU
SUHYHQWVGDLO\
DFWLYLW\
1HFURVLV
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12.1.3.5
INFECTION 
$OOVXEMHFWVVKRXOGEHPRQLWRUHGIRUVLJQVDQGV\PSWRPVRI1HLVVHULDPHQLQJLWLGLVLQIHFWLRQ
6XEMHFWVDUHPRQLWRUHGHYHU\ZHHNVIRUDGYHUVHHYHQWV
7RUHGXFHWKHULVNRILQIHFWLRQGXULQJWKHVFUHHQLQJSHULRGDOOVXEMHFWVPXVWKDYHDQHJDWLYH
UHVXOWIRU1HLVVHULDPHQLQJLWLGLVFRORQL]DWLRQYLDWKURDWVZDESULRUWRVWXG\HQWU\$OOVXEMHFWV
PXVWKDYHGRFXPHQWDWLRQRISULRU1HLVVHULDPHQLQJLWLGLVYDFFLQDWLRQDQGERRVWHULIDSSURSULDWH
SULRUWRVWXG\HQWU\
'XULQJWKH7UHDWPHQW3HULRGWRPLWLJDWHWKHULVNRILQIHFWLRQVXEMHFWVZLOOEHFRXQVHOHGDQG
UHPLQGHGRIHDUO\VLJQVDQGV\PSWRPVRI1HLVVHULDPHQLQJLWLGLVLQIHFWLRQ$SDWLHQWVDIHW\FDUG
GHWDLOLQJWKHVLJQVDQGV\PSWRPVRILQIHFWLRQZLWKLQVWUXFWLRQVWRVHHNLPPHGLDWHPHGLFDO
DWWHQWLRQZLOOEHSURYLGHGWRHDFKVXEMHFW7KHFDUGZLOODOVRGHVFULEHWKHVXEMHFW¶VSDUWLFLSDWLRQ
LQWKHVWXG\DQGWKHULVNVRILQIHFWLRQDVVRFLDWHGZLWKLQKLELWLRQRIWKHWHUPLQDOFRPSOHPHQW
V\VWHP7KHSDWLHQWVDIHW\FDUGPXVWEHFDUULHGZLWKWKHSDWLHQWDWDOOWLPHVZKLOHRQWUHDWPHQW
$OO$(VVKRXOGEHUHFRUGHGDV$(VSHU6HFWLRQDQG6HFWLRQ
12.1.3.6
DOSE MODIFICATION FOR OTHER ADVERSE EVENTS   
)RUDOO*UDGHWUHDWPHQWHPHUJHQW$(VRWKHUWKDQWKHKHSDWLFDQGSDQFUHDWLF$(VGHVFULEHG
LQVHFWLRQVDQGVWXG\GUXJVKRXOGEHGRVHUHGXFHGLIDWWKHPJNJGDLO\
GRVHRUSHUPDQHQWO\GLVFRQWLQXHGLIDWWKHPJNJGDLO\GRVH
$OO$(VVKRXOGEHUHFRUGHGDV$(VSHU6HFWLRQDQG6HFWLRQ
12.2
EVALUATION AND CLASSIFICATIONS 
12.2.1
SEVERITY 
7KHLQYHVWLJDWRUVKRXOGGHWHUPLQHWKHVHYHULW\RIWKHUHSRUWHG$(E\XVLQJWKH1&,&7&$(
9HUVLRQ7KHVHFULWHULDZLOOEHSURYLGHGLQDVHSDUDWHPDQXDO
)RUDQ\UHSRUWHG$(QRWGHVFULEHGLQWKH1&,&7&$(WKHIROORZLQJJXLGHOLQHVPXVWEH
FRQVLGHUHGIRUVHYHULW\HYDOXDWLRQ
Adverse Event Severity
0LOG
6\PSWRPVEDUHO\QRWLFHDEOHWRVXEMHFWRUGRHVQRWPDNHVXEMHFW
XQFRPIRUWDEOHGRHVQRWLQIOXHQFHSHUIRUPDQFHRUIXQFWLRQLQJ
SUHVFULSWLRQGUXJQRWRUGLQDULO\QHHGHGIRUUHOLHIRIV\PSWRPV
0RGHUDWH
6\PSWRPVRIDVXIILFLHQWVHYHULW\WRPDNHVXEMHFWXQFRPIRUWDEOH
SHUIRUPDQFHRIGDLO\DFWLYLW\LVLQIOXHQFHGVXEMHFWLVDEOHWRFRQWLQXHLQ
VWXG\WUHDWPHQWIRUV\PSWRPVPD\EHQHHGHG
6HYHUH
6\PSWRPVFDXVHVHYHUHGLVFRPIRUWV\PSWRPVFDXVHLQFDSDFLWDWLRQRU
VLJQLILFDQWLPSDFWRQVXEMHFW¶VGDLO\OLIHVHYHULW\PD\FDXVHFHVVDWLRQRI
WUHDWPHQWZLWKVWXG\WUHDWPHQWWUHDWPHQWIRUV\PSWRPVPD\EHJLYHQ

5$
3URWRFRO5$$PHQGPHQW''-DQXDU\
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Adverse Event Severity
0LOG
6\PSWRPVEDUHO\QRWLFHDEOHWRVXEMHFWRUGRHVQRWPDNHVXEMHFW
XQFRPIRUWDEOHGRHVQRWLQIOXHQFHSHUIRUPDQFHRUIXQFWLRQLQJ
SUHVFULSWLRQGUXJQRWRUGLQDULO\QHHGHGIRUUHOLHIRIV\PSWRPV
DQGRUVXEMHFWKRVSLWDOL]HG
12.2.2
CAUSALITY 
7KHFDXVDOUHODWLRQVKLSRIWKH$(WRVWXG\PHGLFDWLRQZLOOEHDVVHVVHGE\ERWKWKHLQYHVWLJDWRU
DQGWKH6SRQVRU7KHDVVHVVPHQWRIFDXVDOUHODWLRQVKLSWRVWXG\GUXJVKRXOGEHHYLGHQFHEDVHG
