A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group, Study to Investigate the Safety and Tolerability of Multiple Dose Administration of CSL112 in Subjects With Moderate Renal Impairment and Acute Myocardial Infarction
Phase: PHASE2
Conditions: Acute Myocardial Infarction, Moderate Renal Impairment
Sponsor: CSL Behring







)LQDO9

3DJHRI
&5'73/
&RQILGHQWLDO


&/,1,&$/678'<35272&2/

$3KDVH0XOWLFHQWHU'RXEOHEOLQG5DQGRPL]HG3ODFHERFRQWUROOHG3DUDOOHOJURXS
6WXG\WR,QYHVWLJDWHWKH6DIHW\DQG7ROHUDELOLW\RI0XOWLSOH'RVH$GPLQLVWUDWLRQRI
&6/LQ6XEMHFWVZLWK0RGHUDWH5HQDO,PSDLUPHQWDQG$FXWH0\RFDUGLDO,QIDUFWLRQ
6WXG\1XPEHU
&6/B
6WXG\3URGXFW
&6/5HFRQVWLWXWHG+LJK'HQVLW\/LSRSURWHLQ
'HYHORSPHQW3KDVH

6SRQVRU
&6/%HKULQJ//&&6/%
)LUVW$YHQXH
.LQJRI3UXVVLD
3$

3URWRFRO9HUVLRQ
),1$/9$PHQGPHQW
(XGUD&71XPEHU

,1'1XPEHU

3URWRFRO'DWH
-XQH
&RPSOLDQFH
7KLVVWXG\ZLOOEHFRQGXFWHGLQDFFRUGDQFHZLWKVWDQGDUGVRI
*RRG&OLQLFDO3UDFWLFHDVGHILQHGE\WKH,QWHUQDWLRQDO&RQIHUHQFH
RQ+DUPRQLVDWLRQHWKLFDOSULQFLSOHVWKDWKDYHWKHLURULJLQLQWKH
'HFODUDWLRQRI+HOVLQNLDQGDOODSSOLFDEOHQDWLRQDODQGORFDO
UHJXODWLRQV

7KLVSURWRFROLQFOXGHVLQIRUPDWLRQDQGGDWDWKDWFRQWDLQWUDGHVHFUHWVDQGSULYLOHJHGRUFRQILGHQWLDOLQIRUPDWLRQ
WKDWLVWKHSURSHUW\RIWKHVSRQVRU³&6/%´7KLVLQIRUPDWLRQPXVWQRWEHPDGHSXEOLFZLWKRXWZULWWHQ
SHUPLVVLRQIURP&6/%7KHVHUHVWULFWLRQVRQGLVFORVXUHZLOODSSO\HTXDOO\WRDOOIXWXUHLQIRUPDWLRQVXSSOLHGWR
\RX7KLVPDWHULDOPD\EHGLVFORVHGWRDQGXVHGE\\RXUVWDIIDQGDVVRFLDWHVDVPD\EHQHFHVVDU\WRFRQGXFWWKH
FOLQLFDOVWXG\
CCI

 
Study Number : 
CSL112_2001_Am1  
Study Product: 
CSL112  
 
Final V2.0  
6 June 2016 
Page 2 of 137 
CRD-TPL-077 
Confidential 
LIST OF PERSONNEL AND ORGANIZATIONS RESPONSIBLE FOR CONDUCT 
OF THE STUDY 
 
A list of personnel and organizations responsible for the conduct of the study will be supplied 
to study sites as part of the Investigator’s Study File. This list will be updated by CSLB (or 
delegate) and provided to the study sites as needed.  
 
 


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
6,*1$785(21%(+$/)2)6321625

6WXG\7LWOH $3KDVH0XOWLFHQWHU'RXEOHEOLQG5DQGRPL]HG3ODFHERFRQWUROOHG
3DUDOOHOJURXS6WXG\WR,QYHVWLJDWHWKH6DIHW\DQG7ROHUDELOLW\RI0XOWLSOH'RVH
$GPLQLVWUDWLRQRI&6/LQ6XEMHFWVZLWK0RGHUDWH5HQDO,PSDLUPHQWDQG$FXWH
0\RFDUGLDO,QIDUFWLRQ
3URWRFRO1XPEHU
&6/B

,KDYHUHDG$PHQGPHQWWRWKHSURWRFRO&6/BWLWOHG³$3KDVH0XOWLFHQWHU
'RXEOHEOLQG5DQGRPL]HG3ODFHERFRQWUROOHG3DUDOOHOJURXS6WXG\WR,QYHVWLJDWHWKH
6DIHW\DQG7ROHUDELOLW\RI0XOWLSOH'RVH$GPLQLVWUDWLRQRI&6/LQ6XEMHFWVZLWK
0RGHUDWH5HQDO,PSDLUPHQWDQG$FXWH0\RFDUGLDO,QIDUFWLRQ´DQGFRQILUPWKDWWRWKHEHVW
RIP\NQRZOHGJHWKHSURWRFRODFFXUDWHO\GHVFULEHVWKHGHVLJQDQGFRQGXFWRIWKHVWXG\







0')$&&


'DWH
''000<<<<



PPD
PPD

 
Study Number : 
CSL112_2001_Am1  
Study Product: 
CSL112  
 
Final V2.0  
6 June 2016 
Page 4 of 137 
CRD-TPL-077 
Confidential 
SIGNATURE OF INVESTIGATOR 
 
Study Title: A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled, 
Parallel-group, Study to Investigate the Safety and Tolerability of Multiple Dose 
Administration of CSL112 in Subjects with Moderate Renal Impairment and Acute 
Myocardial Infarction. 
Protocol Number: 
CSL112_2001  
I have read Amendment 1 to the protocol CSL112_2001 titled “A Phase 2, Multicenter, 
Double-blind, Randomized, Placebo-controlled, Parallel-group, Study to Investigate the 
Safety and Tolerability of Multiple Dose Administration of CSL112 in Subjects with 
Moderate Renal Impairment and Acute Myocardial Infarction.”  
By signing this protocol, I agree to conduct the clinical study, after approval by an 
Institutional Review Board or Independent Ethics Committee (as appropriate), in accordance 
with the protocol, the principles of the Declaration of Helsinki (2008), the standards of Good 
Clinical Practice (as defined by the International Conference on Harmonisation) and 
applicable regulatory requirements.   
Changes to the protocol will only be implemented after written approval is received from 
CSL Behring LLC (CSLB) and the Institutional Review Board or Independent Ethics 
Committee (as appropriate), with the exception of medical emergencies.   
I will ensure that study staff fully understand and follow the protocol. 
 
 
 
Investigator Signature  
 
 
________________________________________________ 
Printed Investigator Name 
 
 
 
_______________________________________________ 
Affiliation of Investigator 
 
 
Date (DD MMM YYYY) 
 

 
Study Number : 
CSL112_2001_Am1  
Study Product: 
CSL112  
 
Final V2.0  
6 June 2016 
Page 5 of 137 
CRD-TPL-077 
Confidential 
Protocol Synopsis 
 
Title 
A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled, 
Parallel-group, Study to Investigate the Safety and Tolerability of 
Multiple Dose Administration of CSL112 in Subjects with Moderate 
Renal Impairment and Acute Myocardial Infarction   
Study Number 
CSL112_2001  
Sponsor 
CSL Behring LLC (CSLB) 
Development Phase 
2 
Study Product 
CSL112 (Reconstituted High Density Lipoprotein) 
Indication 
Reduction of early recurrent atherothrombotic events in acute myocardial 
infarction patients (ST segment elevation myocardial infarction [STEMI] 
or non-ST segment elevation myocardial infarction [NSTEMI]) who are 
at high risk of subsequent events. 
Study Summary 
CSL112 drug product resembles nascent high density lipoprotein (HDL). 
It is a novel formulation of apolipoprotein A-I (apoA-I), 
phosphatidylcholine (PC), and cholate; and is stabilized by sucrose. 
CSL112 is being developed for the reduction of recurrent cardiovascular 
(CV) events after acute myocardial infarction (AMI). The premise of the 
CSL112 mechanism of action and the resulting treatment strategy is that 
infusion of apoA-I after the index ACS event, and during the subacute 
period after the event, will reduce the size and/or instability of 
atherosclerotic plaque, thereby reducing the risk of plaque rupture or 
erosion that would lead to a recurrent CV event in patients with AMI.  
Renal impairment (RI) is a prevalent and increasingly common 
concurrent condition in patients with AMI. Patients who experience an 
AMI event are at high risk for a recurrent CV event and mortality is 
inversely related to renal function status: subjects with mild, moderate, 
and severe RI have, respectively, progressively poorer long-term 
prognosis as compared with patients with normal renal function. As the 
number of AMI patients with RI is relatively high (~15% to 30%) 
(Gibson et al, 2004; Fox et al, 2010), the identification of therapies that 
are safe and effective in these patients would represent an important 
advancement in medical therapy. 
This study is a phase 2, multicenter, double-blind, randomized, 
placebo-controlled, parallel-group study to investigate the safety and 
tolerability of up to 4 weekly intravenous (IV) administrations of 
CSL112 compared with placebo in subjects with moderate RI (estimated 
glomerular fitration rate [eGFR] ≥ 30 and < 60 mL/min/1.73 m2) and 
acute myocardial infarction (AMI).  

 
Study Number : 
CSL112_2001_Am1  
Study Product: 
CSL112  
 
Final V2.0  
6 June 2016 
Page 6 of 137 
CRD-TPL-077 
Confidential 
CSL112 drug product contains sucrose as a stabilizer. Administration of 
sucrose by IV infusion has been associated with reports of acute kidney 
injury (AKI) attributed to osmotic nephrosis when immune globulin 
intravenous (IGIV) products formulated with sucrose were administered 
at high doses or high rates of administration (Epstein and Zoon, 2000). 
Thus, evaluation of the renal safety of CSL112 is warranted, specifically 
in the subpopulation of patients with moderate RI who have experienced 
a recent AMI event. No renal safety concerns were identified in the 4 
completed CSL112 phase 1 and 2a studies, including a phase 1 
multicenter center, double-blind, placebo-controlled, ascending single-
dose phase 1 study in adult subjects with moderate RI (eGFR ≥ 30 and 
< 60 mL/min/1.73 m2) and in healthy adult subjects with normal renal 
function (eGFR ≥ 90 mL/min/1.73 m2) (Study CSL112_1001). In 
addition, a phase 2b study (Study CSLCT-HDL-12-77), a multicenter, 
randomized, placebo-controlled study to investigate the hepatic and renal 
safety and tolerability of multiple dose administration of 2 IV infusion 
regimens of CSL112 versus placebo in approximately 1200 subjects with 
acute myocardial infarction (AMI) was initiated in the third quarter of 
2014 and completed in the first quarter of 2016. To date, the program 
level Data and Safety Monitoring Board (DSMB) has reviewed safety 
and pharmacokinetic (PK) data from the Active Treatment Period after 
5%, 10%, 25%, 50%, and 75% of subjects were enrolled, and 
recommended the study continue without change. Data are not yet 
available for this study. Further evaluation of the safety and tolerability 
of multiple dose administration of CSL112 in subjects with moderate RI 
and AMI are warranted before inclusion of this population in a phase 3 
morbidity and mortality outcomes trial. 
This phase 2 study is intended to characterize the renal risk profile of 
CSL112 in subjects with moderate RI who have experienced a recent 
AMI. The occurrence of clinically important renal serious adverse events 
(SAEs) as reported by the Investigator and AKI will be evaluated. In 
subjects with moderate RI who have undergone percutaneous coronary 
intervention (PCI), the occurrence of AKI as defined by the Acute 
Kidney Injury Network (AKIN) criteria is approximately 10% (Tsai et al, 
2014). After excluding subjects with evidence of AKI at screening, the 
occurrence of renal SAEs and AKI will be assessed in this post-AMI 
moderate RI patient population.   
Primary Objective(s) 
To assess the renal safety of CSL112 in subjects with moderate RI and 
AMI after administration of up to 4 weekly infusions of CSL112. 
Primary Endpoint(s) 
Co-primary endpoints of the incidences of treatment-emergent: 
1. Renal SAEs, defined in Section 2.1.2  
2. AKI, defined as an absolute increase in serum creatinine from 
baseline of ≥ 0.3 mg/dL (26.5 µmol/L) during the Active Treatment 
Period that is sustained upon repeat measurement by the central 

 
Study Number : 
CSL112_2001_Am1  
Study Product: 
CSL112  
 
Final V2.0  
6 June 2016 
Page 7 of 137 
CRD-TPL-077 
Confidential 
laboratory no earlier than 24 hours after the elevated value. If no 
repeat value is obtained, a single serum creatinine value that is 
increased from baseline ≥ 0.3 mg/dL (26.5 μmol/L) during the Active 
Treatment Period would also fulfil the definition of AKI. 
Treatment-emergent is defined as occurring at or after the start of the first 
infusion. Baseline for determination of AKI is defined as the pre-infusion 
central laboratory serum creatinine level on Study Day 1. 
Secondary Objective(s) 
Secondary objectives of the study are:  
1. To further characterize the safety and tolerability of CSL112 in 
subjects with moderate RI and AMI.   
2. To characterize the PK of CSL112 after multiple dose administration 
in subjects with moderate RI and AMI. 
Secondary Endpoint(s) 
Secondary safety and tolerability endpoints include:  
1. The occurrence of any treatment-emergent adverse event (TEAE) 
throughout the study 
2. Occurrence of treatment-emergent adverse drug reactions or 
suspected adverse drug reactions defined as:  
a. All TEAEs, including local tolerability events, that begin 
during or within 1 hour after the end of an infusion, or  
b. Those TEAEs which the Investigator or Sponsor indicates 
may be causally related to the administration of the 
investigational product (CSL112 or placebo), or  
c. All TEAEs for which the Investigator's causality assessment is 
missing or indeterminate, or  
d. All TEAEs for which the incidence in an active treatment arm 
exceeds the exposure-adjusted incidence rate in the placebo 
arm by 30% or more, provided the difference in incidence 
rates is 1% or more. 
3. Changes from baseline (ie, pre-infusion on Study Day 1) through to 
the end of the Active Treatment Period in renal status defined as: 
a. Absolute increases from baseline in serum creatinine as 
follows: 
i. ≤ baseline value 
ii. > 0 to < 0.3 mg/dL 
iii. ≥0.3 to ≤0.5 mg/dL 
iv. > 0.5 mg/dL 
b. Increases in serum creatinine that are sustained for 

 
Study Number : 
CSL112_2001_Am1  
Study Product: 
CSL112  
 
Final V2.0  
6 June 2016 
Page 8 of 137 
CRD-TPL-077 
Confidential 
≥ 24 hours upon repeat measurement as follows: 
i. ≥ 1.5 x baseline value  
ii. ≥ 2 x baseline value 
iii. ≥ 3.0 x baseline value 
iv. serum creatinine ≥ 4.0 mg/dL (353.6 µmol/L)  
c. Initiation of renal replacement therapy 
d. Decrease in eGFR ≥ 25% from baseline starting during the  
Active Treatment Period and that is sustained at the final 
study visit 
4. Change from baseline (ie, after infusion on Study Day 1) in hepatic 
status that occurs during the Active Treatment Period and that are 
sustained for ≥ 24 hours upon repeat measurement as follows: 
a. Alanine aminotransferase (ALT) > 3 x upper limit of normal 
(ULN) 
b. ALT > 5 x ULN 
c. ALT > 10 x ULN 
d. Serum total bilirubin > 1.5 x ULN (Note: For subjects with a 
history of Gilbert’s syndrome, this assessment will be based 
on indirect bilirubin.) 
e. Serum total bilirubin > 2 x ULN (Note: For subjects with a 
history of Gilbert’s syndrome, this assessment will be based 
on indirect bilirubin.) 
f. Possible Hy's Law cases, as defined in the FDA Guidance for 
Industry: Drug-Induced Liver Injury: Premarketing Clinical 
Evaluation (July 2009; see Section 9.1.3.3 for definition of 
Hy’s Law) 
5. The occurrence of treatment-emergent bleeding events as defined by 
the Bleeding Academic Research Consortium (BARC) criteria 
(Mehran et al, 2011) from start of the first infusion until the end of 
the Safety Follow-up Period. 
6. Clinically significant changes in clinical laboratory test results 
(serum biochemistry, hematology, and urinalysis), physical 
examination findings, body weight, electrocardiograms (ECGs), and 
vital signs (blood pressure, pulse rate, and body temperature). 
7. The occurrence of binding antibodies specific to apoA-I and/or 
CSL112. 
Secondary PK endpoints include: 
1. Baseline (ie, pre- infusion on Study Day 1)-corrected plasma apoA-I 


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
FRQFHQWUDWLRQV
 %DVHOLQHFRUUHFWHGSODVPD3&FRQFHQWUDWLRQV
 &RQFHQWUDWLRQLQSODVPDDW(QGRI,QIXVLRQIRUDSR$,DQG3&
 $FFXPXODWLRQUDWLR5IRUDSR$,DQG3&













6WXG\'HVLJQ
7KLVLVDSKDVHPXOWLFHQWHUGRXEOHEOLQGUDQGRPL]HG
SODFHERFRQWUROOHGSDUDOOHOJURXSVWXG\WRDVVHVVWKHVDIHW\DQG
WROHUDELOLW\RIXSWRZHHNO\,9DGPLQLVWUDWLRQVRIJ&6/
FRPSDUHGZLWKSODFHERLQVXEMHFWVZLWKPRGHUDWH5,DQG$0,
7KHPDLQVWXG\ZLOOHQUROODSSUR[LPDWHO\VXEMHFWVZKRZLOOEH
UDQGRPO\DVVLJQHGLQDUDWLRWRUHFHLYHJ&6/VXEMHFWV
YHUVXVSODFHERVXEMHFWV7RHQVXUHWKDWDWOHDVWRQHWKLUGRIWKHVWXG\
SRSXODWLRQKDVDQH*)5LQWKH&KURQLF.LGQH\'LVHDVH&.'EUDQJH
WRP/PLQPQRPRUHWKDQWZRWKLUGVRIWKHVWXG\
SRSXODWLRQZLOOKDYHDQH*)5LQWKH&.'DUDQJH
WRP/PLQP5DQGRPL]DWLRQRIWKHVXEMHFWVZLOOEH
VWUDWLILHGE\H*)5WRP/PLQPRU
WRP/PLQPDVFDOFXODWHGE\WKH&KURQLF.LGQH\'LVHDVH
(SLGHPLRORJ\&ROODERUDWLRQ&.'(3,HTXDWLRQDQGE\PHGLFDOKLVWRU\
RIGLDEHWHVUHTXLULQJFXUUHQWWUHDPHQWZLWKDQ\DQWLGLDEHWLFPHGLFDWLRQ
\HVRUQR&OLQLFDOSURFHGXUHVIRUWKHVHVXEMHFWVZLOOLQFOXGH
DVVHVVPHQWVIRUVDIHW\LQFOXGLQJUHQDODQGKHSDWLF3.DQG


CCI
CCI
CCI
CCI
CCI

6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/
)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO






$VXPPDU\RIVWXG\DVVHVVPHQWVDQGSURFHGXUHVE\YLVLWLVVKRZQLQWKH
6FKHGXOHRI$VVHVVPHQWV7KHVWXG\ZLOOFRQVLVWRIVFUHHQLQJDQGVWXG\
SHULRGVDQ$FWLYH7UHDWPHQW3HULRGDSSUR[LPDWHO\GD\VDQGD
6DIHW\)ROORZXS3HULRGDSSUR[LPDWHO\GD\VIURPWKHHQGRIWKH
$FWLYH7UHDWPHQW3HULRG6XEMHFWVZLOOEHDVVHVVHGIRUHOLJLELOLW\GXULQJ
VFUHHQLQJDQGXSWRDQGLQFOXGLQJUDQGRPL]DWLRQ9LVLWDQG9LVLW
EHIRUHLQIXVLRQZKLFKPXVWRFFXUZLWKLQGD\VDIWHUILUVWPHGLFDO
FRQWDFW)0&IRUWKHLQGH[$0,(OLJLEOHVXEMHFWVPHHWLQJDOOLQFOXVLRQ
FULWHULDDQGQRQHRIWKHH[FOXVLRQFULWHULDZLOOUHFHLYHIRXUKRXU,9
LQIXVLRQVRILQYHVWLJDWLRQDOSURGXFWJ&6/RUSODFHERDPLQLPXP
RIGD\VDSDUWGXULQJDZHHN$FWLYH7UHDWPHQW3HULRG
%HIRUHWKHILUVWLQIXVLRQRILQYHVWLJDWLRQDOSURGXFWWKHVXEMHFWPXVWEH
FOLQLFDOO\VWDEOHKDYHKHSDWLFIXQFWLRQWHVWVZLWKLQDFFHSWDEOHOLPLWVDQG
KDYHGRFXPHQWHGHYLGHQFHRIVWDEOHUHQDOIXQFWLRQDQGQRVXVSLFLRQRI
$.,DWOHDVWKRXUVDIWHU)0&IRUWKHLQGH[$0,IRUWKRVHVXEMHFWV
XQGHUJRLQJDQJLRJUDSK\ZLWKRUZLWKRXW3&,UHQDOIXQFWLRQPXVWEH
GRFXPHQWHGWREHVWDEOHDWOHDVWKRXUVDIWHUDGPLQLVWUDWLRQRI,9
FRQWUDVWDJHQWVHHHOLJLELOLW\FULWHULDEHORZ
6FUHHQLQJDQGUDQGRPL]DWLRQRIVXEMHFWVPD\RFFXURQWKHVDPHGD\
6WXG\'D\RIWKH$FWLYH7UHDWPHQW3HULRGSURYLGHGWKDWWKHPLQLPXP
WLPHZLQGRZDIWHU)0&IRUWKHLQGH[HYHQWRUDGPLQLVWUDWLRQRI,9
FRQWUDVWDJHQWIRUVXEMHFWVXQGHUJRLQJDQJLRJUDSK\LVDGKHUHGWRIRU
DVVHVVPHQWRIVWDELOLW\RIUHQDOIXQFWLRQEHIRUHDGPLQLVWUDWLRQRIWKHILUVW
LQIXVLRQRILQYHVWLJDWLRQDOSURGXFW6HFWLRQDQG6HFWLRQ
2QJRLQJHOLJLELOLW\IRUDOOVXEVHTXHQWLQIXVLRQVRILQYHVWLJDWLRQDOSURGXFW
ZLOOEHFRQILUPHGEHIRUHHDFKLQIXVLRQDQGZLOOLQFOXGHDVVHVVPHQWVRI
UHQDODQGKHSDWLFIXQFWLRQ6HFWLRQ(DFKLQIXVLRQVKRXOGEH
FRPSOHWHGDVFORVHWRWKHSURWRFROVSHFLILHGYLVLWVFKHGXOHDVSRVVLEOHLH
QRIHZHUWKDQGD\VDQGQRPRUHWKDQGD\VEHWZHHQHDFKLQIXVLRQ
$QLQIXVLRQPD\EHVNLSSHGRUGHOD\HGDWWKHGLVFUHWLRQRIWKH
,QYHVWLJDWRULIPRUHWLPHLVQHFHVVDU\WRFRQILUPUHQDOIXQFWLRQVWDELOLW\
RUWRHYDOXDWHDQGWUHDWDQ$(EHIRUHWKHQH[WLQIXVLRQ6HFWLRQ
,IDQLQIXVLRQLVVNLSSHGRUGHOD\HGIRUDPHGLFDORUVDIHW\UHDVRQWKH
PHGLFDOPRQLWRUVKRXOGEHFRQWDFWHGIRUIXUWKHUJXLGDQFH
7KHHQGRIWKH$FWLYH7UHDWPHQW3HULRGRFFXUVXSRQFRPSOHWLRQRI9LVLW
6WXG\'D\7KH6DIHW\)ROORZXS3HULRGGXUDWLRQRI
DSSUR[LPDWHO\GD\VZLOOEHJLQLPPHGLDWHO\DIWHU9LVLW6XEMHFWV
ZLOOUHWXUQWRWKHVWXG\FOLQLFDW9LVLW6WXG\'D\IRUDVVHVVPHQWRI
$(VDQGRWKHUVDIHW\SURFHGXUHV
CCI

 
Study Number : 
CSL112_2001_Am1  
Study Product: 
CSL112  
 
Final V2.0  
6 June 2016 
Page 11 of 137 
CRD-TPL-077 
Confidential 
Number of Subjects 
Approximately 81 subjects will be enrolled into this study.  
Study Duration 
The maximum duration of the study for an individual subject is expected 
to be approximately 9 weeks. This estimation is based on:  
• 
a 5-day Screening Period  
• 
a 4-week Active Treatment Period  
• 
a 4-week Safety Follow-up Period  
The overall study duration (ie, first subject’s screening visit to last 
subject’s end of study visit) is estimated to be approximately 9 months. 
Study Population and 
Main Criteria for 
Eligibility 
 
Men or women at least 18 years of age with moderate RI (eGFR ≥ 30 and 
< 60 mL/min/1.73 m2, as calculated by the CKD-EPI equation). Subjects 
must also have evidence of myocardial necrosis in a clinical setting 
consistent with a type I (spontaneous) AMI as defined by the following: 
• 
Detection of a rise and/or fall in cardiac troponin I or T with at least 
1 value above the 99th percentile upper reference limit.  
AND, 
• 
Any 1 or more of the following: 
− 
Symptoms of ischemia 
− 
New (or presumably new) significant ST/T wave changes or left 
bundle-branch block (LBBB) 
− 
Development of pathological Q waves on ECG 
− 
Imaging evidence of new loss of viable myocardium or regional 
wall motion abnormality 
− 
Identification of intracoronary thrombus by angiography 
Before the first infusion of investigational product, the subject must be 
clinically stable, have hepatic function tests within acceptable limits, and 
have documented evidence of stable renal function and no suspicion of 
AKI at least 12 hours after FMC for the index AMI. For subjects 
undergoing angiography, with or without PCI, stable renal function is 
defined as a serum creatinine value at least 12 hours after IV contrast 
administration that is increased < 0.3 mg/dL from the pre-contrast 
administration value.  
If the local laboratory post-contrast serum creatinine value is increased 
> 0.3 mg/dL from the pre-contrast administration value, the laboratory 
test may be repeated once at least 24 hours after the initial assessment to 
determine eligibility and stable renal function. The repeat serum 
creatinine value must be increased < 0.3 mg/dL from the pre-contrast 
administration value and there must be no clinical suspicion of AKI for 
the subject to be eligible to receive the first infusion (Table 7). 


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
6WXG\3URGXFW'RVH
'RVLQJ5HJLPHQDQG
$GPLQLVWUDWLRQ
%DVHGXSRQWKHUHVXOWVRIWKHSKDVH3.DQGVDIHW\VWXG\LQVXEMHFWV
ZLWKPRGHUDWH5,6WXG\&6/BDGRVHRIJ&6/KDVEHHQ
VHOHFWHGIRUWKLVVWXG\
&6/ZLOOEHDGPLQLVWHUHGDVDKRXU,9LQIXVLRQLQWRDVXLWDEOHYHLQ
SHULSKHUDORUFHQWUDORQFHZHHNO\IRUFRQVHFXWLYHZHHNVLQIXVLRQV
WRWDO
&RPSDUDWRU3URGXFW
'RVH'RVLQJ5HJLPHQ
DQG$GPLQLVWUDWLRQ
3ODFHERFRQWUROZHLJKWYROXPHVRGLXPFKORULGHVROXWLRQLH
QRUPDOVDOLQHDGPLQLVWHUHGDVDKRXU,9LQIXVLRQLQWRDVXLWDEOHYHLQ
SHULSKHUDORUFHQWUDORQFHZHHNO\IRUFRQVHFXWLYHZHHNVLQIXVLRQV
WRWDOLQDYROXPHPDWFKHGWRWKH&6/LQIXVLRQYROXPH

6DIHW\$VVHVVPHQWV
0RQLWRULQJRIDOO$(V(&*VSK\VLFDOH[DPLQDWLRQILQGLQJVERG\
ZHLJKWYLWDOVLJQVEORRGSUHVVXUHSXOVHUDWHERG\WHPSHUDWXUHFOLQLFDO
ODERUDWRU\WHVWVVHUXPELRFKHPLVWU\KHPDWRORJ\>LQFOXGLQJKHPRO\VLV
LILQGLFDWHG@XULQDO\VLVVSRWXULQHDQGLPPXQRJHQLFLW\SUHVHQFHRI
ELQGLQJDQWLERGLHVVSHFLILFWR&6/DQGDSR$,
3KDUPDFRNLQHWLFV
%ORRGVDPSOHVZLOOEHFROOHFWHGIRUDVVHVVPHQWRISODVPDDSR$,DQG3&
FRQFHQWUDWLRQV












2WKHU$VVHVVPHQWV
%ORRGVDPSOHVZLOOEHFROOHFWHGDQGVWRUHGIRUSRVVLEOHIXWXUHYLURORJ\
DVVHVVPHQWDQGDQDO\VLVRIHPHUJLQJSDWKRJHQV$QDO\VLVRIWKHVWRUHG
YLURORJ\VDPSOHZLOORQO\EHGRQHLIFRQVHQWLVREWDLQHGIURPWKHVWXG\
VXEMHFW
6WDWLVWLFDO$QDO\VHV
6DIHW\$QDO\VHV$OOVXEMHFWVZKRUHFHLYHGDWOHDVWDSDUWLDOLQIXVLRQRI
LQYHVWLJDWLRQDOSURGXFW&6/RUSODFHERZLOOEHHYDOXDWHGIRUVDIHW\
7UHDWPHQWJURXSFODVVLILFDWLRQZLOOEHDFFRUGLQJWRWKHWUHDWPHQWDFWXDOO\
UHFHLYHG$GYHUVHHYHQWV$(VZLOOEHVXPPDUL]HGE\WUHDWPHQWJUDGH
UHODWHGQHVVDQGVHULRXVQHVV&KDQJHVIURPEDVHOLQHLHSUHLQIXVLRQRQ
6WXG\'D\LQFOLQLFDOODERUDWRU\DVVHVVPHQWVYLWDOVLJQPHDVXUHPHQWV
(&*LQWHUYDOPHDVXUHPHQWVDQGLPPXQRJHQLFLW\ZLOOEHVXPPDUL]HGE\
WUHDWPHQWDQGWKHFOLQLFDOVLJQLILFDQFHRIWKHFKDQJHVZLOOEHDVVHVVHG
'HVFULSWLYHVWDWLVWLFVZLOOEHXVHGWRVXPPDUL]HWKHH[SRVXUHWRWKH
LQYHVWLJDWLRQDOSURGXFWVDQGWKHVDIHW\DVVHVVPHQWV
CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
)RUWKHFRSULPDU\VDIHW\HQGSRLQWVRIWUHDWPHQWHPHUJHQWUHQDO6$(V
DQG$.,UDWHVLQFLGHQFHUDWHVZLOOEHEDVHGRQWKHQXPEHURIVXEMHFWV
ZLWKDWOHDVWRFFXUUHQFHRIWKHHYHQWRILQWHUHVWWKDWLVDVXEMHFWZLWK
WUHDWPHQWHPHUJHQWUHQDO6$(VRULQVWDQFHVRI$.,ZLOOEHFRXQWHG
RQFH7KHGLIIHUHQFHLQLQFLGHQFHUDWHVZLOOEHFRPSXWHGE\VXEWUDFWLQJ
WKHUDWHLQWKHSODFHERDUPIURPWKHLQFLGHQFHUDWHLQWKH&6/DUPVR
WKDWDSRVLWLYHGLIIHUHQFHLQGLFDWHVDKLJKHULQFLGHQFHUDWHLQWKH&6/
DUP)RUHDFKFRSULPDU\HQGSRLQW1HZFRPEH:LOVRQVLGHG
FRQILGHQFHLQWHUYDOVDURXQGWKHGLIIHUHQFHLQLQFLGHQFHUDWHVZLOOEH
FDOFXODWHGLIDWOHDVWHYHQWRFFXUV2WKHUZLVHDQH[DFWVLGHGXSSHU
FRQILGHQFHLQWHUYDOZLOOEHUHSRUWHGIRUWKHLQFLGHQFHUDWHLQHDFK
WUHDWPHQWDUP
3.
$QDO\VHV0HDVXUHGSODVPDFRQFHQWUDWLRQVRIDSR$,DQG
3&DQGEDVHOLQHFRUUHFWHGFRQFHQWUDWLRQVLHFKDQJHIURPEDVHOLQHZLOO
EHOLVWHGDQGVXPPDUL]HGE\WLPHSRLQW3ODVPD3.SDUDPHWHUVIRUDSR$
,DQG3&ZLOOEHVXPPDUL]HGGHVFULSWLYHO\7KHIROORZLQJSDUDPHWHUV
ZLOOEHFDOFXODWHG
x
0D[LPXPFRQFHQWUDWLRQLQSODVPD&PD[
x
$FFXPXODWLRQ5DWLR
1RQOLQHDUPL[HGHIIHFWVPRGHOLQJZLOOEHSHUIRUPHGWRDVVHVVWKH3.
GDWDIRUDSR$,DQG3&7KLVSRSXODWLRQEDVHGDSSURDFKZLOOEHXVHGWR
H[SORUHDQGTXDQWLI\FOLQLFDOO\UHOHYDQWFRYDULDWHVVXFKDVDJHVH[DQG
UHQDOIXQFWLRQRQSRSXODWLRQ3.SDUDPHWHUV




6DIHW\5HYLHZV
$QH[WHUQDOSURJUDPOHYHO'60%ZLOOLQGHSHQGHQWO\HYDOXDWHVDIHW\GDWD
GXULQJWKHFRQGXFWRIWKHVWXG\
,QRUGHUWRHQVXUHWKDWDVDIHW\VLJQDOKDVQRWHPHUJHGWKDWZRXOGDIIHFW
WKHFRQGXFWRIWKHVWXG\WKH'60%ZLOOUHYLHZVDIHW\GDWDDIWHUHYHU\
VXEMHFWVKDYHUHFHLYHGLQIXVLRQVRILQYHVWLJDWLRQDOSURGXFWDQGKDYH
SUHLQIXVLRQVDIHW\GDWDDYDLODEOHEHIRUHWKHWKLUGLQIXVLRQDW9LVLW
7KHVHUHYLHZVZLOOFRQWLQXHXQWLODWOHDVWVXEMHFWVDSSUR[LPDWHO\
RIVXEMHFWVFRPSOHWH9LVLW,QDGGLWLRQWKHLQGHSHQGHQW'60%ZLOO
KDYHLQWHULPVDIHW\UHYLHZVZKHQDSSUR[LPDWHO\RIVXEMHFWV
KDYHFRPSOHWHGWKH$FWLYH7UHDWPHQW3HULRG9LVLWDSSUR[LPDWHO\
RIVXEMHFWVKDYHFRPSOHWHG9LVLWDQGDSSUR[LPDWHO\RI
VXEMHFWVKDYHFRPSOHWHGWKH$FWLYH7UHDWPHQW3HULRG9LVLW,IDQ\RI
WKHVDIHW\FULWHULDDVVSHFLILHGLQWKH'60%FKDUWHUDUHPHWDWWKHVH
UHYLHZVFRQWLQXDWLRQRIWKHVWXG\ZLWKRXWDOWHUDWLRQVKRXOGEH
CCI
CCI

 
Study Number : 
CSL112_2001_Am1  
Study Product: 
CSL112  
 
Final V2.0  
6 June 2016 
Page 14 of 137 
CRD-TPL-077 
Confidential 
questioned as it may be an early indication of an unacceptable safety 
profile in the broader population. The DSMB may recommend a change 
to the protocol to ameliorate any safety concerns or provide 
recommendations regarding subsequent dosing and/or study 
progression/stopping. The DSMB will also be convened to review all 
available data if 1 or more of the study stopping rules is met (see 
Section 3.6.2). 

 
Study Number:  
CSL112_2001_Am01 
Study Product: 
CSL112 
 
Final V1.0 
X May 2016 
Page 15 of 137 
CRD-TPL-077 
Confidential 
Schedule of Assessments 
Study Period  
Screeninga 
Active Treatment Period 
Safety  
Follow-
up 
Visit # 
1 
2 
3 
4 
5 
6 
7 
8 
Study Day(s) (range) 
(-5 to -1)b 
1 
2 (+1) 
8 (+3)  
15 (+3)  
22 (+3) 
29 
(+3)f 60 (+7)  
Infusion # 
 
1c, d 
 
2c, e 
3c, e 
4c, e 
 
 
Time relative to infusion  
 
Before 
infusion/ 
Baseline 
SOI 
(0 h) EOI 
24 to 48h 
post SOI  
(±6h) 
Before 
infusion SOI EOI 
Before 
infusion SOI EOI 
Before 
infusion SOI EOI 
 
 
ADMINISTRATIVE PROCEDURES 
Informed Consent  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and Surgical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(Prior) Concomitant Medications 
Review  
X 
X 
 
 
X 
X 
 
 
X 
 
 
X 
 
 
X 
X 
Inclusion & Exclusion Criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IRT Subject Registration, eGFR 
Calculation and Randomizationg 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CLINICAL PROCEDURES/ ASSESSMENTS 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body weight 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
ECG (12-Lead) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Physical Examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Vital Signsh 
X 
X 
 
X 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
Hypovolemia Assessmenti 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
 
 
Investigational Product 
Infusionc,d,e
 
 
Xd 
 
 
 
Xe 
 
 
Xe 
 
 
Xe 
 
 
 
Infusion Site Assessmentj 
 
X 
 
X 
X 
X 
 
X 
X 
 
X 
X 
 
X 
 
 
Bleeding Event Assessmentk 
 
X 
 
 
X 
X 
 
 
X 
 
 
X 
 
 
X 
X 
Drug Hypersensitivity 
Assessmentl 
 
 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
AE Assessmentm 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
;0D\
3DJHRI
&5'73/
&RQILGHQWLDO
6WXG\3HULRG
6FUHHQLQJD
$FWLYH7UHDWPHQW3HULRG
6DIHW\
)ROORZ
XS
9LVLW








6WXG\'D\VUDQJH
WRE






I 
,QIXVLRQ

FG

FH
FH
FH


7LPHUHODWLYHWRLQIXVLRQ

%HIRUH
LQIXVLRQ
%DVHOLQH
62,
K (2,
WRK
SRVW62,
K
%HIRUH
LQIXVLRQ 62, (2,
%HIRUH
LQIXVLRQ 62, (2,
%HIRUH
LQIXVLRQ 62, (2,


/$%25$725<352&('85(6$66(660(176
8ULQH3UHJQDQF\7HVWQ
;













;
;
)6+0HDVXUHPHQWFHQWUDOODER
;















6HUXP%LRFKHPLVWU\FHQWUDOODE
;
;


;
;


;


;


;
;
$/77RWDO%LOLUXELQ
6HUXP&UHDWLQLQHORFDOODES
;
;


;
;


;


;






;


;
;





;


;

+HPDWRORJ\FHQWUDOODETU

;

;T
;T
;


;


;


;
;
8ULQDO\VLV
;6
;


;
;


;


;


;



;


;
;


;


;


;

$UFKLYDO8ULQH6DPSOH

;


;
;


;


;


;

9LURORJ\6DPSOH&ROOHFWLRQW

;












;
;
,PPXQRJHQLFLW\7HVWLQJX

;












;
;
3.6DPSOLQJY

;

;
;






;

;




;

;
;








;




;

;
;








;




;


;









;
;


;

;
;
;


;


;


;
;
$UFKLYDO%ORRG6DPSOH]

;












;
;
$( DGYHUVHHYHQW$/7 DODQLQHDPLQRWUDQVIHUDVH$0, DFXWHP\RFDUGLDOLQIDUFWLRQDSR$, DSROLSRSURWHLQ$,
%%$5& 
%OHHGLQJ$FDGHPLF5HVHDUFK&RQVRUWLXP&.'(3, &KURQLF.LGQH\'LVHDVH(SLGHPLRORJ\&ROODERUDWLRQ&9 FDUGLRYDVFXODU'60% 'DWDDQG
6DIHW\0RQLWRULQJ%RDUG(&* HOHFWURFDUGLRJUDPH&5) HOHFWURQLFFDVHUHSRUWIRUPH*)5 HVWLPDWHGJORPHUXODUILOWUDWLRQUDWH(2, (QGRI
CCI
CCI
CCI
CCI
CCI
CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
;0D\
3DJHRI
&5'73/
&RQILGHQWLDO
,QIXVLRQ)0& ILUVWPHGLFDOFRQWDFW)6+ IROOLFOHVWLPXODWLQJKRUPRQHK KRXU

,9 LQWUDYHQRXV,57 LQWHUDFWLYHUHVSRQVHWHFKQRORJ\/DE ODERUDWRU\

P51$ PHVVHQJHUULERQXFOHLFDFLG
3& SKRVSKDWLG\OFKROLQH

3(* SRO\HWK\OHQHJO\FRO3. SKDUPDFRNLQHWLF6$( VHULRXVDGYHUVHHYHQW62, 6WDUWRI,QIXVLRQ8/1 XSSHUOLPLWRIQRUPDO
:%& ZKLWHEORRGFRXQW

D
6FUHHQLQJDQGUDQGRPL]DWLRQRIVXEMHFWVPD\RFFXURQWKHVDPHGD\6WXG\'D\RIWKH$FWLYH7UHDWPHQW3HULRGSURYLGHGWKDWWKHPLQLPXPWLPH
DIWHU)0&IRUWKHLQGH[$0,RUDIWHUDGPLQLVWUDWLRQRI,9FRQWUDVWDJHQWLVDGKHUHGWRVRUHQDOIXQFWLRQVWDELOLW\LVDVVHVVHGEHIRUHDGPLQLVWUDWLRQRI
WKHILUVWLQIXVLRQRILQYHVWLJDWLRQDOSURGXFW6HFWLRQVDQG$OOSURFHGXUHVDQGDVVHVVPHQWVVSHFLILHGDW9LVLWDQG9LVLWEHIRUH
LQIXVLRQEDVHOLQHPXVWVWLOOEHSHUIRUPHGLIVFUHHQLQJDQGUDQGRPL]DWLRQDUHFRQGXFWHGRQWKHVDPHGD\,I9LVLWVDQGFRPELQHGWKHUH
PD\EHDVLQJOHEORRGGUDZIRUFHQWUDOODERUDWRU\VHUXPELRFKHPLVWU\DQGORFDOODERUDWRU\$/7WRWDOELOLUXELQDQGVHUXPFUHDWLQLQH%RWKDORFDO
ODERUDWRU\DQGFHQWUDOODERUDWRU\XULQDO\VLVVKRXOGEHSHUIRUPHG7KHUHPD\EH(&*6LQJOHDVVHVVPHQWVRIYLWDOVLJQVFRQFRPLWDQWPHGLFDWLRQV
DQG$(VDUHDOVRDFFHSWDEOH
E
'HSHQGLQJRQWLPHRIHYHQWDQGWLPHUHTXLUHGIURPHYDOXDWLRQLQWKH(PHUJHQF\'HSDUWPHQWFDUGLDFFDWKHWHUL]DWLRQODERUDWRU\DGPLQLVWUDWLRQRI
FRQWUDVWG\HDQGDVVHVVPHQWRIUHQDODQGKHSDWLFIXQFWLRQVFUHHQLQJGXUDWLRQXSWRDQGLQFOXGLQJUDQGRPL]DWLRQPXVWRFFXUZLWKLQGD\VRI)0&
IRUWKHLQGH[$0,
F
,QYHVWLJDWLRQDOSURGXFWZLOOEHLQIXVHGLQWUDYHQRXVO\RYHUKRXUV7LPH]HURKRXUVLVDWWKHVWDUWRIWKHILUVWLQIXVLRQDOOWLPHVWKHUHDIWHUDUH
UHODWLYHWRWLPH]HURWKHVWDUWRIWKHILUVWLQIXVLRQ,IWKHLQIXVLRQLVLQWHUUXSWHGIRUDQ\UHDVRQWKHWRWDOGXUDWLRQRIWKHLQIXVLRQVKRXOGQRWH[FHHG
KRXUV7KHLQIXVLRQRILQYHVWLJDWLRQDOSURGXFWPD\RFFXULQWKHKRVSLWDORULQWKHRXWSDWLHQWVHWWLQJ'RVHVRILQYHVWLJDWLRQDOSURGXFWVKRXOGEH
DGPLQLVWHUHGWRGD\VDSDUWZLWKDOOLQIXVLRQVDGPLQLVWHUHGZLWKLQGD\VIURP6WXG\'D\9LVLW
G
%HIRUHWKHILUVWLQIXVLRQRILQYHVWLJDWLRQDOSURGXFWDOOVXEMHFWVPXVWEHFOLQLFDOO\VWDEOHKDYHKHSDWLFIXQFWLRQWHVWVZLWKLQDFFHSWDEOHOLPLWVDQG
KDYHHYLGHQFHRIVWDEOHUHQDOIXQFWLRQDWOHDVWKRXUVDIWHU)0&IRUWKHLQGH[HYHQW)RUVXEMHFWVZKRXQGHUJRDQJLRJUDSK\VWDEOHUHQDOIXQFWLRQ
LVGHILQHGDVDVHUXPFUHDWLQLQHYDOXHREWDLQHGDWOHDVWKRXUVDIWHUFRQWUDVWDGPLQLVWUDWLRQWKDWLVLQFUHDVHGPJG/IURPWKHSUHFRQWUDVW
DGPLQLVWUDWLRQYDOXH7DEOH
H
2QJRLQJHOLJLELOLW\IRUDOOVXEVHTXHQWLQIXVLRQVRILQYHVWLJDWLRQDOSURGXFWZLOOEHFRQILUPHGEHIRUHDGPLQLVWUDWLRQRIHDFKVXEVHTXHQWLQIXVLRQDQG
ZLOOEHEDVHGRQWKHFULWHULDSUHVHQWHGLQ6HFWLRQ7DEOH$QLQIXVLRQPD\EHVNLSSHGRUGHOD\HGDWWKHGLVFUHWLRQRIWKH,QYHVWLJDWRULI
PRUHWLPHLVQHFHVVDU\WRFRQILUPUHQDOIXQFWLRQVWDELOLW\RUWRHYDOXDWHDQGWUHDWDQ$(EHIRUHWKHQH[WLQIXVLRQ6HFWLRQ,IDQLQIXVLRQLV
VNLSSHGRUGHOD\HGIRUDPHGLFDORUVDIHW\UHDVRQWKHPHGLFDOPRQLWRUVKRXOGEHFRQWDFWHGIRUIXUWKHUJXLGDQFH
I
9LVLWPXVWEHDWOHDVWGD\VDIWHUWKHIRXUWKLQIXVLRQRILQYHVWLJDWLRQDOSURGXFW+RZHYHUGHSHQGLQJRQWKHDFWXDOWLPLQJRIWKHLQIXVLRQV
6WXG\'D\FRXOGRFFXUEHWZHHQWRGD\VDIWHUWKHILUVWLQIXVLRQ
J
,QWHUDFWLYHUHVSRQVHWHFKQRORJ\,57LVXVHGWRDVVLJQDVXEMHFWLGHQWLILFDWLRQQXPEHUDW9LVLWDQGDXWRPDWLFDOO\FDOFXODWHH*)5EDVHGRQ
WKHVXEMHFW¶VDJHVH[UDFHDQGVHUXPFUHDWLQLQHDQGUDQGRPL]HHOLJLEOHVXEMHFWVDW9LVLW7KHVHUXPFUHDWLQLQHXVHGIRU,57H*)5FDOFXODWLRQ
VKRXOGEHWKHORFDOODERUDWRU\YDOXHDW9LVLW6WHSVDQGFDQEHFRPSOHWHGDWDVLQJOHYLVLWLIVFUHHQLQJDQGUDQGRPL]DWLRQRFFXUVRQWKHVDPH
GD\6HFWLRQ
CCI
CCI
CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
;0D\
3DJHRI
&5'73/
&RQILGHQWLDO
K
9LWDOVLJQVLQFOXGHEORRGSUHVVXUHV\VWROLFDQGGLDVWROLFDIWHUWKHVXEMHFWKDVUHVWHGLQDVLWWLQJRUVXSLQHSRVLWLRQPLQXWHVSXOVHUDWHSHU
PLQXWHDQGERG\WHPSHUDWXUHXVLQJRUDORUW\PSDQLFPHDVXUHPHQW1RWHWKDWERG\ZHLJKWLVPHDVXUHGVHSDUDWHO\DQGQRWHDFKWLPHWKDWYLWDO
VLJQVDUHWREHDVVHVVHG
L
%HIRUHVWDUWLQJDQLQIXVLRQRILQYHVWLJDWLRQDOSURGXFWWKH,QYHVWLJDWRURUDPHGLFDOO\TXDOLILHGGHOHJDWHVKRXOGDVVHVVHDFKVXEMHFWIRUSUHVHQFHRI
K\SRYROHPLD7KLVDVVHVVPHQWPD\LQFOXGHDVVHVVPHQWRIGU\PRXWKVNLQWHQWLQJRUWKRVWDVLVGL]]LQHVVHWF,IK\SRYROHPLDLVVXVSHFWHGRU
FRQILUPHGWKH,QYHVWLJDWRURUDPHGLFDOO\TXDOLILHGGHOHJDWHVKRXOGDGPLQLVWHU,9UHSODFHPHQWIOXLGDVFOLQLFDOO\LQGLFDWHG'XULQJWKHLQIXVLRQ
VXEMHFWVVKRXOGEHHQFRXUDJHGWRGULQNIOXLGV%HIRUHGHSDUWLQJIURPWKHFOLQLFDQGDIWHUFRPSOHWLRQRIWKHLQIXVLRQDQGDOORWKHUVWXG\DVVHVVPHQWV
DOOVXEMHFWVVKRXOGEHDVNHGWRYRLG,IDVXEMHFWLVXQDEOHWRYRLGEHIRUHOHDYLQJWKHFOLQLFKHVKHVKRXOGEHFRQWDFWHGDWKRPHWRGHWHUPLQHZKHWKHU
RUQRWWKH\KDYHEHHQDEOHWRYRLG
M
$Q\DEQRUPDOILQGLQJDWWKHLQYHVWLJDWLRQDOSURGXFWLQIXVLRQVLWHLQFOXGLQJEUXLVLQJUHGQHVVDQGRUVZHOOLQJVKRXOGEHUHFRUGHGDVDQ$(%UXLVLQJ
VKRXOGEHDVVHVVHGXVLQJWKH%$5&FULWHULD$SSHQGL[,9
N
%OHHGLQJHYHQWVZLOOEHDVVHVVHGDFFRUGLQJWRWKH%$5&GHILQLWLRQIRUEOHHGLQJVHH$SSHQGL[,97KHH&5)SDJHIRUEOHHGLQJDVVHVVPHQWVPXVW
EHFRPSOHWHGIRUHDFKVXVSHFWHGEOHHGLQJHYHQW%OHHGLQJHYHQWVVKRXOGEHUHSRUWHGDV$(V
O
$OOVXEMHFWVZLOOEHREVHUYHGIRUK\SHUVHQVLWLYLW\UHDFWLRQIRUDWOHDVWKRXUDIWHUWKHHQGRIWKHILUVWDQGVHFRQGLQIXVLRQVRILQYHVWLJDWLRQDO
SURGXFW2EVHUYDWLRQIRUK\SHUVHQVLWLYLW\UHDFWLRQIRUDWOHDVWKRXUDIWHUWKHWKLUGDQGIRXUWKLQIXVLRQVRIWKHLQYHVWLJDWLRQDOSURGXFWLVXQGHUWKH
FOLQLFDOGLVFUHWLRQRIWKH,QYHVWLJDWRU,IDVHULRXVGUXJK\SHUVHQVLWLYLW\UHDFWLRQLVVXVSHFWHGDVVHVVPHQWVVKRXOGEHSHUIRUPHGDVSHU
6HFWLRQ
P
5HSRUWLQJRIEOHHGLQJHYHQWVDQGUHQDO6$(VLQFOXGHVFRPSOHWLRQRIWKH%OHHGLQJ(YHQWH&5)SDJHRU5HQDO6$(H&5)SDJHUHVSHFWLYHO\ZLWK
VXSSRUWLQJGRFXPHQWDWLRQKRVSLWDOUHFRUGVDQGWHVWV
Q
5HTXLUHGIRUDOOZRPHQRIFKLOGEHDULQJSRWHQWLDO
R
7REHDVVHVVHGRQO\IRUDPHQRUUKHLFIHPDOHVEHWZHHQWKHDJHVRIDQG\HDUVWRGRFXPHQWWKDWWKHVXEMHFWLVQRWRIFKLOGEHDULQJSRWHQWLDO
S
/RFDOODERUDWRU\EORRGVDPSOHVIRUVHUXPFUHDWLQLQH$/7DQGWRWDOELOLUXELQZLOOEHXVHGWRDVVHVVIRUVWXG\HOLJLELOLW\LQFOXGLQJGHWHUPLQDWLRQRI
UHQDOIXQFWLRQEDVHGRQH*)5XVLQJWKH&.'(3,HTXDWLRQ6HFWLRQDQGVDIHW\IRUFRQWLQXHGDGPLQLVWUDWLRQRILQYHVWLJDWLRQDOSURGXFW
6HFWLRQ5HVXOWVPXVWEHUHYLHZHGE\WKH,QYHVWLJDWRUEHIRUHLQIXVLRQVRQ6WXG\'D\VDQG7KHVDPSOHPD\EHREWDLQHGXSWR
KRXUVEHIRUHLQIXVLRQVDQG)RUDOOWLPHSRLQWVDWZKLFKDORFDOODERUDWRU\YDOXHLVFROOHFWHGDVDPSOHVKRXOGDOVRJRWRWKHFHQWUDO
ODERUDWRU\IRUDQDO\VLV,I$/7LVHOHYDWHGWR![8/1ZLWKDFRQFRPLWDQWHOHYDWLRQLQWRWDOELOLUXELQWR![8/125LI$/7LVHOHYDWHGWR
![8/1DGGLWLRQDODVVHVVPHQWVVKRXOGEHSHUIRUPHGSHU6HFWLRQ7DEOH
T
%ORRGVDPSOHWREHFROOHFWHGIRU:%&GLIIHUHQWLDOFRXQWDORQHDWWKHVHWLPHSRLQWV

U
,IDGHFUHDVHLQKHPRJORELQSRVWLQIXVLRQWKDWLVJG/IURPEDVHOLQHLVREVHUYHGDQGLVQRWH[SODLQHGE\RYHUWEORRGORVVWKHQUHSHDW
KHPRJORELQDQGDGGLWLRQDODVVHVVPHQWVVKRXOGEHREWDLQHGVHH6HFWLRQ+HPRO\VLVVKRXOGDOVREHFRQVLGHUHGLIWRWDOELOLUXELQ![8/1
LVREVHUYHG
V
$WVFUHHQLQJRQO\XULQDO\VLVZLOOEHSHUIRUPHGE\ORFDOODERUDWRU\XULQHGLSVWLFN,IGLSVWLFNGHPRQVWUDWHVKLJKJUDGHSURWHLQXULDDXULQHVDPSOH
VKRXOGEHVHQWWRWKHFHQWUDOODERUDWRU\IRUXULQDO\VLV)RUDOORWKHUYLVLWVDXULQHVDPSOHZLOOEHVHQWWRWKHFHQWUDOODERUDWRU\IRUXULQDO\VLV
W
9LURORJ\VDPSOHVZLOOEHFROOHFWHGDQGVWRUHGIRU\HDUDIWHUFRPSOHWLRQRIWKHFOLQLFDOVWXG\UHSRUWIRUSRVVLEOHIXWXUHDVVHVVPHQWRIFXUUHQWO\
XQVSHFLILHGYLUDODJHQWVDVVHVVPHQWWRRFFXURQO\LIUHTXLUHGDQGDIWHUDGGLWLRQDOFRQVHQWLVREWDLQHGIURPWKHVXEMHFW
X
,PPXQRJHQLFLW\WHVWLQJLQFOXGHVVHUXPDQWLERGLHVWR&6/DQGDSR$,
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
;0D\
3DJHRI
&5'73/
&RQILGHQWLDO
Y
%ORRGVDPSOHVIRU3.ZLOOEHDQDO\VHGIRUSODVPDFRQFHQWUDWLRQVRIDSR$,DQG3&
Z


[

\

]
%ORRGVDPSOHVZLOOEHFROOHFWHGDQGVWRUHG$QDO\VLVZLOOEHGLUHFWHGE\WKH6WHHULQJ&RPPLWWHHDQGEDVHGRQWKHODWHVWDYDLODEOHLQIRUPDWLRQRQ
WKHXWLOLW\RIVXFKPHDVXUHPHQWV
127($VVHVVPHQWVDUHWREHFRQGXFWHGDWDOOWLPHVDQGGD\VPDUNHGZLWKDQ;
CCI
CCI
C
C
I


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
7DEOHRI&RQWHQWV
35272&2/6<1236,6 
6&+('8/(2)$66(660(176 
7$%/(2)&217(176 
/,672)7$%/(6 
/,672)),*85(6 
/,672)$%%5(9,$7,216 
 
,1752'8&7,21 
 
%$&.*5281',1)250$7,2121&6/ 
 2YHUYLHZ 
 1RQFOLQLFDO(YDOXDWLRQ 
 3UHYLRXV&OLQLFDO([SHULHQFH 
 
678'<29(59,(: 
 
327(17,$/5,6.6$1'%(1(),76 
 
678'<2%-(&7,9(6$1'(1'32,176 
 
35,0$5<2%-(&7,9($1'(1'32,17 
 3ULPDU\2EMHFWLYH 
 &RSULPDU\(QGSRLQWV 
 
6(&21'$5<2%-(&7,9(6$1'(1'32,176 
 6HFRQGDU\2EMHFWLYHV 
 6HFRQGDU\(QGSRLQWV 
 
 
 
 
 
 
 