DQGQRWEDVHGRQWKHSUHPLVHWKDWDOO$(VDUHFDXVDOO\UHODWHGWRVWXG\GUXJXQWLOSURYHQ
RWKHUZLVH'HIDXOWFDWHJRUL]DWLRQRIµUHODWHG¶ZLWKRXWVXSSRUWLYHHYLGHQFHIRUDFDXVDO
UHODWLRQVKLSWRVWXG\GUXJLVJHQHUDOO\XQLQIRUPDWLYHDQGGRHVQRWFRQWULEXWHWRXQGHUVWDQGLQJRI
WKHVDIHW\SURILOHRIWKHGUXJZLWKUHVSHFWWRWKHLQWHQGHGSRSXODWLRQ
([DPSOHVRIHYLGHQFHWKDWZRXOGVXJJHVWDFDXVDOUHODWLRQVKLSEHWZHHQWKHGUXJDQGWKH$(
LQFOXGHRFFXUUHQFHRIDQ$(WKDWLVNQRZQWREHVWURQJO\DVVRFLDWHGZLWKGUXJH[SRVXUHHJ
LQMHFWLRQVLWHUHDFWLRQRUDQ$(WKDWLVRWKHUZLVHXQFRPPRQLQWKHVWXG\SRSXODWLRQ/DFNRI
HIILFDF\RIVWXG\GUXJLQLVRODWLRQOHDGLQJWRXQPDVNLQJRIXQGHUO\LQJV\PSWRPVDQGVLJQVRI
GLVHDVHVKRXOGQRWEHFRQVLGHUHGHYLGHQFHRIUHODWHGQHVV
7KHFDXVDOUHODWLRQVKLSRIHDFK$(LVDVVHVVHGXVLQJDELQDU\V\VWHPZLWKDOO$(VFODVVLILHGDV
HLWKHUµUHODWHG¶RUµQRWUHODWHG¶
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UHDVRQDEOHWHPSRUDODVVRFLDWLRQIURPWKHWLPHRIVWXG\GUXJDGPLQLVWUDWLRQ7KHUHLVVXSSRUWLYH
HYLGHQFHWRVXJJHVWDSRVVLEOHFDXVDOUHODWLRQVKLSLUUHVSHFWLYHRIWKHGHJUHHRIFHUWDLQW\
EHWZHHQWKHREVHUYHG$(DQGWKHVWXG\GUXJ7KHUHLVQRDOWHUQDWLYHPRUHOLNHO\H[SODQDWLRQIRU
WKH$(/DFNRIVWXG\GUXJHIILFDF\LVQRWFRQVLGHUHGE\LWVHOIWREHHYLGHQFHRIUHODWHGQHVV
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GUXJDQGWKHRFFXUUHQFHRIWKH$(7KHUHLVHYLGHQFHRIDQDOWHUQDWLYHH[SODQDWLRQWKDWLVPRUH
OLNHO\DVDFDXVHRIWKH$(
12.3
RECORDING, REPORTING, AND MONITORING 
12.3.1
RECORDING AND REPORTING 
7KHLQYHVWLJDWRUPXVWPDNHHYHU\HIIRUWWRSURSHUO\HYDOXDWHDOOLQIRUPDWLRQUHOHYDQWWRWKH
UHSRUWHG$(LQVXFKDZD\WKDWDGLDJQRVLVFDQEHFRQILGHQWO\PDGHDQGUHSRUWHG)RUH[DPSOH
LWLVSUHIHUDEOHWRUHSRUW³SQHXPRQLD´DVWKH$(UDWKHUWKDQLWVV\PSWRPVHJ³UDOHV´RU³IHYHU´
DVVHSDUDWH$(V
:KHQUHFRUGLQJDQGRUUHSRUWLQJ$(VRU6$(VWKHIROORZLQJHOHPHQWVPXVWEHLQFOXGHG
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WKHIXOILOOHGFULWHULDIRUVHULRXVQHVVDVSUHVHQWHGLQ6HFWLRQ

5$
3URWRFRO5$$PHQGPHQW''-DQXDU\
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UHGXFHGGRVHLQFUHDVHGFRQFRPLWDQWPHGLFDWLRQRWKHUDFWLRQHJGLDJQRVWLFWHVWLQJRUQR
DFWLRQ$Q\PHGLFDWLRQJLYHQWRWUHDWWKH$(ZLOOEHUHFRUGHGVHSDUDWHO\LQWKHFRQFRPLWDQW
PHGLFDWLRQOLVWRIWKHH&5)
7KHRXWFRPHRIWKH$(ZLOOEHUHFRUGHGDVGDWHHQGHGRQJRLQJRUUHVXOWLQJLQGHDWKZLWKGDWH
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12.3.1.1
ADVERSE EVENTS 
3UHH[LVWLQJFRQGLWLRQVWKDWDUHGHWHFWHGSULRUWRDGPLQLVWUDWLRQRIWKHILUVWGRVHRIVWXG\GUXJ
ZLOOEHUHFRUGHGDVSDUWRIPHGLFDOKLVWRU\)RUDOOVXEMHFWVWKH$(UHSRUWLQJSHULRGZLOOVWDUW
ZLWKWKHILUVWDGPLQLVWUDWLRQRIVWXG\GUXJRQ'D\DQGZLOOHQGZLWKWKHILQDOVWXG\YLVLWDIWHU
ZKLFKQRQHZ$(VDUHWREHUHSRUWHG:KHQSRVVLEOHRQJRLQJ$(VDVVHVVHGDVUHODWHGWRWKH
VWXG\GUXJZLOOEHIROORZHGXQWLOUHVROYHGRUVWDELOL]HG