678'<'(6,*1 
 
678'<'(6,*1$1'5$7,21$/( 
 
'26($1''26,1*5(*,0(1 
 
3/$11('678'<'85$7,21 
 
3/$11('180%(52)6,7(6 
 
3/$11('180%(52)68%-(&76 
 
678'<021,725,1*352&('85(6 
 'DWDDQG6DIHW\0RQLWRULQJ%RDUG 
 6WXG\OHYHO6WRSSLQJ5XOHV 
 6WHHULQJ&RPPLWWHH 
 &OLQLFDO(YHQWV&RPPLWWHH 
CCI
CCI
CCI

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 21 of 137 
CRD-TPL-077 
Confidential 
4. 
SELECTION AND WITHDRAWAL OF SUBJECTS ............................................ 51 
4.1 
ELIGIBILITY CRITERIA .................................................................................... 51 
4.1.1 Inclusion Criteria ....................................................................................... 52 
4.1.2 Exclusion Criteria ...................................................................................... 54 
4.1.3 Infusion Delay and Stopping Rules ........................................................... 56 
4.1.4 Study and Subject Completion, Study Treatment Discontinuation and 
Withdrawal from Study ............................................................................. 57 
4.1.5 Procedures for Handling Withdrawals....................................................... 60 
4.1.6 Replacement Policy ................................................................................... 61 
5. 
STUDY INTERVENTIONS ....................................................................................... 61 
5.1 
DESCRIPTION OF INVESTIGATIONAL PRODUCT(S) ................................. 61 
5.1.1 CSL112 ...................................................................................................... 61 
5.1.2 Comparator Product ................................................................................... 62 
5.2 
PACKAGING, LABELING, SUPPLY AND STORAGE ................................... 62 
5.2.1 Packaging and Labeling ............................................................................. 62 
5.2.2 Supply and Storage .................................................................................... 62 
5.3 
ACCOUNTABILITY AND DESTRUCTION ..................................................... 63 
5.4 
OTHER INTERVENTION(S) .............................................................................. 63 
5.5 
RESCUE THERAPY ............................................................................................ 63 
6. 
ALLOCATION, DOSING AND ADMINISTRATION ........................................... 64 
6.1 
ALLOCATION TO TREATMENT ..................................................................... 64 
6.1.1 Subject Assignment ................................................................................... 64 
6.1.2 Randomization Procedures ........................................................................ 64 
6.1.3 Blinding Procedures................................................................................... 64 
6.2 
DOSING AND ADMINISTRATION .................................................................. 67 
6.3 
TREATMENT COMPLIANCE ........................................................................... 69 
7. 
CONTRAINDICATIONS, PERMITTED THERAPIES AND PROHIBITTED 
THERAPIES ........................................................................................... 69 
7.1 
CONTRAINDICATIONS AND PRECAUTIONS TO FURTHER DOSING..... 69 
7.2 
PERMITTED THERAPIES .................................................................................. 70 
7.3 
PROHIBITED THERAPIES ................................................................................ 70 
7.4 
DIETARY AND LIFESTYLE RESTRICTIONS ................................................ 71 
7.5 
OVERDOSE ......................................................................................................... 71 
8. 
STUDY PROCEDURES, ASSESSMENTS AND VISIT SCHEDULE .................. 71 
8.1 
CLINICAL PROCEDURES ................................................................................. 71 
8.1.1 Demographics and Baseline Characteristics .............................................. 72 


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
 6DIHW\ 
 3KDUPDFRNLQHWLFV
 
 
0(7+2'62)$66(660(17 
 'HPRJUDSKLFDQG%DVHOLQH&KDUDFWHULVWLFV 
 ,QIXVLRQ(OLJLELOLW\ 
 6DIHW\ 
 3KDUPDFRNLQHWLFV 
 
 
 
5(7(17,212)6$03/(6 
 
&21&20,7$177+(5$3,(6 
 
9,6,76&+('8/( 
 6FUHHQLQJ9LVLW6WXG\'D\WR6WXG\'D\ 
 $FWLYH7UHDWPHQW3HULRG 
 6DIHW\)ROORZXS3HULRG 
 
$'9(56((9(176 
 
'(),1,7,216 
 $GYHUVH(YHQW 
 6HULRXV$GYHUVH(YHQW 
 $GYHUVH(YHQWVRI6SHFLDO,QWHUHVW 
 
6(9(5,7<2)$'9(56((9(176 
 
&$86$/,7<2)$'9(56((9(176 
 
2%6(59$7,213(5,2')25$'9(56((9(176 
 
$'9(56((9(175(3257,1* 
 $GYHUVH(YHQWVRI6SHFLDO,QWHUHVW 
 
6(5,286$'9(56((9(175(3257,1* 
 5HTXLUHPHQWVIRU,PPHGLDWH5HSRUWLQJRI6HULRXV$GYHUVH(YHQWV 
 
27+(56,*1,),&$17(9(175(3257,1* 
 2YHUGRVH 
 3UHJQDQF\DQG/DFWDWLRQ 
 
,167,787,21$/5(9,(:%2$5',1'(3(1'(17(7+,&6
&200,77((5(3257,1*5(48,5(0(176 
 
)2//2:832)$'9(56((9(176 
 
67$7,67,&6 
 6$03/(6,=((67,0$7,21 
 678'<3238/$7,216 
 6FUHHQHG3RSXODWLRQ 
CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
 ,QWHQWWR7UHDW3RSXODWLRQ 
 6DIHW\3RSXODWLRQ 
 3KDUPDFRNLQHWLF3RSXODWLRQ 
 
 
 67$7,67,&$/$1$/<6(6$1'0(7+2'6 
 6XEMHFW'LVSRVLWLRQ'HPRJUDSKLFVDQG%DVHOLQH&KDUDFWHULVWLFV 
 6DIHW\$QDO\VHV 
 3KDUPDFRNLQHWLF
 
 6DIHW\5HYLHZ 
 2WKHU$QDO\VHV 
 
48$/,7<$6685$1&( 
 
5(*8/$725<$1'(7+,&6&216,'(5$7,216 
 5(*8/$725<&216,'(5$7,216 
 ,167,787,21$/5(9,(:%2$5',1'(3(1'(17(7+,&6
&200,77(( 
 68%-(&7,1)250$7,21$1',1)250('&216(17 
 68%-(&7,'(17,),&$7,21$1'&21),'(17,$/,7< 
 ,1'(01,7<$1'&203(16$7,21 
 
$'0,1,675$7,9(&216,'(5$7,216 
 &/,1,&$/75,$/$*5((0(17 
 &/,1,&$/678'<5(*,675$7,21$1'5(68/76',6&/2685( 
 ,03/(0(17$7,212)7+(35272&2/35272&2/$0(1'0(176
 
 35272&2/'(9,$7,216 
 '2&80(17$7,21$1'5(&25'.((3,1* 
 'DWD&ROOHFWLRQ 
 'DWD4XDOLW\$VVXUDQFH 
 5HFRUG5HWHQWLRQ 
 678'<$1'6,7(&/2685( 
 &/,1,&$/678'<5(3257 
 86(2)'$7$$1'38%/,&$7,216 
CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
 
5()(5(1&(6 
$33(1',;, 
&$/&8/$7,212)(67,0$7('*/20(58/$5),/75$7,21
5$7(%<7+(&+521,&.,'1(<',6($6((3,'(0,2/2*<
&2//$%25$7,21(48$7,21 
$33(1',;,, 
7+,5'81,9(56$/'(),1,7,212)0<2&$5',$/
,1)$5&7,21 
$33(1',;,,, .,//,3&/$66,),&$7,21 
$33(1',;,9 $66(660(172)%/((',1*(9(176%<%/((',1*
$&$'(0,&5(6($5&+&216257,80%$5&'(),1,7,21
)25%/((',1* 

/LVWRI7DEOHV
7DEOH 
.H\&RPSRQHQWVRI&6/ 
7DEOH 
,QYHVWLJDWLRQDO3URGXFW'RVLQJ&KDUDFWHULVWLFV 
7DEOH 
&OLQLFDO3URFHGXUHV'HPRJUDSKLFVDQG%DVHOLQH&KDUDFWHULVWLFV 
7DEOH 
&OLQLFDO3URFHGXUHV6DIHW\$VVHVVPHQWV 
7DEOH 
&OLQLFDO3URFHGXUHV3KDUPDFRNLQHWLF$VVHVVPHQWV 
7DEOH 
 
7DEOH 
.H\+HSDWLFDQG5HQDO/DERUDWRU\3DUDPHWHUVDQG3URWRFRO
5HTXLUHPHQWVIRU6WXG\)LUVW,QIXVLRQ(OLJLELOLW\ 
7DEOH 
.H\+HSDWLFDQG5HQDO/DERUDWRU\3DUDPHWHUVDQG3URWRFRO
5HTXLUHPHQWVIRU6XEVHTXHQW&RQWLQXLQJ,QIXVLRQ(OLJLELOLW\ 
7DEOH 
7LPH:LQGRZVIRU$VVHVVPHQWV 

/LVWRI)LJXUHV
)LJXUH 
6WXG\2YHUYLHZ 


CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
/LVWRI$EEUHYLDWLRQV
$EEUHYLDWLRQ
'HILQLWLRQ
$&6
$FXWHFRURQDU\V\QGURPH
$(V
$GYHUVHHYHQWV
$.,
$FXWHNLGQH\LQMXU\
$.,1
$FXWH.LGQH\,QMXU\1HWZRUN
$/7
$ODQLQHDPLQRWUDQVIHUDVH
$0,
$FXWHP\RFDUGLDOLQIDUFWLRQ
DSR$,
$SROLSRSURWHLQ$,


$67
$VSDUWDWHDPLQRWUDQVIHUDVH
$8&
$UHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYH
%$5&
%OHHGLQJ$FDGHPLF5HVHDUFK&RQVRUWLXP
&$%*
&RURQDU\DUWHU\E\SDVVJUDIW
&(&
&OLQLFDO(YHQWV&RPPLWWHH
&.'
&KURQLFNLGQH\GLVHDVH
&.'(3,
&KURQLF.LGQH\'LVHDVH(SLGHPLRORJ\&ROODERUDWLRQ
&PD[
0D[LPXPSODVPDFRQFHQWUDWLRQ
&53
&UHDFWLYHSURWHLQ
&6/%
&6/%HKULQJ//&
&6/
&RPSDQ\FRGHQDPHIRUUHFRQVWLWXWHGKLJKGHQVLW\OLSRSURWHLQ
&7&$(
&RPPRQ7HUPLQRORJ\&ULWHULDIRU$GYHUVH(YHQWV
&9
&DUGLRYDVFXODU
'60%
'DWDDQG6DIHW\0RQLWRULQJ%RDUG
(&*V
(OHFWURFDUGLRJUDPV
H&5)
(OHFWURQLFFDVHUHSRUWIRUP
H*)5
(VWLPDWHGJORPHUXODUILOWUDWLRQUDWH
(2,
(QGRILQIXVLRQ
)'$
)RRGDQG'UXJ$GPLQLVWUDWLRQ
)0&
)LUVWPHGLFDOFRQWDFW
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
)6+
)ROOLFOHVWLPXODWLQJKRUPRQH
*&3
*RRG&OLQLFDO3UDFWLFH
*,
*DVWURLQWHVWLQDO
K
KRXUV


KV
+LJKVHQVLWLYLW\
,%
,QYHVWLJDWRU¶V%URFKXUH
,&)
,QIRUPHGFRQVHQWIRUP
,&+
,QWHUQDWLRQDO&RQIHUHQFHRQ+DUPRQLVDWLRQ
,(&
,QGHSHQGHQW(WKLFV&RPPLWWHH
,J$*(RU0
,PPXQRJOREXOLQ$*(RU0
,*,9
LPPXQHJOREXOLQLQWUDYHQRXV


,1'
,QYHVWLJDWLRQDO1HZ'UXJ
,5%
,QVWLWXWLRQDO5HYLHZ%RDUG
,57
,QWHUDFWLYHUHVSRQVHWHFKQRORJ\
,9
,QWUDYHQRXV


/9()
/HIWYHQWULFXODUHMHFWLRQIUDFWLRQ
0HG'5$
0HGLFDO'LFWLRQDU\IRU5HJXODWRU\$FWLYLWLHV
0,
0\RFDUGLDOLQIDUFWLRQ
P51$
0HVVHQJHUULERQXFOHLFDFLG
12$(/
1RREVHUYHGDGYHUVHHIIHFWOHYHO


1<+$
1HZ<RUN+HDUW$VVRFLDWLRQ
3&
SKRVSKDWLG\OFKROLQH
3&,
3HUFXWDQHRXVFRURQDU\LQWHUYHQWLRQ
3'
3KDUPDFRG\QDPLFV
3.
3KDUPDFRNLQHWLFV
35%&V
3DFNHGUHGEORRGFHOOV
CCI
CCI
CCI
CCI

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 27 of 137 
CRD-TPL-077 
Confidential 
PT 
Preferred Term 
RBC 
red blood cell 
RI 
Renal impairment 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SMQ 
Standard MedDRA query 
SOI 
Start of infusion 
TEAE 
Treatment-emergent adverse events 
ULN 
Upper limit of normal 
w / v 
Weight per volume 
WBC 
White blood cell 
WFI 
Water for Injection 
 
 
 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 28 of 137 
CRD-TPL-077 
Confidential 
1. 
INTRODUCTION 
1.1 
BACKGROUND INFORMATION ON CSL112 
1.1.1 Overview 
Acute coronary syndrome (ACS) is a life-threatening condition, that most commonly occurs 
when an atherosclerotic plaque ruptures or erodes, leading to thrombus formation within a 
coronary artery. A thrombus within a coronary artery can result in unstable angina (UA), a 
myocardial infarction (MI [ie, heart attack]) or sudden death. Even after recovery from an 
acute episode of ACS, patients continue to be at heightened risk. The short-term morbidity 
and mortality associated with both the index coronary event and recurrent cardiovascular 
(CV) events can be as high as 20% per year (Fox et al, 2006), and are inversely related to 
renal function status, such that subjects with mild, moderate, and severe renal impairment 
(RI) have progressively poorer long-term prognosis as compared with patients with normal 
renal function (Gibson et al, 2004; Fox et al, 2010). In patients with ACS and RI, the 
prognosis, both short- and long-term, is worse than for those with normal renal function, as 
the risk of CV events and mortality is inversely proportional to the estimated glomerular 
filtration rate (eGFR [Nabais et al, 2008; Bhandari and Jain, 2012]). Therefore, the 
identification of therapies that are safe and effective in patients with concurrent RI and ACS 
would represent an important advancement in medical therapy. 
Renal impairment is a prevalent and growing concurrent condition in ACS and acute 
myocardial infarction (AMI). Among 13,307 patients who participated in the Non-ST-
Segment Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 
(NSTE-ACS TIMI) trials, 37.2% of patients had normal renal function (GFR ≥ 90 
mL/min/1.73 m2), 47.1% of patients had mildly impaired GFR (GFR ≥ 60 to < 90 
mL/min/1.73 m2), and 15.1% of patients had moderately impaired GFR (GFR ≥ 30 to <60 
mL/min/1.73 m2 [Gibson et al, 2004]). In a more recent analysis of 49,491 AMI patients from 
the US-based National Cardiovascular Data Acute Coronary Treatment and Intervention 
Outcomes Network (ACTION) Registry, which collects data from 280 hospitals for all 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 29 of 137 
CRD-TPL-077 
Confidential 
patients with a primary diagnosis of MI (either non-ST segment elevation myocardial 
infarction [NSTEMI] or ST segment elevation myocardial infarction [STEMI]) who 
presented within 24 hours of the onset of an ischemic syndrome, approximately 30.5% of 
patients had Stage 3 chronic kidney disease (CKD, ie, moderate RI [Fox et al, 2010]). Given 
the growing prevalence of RI in patients with AMI coupled with the subsequent heightened 
risk of recurrent CV events in this population, identification of therapies that are safe and 
effective in these patients is critical.   
High density lipoprotein (HDL) cholesterol exerts a protective effect in experimental models 
of atherosclerotic CV disease. The proposed mechanism(s) for the atheroprotective properties 
of HDL are multifaceted (Remaley et al, 2008; Tardif et al, 2009). High density lipoprotein is 
believed to bring about beneficial effects mainly by reverse cholesterol transport, whereby 
excess cholesterol is removed from arteries containing atherosclerotic plaques back to the 
liver for excretion. This removal of cholesterol is mediated by the dominant protein of HDL, 
apolipoprotein A-I (apoA-I, Tall, 1998).   
CSL112 is a novel formulation of apoA-I purified from human plasma and reconstituted to 
form HDL particles. It is being developed for use in patients with AMI for the reduction in 
risk of recurrent CV events via the action of apoA-I. Apolipoprotein A-I is the active 
component of CSL112 and other components include phosphatidylcholine (PC), sodium 
cholate, and sucrose. Additional information about the disposition of components of 
administered CSL112 can be found in the Investigator’s Brochure (IB) for CSL112. 
1.1.2 Nonclinical Evaluation 
CSL112 single and repeat dose nonclinical safety studies have been conducted. After a single 
intravenous (IV) infusion of 1-hour duration, a no observed adverse effect level (NOAEL) of 
300 mg/kg was established in both the rat and cynomolgus monkey. In the repeat dose studies 
(CSL112 administered once every 3 days for 4 weeks by 2-hour IV infusion), a NOAEL of 
80 mg/kg was established in the rat; however, a NOAEL was not established in the 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 30 of 137 
CRD-TPL-077 
Confidential 
cynomolgus monkey because some adverse effects were observed at the lowest dose tested 
(80 mg/kg). No treatment-related deaths occurred in any of the toxicity studies. 
After IV administration of CSL112 to both rats and monkeys, the primary toxicological 
effects were hepatic and hematologic in nature. The effects were generally reversible, 
asymptomatic, and exhibited a moderate dose-response relationship. Some minor effects on 
renal parameters were also observed; however, as there were no correlative histopathology 
findings in the kidney, the toxicological significance is unclear. 
Further details on the hepatic and hematologic effects in the nonclinical studies, as well as 
other observations with CSL112, can be found in the IB for CSL112. 
1.1.3 Previous Clinical Experience 
CSL112 has been evaluated in 2, single center, randomized, placebo-controlled, phase 1, 
healthy adult, non-Investigational New Drug (IND) studies conducted in Australia 
(CSLCT-HDL-09-63 – Single Ascending Dose [SAD] study; CSLCT-HDL-10-68 – Multiple 
Ascending Dose [MAD] study) and 1 multicenter center, double-blind, placebo-controlled, 
ascending single-dose phase 1 non-IND study in adult subjects with moderate RI (eGFR ≥ 30 
and < 60 mL/min/1.73 m2) and in healthy adult subjects with normal renal function (eGFR ≥ 
90 mL/min/1.73 m2) (Study CSL112_1001) conducted in Germany and the United Kingdom. 
Study CSL112_1001 was initiated in the second quarter of 2015, enrolment was completed as 
of 16 November 2015, and last subject last visit occurred on 15 February 2016. This study 
was conducted to investigate the pharmacokinetic (PK), safety, and tolerability of CSL112 in 
adult subjects with moderate RI and in age, gender, and weight matched healthy adult 
subjects with normal renal function. The primary objective of the study was to assess the 
effect of moderate RI on the PK of CSL112. Subjects were randomized 3:1 active to placebo 
within a cohort (4 cohorts total: 2 moderate RI and 2 healthy adult subject cohorts at 2 
different doses, each with 8 subjects). Twenty-four subjects received 1 infusion of CSL112 in 
this study, 12 with normal renal function and 12 with moderate RI. Based on Data and Safety 
Monitoring (DSMB) review of PK and safety data from 12 moderate RI subjects receiving 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 31 of 137 
CRD-TPL-077 
Confidential 
either the CSL112 2 g or 6 g dose, the 6 g dose has been selected for the current study. Data 
from the Active Treatment Period are available and demonstrate an acceptable safety profile 
of a single dose of CSL112 in adult subjects with moderate RI (Section 1.3). The rationale for 
the 6 g CSL112 dose based on PK data from this phase 1 study is presented in Section 3.2. 
In addition, a phase 2a IND study (CSLCT-HDL-10-70a) has been conducted in subjects 
diagnosed with stable atherothrombotic disease; in essence, the AMI target population after 
their initial acute presentation. The phase 2a subjects were representative of the target phase 3 
population in age, sex, concurrent medical conditions (eg, diabetes, hypertension) and 
chronic concomitant medications (eg, dual anti-platelet therapy, statins) and were stratified 
by renal function (ie, normal renal function or mild RI). The goals of the phase 2a study were 
to evaluate the comparability of the PK and safety profile in patients with stable 
atherothrombotic disease as compared to that of healthy adults and to evaluate a range of 
doses to be administered in future CSL112 clinical studies in AMI patients who are at high 
risk of subsequent CV events.  
A total of 126 subjects (93 healthy adults, including 12 with moderate RI, and 33 patients) 
have received at least 1 dose of CSL112 in 4 completed studies. The results of the phase 1 
and 2a studies showed acceptable safety, PK, and pharmacodynamic (PD) profiles of CSL112 
across a range of doses and renal function groups. 
A phase 2b study (Study CSLCT-HDL-12-77) was initiated in the third quarter of 2014 and 
completed in the first quarter of 2016. It is a multicenter, randomized, placebo-controlled 
study to investigate the hepatic and renal safety and tolerability of multiple dose 
administration of 2 IV infusion regimens of CSL112 (low [2 g] and high dose [6 g]) versus 
placebo in approximately 1200 subjects with acute myocardial infarction (AMI). Subjects are 
stratified by renal function (normal renal function [eGFR ≥ 90 mL/min/1.73 m2] or mild RI 
[eGFR ≥ 60 and < 90 mL/min/1.73 m2]). The study consisted of a Safety Lead-in Period, 
during which subjects received a single 2-hour infusion of CSL112 (2 g) or placebo, followed 
by the main study, during which subjects receive four 2-hour infusions of investigational 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 32 of 137 
CRD-TPL-077 
Confidential 
product (CSL112 low [2 g] or high dose [6 g] or placebo), a minimum of 7 days apart, during 
the 4-week Active Treatment Period. The data from the Safety Lead-in Period were evaluated 
by the program level DSMB on 9 January 2015 and enrolment of subjects into the main study 
began in January 2015. Enrolment in the main study completed as of 15 November 2015 and 
the last subject last visit occurred on 21 March 2016. Based on a randomization ratio 
(CSL112:placebo) of 2:1 and final enrolment of 1258 randomized subjects, approximately 
839 subjects will have received at least 1 infusion of CSL112 in the phase 2b study. To date, 
the program level DSMB has reviewed safety and PK data from the Active Treatment Period 
after 5%, 10%, 25%, 50%, and 75% of subjects were enrolled, and have recommended the 
study to continue without change. Data are not yet available for this study. Further details 
regarding the phase 2 study may be found in the IB for CSL112. 
Thus, as of 16 November 2015, approximately 965 subjects have received at least 1 infusion 
of CSL112 in completed studies of the CSL112 clinical development program. 
1.2 
STUDY OVERVIEW 
CSL112 drug product resembles nascent HDL. It is a novel formulation of apoA-I, PC, and 
cholate; and is stabilized by sucrose. CSL112 is being developed for the reduction of 
recurrent CV events after AMI. The premise of the CSL112 mechanism of action and the 
resulting treatment strategy is that infusion of apoA-I after the index AMI event, and during 
the subacute period after the event, will reduce the size and/or instability of atherosclerotic 
plaque, thereby reducing the risk of plaque rupture or erosion that would lead to a recurrent 
CV event in patients with AMI.  
Renal impairment (RI) is a prevalent and increasingly common concurrent condition in 
patients with AMI. Patients who experience an AMI event are at high risk for a recurrent CV 
event and mortality is inversely related to renal function status: subjects with mild, moderate, 
and severe RI have, respectively, progressively poorer long-term prognosis as compared with 
patients with normal renal function. As the number of AMI patients with RI is relatively high 
(~15% to 30%) (Gibson et al, 2004; Fox et al, 2010), the identification of therapies that are 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 33 of 137 
CRD-TPL-077 
Confidential 
safe and effective in these patients would represent an important advancement in medical 
therapy. 
This study is a phase 2, multicenter, double-blind, randomized, placebo-controlled, 
parallel-group, study to investigate the safety and tolerability of up to 4 weekly IV 
administrations of CSL112 compared with placebo in subjects with moderate RI (eGFR ≥ 30 
and < 60 mL/min/1.73 m2) and AMI.  
CSL112 drug product contains sucrose as a stabilizer. Administration of sucrose by IV 
infusion has been associated with reports of acute kidney injury (AKI) attributed to osmotic 
nephrosis when immune globulin intravenous (IGIV) products formulated with sucrose were 
administered at high doses or high rates of administration (Epstein and Zoon, 2000). Thus, 
evaluation of the renal safety of CSL112 is warranted, specifically in the subpopulation of 
patients with moderate RI who have experienced a recent AMI event. Although no renal 
safety concerns were identified in the completed CSL112 phase 1 and 2a studies (n=126 total 
subjects treated with CSL112: 96 with normal renal function, 15 with mild RI, and 15 with 
moderate RI), further evaluation is warranted before the inclusion of AMI patients with 
moderate RI in a phase 3 morbidity and mortality outcomes trial.   
This study is intended to characterize the renal risk profile in subjects with moderate RI who 
have experienced a recent AMI. The occurrence of clinically important renal serious adverse 
events (SAEs) as reported by the Investigator and AKI, defined as an increase in serum 
creatinine of  ≥ 0.3 mg/dL (26.5 µmol/L) from baseline that is sustained upon repeat 
measurement, will be evaluated. In subjects with moderate RI who have undergone 
percutaneous coronary intervention (PCI), the occurrence of AKI as defined by the Acute 
Kidney Injury Network (AKIN) criteria is approximately 10% (Tsai et al, 2014). After 
excluding subjects with evidence of AKI at screening, the effect of 4 weekly infusions of 
CSL112 or placebo on the incidences of renal SAEs and AKI will be evaluated in this study 
of post-AMI moderate RI patients. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 34 of 137 
CRD-TPL-077 
Confidential 
1.3 
POTENTIAL RISKS AND BENEFITS  
The Development Core Safety Information document (appended to the IB for CSL112) 
outlines the potential risks to subjects administered CSL112 and precautions for its use.  
The most frequently reported AEs in completed clinical studies of CSL112 included: Infusion 
Site Pain, Infusion Site Swelling, Infusion Site Induration, Infusion Site Erythema, Infusion 
Site Coldness, Injection Site Phlebitis, Catheter Site Phlebitis, Infusion Site Haematoma, 
Injection Site Haematoma, Vessel Puncture Site Haematoma, and Vessel Puncture Site 
Haemorrhage. Headache was also frequently reported in these studies. Events related to 
injection or infusion site reactions, local tolerability events related to bruising (coded to a 
Preferred Term [PT] Haematoma in the Medical Dictionary for Regulatory Activities 
[MedDRA]), and Headache were reported more frequently in subjects who received CSL112 
as compared with placebo. Most of these events were mild and transient. Adverse events 
(AEs) reported within other System Organ Classes (SOCs) occurred with similar frequency in 
the placebo and active treatment groups across the 4 completed CSL112 studies. No renal 
safety concerns were identified in the completed CSL112 phase 1 or 2a studies. 
A thorough panel for renal assessment has been integrated into the current study, as CSL112 
contains sucrose as a stabilizer, and administration of sucrose IV has been associated with 
reports of AKI attributed to osmotic nephrosis when IGIV products formulated with sucrose 
were administered at high doses or at high rates of administration. The highest dose of 
sucrose administered in the completed phase 2a study in patients with stable atherothrombotic 
disease and normal renal function or mild RI did not exceed the lowest dose published in the 
literature associated with potential nephrotoxicity (Anderson and Bethea, 1940). CSL112 has 
been reformulated such that the maximum dose of sucrose to be administered in this study is 
approximately 2.5-fold less than this lowest single dose of sucrose that was associated with 
histopathologic changes in the kidney but without clinical evidence of nephrotoxicity. In 
addition, the maximum infusion rate for CSL112 of 6 g/2 hour (50 mg/min) ensures a sucrose 
infusion rate of ≤ 1.7 mg sucrose/kg/min for a 50-kg adult, which is well within the published 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 35 of 137 
CRD-TPL-077 
Confidential 
guideline for safe administration of sucrose containing IGIV products (Epstein and Zoon, 
2000).  
In the completed phase 1 and 2a clinical studies with CSL112, no clinically significant 
elevations (> 3 x upper limit of normal [ULN]) in aspartate aminotransferase (AST) or 
alanine aminotransferase (ALT) have been reported in 126 subjects who have received 
CSL112. One subject treated with a single 135 mg/kg dose of CSL112 in the SAD study 
experienced a transient elevation in total bilirubin > 2 x ULN at a single time point. No AEs 
were reported in association with this laboratory finding. Two subjects with moderate RI 
treated with CSL112 6 g in Study CSL112_1001 had treatment-emergent non-serious AEs of 
“Blood Bilirubin Increased” for transient elevations at a single time point on Study Day 2 
(maximum of 1.16 x ULN). One subject with normal renal function treated with CSL112 6 g 
in Study CSL112_1001 had an elevation in total bilirubin to > 1.5 x ULN but less than 2 x 
ULN at a single time point on Study Day 2 that was not reported as a treatment-emergent AE 
(TEAE). In the phase 2b study (Study CSLCT-HDL-12-77), 2 reports of serious liver 
dysfunction (Liver Disorder and Hepatic Function Abnormal) have been received as of 
2 May 2016. Each event was assessed as related to investigational product by the 
Investigator. Both cases demonstrated a mixed cholestatic and hepatocellular picture, and 
neither subject was considered as meeting Hy’s Law criteria. These cases were reviewed by 
the DSMB immediately after they were reported, and the DSMB determined that the study 
may continue without modification. A thorough panel for hepatic assessment has also been 
incorporated into the protocol and the study will be conducted under oversight by the 
program level DSMB. 
No SAEs were reported in the SAD or MAD phase 1 studies and no SAEs were reported in 
the phase 2a study in subjects who received CSL112.  
In Study CSL112_1001, 2 subjects with normal renal function who received CSL112 6 g 
experienced a total of 2 SAEs during the Active Treatment Period that were not related to 
investigational product (pain in right shoulder [due to loosened osteosynthesis plate], injury 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 36 of 137 
CRD-TPL-077 
Confidential 
of right meniscus). There were no deaths and no subject discontinued from the study because 
of a TEAE.  
In the phase 2b study (Study CSLCT-HDL-12-77), as of 2 May 2016, 4 SAEs were reported 
for 4 subjects as related to investigational product by the Investigator (Pharyngeal Oedema 
[1 subject], Hepatic Function Abnormal [2 subjects], Gastrointestinal Haemorrhage 
[1 subject]). Eight subjects had 18 SAEs with a fatal outcome and were assessed as not 
related to investigational product by the Investigator (Pneumonia, Acute Respiratory Failure, 
Cardiac Arrest, Pneumothorax, Chronic Obstructive Pulmonary Disease, Hypoxic Ischemic 
Encephalopathy; Septic Shock; Basal Ganglia Haemorrhage; Cerebral Haemorrhage, Brain 
Metastatic Cancer; Cardiac Failure [2 events]; Shock Haemorrhagic, Multiple Organ 
Dysfunction Syndrome; Cardiac Aneurysm, Pulmonary Embolus, and Death). On 21 
December 2015, based on review of safety and PK data after 75% of subjects had completed 
the Active Treatment Period, the program level DSMB determined that there were no 
significant safety or PK concerns and recommended that the study continue under the current 
protocol without modification. 
The risk of viral and prion contamination is a feature common to all biologic agents where 
the manufacture involves the use of materials of animal or human origin. CSL112 may carry 
a risk of transmitting infectious agents (eg, viruses and, theoretically, the Creutzfeldt-Jakob 
disease agent) because it is made from human blood. However, the risk of infectious agent 
transmission has been reduced by screening plasma donors for prior exposure to certain 
viruses, testing for the presence of certain current virus infections, and including virus 
inactivation / removal steps in the manufacturing process. 
There is potential for allergic reactions or hypersensitivity to CSL112 in certain individuals, 
given the constituents of the product. CSL112 consists of apoA-I isolated from human plasma 
that may contain immunoglobulin A (IgA) and also contains PC derived from soy beans. 
Therefore, subjects with a positive history of IgA deficiency, antibodies to IgA, or allergy to 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 37 of 137 
CRD-TPL-077 
Confidential 
either soy bean or peanuts will be excluded from the study. In addition, study level stopping 
rules will provide guidance if there are occurrences of serious drug hypersensitivity AEs. 
It is the central premise of the CSL112 program that infusion of apoA-I via reconstituted 
HDL will provide therapeutic benefit to patients with AMI. Based on the previous clinical 
data, the dose of CSL112 selected for use in this study should raise cholesterol efflux 
capacity by a meaningful amount. The increase in cholesterol efflux capacity of blood plasma 
may enable the acceptance of excess cholesterol from atherosclerotic plaque. The resulting 
reduction in plaque cholesterol should render the plaques more stable and less likely to 
rupture. This and other purported apoA-I related actions may translate to a reduction in the 
subacute risk of cardiac ischemia and recurrent CV events in patients with AMI. 
Thus, the associated benefit risk assessment of the study is acceptable for subjects enrolled in 
the study. 
2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1 
PRIMARY OBJECTIVE AND ENDPOINT 
2.1.1 Primary Objective 
The primary objective of this study is to assess the renal safety of CSL112 in subjects with 
moderate RI and AMI after administration of up to 4 weekly infusions of CSL112. 
2.1.2 Co-primary Endpoints 
The renal safety profile of CSL112 in subjects with moderate RI and AMI who receive up to 
4 weekly administrations of CSL112 will be assessed by co-primary endpoints of the 
incidences of treatment-emergent (1) renal SAEs as defined below, and (2) AKI, defined as 
an absolute increase in serum creatinine from baseline ≥ 0.3 mg/dL (26.5 μmol/L) during the 
Active Treatment Period that is sustained upon repeat measurement by the central laboratory 
no earlier than 24 hours after the elevated value. If no repeat value is obtained [due, for 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 38 of 137 
CRD-TPL-077 
Confidential 
example, to loss of follow-up or protocol violation], a single serum creatinine value that is 
increased from baseline ≥ 0.3 mg/dL (26.5 μmol/L) during the Active Treatment Period 
would also fulfil the definition of AKI.  
Treatment-emergent is defined as occurring at or after the start of the first infusion. Baseline 
for determination of AKI is defined as the pre-infusion central laboratory serum creatinine 
level on Study Day 1.  
A renal SAE is defined as any SAE with a MedDRA PT included in the Acute Renal Failure 
narrow Standard MedDRA Query (SMQ) or a PT of Renal Tubular Necrosis, Renal Cortical 
Necrosis, Renal Necrosis, or Renal Papillary Necrosis. 
Incidence rates will be based on the number of subjects with at least 1 occurrence of the event 
of interest; that is, a subject with 2 treatment-emergent renal SAEs or 2 instances of AKI will 
be counted once. 
2.2 
SECONDARY OBJECTIVES AND ENDPOINTS 
2.2.1 Secondary Objective(s) 
The secondary objectives of the study are: 
1. To further characterize the safety and tolerability of CSL112 in subjects with moderate RI 
and AMI. 
2. To characterize the PK of CSL112 after multiple dose administration in subjects with 
moderate RI and AMI. 
2.2.2 Secondary Endpoints 
Secondary safety and tolerability endpoints include: 
1. The occurrence of any TEAEs throughout the study. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 39 of 137 
CRD-TPL-077 
Confidential 
2. The occurrence of treatment-emergent adverse drug reactions or suspected adverse drug 
reactions defined as:  
a. All TEAEs, including local tolerability events, that begin during or within 1 hour after 
the end of an infusion, or 
b. Those TEAEs which the Investigator or Sponsor indicate may be causally related to 
the administration of the investigational product (CSL112 or placebo), or  
c. All TEAEs for which the Investigator's causality assessment is missing or 
indeterminate, or  
d. All TEAEs for which the incidence in an active treatment arm exceeds the 
exposure-adjusted incidence rate in the placebo arm by 30% or more, provided the 
difference in incidence rates is 1% or more. 
3. Changes from baseline (ie, pre-infusion on Study Day 1) through to the end of the Active 
Treatment Period in renal status defined as: 
a. Absolute increases from baseline in serum creatinine as follows: 
i. ≤ baseline value 
ii. > 0 to < 0.3 mg/dL 
iii. ≥ 0.3 to ≤ 0.5 mg/dL 
iv. ˃ 0.5 mg/dL 
b. Increases in serum creatinine that are sustained for ≥ 24 hours upon repeat 
measurement as follows: 
i. ≥ 1.5 x baseline values 
ii. ≥ 2 x baseline value 
iii. ≥ 3 x baseline value 
iv. serum creatinine ≥ 4.0 mg/dL (353.6 μmol/L) 
c. Initiation of renal replacement therapy 
d. Decrease in eGFR by ≥ 25% from baseline starting during the Active Treatment 
Period and that is sustained at the final study visit  