7KHVXEMHFWVZLOOEHPRQLWRUHGWKURXJKRXWWKHVWXG\IRUDQ\$(VLQFOXGLQJDEQRUPDOFOLQLFDOO\
VLJQLILFDQWODERUDWRU\YDOXHVFOLQLFDOO\VLJQLILFDQWILQGLQJVDWYLWDOVLJQVPHDVXUHPHQWV
VSRQWDQHRXVUHSRUWVE\VWXG\VXEMHFWVDQGREVHUYDWLRQVE\WKHVWXG\SHUVRQQHO$GYHUVHHYHQWV
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LQYHVWLJDWRU
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DQRQJRLQJHYHQWZLOOQRWEHFORVHGXQWLOUHVROYHGRUDWWKHHQGRIVWXG\)RUWKH$(GHVFULSWLRQ
DGLDJQRVLVLVSUHIHUUHGRYHUV\PSWRPV,IQRGLDJQRVLVFDQEHPDGHHDFKV\PSWRPZLOOEH
UHSRUWHGDVDVHSDUDWH$($EEUHYLDWLRQVVKRXOGEHDYRLGHG'HVFULSWLYHZRUGVVKRXOGEHXVHG
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12.3.1.2
SERIOUS ADVERSE EVENTS 
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RIVWXG\GUXJUHJDUGOHVVRIVHYHULW\RUFDXVDOLW\PXVWEHUHFRUGHGRQWKHH&5)DQG6$()RUP
7KHVWXG\VLWHPXVWIRUPDOO\QRWLI\WKH6SRQVRURIWKH6$(ZLWKLQKRXUVIURPWKHWLPHWKH
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5$
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12.3.1.3
DEATH 
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ILQGLQJVLQFOXGLQJDFRURQHU¶VUHSRUWVKRXOGEHSURYLGHGZKHQDYDLODEOH
12.3.2
MONITORING 
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12.3.2.1
POST-STUDY EVENTS 
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12.4
SPECIAL CIRCUMSTANCES 
12.4.1
PREGNANCY 
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12.4.2
OTHER 
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13
STATISTICAL AND ANALYTICAL PLANS 
13.1
SAMPLE SIZE DETERMINATION 
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13.2
ANALYSIS POPULATIONS 
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13.2.1
SAFETY POPULATION 
7KH6DIHW\3RSXODWLRQZLOOLQFOXGHDOOVXEMHFWVZKRUHFHLYHDWOHDVWRQHLQMHFWLRQRI5$
13.2.2
EFFICACY EVALUABLE POPULATION 
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FRPSOHWHWKHZHHN7UHDWPHQW3HULRG
13.2.3
PER PROTOCOL POPULATION 
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13.2.4
PHARMACOKINETIC POPULATION 
7KH3.3RSXODWLRQZLOOLQFOXGHDOOVXEMHFWVLQWKH6DIHW\3RSXODWLRQZKRKDYHDWOHDVWSODVPD
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13.2.5
PHARMACODYNAMIC POPULATION 
7KH3'3RSXODWLRQZLOOLQFOXGHDOOVXEMHFWVLQWKH6DIHW\3RSXODWLRQZKRKDYHDWOHDVWSODVPD
VDPSOHREWDLQHGIRU3'DVVHVVPHQW
13.3
STATISTICAL PLAN 
13.3.1
GENERAL CONSIDERATIONS 
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SURYLGHGLQD6WDWLVWLFDO$QDO\VLV3ODQ
13.3.2
SUBJECT DISPOSITION 
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5$
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13.3.3
DEMOGRAPHY AND BASELINE DISEASE CHARACTERISTICS 