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 40 of 137 
CRD-TPL-077 
Confidential 
4. Change from baseline (ie, pre-infusion on Study Day 1) in hepatic status that occurs 
during the Active Treatment Period and that is sustained for ≥ 24 hours upon repeat 
measurement as follows: 
a. ALT > 3 x ULN 
b. ALT > 5 x ULN 
c. ALT > 10 x ULN 
d. Serum total bilirubin > 1.5 x ULN (Note: For subjects with a history of Gilbert’s 
syndrome, this assessment will be based on indirect bilirubin.) 
e. Serum total bilirubin > 2 x ULN (Note: For subjects with a history of Gilbert’s 
syndrome, this assessment will be based on indirect bilirubin.) 
f. Possible Hy's Law cases, as defined in the FDA Guidance for Industry: Drug-Induced 
Liver Injury: Premarketing Clinical Evaluation (July 2009; see Section 9.1.3.3 for 
definition of Hy’s Law). 
5. The occurrence of treatment-emergent bleeding events as defined by the Bleeding 
Academic Research Consortium (BARC) criteria (Mehran et al, 2011) from the start of 
the first infusion until the end of the Safety Follow-up Period. 
6. Clinically significant changes in clinical laboratory tests results (serum biochemistry, 
hematology, and urinalysis), physical examinations findings, body weight, 
electrocardiograms (ECGs), and vital signs (blood pressure, pulse rate, and body 
temperature). 
7. The occurrence of binding antibodies specific to apoA-I and/or CSL112. 
 
Secondary PK endpoints include: 
1. Baseline (ie, pre-infusion on Study Day 1)-corrected plasma apoA-I concentrations 
2. Baseline-corrected plasma PC concentrations  
3. Concentration in plasma at End-of-Infusion for apoA-I and PC 
4. Accumulation ratio (R) for apoA-I and PC 


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO






















678'<'(6,*1

678'<'(6,*1$1'5$7,21$/(
7KLVLVDSKDVHPXOWLFHQWHUGRXEOHEOLQGUDQGRPL]HGSODFHERFRQWUROOHGSDUDOOHOJURXS
VWXG\WRDVVHVVWKHVDIHW\DQGWROHUDELOLW\RIXSWRZHHNO\,9DGPLQLVWUDWLRQVRIJ&6/
FRPSDUHGZLWKSODFHERLQVXEMHFWVZLWKPRGHUDWH5,DQG$0,7KHJ&6/GRVHZDV
VHOHFWHGDIWHU'60%UHYLHZRIVDIHW\DQG3.GDWDIURPWKHRQJRLQJSKDVH3.DQGVDIHW\
CCI
CCI
CCI
CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
VWXG\LQVXEMHFWVZLWKPRGHUDWH5,6WXG\&6/B'HWDLOVUHJDUGLQJWKHUDWLRQDOHIRU
GRVHVHOHFWLRQDUHRXWOLQHGLQ6HFWLRQ
7KHPDLQVWXG\ZLOOHQURODSSUR[LPDWHO\VXEMHFWVZKRZLOOEHUDQGRPO\DVVLJQHGLQD
UDWLRWRUHFHLYHLQIXVLRQVRIJ&6/VXEMHFWVYHUVXVSODFHERVXEMHFWVWR
HYDOXDWHVDIHW\7RHQVXUHWKDWDWOHDVWRQHWKLUGRIWKHVWXG\SRSXODWLRQKDVDQH*)5LQWKH
&.'VWDJHEUDQJHH*)5WRP/PLQPQRPRUHWKDQWZRWKLUGVRIWKH
VWXG\SRSXODWLRQLHVXEMHFWVZLOOKDYHDQH*)5LQWKH&.'DUDQJH
WRP/PLQP5DQGRPL]DWLRQZLOOEHVWUDWLILHGE\H*)5
WRP/PLQPRUWRP/PLQPDVFDOFXODWHGE\WKH&KURQLF
.LGQH\'LVHDVH(SLGHPLRORJ\&.'(3,HTXDWLRQ/HYH\HWDO6WHYHQVHWDO
DQGE\PHGLFDOKLVWRU\RIGLDEHWHVUHTXLULQJFXUUHQWWUHDWPHQWZLWKDQ\DQWLGLDEHWLF
PHGLFDWLRQ\HVRUQR&OLQLFDOSURFHGXUHVIRUWKHVHVXEMHFWVZLOOLQFOXGHDVVHVVPHQWVIRU
VDIHW\LQFOXGLQJUHQDODQGKHSDWLF3.
 





7KHVWXG\ZLOOFRQVLVWRIVFUHHQLQJDQGVWXG\SHULRGVDQ$FWLYH7UHDWPHQW3HULRGGXULQJ
ZKLFKSDWLHQWVZLOOUHFHLYH,9LQIXVLRQVRILQYHVWLJDWLRQDOSURGXFWLH&6/RUSODFHER
RYHUDSSUR[LPDWHO\GD\VDQGD6DIHW\)ROORZXS3HULRGDSSUR[LPDWHO\GD\VIURPWKH
$FWLYH7UHDWPHQW3HULRG)LJXUH$VXPPDU\RIVWXG\DVVHVVPHQWVDQGSURFHGXUHVE\
YLVLWLVVKRZQLQWKH6FKHGXOHRI$VVHVVPHQWV
6XEMHFWVZLOOEHDVVHVVHGIRUHOLJLELOLW\DWVFUHHQLQJDQGEHIRUHUDQGRPL]DWLRQ9LVLWDQG
9LVLWEHIRUHLQIXVLRQ7KHVFUHHQLQJSHULRGXSWRDQGLQFOXGLQJUDQGRPL]DWLRQPXVWRFFXU
ZLWKLQGD\VRIILUVWPHGLFDOFRQWDFW)0&IRUWKHLQGH[$0,)LJXUH6XEMHFWVPHHWLQJ
DOOLQFOXVLRQFULWHULDDQGQRQHRIWKHH[FOXVLRQFULWHULD6HFWLRQVDQGZLOOUHFHLYH
CCI
C
C
I
CCI

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 43 of 137 
CRD-TPL-077 
Confidential 
four 2-hour IV infusions of investigational product (6 g CSL112 or placebo), a minimum of 7 
days apart, during a 4-week Active Treatment Period. Study assessments for all subjects will 
be conducted before and after infusions during Visits 2, 4, 5, 6 (Study Days 1, 8, 15, 22), 
within 24 to 48 hours after the first infusion (Visit 3) and at the end of the Active Treatment 
Period (Visit 7/Study Day 29). Follow-up safety assessments will be conducted at a final visit 
(Visit 8) on Study Day 60. 
Depending on the time of the index event, time required for evaluation in the emergency 
department and cardiac catheterization laboratory, administration of contrast agent, and 
assessment of renal function stability, screening duration may last up to 5 days after FMC for 
the index AMI. First medical contact is defined as the point in time (ie, clock start) at which 
the subject arrives at the hospital emergency department (ie, door time) or cardiac 
catheterization laboratory, for evaluation and treatment of AMI. A diagnosis of AMI as per 
Section 4.1.1 is critical to determining subject eligibility.  
Before the first infusion of investigational product, the subject must be clinically stable, have 
hepatic function test within acceptable limits, and have documented evidence of stable renal 
function and no suspicion of AKI at least 12 hours after FMC for the index AMI. In addition, 
for those subjects undergoing angiography with or without PCI, stable renal function, defined 
as a serum creatinine value that is increased < 0.3 mg/dL (26.5 µmol/L) from the pre-contrast 
administration value, must be demonstrated at least 12 hours after IV contrast administration 
(see Section 8.2.2.1, Table 7). The first infusion of investigational product should occur no 
earlier than 12 hours after FMC or, for subjects undergoing angiography, no earlier than 
12 hours after contrast administration. The first infusion should start no later than 5 days after 
FMC for the index AMI. Within this screening window, earlier administration of the first 
infusion of investigational product is encouraged. 
Screening and randomization of subjects may occur on the same day (Study Day 1 of the 
Active Treatment Period) provided that the minimum time window after FMC for the index 
event or administration of IV contrast agent (for subjects undergoing angiography) is adhered 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 44 of 137 
CRD-TPL-077 
Confidential 
to for assessment of stability of renal function before administration of the first infusion of 
investigational product (Section 8.2.2.1).  
Ongoing eligibility for all subsequent infusions of investigational product will be confirmed 
before administration of each subsequent dose. Eligibility for continued administration of 
investigational product will be based on the criteria presented in Section 8.2.2.2, Table 8. 
Each infusion should be completed as close to the protocol-specified visit schedule as 
possible, ie, no fewer than 7 days and no more than 10 days between each infusion. An 
infusion may be skipped or delayed at the discretion of the Investigator if more time is 
necessary to confirm renal function stability or to evaluate and treat an AE before the next 
infusion (Section 8.2.2.2). If an infusion is skipped or delayed for a medical or safety reason, 
the medical monitor should be contacted for further guidance.  
Using the maximum interval of 10 days between infusions, the 4 infusions should be 
administered within 30 days from Study Day 1 (Visit 2). Visit 7 (Study Day 29) must be at 
least 7 (+3) days after the fourth infusion of investigational product. However, depending on 
the actual timing of the 4 infusions, Study Day 29 could occur between 28 to 40 days after 
the first infusion. Where administration of all 4 infusions may exceed the duration of 30 days 
the medical monitor should be informed for further guidance. 
The end of the Active Treatment Period is upon completion of Visit 7 (Study Day 29). The 
Safety Follow-up Period (approximately 30 days in duration) will begin after Visit 7.  
Visit 8 will occur approximately 60 (+7) days after the first infusion and must occur no 
sooner than 25 days after the last administration of investigational product. Subjects will 
return to the study clinic and be seen by the Investigator or qualified delegate for study 
assessments at Visit 8. Adverse events will be assessed at each visit between signing of 
informed consent and Visit 8. 
Subjects who have prematurely discontinued receiving infusion(s) of investigational product 
should complete an early termination visit (Section 4.1.4). All study assessments to be 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 45 of 137 
CRD-TPL-077 
Confidential 
performed at the early termination visit should be the same assessments as conducted at 
Visit 7. Subjects who have discontinued investigational product early should continue to be 
followed for safety through Visit 8. If the subject cannot be contacted directly to obtain vital 
status (ie, living or deceased), at a minimum, sites should obtain as much information as 
possible through telephone contact with healthcare providers, registered mail contact, contact 
through family or friends or utilization of publically available information. 
An external program level DSMB will independently evaluate safety data during the conduct 
of the study. In order to ensure that an early safety signal has not emerged that would affect 
the conduct of the study the DSMB will review safety data after every 6 subjects have 
received 2 infusions of investigational product and have pre-infusion safety data available 
before the third infusion at Visit 5. These reviews will continue until at least 60 subjects 
(approximately 75% of subjects) complete Visit 5. In addition, the independent DSMB will 
have interim safety reviews when: (1) approximately 25% of subjects have completed the 
Active Treatment Period (Visit 7), (2) approximately 50% of subjects have completed Visit 5, 
and (3) approximately 50% of subjects have completed the Active Treatment Period (Visit 7). 
At these reviews the DSMB will assess for any safety signal that has emerged and that would 
warrant a change in the conduct of the study. The DSMB will also be convened to review all 
available data if 1 or more of the study level stopping rules is met (see Section 3.6.2).  
 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 46 of 137 
CRD-TPL-077 
Confidential 
Figure 1. Study Overview 
 
AMI = acute myocardial infarction; IV = intravenous; FMC = first medical contact 
The study will consist of screening and 2 study periods: an Active Treatment Period (approximately 29 days) 
and a Safety Follow-up Period (approximately 30 days from the end of the Active Treatment Period).  
Subjects will be assessed for eligibility during screening and up to and including randomization (Visit 1 and 
Visit 2 before infusion), which may occur no later than 5 days after FMC for the index AMI. Eligible subjects 
meeting all inclusion criteria and none of the exclusion criteria will receive four 2-hour IV infusions of 
investigational product (6 g CSL112 or placebo), a minimum of 7 days apart, during a 4-week Active Treatment 
Period. 
3.2 
DOSE AND DOSING REGIMEN 
CSL112 (6 g) or a matched volume of placebo (0.9% weight/volume [w / v] sodium chloride 
solution, ie, normal saline) will be administered as a 2-hour IV infusion into a suitable vein 
(peripheral or central) once weekly for 4 consecutive weeks (4 infusions total). 
A 6 g dose of CSL112 has been selected for this study, based upon the DSMB review of 
safety and PK data from the ongoing phase 1 PK and safety study in subjects with moderate 
RI (Study CSL112_1001).  


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
5HODWLYHWRKHDOWK\DGXOWVXEMHFWVLQ6WXG\&6/BWKHEDVHOLQHOHYHOVRIDSR$,DQG
3&EHIRUH&6/GRVLQJDUHFRPSDUDEOHLQVXEMHFWVZLWKPRGHUDWH5,:KHQDGMXVWHGIRU
EDVHOLQHWKHPHDQ3.SURILOHVRIDSR$,IURPWKHUHQDOIXQFWLRQJURXSVRYHUODS
VXEVWDQWLDOO\6LPLODUO\WKHPHDQ3.SURILOHVRI3&IURPWKHUHQDOIXQFWLRQJURXSVDOVR
RYHUODSSHG7KHUHIRUHWKHFRPSDUDEOHH[SRVXUHEHWZHHQWKHUHQDOIXQFWLRQJURXSVZDV
VXSSRUWHGIURPWKH3.DQDO\VLVLQ6WXG\&6/B'DWDIURPVXEMHFWVZLWKPRGHUDWH5,
ZKRUHFHLYHG&6/JUHYHDOHGH[SRVXUHVRIDSR$,PHDQDUHDXQGHUWKHFRQFHQWUDWLRQ
WLPHFXUYH>$8&@±PJKG/DQGPHDQPD[LPXPSODVPDFRQFHQWUDWLRQ>&PD[@±
PJG/DQG3&PHDQ$8&±PJKG/DQGPHDQ&PD[±PJG/WKDWZHUH
VLPLODUWRH[SRVXUHVREVHUYHGLQDJHJHQGHUDQGZHLJKWPDWFKHGKHDOWK\DGXOWVZLWK
QRUPDOUHQDOIXQFWLRQGRVHGZLWK&6/J7KHFRUUHVSRQGLQJYDOXHVIRUDGXOWVZLWK
QRUPDOUHQDOIXQFWLRQDUHPJKG/IRUDSR$,$8&PJG/IRUDSR$,&PD[
PJKG/IRU3&$8&DQGPJG/IRU3&&PD[,QDGGLWLRQUHVXOWVIURP6WXG\
&6/BDUHFRPSDUDEOHWRWKRVHIURPHDUOLHUKHDOWK\VXEMHFWVWXGLHV6WXGLHV&6/&7
+'/DQG&6/&7+'/DQGWKRVHIURPVXEMHFWVZLWKVWDEOHDWKHURWKURPERWLF
GLVHDVH6WXG\&6/&7+'/D7KH3.DQGVDIHW\GDWDIURPWKH&6/JFRKRUWLQ
6WXG\&6/BVXSSRUWWKHSULRU'60%UHFRPPHQGDWLRQRIJRI&6/DVVDIHIRU
IXUWKHUHYDOXDWLRQLQVXEMHFWVZLWKPRGHUDWH5,







CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO


%DVHGRQWKHVDIHW\DQG3.DQDO\VHVFRQGXFWHGWRGDWHDJGRVHDGPLQLVWHUHGWRVXEMHFWV
ZLWKPRGHUDWH5,LVH[SHFWHGWRSURGXFHDSR$,DQG3&H[SRVXUHOHYHOVWKDWDUHVLPLODUWR
WKRVHREVHUYHGLQVXEMHFWVZLWKQRUPDODQGPLOG5,

3/$11('678'<'85$7,21
7KHPD[LPXPGXUDWLRQRIWKHVWXG\IRUDQLQGLYLGXDOVXEMHFWLVH[SHFWHGWREHDSSUR[LPDWHO\
ZHHNV7KLVHVWLPDWLRQLVEDVHGRQ
x $GD\6FUHHQLQJ3HULRG
x $ZHHN$FWLYH7UHDWPHQW3HULRG
x $ZHHN6DIHW\)ROORZXS3HULRG
7KHRYHUDOOVWXG\GXUDWLRQLHILUVWVXEMHFW¶VVFUHHQLQJYLVLWWRODVWVXEMHFW¶VHQGRIVWXG\
YLVLWZLOOEHDSSUR[LPDWHO\PRQWKV

3/$11('180%(52)6,7(6
7KHVWXG\LVSODQQHGWREHFRQGXFWHGDWDSSUR[LPDWHO\VLWHV

3/$11('180%(52)68%-(&76
$SSUR[LPDWHO\VXEMHFWVZLOOEHHQUROOHGLQWRWKLVVWXG\

678'<021,725,1*352&('85(6
 'DWDDQG6DIHW\0RQLWRULQJ%RDUG
7KHLQGHSHQGHQWSURJUDPOHYHO'60%ZLOOPRQLWRUWKHVDIHFRQGXFWRIWKHVWXG\7KH
'60%FKDUWHURXWOLQHVWKHUROHVDQGUHVSRQVLELOLWLHVRIWKHFRPPLWWHHDQGZLOOJXLGHLWV
RSHUDWLRQV7KH'60%FRQVLVWVRILQGLYLGXDOVH[WHUQDOWR&6/ZKRKDYHUHOHYDQWFOLQLFDO
WULDOH[SHUWLVHDQGH[SHULHQFHLQVDIHW\DVVHVVPHQW
CCI

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 49 of 137 
CRD-TPL-077 
Confidential 
The program level DSMB will: 
• Provide recommendations to CSL surrounding study conduct matters that affect safety. 
• Review the safety data at the planned interim safety reviews (see Section 10.3.4) and 
identify if significant safety concerns arise during the study. 
• Review all available data if 1 or more of the study level stopping rules is met (see Section 
3.6.2) 
• Review PK data and any other data that may affect subject or study continuation. 
• Make recommendations regarding study progression. 
In order to ensure that a safety signal has not emerged that would affect the conduct of the 
study, the DSMB will review safety data after every 6 subjects have received 2 infusions of 
investigational product and have pre-infusion safety data available before the third infusion at 
Visit 5. These reviews will continue until at least 60 subjects (approximately 75% of 
subjects) complete Visit 5. In addition, the independent DSMB will have interim safety 
reviews when: (1) approximately 25% of subjects have completed the Active Treatment 
Period (Visit 7), (2) approximately 50% of subjects have completed Visit 5, and (3) 
approximately 50% of subjects have completed the Active Treatment Period (Visit 7). 
If any of the safety criteria as specified in the DSMB charter are met at these reviews, 
continuation of the study without alteration should be questioned as it may be an early 
indication of an unacceptable safety profile in the broader population. The DSMB may 
recommend a change to the protocol to ameliorate any safety concerns or provide 
recommendations regarding subsequent dosing and/or study progression/stopping as 
discussed in the following paragraph.  
The DSMB will also be convened to review all available data if 1 or more of the study level 
stopping rules is met (Section 3.6.2). If any of the criteria listed below are met, the DSMB 
will be notified in an expedited fashion and will convene in a timely manner to review all 
available study data and to provide recommendations regarding subsequent dosing and/or 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 50 of 137 
CRD-TPL-077 
Confidential 
study progression/stopping. A decision to pause enrolment until the DSMB has reviewed the 
data and reached a final recommendation will be made using best clinical judgment by the 
DSMB chairman. Any modification recommended by the DSMB in regards to the conduct of 
the study will be implemented as an amendment to the protocol. In addition, the DSMB may 
decide to meet and review all available safety data based on other safety signals not described 
below. The stopping rule triggers for DSMB decision are: 
• After 2 subjects experience a treatment-emergent SAE of AKI and after each subsequent 
subject experiences such an event. 
• After 2 subjects experience an increase in serum creatinine ≥ 3 x the baseline value or a 
serum creatinine of ≥ 4.0 mg/dL (353.6 μmol/L) and after each subsequent subject 
experiences such an event. 
• After 1 subject experiences a treatment-emergent SAE of acute hepatic injury and after 
each subsequent subject experiences such an event. 
• After 1 subject experiences a treatment-emergent elevation in ALT > 3 x ULN with a 
concomitant elevation in total bilirubin > 2 x ULN and after each subsequent subject 
experiences such an event. 
• After 2 subjects experience a treatment-emergent SAE of drug hypersensitivity reaction 
and after each subsequent subject experiences such an event. 
All of the above criteria will be reported by the Investigator as SAEs in order to ensure 
expedited reporting of these events to the Sponsor and the DSMB as per Section 9.5.1. 
3.6.2 Study-level Stopping Rules 
The DSMB could recommend stopping the study based on: 
• ≥ 2 subjects experience a treatment-emergent SAE of AKI  

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 51 of 137 
CRD-TPL-077 
Confidential 
• ≥ 2 subjects experience an increase in serum creatinine to ≥ 3 x the baseline value or a 
serum creatinine of ≥ 4.0 mg/dL (353.6 μmol/L) 
• ≥ 1 subjects experience a treatment-emergent SAE of acute hepatic injury  
• ≥ 1 subjects experience a treatment-emergent elevation in ALT > 3 x ULN with a 
concomitant elevation in total bilirubin > 2 x ULN (ie, criteria for Hy’s Law are fulfilled) 
• ≥ 2 subjects experience a treatment-emergent SAE of drug hypersensitivity reaction 
In addition, individual subject level criteria for discontinuation of investigational product are 
detailed in Section 7.1. 
3.6.3 Steering Committee 
A Steering Committee will provide clinical guidance on study implementation, conduct, and 
interpretation of results. The Steering Committee will comprise designated representatives 
from among the Principal Investigators, other recognized thought leaders in the field of ACS 
AKI, and lipidology, as well as sponsor representatives. The Steering Committee will be 
described in further detail in its charter.  
3.6.4 Clinical Events Committee 
The independent program level Clinical Events Committee (CEC) will review and adjudicate 
in a blinded fashion the occurrence of renal SAEs and bleeding events. A common group of 
qualified scientists and physicians will prepare the definitions of endpoints and instructions 
for interpretation based on available guidance. The CEC is described in further detail in its 
charter. 
4. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1 
ELIGIBILITY CRITERIA 
The study population will be selected on the basis of the inclusion and exclusion criteria 
described in the sections below. Subject eligibility should be reviewed and documented by 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 52 of 137 
CRD-TPL-077 
Confidential 
the Investigator or an appropriately medically qualified member of the Investigator’s study 
team before subjects are included in the study. 
4.1.1 Inclusion Criteria 
Subjects may be enrolled in the study if all of the following inclusion criteria are met: 
1. Capable of providing written informed consent and willing and able to adhere to all 
protocol requirements.  
2. Males or females aged at least 18 years at the time of providing written informed consent. 
3. Evidence of moderate RI (eGFR ≥ 30 and < 60 mL/min/1.73 m2) before randomization, 
as calculated by the interactive response technology (IRT) using the CKD-EPI equation 
(Levey et al., 2009; Stevens et al., 2010). The local laboratory serum creatinine value 
obtained at Visit 2 (Study Day 1) should be used for this calculation. 
NOTE: The eGFR calculator on the National Kidney Foundation’s website can be used 
for pre-screening purposes 
(http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm) and the equation can be 
found in Appendix I. 
4. Evidence of myocardial necrosis in a clinical setting consistent with a type I 
(spontaneous) AMI as defined by the following: 
a. Detection of a rise and/or fall in cardiac troponin I or T with at least 1 value above the 
99th percentile upper reference limit. 
AND, 
b. Any 1 or more of the following: 
i. Symptoms of ischemia 
ii. New (or presumably new) significant ST/T wave changes or left bundle-branch 
block (LBBB) 
iii. Development of pathological Q waves on ECG 
iv. Imaging evidence of new loss of viable myocardium or regional wall motion 
abnormality 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 53 of 137 
CRD-TPL-077 
Confidential 
v. Identification of intracoronary thrombus by angiography 
5. Documented evidence of stable renal function and no clinical suspicion of AKI at least 
12 hours after FMC for the index AMI. For subjects undergoing angiography with or 
without PCI, stable renal function must be confirmed at least 12 hours after IV contrast 
and is defined as a serum creatinine value that is < 0.3 mg/dL increased from the pre-
contrast administration value. If the local laboratory post-contrast serum creatinine value 
is increased ≥ 0.3 mg/dL from the pre-contrast administration value, the laboratory test 
may be repeated once at least 24 hours after the initial assessment to assess stable renal 
function. The repeat serum creatinine value must be increased < 0.3 mg/dL from the 
pre-contrast administration value and there must be no suspicion of AKI for the subject to 
be eligible to receive the first infusion (Table 7).  
NOTE: If multiple local laboratory tests are obtained before the administration of 
contrast agent, the serum creatinine value closest in time but before contrast 
administration should be used as the reference value used to assess stability of renal 
function. 
6. Female subjects must be post-menopausal or with a negative urine pregnancy test at the 
screening visit and before randomization.   
a. Menopause is defined as being over the age of 60 years, or an age 45 to 60 years 
(inclusive) with amenorrhea for at least 1 year and a confirmatory follicle stimulating 
hormone (FSH) level > 30 IU/L. 
b. Women from the ages 45 to 60 years (inclusive) who are not amenorrheic for at least 
1 year or who have a screening FSH ≤ 30 IU/L must use an acceptable method of 
contraception during the study as described below. 
c. Females of childbearing potential must be willing and able to cease breastfeeding, and 
use an acceptable method of contraception to avoid pregnancy during the study and 
for 3 months after receipt of the last dose of investigational product.   
7. NOTE: Acceptable methods of contraception are: (1) abstinence where abstinence is the 
preferred and usual lifestyle of the subject, including refraining from heterosexual 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 54 of 137 
CRD-TPL-077 
Confidential 
intercourse during the entire period of risk associated with the study treatments. Periodic 
abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus 
interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not 
acceptable definitions of abstinence; (2) hormonal method; (3) 2 barrier methods, where 1 
method is the male condom; or (4) use of intrauterine device (placed more than 3 months 
before randomization); or (5) surgical sterilization (more than 3 months before 
randomization). Acceptable hormonal methods include: oral contraceptives, contraceptive 
medication patch, contraceptive medication injection, estrogen/progestin vaginal ring, or 
contraceptive medication implant. Acceptable barrier methods include: female or male 
condoms, with spermicidal foam or spermicidal jelly, or diaphragm, with spermicidal 
foam or spermicidal jelly. Female condom and male condom should not be used together. 
7. Investigator believes that the subject is willing and able to adhere to all protocol 
requirements. 
8. Willing not to participate in another interventional clinical study until completion of the 
final study visit. 
4.1.2 Exclusion Criteria 
Subjects are excluded from participating in this study if 1 or more of the following exclusion 
criteria are met: 
1. Symptoms, biomarker elevation or ECG changes other than those of the index event that 
are consistent with a diagnosis of AMI but are likely not due to primary myocardial 
ischemia (eg, PCI or coronary artery bypass graft [CABG]-related MI, stent thrombosis, 
arrhythmia, heart failure, trauma, renal insufficiency, etc.) (See Third Universal 
Definition of MI in Appendix II) 
2. Ongoing hemodynamic instability defined as any of the following: 
a. A history of New York Heart Association (NYHA) Class III or IV Heart Failure 
within the last year 
b. Killip Class III or IV (Appendix III) 
c. Sustained and/or symptomatic hypotension (systolic blood pressure < 90 mm Hg) 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 55 of 137 
CRD-TPL-077 
Confidential 
d. Left ventricular ejection fraction (LVEF) < 30%  
3. Planned CABG during the Active Treatment Period 
4. Evidence of hepatobiliary disease as indicated by any 1 or more of the following at 
screening: 
a. Current active hepatic dysfunction or active biliary obstruction 
b. Chronic or prior history of cirrhosis or of active infectious/inflammatory hepatitis 
Note: If subject has a past medical history of recovered hepatitis A, B, or C without 
evidence of cirrhosis, he/she could be considered for inclusion if there is documented 
evidence that there is no active infection (ie, antigen and/or polymerase chain reaction 
[PCR] negative). 
c. ALT > 3 x ULN or total bilirubin > 1.5 x ULN at time of randomization. However, 
subjects with a known or suspected history of Gilbert's syndrome may be eligible for 
study participation. The medical monitor must be contacted before enrolment of the 
subject to confirm eligibility (see Section 8.2.2.1, Table 7). 
5. History of AKI after previous exposure to an IV contrast agent. Subjects with a history of 
allergy to IV contrast agent may participate in the study if they have no evidence of 
serious clinical sequelae at the time of consent. The medical monitor should be contacted 
to discuss eligibility. 
6. History of current nephrotic range proteinuria defined as > 3500 mg/24 hours or 
> 3000 mg/g creatinine, or 4+ proteinuria on urine dipstick at screening, despite the use of 
angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker therapy. 
7. Body weight < 50 kg 
8. Known history of allergies, hypersensitivity or deficiencies as follows: 
a. Allergy to soybean or peanuts 
b. Known or suspected hypersensitivity to the investigational product, or to any 
excipients of the investigational product 
c. A known history of IgA deficiency or antibodies to IgA 
9. Other severe comorbid condition, concurrent medication, or other issue that renders the 
subject unsuitable for participation in the study, including but not limited to: 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 56 of 137 
CRD-TPL-077 
Confidential 
a. A comorbid condition with an estimated life expectancy of ≤ 6 months 
b. Women who are pregnant or breastfeeding 
c. Participated in another interventional clinical study or had extensive blood sampling 
(≥ 500 mL) within 3 months. Includes administration of any other investigational 
agents within 3 months before the first administration of current investigational 
product or at any time during the study 
d. Alcohol, drug, or medication abuse within 1 year before consent to this study 
e. Treatment with anticancer therapy (chemotherapy, immunotherapy, radiotherapy, 
targeted therapy or gene therapy) within 3 months before the first administration of 
investigational product or at any time during the study. Recovery from associated 
toxicities (eg, hematologic) must be documented in the source document.  
NOTE: Use of low dose chemotherapy for treatment of a condition other than cancer 
(eg, rheumatic disease) may be permissible. The medical monitor should be contacted 
to discuss eligibility. 
f. Previously randomized or participating in this study or previously exposed to CSL112 
g. Mental condition rendering the subject (or the subject's legally acceptable 
representative[s]) unable to understand the nature, scope and possible consequences 
of the study 
h. Subjects who are incarcerated, including prisoners or subjects compulsorily detained 
for treatment of either a psychiatric or physical (eg, infectious disease) illness 
i. Inability or unwillingness to comply with all follow-up, and/or unwilling to allow 
review of medical records through end of follow-up 
4.1.3 Infusion Delay and Stopping Rules 
Hepatic function (ALT and total bilirubin) must be within acceptable limits and stability of 
renal function (serum creatinine) must be confirmed by the Investigator before administration 
of the first infusion of investigational product. Eligibility for the first infusion of 
investigational product will be determined based on local laboratory values obtained at 
screening according to the criteria presented in Section 8.2.1.2 and Section 8.2.2.1, Table 7.   

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 57 of 137 
CRD-TPL-077 
Confidential 
Ongoing eligibility for all subsequent infusions of investigational product must be confirmed 
based on local laboratory values before each infusion according to the continuing infusion 
eligibility criteria presented in Section 8.2.2.2, Table 8.  
Each infusion should be completed as close to the protocol-specified visit schedule as 
possible, ie, no fewer than 7 days and no more than 10 days between each infusion, with all 
4 infusions administered within 30 days from Study Day 1 (Visit 2). An infusion may be 
skipped or delayed at the discretion of the Investigator if more time is necessary to confirm 
renal function stability or to evaluate and treat an AE before the next infusion 
(Section 8.2.2.2). If an infusion is skipped or delayed for a medical or safety reason, the 
medical monitor should be contacted, and the remaining infusions should be completed as 
close to the protocol-specified visit schedule as possible. 
4.1.4 Study and Subject Completion, Study Treatment Discontinuation and 
Withdrawal from Study 
4.1.4.1 Study Completion 
The study will be considered completed when either the pre-specified study completion is 
reached (all randomized subjects either complete Visit 8/Study Day 60, have withdrawn from 
the study, or have been lost to follow-up) or the study is terminated early based on 
recommendation of the independent DSMB and endorsement by the Steering Committee. 
Subjects for whom infusions of investigational product have been discontinued early should 
complete early termination procedures (Visit 7) and should be encouraged, if consent is not 
withdrawn, to continue follow-up for safety as specified through Visit 8 (Schedule of 
Assessments). 
4.1.4.2 Subject Completion 
A subject will be considered as having completed the study if he or she has completed 
Visit 8. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 58 of 137 
CRD-TPL-077 
Confidential 
Until the study completes, all subjects who are randomized will have follow-up visits as 
specified by protocol (Schedule of Assessments).  
If a subject is unwilling or unable to return for scheduled on-site follow-up visits, sites should 
attempt to collect as much visit information as possible, through telephone contact, registered 
mail contact, contact through family or friends, or use of publically available information. 
This latter source may be the only available option for subjects who withdraw consent during 
the study (see Section 4.1.4.4). All efforts should be made to confirm vital status at a 
minimum. 
4.1.4.3 Study Treatment Discontinuation 
Subjects may request at any time that further investigational product administration be 
discontinued, or it may be discontinued at any time at the discretion of the Investigator or 
CSL Behring LLC (CSLB) for safety, behavioral or administrative reasons (eg, due to an AE, 
protocol deviation, or study termination). The reason for early discontinuation of 
investigational product should be documented in the electronic case report form (eCRF).  
In accordance with International Conference on Harmonisation (ICH) principles of Good 
Clinical Practice (GCP), the Investigator always has the option to advise a subject to stop 
further administration of investigational product if the subject's safety or well-being is 
compromised by the continued administration of investigational product. Concern for the 
interests of the subject must always prevail over the interests of the study.  
If a subject prematurely discontinues study treatment and if consent is not withdrawn, every 
effort should be made to inform the subject of the importance of continuing in the study to 
ensure that the relevant follow-up safety assessments of Visit 7 (7 to 10 days after last 
infusion) and Visit 8 (at least 25 days after last infusion) are performed (Schedule of 
Assessments). If only 1 additional study visit is to be performed after subject discontinuation, 
the procedures in study Visit7 should be performed. At minimum, all efforts should be made 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 59 of 137 
CRD-TPL-077 
Confidential 
to confirm vital status if a subject is unwilling or unable to return for scheduled on-site visits 
or refuses to be contacted by telephone. 
In addition to the above considerations, serum creatinine, total bilirubin, and ALT must be 
assessed during the Active Treatment Period by the local laboratory and reviewed by the 
Investigator before administration of investigational product infusions 2, 3, and 4 to 
determine continuing eligibility; see criteria presented in Section 8.2.2.2, Table 8. 
In the event that a subject experiences a hypersensitivity reaction during the infusion of 
investigational product, the infusion must be immediately discontinued and the subject must 
receive immediate medical assessment and indicated supportive management per the 
institutional standard of care (see Section 7.1).  
If a female subject becomes pregnant, she must discontinue treatment with the investigational 
product, but will continue other study procedures unless not advised to do so at the discretion 
of the Investigator. All pregnancies must be reported according to Section 9.7.2.  
4.1.4.4 Subject Withdrawal from the Study 
Subject withdrawal from the study is defined as the subject’s withdrawal of consent from 
further participation in the study, including any contact by the investigational site personnel 
to determine the health status of the subject.   
When a subject is contemplating withdrawal from the study, the Investigator (not 
coordinator) must discuss with the subject the importance of further follow-up and how 
follow-up information can be obtained (in-person visit, phone, mail, via 3rd party, review of 
medical records). The above discussion must be documented in the subject’s medical record. 
If at all possible, in-person visits for subjects contemplating early withdrawal should include 
an early termination visit including procedures specified at Visit 7 (Schedule of 
Assessments). If no further follow-up is allowed due to subject’s decision, the reason must be 
documented in the eCRF. In such instances, the site should collect vital status at a minimum 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 60 of 137 
CRD-TPL-077 
Confidential 
in all randomized subjects using publicly available records as permitted by national and/or 
local regulatory requirements.  
In accordance with ICH principles of GCP, the Investigator always has the option to advise a 
subject to withdraw from the study. Concern for the interests of the subject must always 
prevail over the interests of the study.  
If a subject withdraws from the study, they will continue to have access to medical care as per 
routine local medical practice. 
If the subject withdraws from the study, CSLB will retain and continue to use any data 
collected before such withdrawal of consent, in accordance with prevailing regulatory 
guidance. 
4.1.5 Procedures for Handling Withdrawals 
Procedures for subjects who decide to withdrawal early from the study or who are withdrawn 
by the Investigator are discussed in Section 4.1.4. 
If a subject declines further participation or is withdrawn from the study, attempts will be 
made to complete and document the final assessment. If at all possible, this final assessment 
should include the assessments and procedures specified for Visit 7 (Schedule of 
Assessments). If the subject withdraws from the study, and also withdraws consent for 
disclosure of future information, CSLB may retain and continue to use any data collected 
before such withdrawal of consent. 
In the event that a subject withdraws from the study, the Investigator should record the reason 
and date of withdrawal in the eCRF and in the subject's medical records. 


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
 5HSODFHPHQW3ROLF\
6XEMHFWVZLWKGUDZQIURPWKHVWXG\RUIURPFRQWLQXHGLQYHVWLJDWLRQDOSURGXFWDGPLQLVWUDWLRQ
ZLOOQRWEHUHSODFHG6XEMHFWLGHQWLILFDWLRQ,'QXPEHUVDQGUDQGRPL]DWLRQQXPEHUVZLOOQRW
EHUHXVHGIRUDQRWKHUVXEMHFWXQGHUDQ\FLUFXPVWDQFHVLQFOXGLQJHUURQHRXVUDQGRPL]DWLRQ

678'<,17(59(17,216

'(6&5,37,212),19(67,*$7,21$/352'8&76
 &6/
7KHVWXG\SURGXFW&6/ZLOOEHPDQXIDFWXUHGE\&6/%LQDFFRUGDQFHZLWK*RRG
0DQXIDFWXULQJ3UDFWLFHJXLGHOLQHVDQGORFDOUHJXODWRU\UHTXLUHPHQWV
&6/ZLOOEHSURYLGHGWRWKHVLWHDVDVWHULOHVOLJKWO\\HOORZO\RSKLOL]HGIULDEOHPDVV
FRQWDLQLQJJWRWDOSURWHLQLQDP/JODVVERWWOHZLWKDUXEEHUVWRSSHUDQGDQDOXPLQXP
FDS%HIRUHXVHHDFKERWWOHRI&6/LVUHFRQVWLWXWHGZLWKP/RI:DWHUIRU,QMHFWLRQ
:),\LHOGLQJ
RISURGXFWUHDG\IRUXVH)RUWKHJ&6/GRVHWR
EHXVHGLQWKLVVWXG\ERWWOHVZLOOEHUHFRQVWLWXWHGIRUD
RISURGXFW
7DEOH
.H\&RPSRQHQWVRI&6/
CCI
CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
)XUWKHUGHWDLOVUHJDUGLQJSUHSDUDWLRQRI&6/DUHVSHFLILHGLQWKHVWXG\UHIHUHQFHPDQXDOV
 &RPSDUDWRU3URGXFW
7KHFRPSDUDWRUSURGXFWZLOOEHSODFHERZHLJKWYROXPHZYVRGLXPFKORULGH
VROXWLRQLH1D&OQRUPDOVDOLQHIRU,9LQIXVLRQ7KHYROXPHRISODFHERDGPLQLVWHUHGZLOO
EHPDWFKHGWRWKHYROXPHRI&6/DGPLQLVWHUHGLH
3ODFHERZLOOEHSURYLGHGWR
WKHVLWHDVDUHJLVWHUHGVWHULOHQRQS\URJHQLFFRORUOHVVVROXWLRQ)XUWKHUGHWDLOVUHJDUGLQJWKH
SUHSDUDWLRQRIWKHSODFHERDUHVSHFLILHGLQWKHVWXG\UHIHUHQFHPDQXDOV

3$&.$*,1*/$%(/,1*6833/<$1'6725$*(
 3DFNDJLQJDQG/DEHOLQJ
&6/ZLOOEHSDFNDJHGDQGODEHOHGDFFRUGLQJWRFXUUHQW,&+*RRG0DQXIDFWXULQJ3UDFWLFH
DQG*&3JXLGHOLQHVDQGQDWLRQDOOHJDOUHTXLUHPHQWV
&RPPHUFLDOO\DYDLODEOHVWHULOH:),ERWWOHVZLOOEHVRXUFHGDQGODEHOHGE\&6/%RULWV
GHOHJDWH/DEHOHG:),ZLOOEHVXSSOLHGWRWKHVWXG\VLWHVWRXVHIRUWKHUHFRQVWLWXWLRQRI
&6/
&RPPHUFLDOO\DYDLODEOHQRUPDOVDOLQHZLOOEHVRXUFHGDQGODEHOHGVSHFLILFDOO\DV
³SODFHER´E\&6/%RUGHOHJDWHV
 6XSSO\DQG6WRUDJH
&6/ZLOOEHVXSSOLHGWRWKHVWXG\VLWHVE\&6/%RUGHOHJDWHV&6/PXVWEHVWRUHG
XQGHUWHPSHUDWXUHPRQLWRUHGFRQGLWLRQV&WR&LQFOXVLYHLQDVHFXUHVWRUDJHDUHD
&6/0867127%()52=(1DVWKLVPD\GLVUXSWLWVSURWHLQVWUXFWXUH
&6/PXVWEHSURWHFWHGIURPOLJKWGXULQJVWRUDJH7KHLQGLYLGXDOSDFNDJLQJKROGLQJWKH
&6/ERWWOHLVVXIILFLHQWIRUOLJKWSURWHFWLRQ
CCI

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 63 of 137 
CRD-TPL-077 
Confidential 
Further details regarding storage of CSL112 and placebo are specified in the study reference 
manuals. 
5.3 
ACCOUNTABILITY AND DESTRUCTION 
All supplies of investigational product must be accounted for throughout the study. At the 
end of the study, the Drug Inventory Report, dated and signed by the Investigator or delegate 
(eg, pharmacist), must be retained at the study site as verification of final accountability of 
CSL112. An unblinded Clinical Monitor will conduct study drug accountability. 
Records for the delivery of investigational product to the study site, the inventory at the study 
site, the use by each subject, and the destruction or return of investigational product to CSLB 
must be maintained by the Investigator (or delegate). The records will include dates, 
quantities, and unique code numbers assigned to investigational product and unique code 
numbers assigned to the subjects. 
Information on the destruction of CSL112 or placebo is provided in the study reference 
manuals. 
5.4 
OTHER INTERVENTION(S) 
Not applicable. 
5.5 
RESCUE THERAPY 
Not applicable. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 64 of 137 
CRD-TPL-077 
Confidential 
6. 
ALLOCATION, DOSING AND ADMINISTRATION 
6.1 
ALLOCATION TO TREATMENT 
6.1.1 Subject Assignment 
After providing written informed consent, the subject will be issued via an IRT system a 
study-level unique subject ID number. The subject ID number will be used to identify the 
subject for the duration of the study. Subject ID numbers will not be reassigned or reused.   
6.1.2 Randomization Procedures 
Eligible subjects will be randomized in a 2:1 ratio to receive active treatment versus placebo 
by means of the IRT. Randomization will be stratified by eGFR (30 to < 45 mL/min/1.73 m2 
or 45 to < 60 mL/min/1.73 m2) as calculated by the IRT using the CKD-EPI equation (Levey 
et al, 2009; Stevens et al, 2010) and by medical history of diabetes requiring current 
treatment with any anti-diabetic medication (yes or no). The IRT will assign the appropriate 
study treatment to each subject. CSLB or a delegate will supply the Investigator with a user 
guide for the IRT system. The IRT will use centralized randomization and fixed-size blocks. 
To ensure the study blind is maintained, a CSLB statistician / delegate not directly involved 
in the analysis of study results will prepare the study randomization code. The unblinded 
CSLB statistician/delegate will keep the randomization code on file. 
6.1.3 Blinding Procedures 
6.1.3.1 Blinding Method 
Physical measures of blinding will be used to mask the identity of the investigational product 
due to the physical characteristics of CSL112 when reconstituted (ie, pale yellow/straw color 
with slight foaming characteristics). Information on the physical measures of blinding used to 
mask the identity of the investigational product will be provided in the study reference 
manuals.   


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
,QYHVWLJDWLRQDOVLWHVWDIILQFOXGLQJWKH,QYHVWLJDWRUZLOOEHEOLQGHGWRWUHDWPHQWDOORFDWLRQ
6XEMHFWVDQG&6/%VWDIISDUWLFLSDWLQJLQWKHFRQGXFWRIWKHVWXG\ZLOODOVREHEOLQGHGWR
WUHDWPHQWDOORFDWLRQGRXEOHEOLQG
8QEOLQGHGVWXG\VLWHSHUVRQQHOGHOHJDWHGE\WKH,QYHVWLJDWRUZLOOSUHSDUHWKHLQYHVWLJDWLRQDO
SURGXFWDQGWKH,9DGPLQLVWUDWLRQEDJDQGLQIXVLRQVHWIRUDGPLQLVWUDWLRQ7KHXQEOLQGHG
VWXG\VLWHSHUVRQQHOZLOODOVRHQVXUHWKHFRQWHQWVUHPDLQEOLQGHGWRWKHVXEMHFWDQGWKH
EOLQGHGVWXG\VLWHSHUVRQQHOZKRZLOOEHFRQGXFWLQJVDIHW\DVVHVVPHQWV8QEOLQGHGVWXG\VLWH
SHUVRQQHOZLOOQRWEHLQYROYHGLQFRQGXFWLQJRUUHFRUGLQJRIDQ\VWXG\DVVHVVPHQW
SURFHGXUHV
6WXG\VLWHSHUVRQQHOGHOHJDWHGE\WKH,QYHVWLJDWRUZLOODGPLQLVWHUWKHLQYHVWLJDWLRQDOSURGXFW
E\,9LQIXVLRQLQDVXLWDEOHSHULSKHUDORUFHQWUDOYHLQ7KHXQEOLQGHGVWXG\VLWHSHUVRQQHO
VKRXOGEHDYDLODEOHWRWURXEOHVKRRWLVVXHVZLWKWKHLQIXVLRQSXPSRUSK\VLFDOPHDVXUHVRI
EOLQGLQJPDWHULDOVLIQHHGHG8QEOLQGHGVWXG\VLWHSHUVRQQHOPD\DVVLVWLQWKHDGPLQLVWUDWLRQ
RIWKHLQYHVWLJDWLRQDOSURGXFWHJWXUQRQWKHSXPSLQWKHHYHQWWKDWDSUREOHPRFFXUVZLWK
WKHLQIXVLRQSXPSLQIXVLRQWXELQJRULIWKHUHLVDFRQFHUQWKDWEOLQGHGVLWHSHUVRQQHOPD\
GLVWXUEWKHSK\VLFDOPHDVXUHVRIEOLQGLQJ
$QXQEOLQGHG&OLQLFDO0RQLWRUZLOOFRQGXFWVWXG\GUXJDFFRXQWDELOLW\
$GHTXDWHSURFHGXUHVZLOOEHLQSODFHWRHQVXUHWKHLQWHJULW\RIWKHEOLQGHGGDWDZLWKLQ&6/%
DQGWKHVWXG\VLWHV

7KH,QYHVWLJDWRUVKRXOGQRWREWDLQD
OLSLGSDQHOWHVWGXULQJWKH$FWLYH7UHDWPHQW3HULRGDVWKHUHVXOWVPD\XQPDVN
WUHDWPHQWDVVLJQPHQW
'HVLJQDWHGVSRQVRUUHSUHVHQWDWLYHVPD\EHXQEOLQGHGWRVSHFLILFGDWDLH3.