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YDULDEOHVZLOOEHVXPPDUL]HGXVLQJFRXQWVDQGSURSRUWLRQV
13.3.4
SAFETY ANALYSIS 
6DIHW\DQDO\VHVZLOOEHSHUIRUPHGRQWKH6DIHW\3RSXODWLRQ
13.3.4.1
ADVERSE EVENTS 
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13.3.4.2
ADVERSE EVENTS OF SPECIAL INTEREST 
13.3.4.2.1
THROMBOTIC ADVERSE EVENTS 
7KURPERWLF$(VZLOOEHVXPPDUL]HGVHSDUDWHO\E\V\VWHPRUJDQFODVVDQGSUHIHUUHGWHUP7KH
HYHQWVLQ7DEOH0$9(FULWHULD>+LOOPHQ@ZLOOEHHYDOXDWHGLQWKHDVVHVVPHQWRI
WKURPERWLF$(V

5$
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Table 6 
Thrombotic Event Description (MAVE Criteria) 
7KURPERSKOHELWLV'HHSYHLQWKURPERVLV
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3XOPRQDU\HPEROXV
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0\RFDUGLDOLQIDUFWLRQ
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5HQDOYHLQWKURPERVLV
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5HQDODUWHULDOWKURPERVLV
0HVHQWHULF9LVFHUDOYHLQWKURPERVLV
2WKHU
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13.3.4.2.2
HEPATIC ADVERSE EVENTS 
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WHUP/LYHUIXQFWLRQWHVWVZLOOEHVXPPDUL]HGE\FKDQJHVIURPEDVHOLQHDQGJUDGHGLQVHYHULW\
XVLQJWKH1&,&7&$(FULWHULD
13.3.4.2.3
PANCREATIC ENZYME ELEVATIONS 
3DQFUHDWLF$(VDQGZLOOEHVXPPDUL]HGVHSDUDWHO\E\V\VWHPRUJDQFODVVDQGSUHIHUUHGWHUP
3DQFUHDWLFHOHYDWLRQVZLOOEHVXPPDUL]HGE\FKDQJHVIURPEDVHOLQHDQGJUDGHGLQVHYHULW\XVLQJ
WKH1&,&7&$(FULWHULD
13.3.4.2.4
INJECTION SITE REACTIONS 
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LQFOXGHDGGLWLRQDOGHWDLOVRQWKHVHHYHQWVDVGHVFULEHGLQ6HFWLRQ
13.3.4.2.5
INFECTION  
$(VUHODWHGWRLQIHFWLRQZLWKNeisseria meningitidisZLOOEHVXPPDUL]HGVHSDUDWHO\E\V\VWHP
RUJDQFODVVDQGSUHIHUUHGWHUP
13.3.4.3
CLINICAL LABORATORY EVALUATION 
4XDQWLWDWLYHODERUDWRU\HQGSRLQWVZLOOEHVXPPDUL]HGE\WLPHSRLQWXVLQJGHVFULSWLYHVWDWLVWLFV
13.3.4.4
ELECTROCARDIOGRAMS 
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SUHVHQWHG

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13.3.4.5
VITAL SIGNS 
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SUHVHQWHG
13.3.4.6
PHYSICAL EXAMINATION 
7KHFRPSOHWHVHWSK\VLFDOH[DPLQDWLRQILQGLQJVZLOOEHSURYLGHGLQOLVWLQJV&OLQLFDOO\
VLJQLILFDQWSK\VLFDOH[DPLQDWLRQDEQRUPDOLWLHVZLOOEHLQFOXGHGDQGVXPPDUL]HGDV$(VLI
DSSURSULDWH
13.3.5
EFFICACY ANALYSIS 
1RIRUPDOVWDWLVWLFDOFRPSDULVRQVZLOOEHSHUIRUPHG6XPPDU\VWDWLVWLFVIRUWKHSULPDU\DQG
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VWDQGDUGHUURU
13.3.6
CLINICAL PHARMACOLOGY ANALYSIS 
13.3.6.1
PHARMACOKINETIC ANALYSIS 
'UXJH[SRVXUHZLOOEHHYDOXDWHGXVLQJ3.SDUDPHWHUVGHULYHGIURPQRQFRPSDUWPHQWDOPHWKRGV
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13.3.6.2