GDWDGXULQJWKHVWXG\7KHVHLQGLYLGXDOVZLOOQRWEHSDUWRIWKHFOLQLFDOVWXG\WHDP7KH
WUDQVODWLRQDOPHGLFLQHVFLHQWLVWDQGSKDUPDFRNLQHWLFLVWSKDUPDFRPHWULFLDQUHVSRQVLEOHIRU
WKHVDPSOHDQDO\VLVDQG3.
HYDOXDWLRQZLOOEHXQEOLQGHG+RZHYHUWKH\ZLOODJUHHQRWWR
CCI
CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
GLVFORVHWKHUDQGRPL]DWLRQFRGH$Q\SUHOLPLQDU\3.
GDWDPDGHDYDLODEOHGXULQJ
WKHFRXUVHRIWKHVWXG\ZLOOUHIHUWRPHDQGDWDE\WUHDWPHQWJURXSZLWKGHVFULSWLYHVWDWLVWLFV
ZLWKRXWUHYHDOLQJDQ\LQGLYLGXDOUDQGRPL]DWLRQQXPEHUVRUVXEMHFWQXPEHUV
$GHTXDWHSURFHGXUHVZLOODOVREHLQSODFHWRHQVXUHWKHLQWHJULW\RIWKHEOLQGHGGDWDZLWKLQ
WKH6WHHULQJ&RPPLWWHHDQG&(&7KHVHZLOOEHRXWOLQHGLQWKHLUUHVSHFWLYHFRPPLWWHH
FKDUWHUV
6DIHW\3.DQGRWKHUVWXG\GDWDDVUHTXHVWHGZLOOEHSURYLGHGWRWKH'60%DVXQEOLQGHG
GDWD7KHVHSURFHGXUHVDUHRXWOLQHGLQWKH'60%FKDUWHU
 %UHDNLQJWKH%OLQGIRUDQ(PHUJHQF\
7KHUDQGRPL]DWLRQFRGHIRUDOORULQGLYLGXDOVXEMHFWVPD\EHXQEOLQGHGWRDVLWHGXULQJWKH
VWXG\LQHPHUJHQF\VLWXDWLRQVIRUUHDVRQVRIVXEMHFWVDIHW\LINQRZLQJWUHDWPHQWDVVLJQPHQW
ZLOOFKDQJHVXEMHFWPDQDJHPHQW,QFDVHRIDQHPHUJHQF\VLWXDWLRQIRUWKHUHDVRQRIVXEMHFW
VDIHW\WKH,QYHVWLJDWRUGHOHJDWHVKRXOGXVH,57WRLGHQWLI\WKHWUHDWPHQWDOORFDWLRQIRUD
VXEMHFW7KHUHDVRQIRUXQEOLQGLQJWKHUDQGRPL]DWLRQFRGHPXVWEHIXOO\UHFRUGHGLQWKH
VXEMHFW¶VVRXUFHGRFXPHQWVDQGWKH,QYHVWLJDWRUPXVWIROORZWKHGHILQHGSURFHGXUHVSURYLGHG
LQWKHVWXG\UHIHUHQFHPDQXDOV
 3ODQQHG8QEOLQGLQJ3URFHGXUHV
7KHUDQGRPL]DWLRQFRGHZLOOEHSURYLGHGWRWKHXQEOLQGHG'60%VWDWLVWLFLDQE\WKH
XQEOLQGHGVWDWLVWLFLDQGHOHJDWHDVUHTXLUHG$WWKHHQGRIWKHVWXG\WKHVWXG\VWDWLVWLFLDQZLOO
UHTXHVWWKDWWKHVWXG\EHXQEOLQGHGDIWHUDXWKRUL]LQJGDWDEDVHORFN7KHUDQGRPL]DWLRQFRGHV
ZLOOWKHQEHSURYLGHGWRWKHVWXG\VWDWLVWLFLDQGHOHJDWH
&6/*OREDO&OLQLFDO6DIHW\	3KDUPDFRYLJLODQFHSHUVRQQHOPD\XQEOLQGWKHUDQGRPL]DWLRQ
FRGHWRIDFLOLWDWHDVVHVVPHQWRIVXVSHFWHGXQH[SHFWHGVHULRXVDGYHUVHUHDFWLRQV686$5V
H[SHULHQFHGE\DQ\VXEMHFWIRUH[SHGLWHGUHSRUWLQJWRUHJXODWRU\DXWKRULWLHV
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO

'26,1*$1'$'0,1,675$7,21
7KH,QYHVWLJDWRURUDPHGLFDOO\TXDOLILHGGHOHJDWHZLOODGPLQLVWHURUGLVSHQVHWKH
LQYHVWLJDWLRQDOSURGXFWRQO\WRVXEMHFWVLQFOXGHGLQWKLVVWXG\IROORZLQJWKHSURFHGXUHVVHW
RXWLQWKLVVWXG\SURWRFRO7DEOH7KHLQIXVLRQVRILQYHVWLJDWLRQDOSURGXFWPD\EH
DGPLQLVWHUHGLQWKHKRVSLWDORUWKHRXWSDWLHQWVHWWLQJ
7DEOH
,QYHVWLJDWLRQDO3URGXFW'RVLQJ&KDUDFWHULVWLFV
$GPLQLVWUDWLRQSDUDPHWHU
&6/
3ODFHER
5RXWH
,QWUDYHQRXV
,QWUDYHQRXV
$QDWRPLFDOORFDWLRQ
9HLQSHULSKHUDORUFHQWUDO
9HLQSHULSKHUDORUFHQWUDO
7RWDOLQIXVLRQYROXPH


'RVH
JSHU
$

D
,QIXVLRQGXUDWLRQ
KE
KE
J JUDPVK KRXUP/ PLOOLOLWHU
D0D[LPXPDQWLFLSDWHGGRVHDQGRUYROXPH
E:LWKLQWHUUXSWLRQVQRWWRH[FHHGK

%HIRUHLQIXVLRQVODERUDWRU\DVVHVVPHQWVDUHUHTXLUHG(OLJLELOLW\IRUWKHILUVWLQIXVLRQRI
LQYHVWLJDWLRQDOSURGXFWZLOOEHFRQILUPHGEDVHGRQORFDOODERUDWRU\YDOXHVREWDLQHGDW
VFUHHQLQJDFFRUGLQJWRWKHFULWHULDSUHVHQWHGLQ6HFWLRQDQG7DEOH+HSDWLFIXQFWLRQ
$/7DQGWRWDOELOLUXELQPXVWEHZLWKLQDFFHSWDEOHOLPLWVDQGVWDELOLW\RIUHQDOIXQFWLRQ
VHUXPFUHDWLQLQHPXVWEHFRQILUPHGE\WKH,QYHVWLJDWRUEHIRUHWKHILUVWDGPLQLVWUDWLRQRI
LQYHVWLJDWLRQDOSURGXFW2QJRLQJHOLJLELOLW\IRUDOOVXEVHTXHQWLQIXVLRQVRILQYHVWLJDWLRQDO
SURGXFWRQ6WXG\'D\VDQGPXVWEHFRQILUPHGE\TXDOLILHGVWXG\VLWHSHUVRQQHO
EHIRUHGRVHDGPLQLVWUDWLRQLHZLWKLQKRXUVRIWKHQH[WLQIXVLRQDFFRUGLQJWRWKH
FRQWLQXLQJLQIXVLRQHOLJLELOLW\FULWHULDSUHVHQWHGLQ6HFWLRQ7DEOH
8QEOLQGHGVWXG\VLWHSHUVRQQHOGHOHJDWHGE\WKH,QYHVWLJDWRUZLOOSUHSDUHWKHLQYHVWLJDWLRQDO
SURGXFWDQGWKH,9DGPLQLVWUDWLRQEDJDQGLQIXVLRQVHWIRUDGPLQLVWUDWLRQ7KHXQEOLQGHG
VWXG\VLWHSHUVRQQHOZLOODOVRHQVXUHWKHFRQWHQWVUHPDLQEOLQGHGWRWKHVXEMHFW
$GPLQLVWUDWLRQRIWKHLQYHVWLJDWLRQDOSURGXFWVKRXOGEHFRPSOHWHGZLWKLQKRXUVRI
CC
I
CC
I

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 68 of 137 
CRD-TPL-077 
Confidential 
preparation of the solution. Blinded study site personnel (or unblinded study site personnel as 
per Section 6.1.3.1) delegated by the Investigator will administer the investigational product 
by IV infusion, in a suitable peripheral or central vein. A dedicated IV line should be used for 
administration of investigational product. Patency of the IV line should be ensured before the 
start of the infusion. After the completion of the infusion the IV line should be flushed with 
saline. If the infusion is interrupted for any reason, the total duration of the infusion should 
not exceed 3 hours. Subjects randomized to the placebo group will receive a volume of 
placebo matched to the corresponding CSL112 infusion volume. 
Before starting an infusion of investigational product, the Investigator or a medically 
qualified delegate should assess each subject for presence of hypovolemia, which may 
include signs of dry mouth, skin tenting, orthostasis, dizziness, etc. If hypovolemia is 
suspected or confirmed, the Investigator or medically qualified delegate should administer IV 
replacement fluid as clinically indicated. During the infusion, subjects should be encouraged 
to drink fluids. 
Subjects should be advised to sit down or lie in a semi-supine position while receiving the 
infusion. If necessary, upon completion of the infusion subjects should be escorted as per 
site's standard of procedures to ensure their safety. 
All subjects should be monitored for drug hypersensitivity reaction for at least 1 hour after 
the end of the first and second infusions of investigational product. Extension of the duration 
of the monitoring time and/or monitoring after administration of the third and fourth 
infusions of investigational product may be done at the discretion of the Investigator as 
clinically indicated. Study site personnel who are medically qualified to recognize and treat 
drug hypersensitivity reactions must be available together with medications and equipment to 
treat such reactions. All possible drug hypersensitivity reactions require follow up until 
resolution (Section 7.1). 
Before departing from the clinic and after completion of the infusion and all other study 
assessments, all subjects should be asked to void. If a subject is unable to void before leaving 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 69 of 137 
CRD-TPL-077 
Confidential 
the clinic, he/she should be contacted at home to determine whether or not they have been 
able to void. 
6.3 
TREATMENT COMPLIANCE 
All doses of investigational product will be administered by IV infusion at the study site. 
Subjects will be considered to have received a complete dose of investigational product if 
they receive at least 80% of investigational product and cumulative infusion interruptions (if 
any) are for no more than a total of 60 minutes. 
7. 
CONTRAINDICATIONS, PERMITTED THERAPIES AND 
PROHIBITTED THERAPIES 
7.1 
CONTRAINDICATIONS AND PRECAUTIONS TO FURTHER DOSING 
CSL112 has previously been administered to humans. Potential risks and guidance to the 
Investigator for use of CSL112 are provided in the Development Core Safety Information 
document (appended to the CSL112 IB). The administration of CSL112 to any subject not 
meeting the eligibility criteria for this study, or to any subject not enrolled in this study, is 
prohibited. 
There is potential for allergic reactions or hypersensitivity to CSL112 in certain individuals, 
given the constituents of the product. CSL112 consists of apoA-I isolated from human plasma 
that may contain IgA and PC derived from soy beans. Therefore, Investigators should ensure 
that subjects do not have a positive history of IgA deficiency or antibodies to IgA and that the 
subjects are not allergic to either soy bean or peanuts (there is a documented risk of cross 
reactions to soy in known peanut allergy sufferers). 
In the event that a subject experiences a hypersensitivity reaction during the infusion, the 
infusion must be immediately discontinued and the subject must receive immediate medical 
assessment and indicated supportive management per the institutional standard of care. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 70 of 137 
CRD-TPL-077 
Confidential 
Additional assessments are to be performed if subjects experience hypersensitivity reactions 
while on the study. In the event of a potential drug hypersensitivity reaction, additional 
assessments should be performed and follow-up is required until resolution (Section 8.2.3.6). 
If a subject experiences a Grade 3 or 4 Common Terminology Criteria for Adverse Events 
(CTCAE) AE within 72 hours of administration of a dose of investigational product that is 
assessed as related to the investigational product by the Investigator, additional doses of 
investigational product should not be administered. 
Because CSL112 is made from human blood, it may carry a risk of transmitting infectious 
agents (eg, viruses and, theoretically, the Creutzfeldt-Jakob disease agent). The risk of 
infectious agent transmission has been reduced by screening plasma donors for prior 
exposure to certain viruses, testing for the presence of certain current virus infections, and 
including virus inactivation/removal steps in the manufacturing process. 
7.2 
PERMITTED THERAPIES 
Concomitant treatment is permitted throughout the study.  
All drugs and/or procedures currently being administered to a subject at the time of signing 
informed consent, and which are taken in addition to the investigational product at any time 
during the study, are regarded as concomitant therapies and must be documented as such in 
the eCRF.   
7.3 
PROHIBITED THERAPIES 
The following therapies are NOT PERMITTED during the study: 
• Treatment with anticancer therapy (chemotherapy, immunotherapy, radiotherapy, targeted 
therapy, or gene therapy) within 3 months before the first administration of 
investigational product or at any time during the study. Recovery from associated 
toxicities (eg, hematologic) must be documented in the source document. 


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
127(8VHRIORZGRVHFKHPRWKHUDS\IRUWUHDWPHQWRIDFRQGLWLRQRWKHUWKDQFDQFHUHJ
UKHXPDWLFGLVHDVHPD\EHSHUPLVVLEOHVHH6HFWLRQ
x $GPLQLVWUDWLRQRIDQ\RWKHULQYHVWLJDWLRQDODJHQWZLWKLQPRQWKVEHIRUHWKHILUVW
DGPLQLVWUDWLRQRILQYHVWLJDWLRQDOSURGXFWRUDWDQ\WLPHEHIRUHWKHVXEMHFW¶VFRPSOHWLRQRI
WKHVWXG\
6XEMHFWVDUHQRWWREHHQUROOHGLQWRWKHVWXG\LIWKH\UHFHLYHDQ\SURKLELWHGWKHUDS\,I
DGPLQLVWUDWLRQRIDQ\SURKLELWHGWKHUDS\EHFRPHVQHFHVVDU\GXULQJWKHVWXG\IRUPHGLFDO
UHDVRQVWKHVXEMHFWPD\EHZLWKGUDZQIURPIXUWKHUVWXG\SDUWLFLSDWLRQ

',(7$5<$1'/,)(67</(5(675,&7,216
7KHUHDUHQRGLHWDU\RUOLIHVW\OHUHVWULFWLRQVIRUVXEMHFWVZKRSDUWLFLSDWHLQWKHVWXG\

29(5'26(
2YHUGRVHLVGHILQHGDVDQ\VLQJOHGRVHDERYHWKHPD[LPXPGRVHDOORZHGE\SURWRFRORU
DQLQIXVLRQUDWHWKDWH[FHHGVPJNJPLQRIVXFURVH7KHHIIHFWVRIDQ\SRWHQWLDORYHUGRVH
ZLWK&6/KDYHQRWEHHQVWXGLHG5HIHUWR6HFWLRQIRUWKHGHILQLWLRQRIDQRYHUGRVH
DQGUHTXLUHPHQWVIRUGRFXPHQWDWLRQ

678'<352&('85(6$66(660(176$1'9,6,76&+('8/(

&/,1,&$/352&('85(6
7KHFOLQLFDOSURFHGXUHVWKDWZLOOEHFRQGXFWHGGXULQJWKLVVWXG\WRDVVHVVSRSXODWLRQ
GHPRJUDSKLFVDQGEDVHOLQHFKDUDFWHULVWLFVVDIHW\3.
DUHRXWOLQHGLQ7DEOH
7DEOH7DEOHDQG7DEOHUHVSHFWLYHO\7KHLQFOXVLRQDQGWLPLQJRIFOLQLFDOSURFHGXUHV
IRUWKLVVWXG\DUHQRWHGLQWKH6FKHGXOHRI$VVHVVPHQWV5HIHUWRWKHVWXG\UHIHUHQFHPDQXDOV
IRUGHWDLOHGLQVWUXFWLRQVRQKRZWKHDVVHVVPHQWVVKRXOGEHSHUIRUPHG
CCI

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 72 of 137 
CRD-TPL-077 
Confidential 
8.1.1 Demographics and Baseline Characteristics 
Clinical procedures to be conducted to collect demographic information and baseline 
characteristics are provided in Table 3. These assessments will be performed at time points as 
detailed in the Schedule of Assessments. 
Table 3.  Clinical Procedures: Demographics and Baseline Characteristics 
Assessment 
Description 
Demographics 
Date of birth, years of age, sex, race, and ethnicity 
Height 
Weight 
Height will be recorded in centimeters (cm)  
Body weight will be recorded in kilograms (kg) 
Medical history 
Relevant medical history, including cause of CKD if knowna 
Gilbert’s syndrome - historical documentation (record in eCRF) 
Prior/Concomitant 
Therapies 
Prior Therapy: All medications taken by subjects in the 4 weeks before 
screening will be recorded, including those administered for the index AMI. 
Concomitant Therapy: All medications currently being administered to a 
subject at the time informed consent is signed and which continue to be 
taken in addition to investigational product during the study will be 
recorded. 
Standard of Care 
Laboratory 
Sample: Serum 
Creatinine  
Local laboratory tests obtained as part of standard of care may include 
serum creatinine measurements that will be used to determine stability of 
renal function after the index event or, for subjects undergoing angiography, 
after administration of intravenous contrast agent. If multiple laboratory 
tests are obtained before the administration of contrast agent, the serum 
creatinine value closest in time but before contrast administration should be 
used as the reference value to assess stability of renal function (Table 7). 
Results of the local laboratory serum creatinine tests used as the reference 
value to assess renal function stability should be recorded in the eCRF.  
eGFR 
The local laboratory serum creatinine value used to confirm stability of renal 
function before the first infusion of investigational product will be used to 
calculate baseline eGFR that will be used for stratification of randomization 
by eGFR. The CKD-EPI equation (see Appendix I) will be used for 
calculation of eGFR. This method for creatinine measurement should be 
traceable to IDMS standards. 
AMI = acute myocardial infarction; CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; eCRF = 
electronic case report form; eGFR = estimated glomerular filtration rate; IDMS = isotope dilution mass 
spectrometry; MI = myocardial infarction; PRBCs = packed red blood cells 
a. Including but not limited to prior MI, history of stable or unstable angina, coronary revascularization or 
surgery, hypertension, dyslipidemia, diabetes, congestive heart failure, peripheral arterial disease, valvular 
heart disease, heart rhythm disorders, cerebrovascular disease, any clinically-significant bleeding event 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 73 of 137 
CRD-TPL-077 
Confidential 
requiring transfusion of at least 2 units PRBCs or a discontinuation of antiplatelet or anticoagulation therapy. 
Also include any relevant renal history, particularly CKD and its cause if known, and historical renal 
function measures. CKD is defined as abnormalities of kidney structure or function, present for greater than 
3 months, with implications for health. 
 
8.1.2 Safety 
The incidence, severity or intensity, and causality of AEs will be evaluated according to the 
criteria and for the duration of the observation period as specified in Section 9.  
Clinical procedures to be conducted before and throughout the study to evaluate safety are 
provided in Table 4. Assessments for safety evaluation will be performed at time points as 
detailed in the Schedule of Assessments. More frequent evaluations may be performed in the 
case of an AE, if clinically indicated, at the discretion of the Investigator. Clinical laboratory 
test results that are outside the normal reference range and are deemed clinically significant 
by the Investigator are to be recorded as AEs or SAEs. If clinically significant abnormal 
laboratory test results are identified after investigational product infusion, the test(s) will be 
repeated until the values return to normal and/or baseline values. Safety assessment 
parameters should be repeated if the specimen is hemolyzed. Refer to the study reference 
manuals for detailed instructions on how the assessments should be performed. 
Table 4. 
Clinical Procedures: Safety Assessments 
Assessment 
Description 
Pregnancy test  
Urine test for beta-human chorionic gonadotropin. Only females of child 
bearing potential are to be tested. 
FSH 
measurement 
FSH measurement in serum to be assessed only in amenorrheic females 
from the ages of 45 through 60 years, to confirm post-menopausal 
status. 


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
$VVHVVPHQW
'HVFULSWLRQ
3K\VLFDO
H[DPLQDWLRQ
$VSHUWKHVLWH¶VVWDQGDUGSURFHGXUHWRLQFOXGHH[DPLQDWLRQRIWKHVNLQ
H[WUHPLWLHVKHDGH\HVHDUVQRVHDQGWKURDWDQGWKHIROORZLQJ
V\VWHPVUHVSLUDWRU\&9*,PXVFXORVNHOHWDOQHXURORJLFDOO\PSKDWLF
DQGDQDVVHVVPHQWRIJHQHUDODSSHDUDQFH
$Q\DEQRUPDOILQGLQJVFRQVLGHUHGE\WKH,QYHVWLJDWRUDVFOLQLFDOO\
VLJQLILFDQWDWWKHWLPHRIVFUHHQLQJZLOOEHGRFXPHQWHGDV0HGLFDO
+LVWRU\$Q\FOLQLFDOO\VLJQLILFDQWFKDQJHVRFFXUULQJEHWZHHQVFUHHQLQJ
DQGWKHHQGRIWKHVWXG\ZLOOEHGRFXPHQWHGLQWKHH&5)DVDQ$(
3K\VLFDOH[DPLQDWLRQVPXVWEHSHUIRUPHGE\WKH,QYHVWLJDWRURUD
PHGLFDOO\TXDOLILHGGHOHJDWH3K\VLFDOH[DPLQDWLRQ±VKRXOGDOVRLQFOXGH
GUXJK\SHUVHQVLWLYLW\ILQGLQJVLIUHOHYDQW6HFWLRQ
OHDG(&*
7DNHQDIWHUWKHVXEMHFWKDVUHVWHGLQDVXSLQHSRVLWLRQIRUPLQXWHV
+HDUWUDWH55LQWHUYDO3435GXUDWLRQ456GXUDWLRQXQFRUUHFWHG47
GXUDWLRQDQGWKH,QYHVWLJDWRU¶VRYHUDOOLQWHUSUHWDWLRQZLOOEHUHFRUGHG
:KHQ(&*VDUHVFKHGXOHGWREHSHUIRUPHGDWWKHVDPHWLPHDVYLWDO
VLJQV3.
WKH(&*VKRXOGEHGRQH
EHIRUHWKHVHRWKHUDVVHVVPHQWVLISRVVLEOH
9LWDOVLJQV
%ORRGSUHVVXUHV\VWROLFDQGGLDVWROLFDIWHUWKHVXEMHFWKDVUHVWHGLQD
VLWWLQJRUVXSLQHSRVLWLRQPLQXWHV3XOVHUDWHSHUPLQXWHZLOOEH
FRXQWHGPDQXDOO\RYHUVHFRQGVDQGDGMXVWHGSHUPLQXWHRU
PHDVXUHGZLWKDQDXWRPDWLFEORRGSUHVVXUHPRQLWRU%RG\WHPSHUDWXUH
ZLOOEHUHFRUGHGLQGHJUHHV&HOVLXV0HDVXUHPHQWFDQEHPDGHXVLQJ
HLWKHURUDORUW\PSDQLFPHWKRGVEXWWKHPHWKRGVKRXOGEHFRQVLVWHQW
WKURXJKRXWWKHVWXG\IRUDJLYHQVXEMHFW
$(PRQLWRULQJ
$OO$(VZLOOEHPRQLWRUHGDQGUHFRUGHGDVGHVFULEHGLQ6HFWLRQ
5HSRUWLQJRIEOHHGLQJHYHQWVDQGUHQDO6$(VLQFOXGHVFRPSOHWLRQRIWKH
%OHHGLQJ(YHQWH&5)SDJHRUWKH5HQDO6$(H&5)SDJHUHVSHFWLYHO\
ZLWKVXSSRUWLQJGRFXPHQWDWLRQKRVSLWDOUHFRUGVDQGWHVWV
%OHHGLQJHYHQW
PRQLWRULQJ
%OHHGLQJHYHQWVGHWHFWHGE\WKH,QYHVWLJDWRURUPHGLFDOO\TXDOLILHG
GHOHJDWHZLOOEHDVVHVVHGDQGGHILQHGXVLQJWKH%$5&GHILQLWLRQIRU
EOHHGLQJ0HKUDQHWDO$SSHQGL[,9$VVHVVPHQWLQFOXGHV
FRPSOHWLRQRIWKH%OHHGLQJ(YHQWH&5)SDJHDQGVXSSRUWLQJ
GRFXPHQWDWLRQKRVSLWDOUHFRUGVDQGWHVWV$Q\EOHHGLQJHYHQWVKRXOG
EHUHSRUWHGDV$(VHH6HFWLRQ
CCI

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 75 of 137 
CRD-TPL-077 
Confidential 
Assessment 
Description 
Hypovolemia 
assessment 
Before starting an infusion of investigational product, the Investigator or 
a medically qualified delegate should assess each subject for presence of 
hypovolemia, which may include signs of dry mouth, skin tenting, 
orthostasis, dizziness, etc. If hypovolemia is suspected or confirmed, the 
Investigator or a medically qualified delegate should administer IV 
replacement fluid as clinically indicated. During the infusion, subjects 
should be encouraged to drink fluids. Before departing from the clinic 
and after completion of the infusion and all other study assessments, all 
subjects should be asked to void. If a subject is unable to void before 
leaving the clinic, he/she should be contacted at home to determine 
whether or not they have been able to void. 
Infusion Site 
Assessment 
An assessment of the investigational product infusion site should be 
performed by the Investigator or a medically qualified delegate with 
each infusion. Any abnormal finding at the infusion site, including 
bruising, redness and/or swelling, should be recorded as an AE. Bruising 
should be assessed using the BARC criteria (Appendix IV). 
Drug 
hypersensitivity 
monitoring 
If a drug hypersensitivity reaction is suspected, blood samples should be 
obtained and sent to the central laboratory for: 
• 
quantitative immunoglobulins (IgG, IgA, IgM, IgE)  
• 
If IgA is low or not detectable, then anti-IgA antibodies will be 
assayed  
• 
complete blood count with differential  
Any drug hypersensitivity reaction should be recorded as an AE.  

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 76 of 137 
CRD-TPL-077 
Confidential 
Assessment 
Description 
Hepatic injury 
assessment 
If any subject has elevation in ALT > 3 x ULN with a concomitant 
elevation in total bilirubin > 2 x ULN OR an elevation in ALT 
> 5 x ULN, blood samples should be obtained and sent to the central 
laboratory within 48 to 72 hours for:  
• 
ALT, AST, total bilirubin, direct bilirubin, alkaline 
phosphatase, GGT, amylase, and lipase 
• 
CBC with differential 
• 
CRP 
• 
PT/INR 
• 
Serology for Hepatitis A, B, C, D, E 
• 
CMV titers (IgM , IgG) 
• 
EBV titers (IgM, IgG) 
• 
Quantitative Immunoglobulins - IgG, IgM, IgE, IgA, 
• 
ANA 
If there is suspicion for autoimmune mediated hepatitis, blood samples 
should be obtained and sent to the central laboratory for: 
• 
dsDNA, anti-smooth muscle Ab, anti-mitochondrial Ab, 
cANCA, pANCA  
Diagnostic imaging of the liver such as liver ultrasound should be 
performed if clinically indicated and should be reported in the eCRF if 
performed. 
Further repeat testing for ALT, AST, total bilirubin, direct bilirubin, 
alkaline phosphatase and GGT should occur as clinically indicated but at 
least every 48 to 72 hours until abnormalities improve or stabilize. 
Retesting may decrease to once a week or less if abnormalities stabilize, 
the investigational product has been discontinued, and subject is 
asymptomatic to resolution. Retesting of other relevant parameters may 
be performed as clinically indicated. Local laboratory assessments may 
be used for this repeat testing. 
Elevations in ALT > 3 x ULN with concomitant elevation in total 
bilirubin > 2 x ULN should be reported as a SAE as per Section 9.5.1. 
Urinalysis 
Urine samples will be collected and analyzed by dipstick for: 
 
• 
Specific gravity 
• 
pH 
• 
Blood 
 
• 
Glucose 
• 
Protein 
• 
Leukocyte esterase 
 
• 
Ketones 
• 
Bilirubin 
• 
Nitrites 


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
$VVHVVPHQW
'HVFULSWLRQ

$WVFUHHQLQJRQO\XULQDO\VLVZLOOEHORFDOO\SHUIRUPHGE\XULQH
GLSVWLFN,IGLSVWLFNGHPRQVWUDWHVKLJKJUDGHSURWHLQXULDGHILQHGDV
LHPJG/DXULQHVDPSOHVKRXOGEHVHQWWRWKHFHQWUDO
ODERUDWRU\IRUXULQDO\VLVZLWKPLFURVFRS\)RUDOORWKHUYLVLWVDXULQH
VDPSOHZLOOEHVHQWWRWKHFHQWUDOODERUDWRU\IRUXULQDO\VLVZLWK
PLFURVFRS\LQFOXGLQJ

x
&DVWV
x
&U\VWDOV
x
(U\WKURF\WHV

x
5HQDOWXEXODU
HSLWKHOLDOFHOOV
x
:%&V
x
%DFWHULD

$QDGGLWLRQDOVDPSOHRIXULQHZLOOEHFROOHFWHGDQGVWRUHGIRUSRVVLEOH
IXWXUHELRPDUNHUDQDO\VLV













+HPDWRORJ\
%ORRGVDPSOHVZLOOEHFROOHFWHGIRUDQDO\VLVE\WKHFHQWUDOODERUDWRU\

x
+HPRJORELQ
x
+HPDWRFULW
x
5%&FRXQWDQGLQGLFHV
x
:%&FRXQWVWRWDODQGGLIIHUHQWLDOEDVRSKLOVHRVLQRSKLOV
O\PSKRF\WHVPRQRF\WHVDQGQHXWURSKLOV
x
3ODWHOHWFRXQW
+HPRO\VLV
,IDSRVWLQIXVLRQKHPRJORELQYDOXHLVJG/EHORZWKHEDVHOLQHYDOXH
LHEHIRUHILUVWLQIXVLRQDQGLVQRWH[SODLQHGE\RYHUWEORRGORVV
DVVHVVPHQWIRUKHPRO\VLVVKRXOGEHSHUIRUPHGE\WKHFHQWUDOODERUDWRU\
x
5HSHDWKHPRJORELQOHYHO
x
7RWDODQGGLUHFWELOLUXELQLQFOXGLQJFDOFXODWLRQRILQGLUHFW
ELOLUXELQ
x
6HUXPKDSWRJORELQOHYHO
x
/'+
x
8ULQHKHPRVLGHULQ
6HUXP
%LRFKHPLVWU\
%ORRGVDPSOHVZLOOEHFROOHFWHGIRUDQDO\VLVE\WKHFHQWUDOODERUDWRU\

x
$ONDOLQH
SKRVSKDWDVH
x
$/7
x
$67

x
7RWDOELOLUXELQ
x
'LUHFWELOLUXELQ
x
$OEXPLQ
CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
$VVHVVPHQW
'HVFULSWLRQ

x
7RWDO3URWHLQ
x
&UHDWLQLQH
x
H*)5
FDOFXODWHG

x
%81
x
8ULFDFLG
x
*OXFRVH

x
&DOFLXP
x
&KORULGH
x
6RGLXP

x
3RWDVVLXP
x
%LFDUERQDWH

$/7WRWDOELOLUXELQ
FUHDWLQLQH
%ORRGVDPSOHVZLOOEHFROOHFWHGIRUORFDOODERUDWRU\DQDO\VLVIRU
DVVHVVPHQWRIVXEMHFWHOLJLELOLW\DQGVDIHW\IRUDGPLQLVWUDWLRQRI
LQYHVWLJDWLRQDOSURGXFW



9LURORJ\EORRG
VDPSOLQJ
%ORRGVDPSOHVZLOOEHFROOHFWHGDQGVWRUHGIRU\HDUDIWHU
FRPSOHWLRQRIWKHFOLQLFDOVWXG\UHSRUWIRUSRVVLEOHIXWXUHDQDO\VLVIRU
XQVSHFLILHGYLUDODJHQWV$QDO\VLVZLOORQO\EHGRQHLIDGGLWLRQDO
LQIRUPHGFRQVHQWLVREWDLQHGIURPWKHVWXG\VXEMHFW
,PPXQRJHQLFLW\
WHVWLQJ
6HUXPZLOOEHDQDO\]HGIRUWKHSUHVHQFHRIELQGLQJDQWLERGLHV
VSHFLILFWR&6/DQGDSR$,
$E DQWLERG\$( DGYHUVHHYHQW$/7 DODQLQHDPLQRWUDQVIHUDVH$1$ DQWLQXFOHDUDQWLERGLHVDSR$, 
DSROLSRSURWHLQ$,$67 DVSDUWDWHDPLQRWUDQVIHUDVH%$5& %OHHGLQJ$FDGHPLF5HVHDUFK&RQVRUWLXP
%81 EORRGXUHDQLWURJHQF$1&$ F\WRSODVPLFDQWLQHXWURSKLOF\WRSODVPLFDQWLERGLHV&%& FRPSOHWH
EORRGFRXQW&09 F\WRPHJDORYLUXV&53 &UHDFWLYHSURWHLQ&9 FDUGLRYDVFXODUGV'1$ GRXEOH
VWUDQGHGGHR[\ULERQXFOHLFDFLG(%9 (SVWHLQ%DUUYLUXV(&* HOHFWURFDUGLRJUDPH&5) HOHFWURQLFFDVH
UHSRUWIRUPH*)5 HVWLPDWHGJORPHUXODUILOWUDWLRQUDWH)6+ IROOLFOHVWLPXODWLQJKRUPRQH**7 *DPPD
JOXWDP\OWUDQVIHUDVH*, JDVWURLQWHVWLQDO,J$*(0 LPPXQRJOREXOLQVXEW\SHV$*(DQG0,15 
LQWHUQDWLRQDOQRUPDOL]HGUDWLR,9 LQWUDYHQRXV/'+ ODFWDWHGHK\GURJHQDVHS$1&$ SHULQXFOHDUDQWL
QHXWURSKLOF\WRSODVPLFDQWLERGLHV
3. SKDUPDFRNLQHWLF37 SURWKURPELQ5%& 
UHGEORRGFHOO8/1 XSSHUOLPLWRIQRUPDO:%& ZKLWHEORRGFHOO

 3KDUPDFRNLQHWLFV

&OLQLFDOSURFHGXUHVWREHFRQGXFWHGWRFROOHFWVDPSOHVIRU3.
DQDO\VLVDUHSURYLGHG
LQ7DEOHDQG7DEOHUHVSHFWLYHO\5HIHUWRWKHWLPLQJDQGIUHTXHQF\RIDOOFOLQLFDO
SURFHGXUHVDVGHVFULEHGLQWKH6FKHGXOHRI$VVHVVPHQWV5HIHUWRWKHVWXG\UHIHUHQFHPDQXDOV
IRUGHWDLOVDERXWWKHFROOHFWLRQVWRUDJHKDQGOLQJDQGWUDQVSRUWDWLRQRIELRORJLFDOVSHFLPHQV
CCI
CCI
CCI
CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
7DEOH
&OLQLFDO3URFHGXUHV3KDUPDFRNLQHWLF$VVHVVPHQWV
$VVHVVPHQW
'HVFULSWLRQ
DSR$,3&FRQFHQWUDWLRQV
%ORRGVDPSOHVZLOOEHFROOHFWHGIRUDVVHVVPHQWRISODVPDDSR$,
DQG3&FRQFHQWUDWLRQV6DPSOHVZLOOEHVWRUHGIRUIXWXUH3.
DVVHVVPHQWVLIQHHGHGLHFKRODWH
DSR$, DSROLSRSURWHLQ$,3& SKRVSKDWLG\OFKROLQH3. SKDUPDFRNLQHWLF

7DEOH


0(7+2'62)$66(660(17
 'HPRJUDSKLFDQG%DVHOLQH&KDUDFWHULVWLFV
$OOGHPRJUDSKLFDQGEDVHOLQHFKDUDFWHULVWLFYDULDEOHVWREHDVVHVVHGDUHSUHVHQWHGDQG
GHVFULEHGLQ7DEOH
CCI
CCI

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 80 of 137 
CRD-TPL-077 
Confidential 
8.2.1.1 Medical History and Assessment for Study Eligibility 
The subjects’ past medical history and demographic information will be documented at 
screening. As defined in the inclusion criteria, Section 4.1.1, assessment of renal function 
status for the presence of moderate RI based on eGFR and evidence of myocardial necrosis in 
a clinical setting consistent with a type I (spontaneous) AMI will be evaluated. A medical 
history will be obtained by the Investigator or a medically qualified delegate. Medical history 
includes all active conditions, and any condition diagnosed within 3 months before the 
screening visit. Such conditions may include but are not limited to prior MI, history of stable 
or unstable angina, coronary revascularization or surgery, hypertension, dyslipidemia, 
diabetes mellitus, congestive heart failure, peripheral arterial disease, valvular heart disease, 
heart rhythm disorders, cerebrovascular disease, or any clinically-significant bleeding event 
requiring transfusion of > 2 units packed red blood cells (PRBCs) within the past 3 months or 
a discontinuation of antiplatelet or anticoagulation therapy. If possible, documented evidence 
of CKD within the 6 months before admission for the index AMI should be obtained (eg, 
prior serum creatinine, eGFR, proteinuria, suspected etiology of CKD). 
8.2.1.2 Screening and Randomization on Same Day 
Screening and randomization of subjects may occur on the same day (Study Day 1 of the 
Active Treatment Period) provided that the minimum time for assessment of renal function 
stability is adhered to before administration of the first infusion of investigational product 
(Section 8.2.2.1). To receive the first infusion of investigational product, subjects must have 
documented evidence of stable renal function and no suspicion of AKI at least 12 hours after 
FMC for the index AMI event. For subjects undergoing angiography, stable renal function is 
defined as a local laboratory serum creatinine value at least 12 hour after contrast 
administration that is increased < 0.3 mg/dL from the pre-contrast administration value. See 
Section 8.2.2.1 for repeating post-contrast assessments of renal function. The screening 
period up to and including randomization must occur within 5 days of FMC for the index 
AMI.  

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 81 of 137 
CRD-TPL-077 
Confidential 
Local laboratory values for serum creatinine, ALT, and total bilirubin obtained as part of 
standard of care may be used for evaluating renal and hepatic function. If multiple laboratory 
tests are obtained before the administration of contrast agent, the serum creatinine value 
closest in time but before IV contrast administration should be used to assess stable renal 
function. Similarly, the serum creatinine value obtained after, but closest in time to the 
minimum window required after FMC or, for subjects undergoing angiography, after IV 
contrast administration should be used to confirm renal function stability before 
administration of the first infusion (Table 7). The pre-contrast and baseline serum creatinine 
values used to confirm renal function stability must be documented in the eCRF.  
If screening and randomization occur on the same day, all protocol specified procedures and 
assessments indicated at Visit 1 and Visit 2 (Baseline/before infusion) in the Schedule of 
Assessments must still be performed, although certain assessments do not need to be 
duplicated. If Visits 1 and 2 are combined, there may be a single blood draw for central 
laboratory serum biochemistry, and local laboratory ALT, total bilirubin, and serum 
creatinine. Both a local laboratory and central laboratory urinalysis should be performed. 
There may be 1 ECG. Single assessments of vital signs, concomitant medications, and AEs 
are also acceptable. 
8.2.2 Infusion Eligibility 
8.2.2.1 First Infusion 
In addition to confirming hemodynamic stability, both hepatic (ALT and total bilirubin) and 
renal (serum creatinine) function, based on local laboratory values, must be reviewed by the 
Investigator and determined to be within acceptable limits before administration of the first 
infusion of investigational product (Table 7). The screening period up to and including 
randomization must occur within 5 days of FMC for the index AMI. 
For the pre-infusion assessment of hepatic function before the first infusion, the following 
criteria apply: 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0 
6 June 2016 
Page 82 of 137 
CRD-TPL-077 
Confidential 
• ALT value must be ≤ 3 x ULN and total bilirubin value must be ≤ 1.5 x ULN 
(Section 4.1.2). 
• If the baseline ALT is > 3 x ULN, the subject is not eligible for dosing. 
• If the baseline total bilirubin value is > 1.5 x ULN, the subject is not eligible for dosing 
unless there is historical documentation of Gilbert’s syndrome. In this instance, the 
Investigator or a medically qualified delegate should confirm historical 
documentation of Gilbert’s syndrome with the medical monitor.   
• A repeat baseline assessment for hepatic function is not permitted. 
All subjects must have documented evidence of stable renal function and no suspicion of AKI 
at least 12 hours after FMC for the index AMI. For subjects undergoing angiography with or 
without PCI, stable renal function is defined as a serum creatinine value at least 12 hours 
after contrast administration that is increased < 0.3 mg/dL from the pre-contrast 
administration value (Table 7).   
If multiple laboratory tests are obtained before the administration of contrast agent, the serum 
creatinine value closest in time but before IV contrast administration should be used as the 
reference value to assess stable renal function. Similarly, the serum creatinine value obtained 
after, but closest in time to the minimum time required after FMC for the index AMI or, for 
subjects undergoing angiography, after IV contrast administration should be the baseline 
value used to confirm renal function stability before administration of the first infusion. 
These pre-contrast and baseline serum creatinine values used to confirm renal function 
stability must be documented in the eCRF. 
If the post-contrast serum creatinine value is increased ≥ 0.3 mg/dL from the pre-contrast 
administration value, the laboratory test may be repeated once at least 24 hours later to assess 
stable renal function. The repeat serum creatinine value must be increased < 0.3 mg/dL from 
the pre-contrast administration value for the subject to be eligible, provided no clinical 
suspicion of AKI exists.  

 
Study Number: 
CSL112_2001_Am01 
 
Study Product: 
CSL112 
 
Final V2.0  
 
6 June 2016 
 
Page 83 of 137 
CRD-TPL-077 
 
Confidential 
Table 7. 
Key Hepatic and Renal Laboratory Parameters and Protocol Requirements for Study/First Infusion Eligibility 
Protocol Parameter 
Alanine Aminotransferase (ALT; absolute level) 
Total Bilirubin (absolute level) 
Post-Contrast Serum Creatinine (change from 
pre-contrast administration value in mg/dL)c 
≤3x ULN 
>3x ULN 
≤1.5x ULN 
>1.5x ULN 
<0.3 increase 
≥0.3 increase 
Initial assessmentsa 
Eligible 
Not eligible 
Eligible 
Not eligible unless 
Gilbert’s Syndromeb 
Eligible 
Delay eligibility and infusion: 
Repeat once at least 24 h after 
initial assessmentd 
Repeat assessment 
N/A 
N/A 
Eligible 
Not eligible 
ALT = alanine aminotransferase; AMI = acute myocardial infarction; CRF=case report form; FMC=first medical contact; h = hour; IV = intravenous; mg/dL= 
milligram per deciliter; N/A = not applicable; ULN = upper limit of normal 
a. 
Laboratory assessments performed during screening (Visits 1 and 2 before infusion) must be reviewed by the Investigator before administration of investigational 
product. Screening and randomization may occur on the same day (Study Day 1) provided that test results are available for ALT, total bilirubin, and serum 
creatinine to assess hepatic function and to confirm renal function stability at least 12 hours after FMC for the index AMI event. For subjects who have received 
IV contrast agent, the values for serum creatinine must have been obtained before and at least 12 hours after the administration of contrast (Section 8.2.1.2). Local 
laboratory values obtained as part of standard of care may be used for this purpose.  
b. 
Confirm historical documentation with the Medical Monitor and record in medical history CRF. If Gilbert’s syndrome, use indirect bilirubin for this 
determination. 
c. 
Serum creatinine 0.3 mg/dL = 26.5 µmol/L 
d. 
The repeated value is assessed to check for any trajectory/continued rise in an effort to establish stable renal function at baseline. There must be no suspicion of 
AKI. 
 
 

 
Study Number: 
CSL112_2001_Am1 
 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 84 of 137 
CRD-TPL-077 Version 1.0 
Confidential 
8.2.2.2 Subsequent Infusions  
For infusions 2, 3, and 4, hepatic (ALT and total bilirubin) and renal (serum creatinine) 
function is to be assessed within 48 hours of the infusion using the local laboratory. The 
results must be reviewed by the Investigator and determined to be clinically stable before 
each administration of investigational product. Eligibility for continued administration of 
investigational product will be based on the criteria presented below and summarized in 
Table 8. 
For assessment of hepatic function before infusion 2 or subsequent infusions, the following 
criteria apply: 
• ALT value must be ≤ 3 x ULN and total bilirubin value must be ≤ 1.5 x ULN for 
eligibility 
• If the ALT value is > 3 x ULN or total bilirubin value is > 1.5 x ULN, the infusion must 
be delayed and ALT and/ or total bilirubin values may be repeated once at least 24 hours 
after the initial assessment to determine dosing eligibility and hepatic stability. If the 
subject has a medical history of Gilbert’s syndrome, indirect bilirubin may be used 
instead of total bilirubin to determine dosing eligibility. 
• If the repeated assessment of ALT value is > 3 x ULN OR total bilirubin value is 
> 1.5 x ULN and the observed variation is not attributable to Gilbert’s syndrome, the 
subject is not eligible for continued dosing and all remaining infusions must be 
discontinued. If the subject has a history of Gilbert’s syndrome, indirect bilirubin may be 
used instead of total bilirubin to determine dosing eligibility. 
For assessment of renal function before infusion 2 or subsequent infusions, the following 
criteria apply: 
• Change from baseline (pre-infusion on Study Day 1) in serum creatinine must be 
< 0.3 mg/dL.   

 
Study Number: 
CSL112_2001_Am1 
 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 85 of 137 
CRD-TPL-077 Version 1.0 
Confidential 
• If the serum creatinine value is increased 0.3 to 0.5 mg/dL from baseline value before 
infusion 2 or subsequent infusions, the subject is eligible for dosing if the observed 
variation may be attributable to changes in concomitant medications with hemodynamic 
effect or other clinical factors (eg, IV fluid discontinued) or falls within range of 
variability previously observed for the subject. If the variation cannot be attributed to 
above, then perform repeat assessments before dosing as per Table 8. 
• If the serum creatinine value is increased > 0.5 mg/dL from baseline value before 
infusion 2 or subsequent infusions, the infusion should be delayed until a minimum of 
2 subsequent serum creatinine determinations performed at least 24 hours apart are 
< 0.3 mg/dL increased from the baseline. If the creatinine does not return to < 0.3 mg/dL, 
on 2 subsequent repeat assessments, the infusion will be delayed, and a repeat serum 
creatinine will be assessed at 7 days (± 24 h) from the pre-infusion assessment (ie, the 
initial assessment before the delayed dose). At the time of the delayed infusion, the 
medical monitor should be contacted for further guidance regarding timing of subsequent 
infusions of investigational product. If after 7 days, the creatinine is < 0.3 mg/dL 
increased from baseline, an additional serum creatinine should be performed at least 
24 hours later in order to confirm that the value is still < 0.3 mg/dL increased from 
baseline before subsequent dosing. The subject will be eligible only if ≥ 2 repeat values 
performed at least 24 hours apart are each < 0.3 mg/dL increased from baseline. In 
addition, dosing should proceed only if the subject is assessed as clinically stable by the 
Investigator. If after 7 days the creatinine is still ≥ 0.3 mg/dL increased from the baseline 
value, all subsequent infusions will be discontinued (see Table 8). 
If any administration of investigational product is discontinued due to these eligibility 
laboratory criteria, the abnormal laboratory parameter should be followed with central 
laboratory testing performed at 48- to 72-hour intervals, or as clinically indicated, until the 
abnormal value returns to the subject’s pre-infusion baseline value or renal and/or hepatic 
function is stabilized. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
 
Final V2.0  
 
6 June 2016 
 
Page 86 of 137 
CRD-TPL-077 
 
Confidential 
Table 8. 
Key Hepatic and Renal Laboratory Parameters and Protocol Requirements for Subsequent/Continuing Infusion 
Eligibility  
Protocol Parameter 
Alanine Aminotransferase  
(ALT; absolute level) 
Total Bilirubin (absolute level) 
Serum Creatinine (change from baseline value in mg/dL) 
≤ 3x 
ULN 
> 3x ULN 
≤ 1.5x 
ULN 
> 1.5x ULN 
< 0.3b 
increase 
0.3 to 0.5 increase 
> 0.5 increase 
Initial assessment 
before infusion 2, 3 or 
4a 
Eligible 
Delay infusion:  
Repeat once at least 
24 h after initial 
assessment 
Eligible 
Delay infusion:  
Repeat once at least  
24 h after initial assessment (If 
Gilbert’s syndrome, use indirect 
bilirubin for this determination.) 
Eligible 
Eligible if meet 
criteria in footnote c 
Delay infusion: Repeat 
creatinine > 24 h after initial 
assessment 
Repeat 
assessment #1d 
Eligible 
Discontinue 
infusions:  
follow-up as per 
protocol 
Eligible 
Discontinue infusions 
 
Perform repeat 
assessment #2 in > 24 h 
to confirm  
Delay current infusion: Repeat serum creatinine in 
7 days (±24 h) to determine subsequent renal 
eligibility and contact medical monitor for further 
guidance. Eligible if  ≥ 2 repeat values performed at 
least 24 hours apart are each < 0.3 mg/dL increased 
from baseline e 
Repeat 
assessment #2d 
N/A 
Eligible if ≥ 2 repeat 
values performed at least 
24 hours apart are each 
 < 0.3 mg/dL increased 
from baseline 
h = hour; IV = intravenous; mg/dL= milligram per deciliter; N/A = not applicable; ULN = upper limit of normal 
a. 
Laboratory assessments are performed up to 48 hours before infusions 2, 3, and 4, and must be reviewed by the Investigator before administration of 
investigational product. 
b. 
0.3 mg/dL = 26.5 µmol/L 
c. 
Eligible if observed variation MAY BE attributable to changes in concomitant medications with hemodynamic effect or other clinical factors (eg, IV fluid 
discontinued) or falls within range of variability previously observed for the subject. If variation cannot be attributable to above, perform repeat assessments. 
d. 
Repeat laboratory assessments should be performed ≥ 24 hours apart to determine eligibility as clinically indicated. 
e. 
If this criterion is met, a repeat serum creatinine assessment will be performed 7 days (±24 h) from the initial pre-infusion assessment (ie, initial assessment before 
the delayed dose). If after 7 days, the creatinine is < 0.3 mg/dL increased from baseline, an additional serum creatinine should be performed at least 24 hours later 
in order to confirm that the value is still < 0.3 mg/dL increased from baseline before subsequent dosing. The subject will be eligible only if ≥ 2 repeat values 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
 
Final V2.0  
 
6 June 2016 
 
Page 87 of 137 
CRD-TPL-077 
 
Confidential 
performed at least 24 hours apart are each < 0.3 mg/dL increased from baseline. In addition, dosing should proceed only if the subject is assessed as clinically 
stable by the Investigator. If at the time of this subsequent (ie, second) creatinine determination, the value is still ≥ 0.3 mg/dL increased from baseline, all 
subsequent infusions will be discontinued. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 88 of 137 
CRD-TPL-077 
Confidential 
8.2.3 Safety 
8.2.3.1 Adverse Events 
Incidence, grade, and causality of AEs, including SAEs, will be evaluated according to the 
criteria specified in Section 9. The period of observation of AEs (and SAEs) extends from the 
time the subject provides signed informed consent until the subject completes the study, as 
specified in Section 9.4. Procedures for reporting AEs, and SAEs, are specified in Section 9.5 
and Section 9.6, respectively. 
Reporting of bleeding events and renal SAEs includes completion of the Bleeding Event 
eCRF page or the Renal SAE eCRF page, respectively, with supporting documentation 
(hospital records and tests). 
Before and at the end of each infusion conducted at the study site, the Investigator or a 
medically qualified delegate will specifically inquire (via non-leading questioning) about any 
AEs that might have occurred since the last infusion conducted at the study site. All AEs (and 
SAEs and AEs of special interest) will be recorded on the AE page of the eCRF page.  
Each individual manifestation of an AE should be graded individually for severity (see 
Section 9.2). 
Details of the definitions and categorization of AEs, and procedures for the reporting of AEs, 
are available in Section 9.   
8.2.3.2 Vital Signs 
The Investigator or qualified delegate will take vital signs at screening, before the each 
infusion of investigational product, at the end of infusion of investigational product, and at 
any follow-up visits as specified in the Schedule of Assessments. Blood pressure (systolic 
and diastolic) and pulse rate must be measured with the subject in a supine or seated position 
after resting for at least 5 minutes.  

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 89 of 137 
CRD-TPL-077 
Confidential 
Blood pressure measurements should be taken from the same arm throughout the study using 
an automated blood pressure monitor that uses an oscillometric method. The same arm should 
not be used for blood sample collections and blood pressure assessments, if possible. At 
screening, blood pressure measurements may be repeated twice. If there is a clinically 
significant change in blood pressure from the previous reading, measurements will be 
repeated immediately to confirm the change.  
Body temperature can be measured either orally or tympanically, but the method should be 
consistent throughout the study for a given subject. Height will be measured at Visit 1 only. 
8.2.3.3 Electrocardiograms 
A standard 12-lead ECG will be performed using local standard procedures. ECG intervals 
(eg, RR, PQ/PR, QRS, and uncorrected QT) will be measured. Clinically significant 
abnormal findings as determined by the Investigator are to be recorded. After the first 
infusion of investigational product, any new clinically significant abnormal findings should 
be recorded as AEs (see Section 9.5). 
8.2.3.4 Bleeding Events 
Assessment of any bleeding events, including assessment of the infusion site for bruising, 
redness or swelling, will be performed at each visit after randomization (including baseline), 
up to and including Visit 8. The event should be recorded as an AE (see Section 9.5) and 
assessed by using the BARC criteria as outlined in Appendix IV. The Bleeding Event eCRF 
page should also be completed along with supporting source documents (hospital records and 
tests). 
8.2.3.5 Physical Examination 
The Investigator or a medically qualified delegate will perform a physical examination 
covering the following body systems (head and neck, CV, respiratory, gastrointestinal (GI), 
musculoskeletal, neurologic, and integumentary systems) during screening and at the end of 
the Active Treatment Period as specified in the Schedule of Assessments. Clinically 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 90 of 137 
CRD-TPL-077 
Confidential 
significant abnormal findings at screening should be recorded as medical history. After the 
first infusion of investigational product, new clinically significant abnormal findings should 
be recorded as AEs (see Section 9.5). Physical examination findings should also include drug 
hypersensitivity reactions if relevant (see Section 8.2.3.6). 
8.2.3.6 Drug Hypersensitivity Monitoring 
Drug hypersensitivity findings may include: allergic reactions, bronchospasm/wheezing, 
generalized rash, anaphylaxis, etc. In the event that a subject experiences a hypersensitivity 
reaction during the infusion, the infusion is to be stopped immediately, and additional 
assessments are to be performed including:   
• Blood samples for quantitative immunoglobulins (IgG, IgM, IgE, and IgA) and complete 
blood count with differential (Section 8.1.2, Table 4). Anti-IgA antibodies will be 
performed if clinically indicated at the central laboratory. 
• The subject should be re-queried to confirm the absence of a history of allergy to soy or 
peanuts.  
• Pertinent positives and negatives should also be assessed and documented in the source 
document and eCRF including:  rash, swelling, hives, itching, wheezing, stridor, and 
involvement of the mucous membranes. 
• Relevant physical examination findings should also be documented (eg, maculopapular 
rash, swelling of the face or oropharynx, etc.). 
8.2.3.7 Laboratory Procedures 
Details regarding laboratory procedures / assessments to be performed in this study are 
provided in the subsequent subsections. The local laboratory is to be used for all laboratory 
assessments that must be reviewed in real time, ie, values taken to determine study eligibility 
and dosing decisions. All laboratory assessment samples should also be sent to the 
central laboratory for analysis. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 91 of 137 
CRD-TPL-077 
Confidential 
Clinical laboratory test results from the central and/or local laboratory that are outside the 
normal reference range and are deemed clinically significant by the Investigator are to be 
recorded as AEs or SAEs. If clinically significant abnormal laboratory test results are 
identified after investigational product infusion, the test(s) will be repeated until the abnormal 
values return to normal and/or baseline or stabilize (Section 8.2.2.2). Safety parameters 
should be repeated if the specimen is hemolyzed. 
An abnormal laboratory value should be deemed clinically significant if any of the following 
conditions is met: 
• The abnormality suggests a disease and/or organ toxicity that is new or has worsened 
since baseline. 
• The abnormality is of a degree that requires active management (ie, change of dose), 
discontinuation of the study product, close observation, more frequent follow-up 
assessments or further diagnostic investigation. 
• If the Investigator is able to provide a differential diagnosis for the abnormal clinical 
laboratory result, the AE is to be recorded accordingly. In the absence of an associated 
clinical sign or symptom, and if only a single laboratory value is deemed clinically 
significant, the abnormal laboratory value is to be recorded as the AE. 
Any laboratory test result abnormality fulfilling the criteria for an AE or and SAE should be 
reported as such (see Section 9.5). 
8.2.3.7.1 Serum Biochemistry 
Sampling for serum biochemistry will be obtained for analysis by the central laboratory at 
time points listed in the Schedule of Assessments and the values will be used for safety 
analysis (Table 4).  
Sampling for ALT, total bilirubin and serum creatinine should be obtained from the local 
laboratory to assess for eligibility and safety for administration of investigational product. 
Results must be reviewed by the Investigator before infusions on Study Days 1, 8, 15, and 22 


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
6HFWLRQDQG7KHVDPSOHPD\EHREWDLQHGXSWRKRXUVEHIRUHWKHLQIXVLRQV
DQGRQ6WXG\'D\VDQG
,IDVXEMHFWLVIRXQGWRKDYHDQ$/7HOHYDWHGWR![8/1ZLWKDFRQFRPLWDQWHOHYDWLRQLQ
WRWDOELOLUXELQWR![8/125DQ$/7HOHYDWHGWR![8/1DGGLWLRQDODVVHVVPHQWV
VKRXOGEHSHUIRUPHGZLWKLQWRKRXUVDQGVHQWWRWKHFHQWUDOODERUDWRU\IRUDQDO\VLVDV
GHWDLOHGLQ6HFWLRQ7DEOH+HSDWLFLQMXU\DVVHVVPHQW
 +HPDWRORJ\DQG+HPRO\VLV
6DPSOLQJIRUKHPDWRORJ\E\WKHFHQWUDOODERUDWRU\ZLOOLQFOXGHKHPRJORELQKHPDWRFULW
SODWHOHWVUHGEORRGFHOO5%&LQGLFHVDQGZKLWHEORRGFHOO:%&FRXQWVDQGGLIIHUHQWLDODV
RXWOLQHGLQ7DEOHDQGDWWLPHSRLQWVOLVWHGLQWKH6FKHGXOHRI$VVHVVPHQWV
,IDQ\VXEMHFWLVIRXQGWRKDYHDGHFUHDVHLQKHPRJORELQJG/IURPWKH9LVLWEDVHOLQH
YDOXHDQGRULVVXVSHFWHGRIKDYLQJKHPRO\VLVLHGHFUHDVHLVQRWH[SODLQHGE\RYHUWEORRG
ORVVWKHVXEMHFWPXVWKDYHDKHPRO\VLVDVVHVVPHQWWKDWLQFOXGHVUHSHDWDVVHVVPHQWRI
KHPRJORELQOHYHOVHUXPKDSWRJORELQOHYHOV/'+WRWDODQGGLUHFWELOLUXELQOHYHOVLQFOXGLQJ
WKHFDOFXODWLRQRILQGLUHFWELOLUXELQDQGXULQHKHPRVLGHULQ+HPRO\VLVVKRXOGDOVREH
FRQVLGHUHGLIWRWDOELOLUXELQ![8/1LVREVHUYHG
 8ULQDO\VLV
8ULQDO\VLVZLOOEHSHUIRUPHGDVRXWOLQHGLQ7DEOHDQGDWWLPHSRLQWVOLVWHGLQWKH6FKHGXOH
RI$VVHVVPHQWV$WVFUHHQLQJLIWKHORFDOO\SHUIRUPHGGLSVWLFNLVSRVLWLYHIRUKLJKJUDGH
SURWHLQXULDGHILQHGDVLHPJG/DXULQHVDPSOHZLOOEHVHQWWRWKHFHQWUDO
ODERUDWRU\IRUXULQDO\VLVDQGPLFURVFRSLFH[DPLQDWLRQ




CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
 3KDUPDFRNLQHWLFV
%ORRGVDPSOHVZLOOEHFROOHFWHGDWWLPHSRLQWVOLVWHGLQWKH6FKHGXOHRI$VVHVVPHQWVIRU
GHWHUPLQDWLRQWKH3.RI&6/WKURXJKDQDO\VLVRIDSR$,DQG3&SODVPDFRQFHQWUDWLRQV
7DEOH6DPSOHDQDO\VLVZLOOEHFRQGXFWHGDVGHWDLOHGLQWKHVWXG\UHIHUHQFHPDQXDOV



















5(7(17,212)6$03/(6
6DPSOHVLQWHQGHGIRUVWRUDJHDQGRUIXWXUHDQDO\VHVHJ$UFKLYDO%ORRG6DPSOH9LURORJ\
6DPSOHDQG8ULQH6DPSOHZLOOEHFROOHFWHGDWWLPHSRLQWVVSHFLILHGLQWKH6FKHGXOHRI
$VVHVVPHQWV
x 7KHGHFLVLRQWRDVVHVVDGGLWLRQDOELRPDUNHUVHJOLSLGFDUGLDFUHQDORULQIODPPDWRU\
IURPDQDUFKLYDOEORRGDQGRUXULQHVDPSOHPD\EHPDGHE\WKH6WHHULQJ&RPPLWWHHDQG
CCI
CCI
CCI
CCI
CCI

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 94 of 137 
CRD-TPL-077 
Confidential 
based on the latest available information on the utility of such measurements. This sample 
will be stored for up to 10 years after completion of the study, or for the duration 
permitted by national or local regulations, and destroyed upon notification by the Steering 
Committee. These analyses may be used for future planning and / or exploratory analyses. 
No genotypic analysis will be performed utilizing these samples. 
• The virology samples are taken for possible future assessment of currently unspecified 
viral agents. A minimum of 2 samples will be stored for up to 1 year after the completion 
of the clinical study report for possible virology testing. If testing is required, a separate 
protocol will be written by the sponsor and Institutional Review Board 
(IRB) / Independent Ethics Committee (IEC) approval for the protocol sought; upon 
IRB / IEC approval, impacted subjects would need to provide written informed consent 
before virology testing of their samples could be conducted. 
8.4 
CONCOMITANT THERAPIES 
All drugs and / or procedures currently being administered to a subject at the time of signing 
informed consent, and which continue to be taken in addition to investigational product 
during the study, are regarded as concomitant therapies and must be documented as such in 
the eCRF. 
8.5 
VISIT SCHEDULE  
This study consists of screening, an Active Treatment Period and a Safety Follow-up Period 
with a total of 8 scheduled visits (Figure 1). The assessments to be conducted at scheduled 
visits within each of these study parts are outlined in the following sections. The timing and 
frequency of the study visits are described in the Schedule of Assessments. Time windows 
for assessments are detailed in Table 9. 
Table 9. 
Time Windows for Assessments 
Visit / Procedure 
Time window (relative to scheduled visit / procedure) 
Visit 1 (Screening)  
Up to 5 days after FMC for index AMI 


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
9LVLW3URFHGXUH
7LPHZLQGRZUHODWLYHWRVFKHGXOHGYLVLWSURFHGXUH
9LVLW6WXG\'D\SUHLQIXVLRQ
EDVHOLQHDQGILUVWLQIXVLRQ
)LUVWLQIXVLRQVWDUWVWRGD\VDIWHU)0&IRU$0,DQGDW
OHDVWKRXUVDIWHUDQJLRJUDSK\LISHUIRUPHG
9LVLW6WXG\'D\
WRKRXUVKDIWHUVWDUWRIILUVWLQIXVLRQ
9LVLWVWRSUHLQIXVLRQ
DVVHVVPHQWVDQGLQIXVLRQVRQ
6WXG\'D\VDQG
UHVSHFWLYHO\
9LVLWLVWRGD\VDIWHU9LVLW9LVLWVWRDUHVHSDUDWHG
E\WRGD\V
9LVLW6WXG\'D\
WRGD\VDIWHU9LVLW
9LVLW6WXG\'D\
GD\VDIWHUILUVWLQIXVLRQSURYLGHGWKDWWKHYLVLWRFFXUV
QROHVVWKDQGD\VDIWHUWKHODVWLQIXVLRQ
%ORRGFROOHFWLRQVIRU3.