PHARMACODYNAMIC ANALYSIS 
1RIRUPDOVWDWLVWLFDOFRPSDULVRQVZLOOEHSHUIRUPHG6XPPDU\VWDWLVWLFVZLOOEHSURYLGHG
LQFOXGLQJWKHPHDQPHGLDQVWDQGDUGGHYLDWLRQDQGVWDQGDUGHUURU
13.3.7
INTERIM ANALYSIS 
'XULQJWKLVRSHQODEHOVWXG\WKH6SRQVRUZLOOUHYLHZVDIHW\DQGHIILFDF\GDWDDVLWEHFRPHV
DYDLODEOHGXULQJWKH7UHDWPHQW3HULRG)ROORZLQJFRPSOHWLRQRIWKHZHHN7UHDWPHQW3HULRG
GDWDZLOOEHFOHDQHGDQGORFNHGDWWKHLQGLYLGXDOVXEMHFWOHYHODQGZLOOEHDYDLODEOHIRUILQDO
DQDO\VLVE\WKH6SRQVRURQDUROOLQJEDVLV

5$
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14
ETHICAL CONSIDERATIONS 
7KLVVWXG\VKDOOEHFRQGXFWHGLQDFFRUGDQFHZLWKWKHHWKLFDOSULQFLSOHVWKDWKDYHWKHLURULJLQLQ
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DSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV
14.1
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE 
COMMUNICATIONS 
3ULRUWRVWXG\LQLWLDWLRQWKHLQYHVWLJDWRULQVWLWXWLRQVKRXOGKDYHZULWWHQDQGGDWHG
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14.1.1
PROGRESS REPORTS 
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14.1.2
FINAL INVESTIGATOR REPORT 
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14.2
INFORMED CONSENT OF STUDY SUBJECTS 
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14.3
PROTOCOL COMPLIANCE 
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14.4
PROTECTION OF CONFIDENTIALITY 
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14.5
DISCLOSURE OF STUDY RESULTS 
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15
REGULATORY AND ADMINISTRATIVE CONSIDERATIONS 
15.1
QUALITY ASSURANCE 
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DSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV4XDOLW\FRQWUROVKDOOEHDSSOLHGWRHDFKVWDJHRIGDWD
KDQGOLQJWRHQVXUHWKDWDOOGDWDDUHUHOLDEOHDQGKDYHEHHQSURFHVVHGFRUUHFWO\
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15.1.1
MONITORING 
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15.1.2
AUDIT 
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15.2
CLINICAL RESEARCH ORGANIZATIONS 
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15.3
DATA MANAGEMENT 
15.3.1
CASE REPORT FORMS 
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15.3.2
SOURCE DOCUMENTS 
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15.4
PREMATURE TERMINATION OR SUSPENSION OF THE STUDY 
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15.5
CLINICAL STUDY REPORT 
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SUHSDUHGDQGSURYLGHGWRWKHUHJXODWRU\DJHQFLHVDVUHTXLUHGE\WKHDSSOLFDEOHUHJXODWRU\
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15.6
PUBLICATION POLICY 
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