%HIRUHLQIXVLRQXSWRPLQEHIRUHVWDUWRILQIXVLRQ

(QGRILQIXVLRQXSWRPLQDIWHUHQGRILQIXVLRQ
$0, DFXWHP\RFDUGLDOLQIDUFWLRQ)0& ILUVWPHGLFDOFRQWDFWIRULQGH[HYHQWK KRXUPLQ PLQXWHV3. 
SKDUPDFRNLQHWLF

 6FUHHQLQJ9LVLW6WXG\'D\WR6WXG\'D\
3RWHQWLDOO\HOLJLEOHVXEMHFWVZKRDUHVXVSHFWHGRI$0,ZLOOEHDVVHVVHGWRGHWHUPLQHLI
LQFOXVLRQFULWHULDDUHPHWDQGQRH[FOXVLRQFULWHULDDUHSUHVHQW7KRVHZKRTXDOLI\ZLOOEH
JLYHQDQRSSRUWXQLW\WRSURYLGHZULWWHQLQIRUPHGFRQVHQW$OOVXEMHFWVPXVWSURYLGHZULWWHQ
LQIRUPHGFRQVHQWEHIRUHDQ\VWXG\VSHFLILFDVVHVVPHQWVRUSURFHGXUHVDUHSHUIRUPHG:ULWWHQ
LQIRUPHGFRQVHQWLVQRWUHTXLUHGIRUDVVHVVPHQWVRUSURFHGXUHVSHUIRUPHGDFFRUGLQJWR
VWDQGDUGRIFDUHHJIRUGLDJQRVLVRUWUHDWPHQWUHVXOWVIURPVXFKDVVHVVPHQWVPD\EHXVHG
LQWKHGHWHUPLQDWLRQRIVWXG\HOLJLELOLW\6SHFLILFDOO\DVHUXPFUHDWLQLQHREWDLQHGDVVWDQGDUG
RIFDUHDVVHVVPHQWDQGEHIRUHREWDLQLQJZULWWHQLQIRUPHGFRQVHQWZLOOEHUHFRUGHGRQWKH
H&5)WRSURYLGHDUHQDOIXQFWLRQUHIHUHQFHSRLQWIRUFRPSDULVRQRIWKHSUHDQJLRJUDSK\
VWDQGDUGRIFDUHYDOXHWRWKHSUHLQIXVLRQLHEDVHOLQHVWXG\YDOXH
'HSHQGLQJRQWLPHRIHYHQWDQGWLPHUHTXLUHGIURPHYDOXDWLRQLQWKH(PHUJHQF\'HSDUWPHQW
FDUGLDFFDWKHWHUL]DWLRQODERUDWRU\DGPLQLVWUDWLRQRIFRQWUDVWG\HDQGDVVHVVPHQWRIUHQDODQG
KHSDWLFIXQFWLRQVFUHHQLQJPD\RFFXUXSWRGD\VDIWHU)0&IRUWKHLQGH[$0,)LUVW
PHGLFDOFRQWDFW)0&LVGHILQHGDVWKHSRLQWLQWLPHLHFORFNVWDUWDWZKLFKWKHVXEMHFW
CCI
CCI

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 96 of 137 
CRD-TPL-077 
Confidential 
arrives at the hospital emergency department (ie, door time) or cardiac catheterization 
laboratory, for evaluation and treatment of AMI. 
The following procedures will be conducted and documented at the screening visit: 
• Informed consent 
− All subjects must provide written informed consent before any study-specific 
assessments or procedures are performed. Written informed consent is not required 
for assessments or procedures performed according to standard of care (eg, for 
diagnosis or treatment); results from such assessments may be used in the 
determination of study eligibility. 
• Medical history, including active medical conditions and medical or surgical history 
diagnosed within 3 months before the screening visit (including but not limited to prior 
MI, diabetes mellitus, GI bleed, or any other clinically-significant bleeding event 
requiring transfusion of > 2 units PRBCs within the past 3 months). Specifically for 
history of CKD, evidence of CKD within the 6 months before admission for the index 
AMI should be obtained if possible (eg, prior serum creatinine, eGFR, proteinuria, or 
suspected etiology of CKD). 
• Demography 
• Prior / concomitant medication review  
• Review of inclusion and exclusion criteria (including relevant clinical laboratory tests and 
method of contraception) 
• Height (in cm) 
• Body weight (in kg) 
• 12-lead ECG 
• Physical examination (includes examination of head and neck, CV, respiratory, GI, 
musculoskeletal, neurologic and integumentary systems; any abnormal findings should be 
recorded on the medical history eCRF) 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 97 of 137 
CRD-TPL-077 
Confidential 
• Vital signs (blood pressure [supine or seated systolic and diastolic], pulse rate [after 
resting for 5 minutes], and body temperature (oral or tympanic) 
• AE assessment 
• Urine pregnancy test 
− Required for all women of child-bearing potential.  
• FSH test by central laboratory (for amenorrheic females between the ages of 45 and 
60 years, to confirm post-menopausal status) 
• Serum biochemistry by central laboratory  
• ALT, total bilirubin, and serum creatinine by local laboratory. These results must be 
reviewed by the Investigator to determine hepatic and renal function stability for study 
eligibility (Section 8.2.2.1).  
• Urinalysis. At screening only, urinalysis will be locally performed by urine dipstick. If 
dipstick demonstrates high grade proteinuria defined as ≥ 3+ (ie, ≥ 300 mg/dL), a urine 
sample should be sent to the central laboratory for urinalysis. 
• Use IRT to assign the subject identification number  
Subjects who complete all of these assessments and who fulfil the eligibility criteria (ie, 
eligible subjects) will be enrolled into the study.  
If the subject is not eligible for the study, the primary reason for screen failure must be 
entered in the IRT system. 
Screening and randomization of subjects may occur on the same day (Study Day 1 of Active 
Treatment Period) provided that the minimum time after FMC for the index AMI event or 
administration of IV contrast agent is adhered to for confirmation of renal function stability 
before administration of the first infusion of investigational product. If the first infusion of 
investigational product is to be administered on the same day that screening assessments were 
performed, the local laboratory test results obtained at screening may be used to assess for 
hepatic function testing within acceptable limits and renal function stability if the criteria 
outlined in Section 8.2.1.2 are met.  


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
 $FWLYH7UHDWPHQW3HULRG
 9LVLW6WXG\'D\
7KHIROORZLQJEDVHOLQHDVVHVVPHQWVDUHWREHPDGHLQWKHVWXG\XQLWLPPHGLDWHO\EHIRUH
DGPLQLVWUDWLRQRIWKHILUVWLQIXVLRQRILQYHVWLJDWLRQDOSURGXFWRQ6WXG\'D\
x &RQFRPLWDQWPHGLFDWLRQUHYLHZ
x &RQILUPLQFOXVLRQDQGH[FOXVLRQFULWHULD
x 9LWDOVLJQV
x OHDG(&*
x $VVHVVPHQWIRUK\SRYROHPLD
x ,QIXVLRQVLWHDVVHVVPHQWQRWHDQ\DEQRUPDOILQGLQJLQFOXGLQJEUXLVLQJUHGQHVVDQGRU
VZHOOLQJDVDQ$(
x %OHHGLQJHYHQWDVVHVVPHQWLIDEOHHGLQJHYHQWRFFXUVWKHEOHHGLQJHYHQWVKRXOGEH
UHFRUGHGDVDQ$(DQGD%$5&VFRUHDVVLJQHG$SSHQGL[,9WKH%OHHGLQJ(YHQWH&5)
SDJHZLWKVXSSRUWLQJVRXUFHGRFXPHQWDWLRQVKRXOGEHFRPSOHWHG
x $(DVVHVVPHQW
x %ORRGFROOHFWLRQIRU
 6HUXPELRFKHPLVWU\E\FHQWUDOODERUDWRU\
6HUXPFUHDWLQLQHWRWDOELOLUXELQDQG$/7E\ORFDOODERUDWRU\7HVWUHVXOWVPXVWEH
UHYLHZHGE\WKH,QYHVWLJDWRUWRDVVHVVIRUKHSDWLFIXQFWLRQWHVWVZLWKLQDFFHSWDEOH
OLPLWVDQGVWDEOHUHQDOIXQFWLRQEHIRUHWKHILUVWLQIXVLRQ6HFWLRQ


 +HPDWRORJ\E\FHQWUDOODERUDWRU\
 9LURORJ\VDPSOH
 ,PPXQRJHQLFLW\WHVWLQJ
 3.DVVHVVPHQW


x

x

CCI
CCI
CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
x

x


 $UFKLYDOEORRGVDPSOHIRUFHQWUDOODERUDWRU\
x 8ULQHFROOHFWLRQIRU
 8ULQDO\VLVLQFOXGLQJGLSVWLFNDQGPLFURVFRSLFH[DPLQDWLRQE\FHQWUDOODERUDWRU\


 $UFKLYDOXULQHVDPSOHIRUFHQWUDOODERUDWRU\IRUSRVVLEOHIXWXUHUHQDOELRPDUNHU
DQDO\VLV
x 8VH,57WRDFDOFXODWHH*)5EDVHGRQWKHVXEMHFW
VDJHVH[UDFHDQGWKHVHUXP
FUHDWLQLQHYDOXHVHHLQFOXVLRQFULWHULRQ6HFWLRQDQGEUDQGRPL]HWKHVXEMHFWLI
HOLJLEOH

,QYHVWLJDWLRQDOSURGXFWLQIXVLRQKRXU,9LQIXVLRQRI&6/RUSODFHER
7KHILUVWLQIXVLRQRILQYHVWLJDWLRQDOSURGXFWVKRXOGRFFXUZKHQWKHVXEMHFWLVFRQVLGHUHGWREH
FOLQLFDOO\VWDEOHE\WKH,QYHVWLJDWRUEXWQRHDUOLHUWKDQKRXUVDIWHU)0&IRUWKHLQGH[$0,
RUIRUWKRVHXQGHUJRLQJDQJLRJUDSK\QRHDUOLHUWKDQKRXUVDIWHUFRQWUDVWDGPLQLVWUDWLRQ
7KHLQIXVLRQRILQYHVWLJDWLRQDOSURGXFWPD\RFFXULQWKHKRVSLWDORULQWKHRXWSDWLHQWVHWWLQJ
DQGPXVWQRWEHDGPLQLVWHUHGDQ\ODWHUWKDQGD\VDIWHU)0&IRUWKHLQGH[$0,HYHQW
,IWKHILUVWLQIXVLRQRILQYHVWLJDWLRQDOSURGXFWLVWREHDGPLQLVWHUHGRQWKHVDPHGD\WKDWWKH
VFUHHQLQJDVVHVVPHQWVDUHSHUIRUPHG6WXG\'D\WKHPLQLPXPWLPHIRUDVVHVVLQJUHQDO
IXQFWLRQVWDELOLW\PXVWEHDGKHUHGWR6HFWLRQ
$VVHVVPHQWVDWWKHVWDUWRILQIXVLRQ62,RILQYHVWLJDWLRQDOSURGXFW
x $(DVVHVVPHQW
$VVHVVPHQWVDIWHUWKHHQGRILQIXVLRQ(2,RILQYHVWLJDWLRQDOSURGXFW
x 9LWDOVLJQVEORRGSUHVVXUH>VXSLQHV\VWROLFDQGGLDVWROLF@SXOVHUDWHERG\WHPSHUDWXUH
CCI
C
C
I
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
x ,QIXVLRQVLWHDVVHVVPHQWQRWHDQ\DEQRUPDOILQGLQJLQFOXGLQJEUXLVLQJUHGQHVVDQGRU
VZHOOLQJDVDQ$(
x 3RVWLQIXVLRQPRQLWRULQJIRUGUXJK\SHUVHQVLWLYLW\UHDFWLRQIRUDWOHDVWKRXUDIWHUWKH
HQGRILQYHVWLJDWLRQDOSURGXFWLQIXVLRQ
x $(DVVHVVPHQW
x %ORRGFROOHFWLRQIRU
 3.DVVHVVPHQW










 9LVLW6WXG\'D\GD\
7KHIROORZLQJSURFHGXUHVZLOOEHSHUIRUPHGWRKRXUVKDIWHUWKHVWDUWRIWKH
ILUVWLQIXVLRQRILQYHVWLJDWLRQDOSURGXFW
x &RQFRPLWDQWPHGLFDWLRQUHYLHZ
x 9LWDOVLJQV
x ,QIXVLRQVLWHDVVHVVPHQWQRWHDQ\DEQRUPDOILQGLQJLQFOXGLQJEUXLVLQJUHGQHVVDQGRU
VZHOOLQJDVDQ$(
x %OHHGLQJHYHQWDVVHVVPHQWLIDEOHHGLQJHYHQWRFFXUVWKHEOHHGLQJHYHQWVKRXOGEH
UHFRUGHGDVDQ$(DQGD%$5&VFRUHDVVLJQHG$SSHQGL[,9WKH%OHHGLQJ(YHQWH&5)
SDJHZLWKVXSSRUWLQJVRXUFHGRFXPHQWDWLRQVKRXOGEHFRPSOHWHG
x $(DVVHVVPHQW
x %ORRGFROOHFWLRQIRU
 6HUXPELRFKHPLVWU\E\FHQWUDOODERUDWRU\
 6HUXPFUHDWLQLQHWRWDOELOLUXELQDQG$/7E\ORFDOODERUDWRU\7HVWUHVXOWVPXVWEH
UHYLHZHGE\WKH,QYHVWLJDWRUWRDVVHVVIRUKHSDWLFIXQFWLRQWHVWVZLWKLQDFFHSWDEOH
OLPLWVDQGVWDEOHUHQDOIXQFWLRQ


C
C
I
CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
 3.DVVHVVPHQW














x 8ULQHFROOHFWLRQIRU
 8ULQDO\VLVLQFOXGLQJGLSVWLFNDQGPLFURVFRSLFH[DPLQDWLRQE\FHQWUDOODERUDWRU\


 $UFKLYDOXULQHVDPSOHIRUFHQWUDOODERUDWRU\IRUSRVVLEOHIXWXUHUHQDOELRPDUNHU
DQDO\VLV

 9LVLW6WXG\'D\GD\V
7KHIROORZLQJDVVHVVPHQWVDUHWREHPDGHLQWKHVWXG\XQLWLPPHGLDWHO\EHIRUH
DGPLQLVWUDWLRQRIWKHVHFRQGLQIXVLRQRILQYHVWLJDWLRQDOSURGXFW
x &RQFRPLWDQWPHGLFDWLRQUHYLHZ
x 9LWDOVLJQV
x $VVHVVPHQWIRUK\SRYROHPLD
x ,QIXVLRQVLWHDVVHVVPHQWQRWHDQ\DEQRUPDOILQGLQJLQFOXGLQJEUXLVLQJUHGQHVVDQGRU
VZHOOLQJDVDQ$(
x %OHHGLQJHYHQWDVVHVVPHQWLIDEOHHGLQJHYHQWRFFXUVWKHEOHHGLQJHYHQWVKRXOGEH
UHFRUGHGDVDQ$(DQGD%$5&VFRUHDVVLJQHG$SSHQGL[,9WKH%OHHGLQJ(YHQWH&5)
SDJHZLWKVXSSRUWLQJVRXUFHGRFXPHQWDWLRQVKRXOGEHFRPSOHWHG
x $(DVVHVVPHQW
x %ORRGFROOHFWLRQIRU
 6HUXPELRFKHPLVWU\E\FHQWUDOODERUDWRU\
C
C
I
CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
 6HUXPFUHDWLQLQHWRWDOELOLUXELQDQG$/7E\ORFDOODERUDWRU\7HVWUHVXOWVPXVWEH
UHYLHZHGE\WKH,QYHVWLJDWRUWRDVVHVVIRUVWDEOHKHSDWLFDQGUHQDOIXQFWLRQEHIRUH
GRVLQJ7KHVDPSOHPD\EHREWDLQHGXSWRKRXUVEHIRUHGRVLQJDQGPD\EH
UHSHDWHGDWOHDVWKRXUVDIWHUWKHLQLWLDODVVHVVPHQWDVSHU7DEOH


 +HPDWRORJ\SDQHOE\FHQWUDOODERUDWRU\



x 8ULQHFROOHFWLRQIRU
 8ULQDO\VLVLQFOXGLQJGLSVWLFNDQGPLFURVFRSLFH[DPLQDWLRQE\FHQWUDOODERUDWRU\


 $UFKLYDOXULQHVDPSOHIRUFHQWUDOODERUDWRU\IRUSRVVLEOHIXWXUHUHQDOELRPDUNHU
DQDO\VLV

,QYHVWLJDWLRQDOSURGXFWLQIXVLRQKRXU,9LQIXVLRQRI&6/RUSODFHER
$VVHVVPHQWVDWWKHVWDUWRILQIXVLRQ62,RILQYHVWLJDWLRQDOSURGXFW
x $(DVVHVVPHQW
$VVHVVPHQWVDIWHUWKHHQGRILQIXVLRQ(2,RILQYHVWLJDWLRQDOSURGXFW
x 9LWDOVLJQV
x ,QIXVLRQVLWHDVVHVVPHQWQRWHDQ\DEQRUPDOILQGLQJLQFOXGLQJEUXLVLQJUHGQHVVDQGRU
VZHOOLQJDVDQ$(
x 3RVWLQIXVLRQPRQLWRULQJIRUGUXJK\SHUVHQVLWLYLW\UHDFWLRQIRUDWOHDVWKRXUDIWHUWKH
HQGRILQYHVWLJDWLRQDOSURGXFWLQIXVLRQ
x $(DVVHVVPHQW
 9LVLW6WXG\'D\GD\V
7KHIROORZLQJDVVHVVPHQWVDUHWREHPDGHLPPHGLDWHO\EHIRUHDGPLQLVWUDWLRQRIWKHWKLUG
LQIXVLRQRILQYHVWLJDWLRQDOSURGXFW
CCI
CCI
C
C
I


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
x &RQFRPLWDQWPHGLFDWLRQUHYLHZ
x 9LWDOVLJQV
x $VVHVVPHQWIRUK\SRYROHPLD
x ,QIXVLRQVLWHDVVHVVPHQWQRWHDQ\DEQRUPDOILQGLQJLQFOXGLQJEUXLVLQJUHGQHVVDQGRU
VZHOOLQJDVDQ$(
x %OHHGLQJHYHQWDVVHVVPHQWLIDEOHHGLQJHYHQWRFFXUVWKHEOHHGLQJHYHQWVKRXOGEH
UHFRUGHGDVDQ$(DQGD%$5&VFRUHDVVLJQHG$SSHQGL[,9WKH%OHHGLQJ(YHQWH&5)
SDJHZLWKVXSSRUWLQJVRXUFHGRFXPHQWDWLRQVKRXOGEHFRPSOHWHG
x $(DVVHVVPHQW
x %ORRGFROOHFWLRQIRU
 6HUXPELRFKHPLVWU\E\FHQWUDOODERUDWRU\
 6HUXPFUHDWLQLQHWRWDOELOLUXELQDQG$/7E\ORFDOODERUDWRU\7HVWUHVXOWVPXVWEH
UHYLHZHGE\WKH,QYHVWLJDWRUWRDVVHVVIRUVWDEOHKHSDWLFDQGUHQDOIXQFWLRQEHIRUH
GRVLQJ7KHVDPSOHPD\EHREWDLQHGXSWRKRXUVEHIRUHGRVLQJDQGPD\EH
UHSHDWHGDWOHDVWKRXUVDIWHUWKHLQLWLDODVVHVVPHQWDVSHU7DEOH
 +HPDWRORJ\SDQHOE\FHQWUDOODERUDWRU\



x 8ULQHFROOHFWLRQIRU
 8ULQDO\VLVLQFOXGLQJGLSVWLFNDQGPLFURVFRSLFH[DPLQDWLRQE\FHQWUDOODERUDWRU\


 $UFKLYDOXULQHVDPSOHIRUFHQWUDOODERUDWRU\IRUSRVVLEOHIXWXUHUHQDOELRPDUNHU
DQDO\VLV

,QYHVWLJDWLRQDOSURGXFWLQIXVLRQKRXU,9LQIXVLRQRI&6/RUSODFHER
$VVHVVPHQWVDWWKHVWDUWRILQIXVLRQ62,RILQYHVWLJDWLRQDOSURGXFW
x $(DVVHVVPHQW
$VVHVVPHQWVDIWHUWKHHQGRILQIXVLRQ(2,RILQYHVWLJDWLRQDOSURGXFW
x 9LWDOVLJQV
CCI
C
C
I


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
x ,QIXVLRQVLWHDVVHVVPHQWQRWHDQ\DEQRUPDOILQGLQJLQFOXGLQJEUXLVLQJUHGQHVVDQGRU
VZHOOLQJDVDQ$(
x 3RVWLQIXVLRQPRQLWRULQJIRUGUXJK\SHUVHQVLWLYLW\UHDFWLRQIRUDWOHDVWKRXUDIWHUWKH
HQGRILQYHVWLJDWLRQDOSURGXFWLQIXVLRQDWWKHGLVFUHWLRQRIWKH,QYHVWLJDWRU
x $(DVVHVVPHQW
 9LVLW6WXG\'D\GD\V
7KHIROORZLQJDVVHVVPHQWVDUHWREHPDGHLPPHGLDWHO\EHIRUHDGPLQLVWUDWLRQRIWKHIRXUWK
LQIXVLRQRILQYHVWLJDWLRQDOSURGXFW
x &RQFRPLWDQWPHGLFDWLRQUHYLHZ
x 9LWDOVLJQV
x $VVHVVPHQWIRUK\SRYROHPLD
x ,QIXVLRQVLWHDVVHVVPHQWQRWHDQ\DEQRUPDOILQGLQJLQFOXGLQJEUXLVLQJUHGQHVVDQGRU
VZHOOLQJDVDQ$(
x %OHHGLQJHYHQWDVVHVVPHQWLIDEOHHGLQJHYHQWRFFXUVWKHEOHHGLQJHYHQWVKRXOGEH
UHFRUGHGDVDQ$(DQGD%$5&VFRUHDVVLJQHG$SSHQGL[,9WKH%OHHGLQJ(YHQWH&5)
SDJHZLWKVXSSRUWLQJVRXUFHGRFXPHQWDWLRQVKRXOGEHFRPSOHWHG
x $(DVVHVVPHQW
x %ORRGFROOHFWLRQIRU
 6HUXPELRFKHPLVWU\E\FHQWUDOODERUDWRU\
 6HUXPFUHDWLQLQHWRWDOELOLUXELQDQG$/7E\ORFDOODERUDWRU\7HVWUHVXOWVPXVWEH
UHYLHZHGE\WKH,QYHVWLJDWRUWRDVVHVVIRUVWDEOHKHSDWLFDQGUHQDOIXQFWLRQEHIRUH
GRVLQJ7KHVDPSOHPD\EHREWDLQHGXSWRKRXUVEHIRUHGRVLQJDQGPD\EH
UHSHDWHGDWOHDVWKRXUVDIWHUWKHLQLWLDODVVHVVPHQWDVSHU7DEOH


 +HPDWRORJ\SDQHOE\FHQWUDOODERUDWRU\
 3.DVVHVVPHQW



x 8ULQHFROOHFWLRQIRU
 8ULQDO\VLVLQFOXGLQJGLSVWLFNDQGPLFURVFRSLFH[DPLQDWLRQE\FHQWUDOODERUDWRU\
CCI
C
C
I


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO


 $UFKLYDOXULQHVDPSOHIRUFHQWUDOODERUDWRU\IRUSRVVLEOHIXWXUHUHQDOELRPDUNHU
DQDO\VLV
,QYHVWLJDWLRQDOSURGXFWLQIXVLRQKRXU,9LQIXVLRQRI&6/RUSODFHER
$VVHVVPHQWVDWWKHVWDUWRILQIXVLRQ62,RILQYHVWLJDWLRQDOSURGXFW
x $(DVVHVVPHQW
$VVHVVPHQWVDIWHUWKHHQGRILQIXVLRQ(2,RILQYHVWLJDWLRQDOSURGXFW
x 9LWDOVLJQV
x ,QIXVLRQVLWHDVVHVVPHQWQRWHDQ\DEQRUPDOILQGLQJLQFOXGLQJEUXLVLQJUHGQHVVDQGRU
VZHOOLQJDVDQ$(
x 3RVWLQIXVLRQPRQLWRULQJIRUGUXJK\SHUVHQVLWLYLW\UHDFWLRQIRUDWOHDVWKRXUDIWHUWKH
HQGRILQYHVWLJDWLRQDOSURGXFWLQIXVLRQDWWKHGLVFUHWLRQRIWKH,QYHVWLJDWRU
x $(DVVHVVPHQW
x %ORRGFROOHFWLRQIRU
 3.DVVHVVPHQW






 9LVLW6WXG\'D\GD\V
7KHIROORZLQJSURFHGXUHVZLOOEHSHUIRUPHGDWWKHODVWYLVLWRIWKH$FWLYH7UHDWPHQW
3HULRG
x &RQFRPLWDQWPHGLFDWLRQUHYLHZ
x %RG\ZHLJKWLQNJ
x OHDG(&*
x 3K\VLFDOH[DPLQDWLRQLQFOXGHVH[DPLQDWLRQRIKHDGDQGQHFN&9UHVSLUDWRU\*,
PXVFXORVNHOHWDOQHXURORJLFDQGLQWHJXPHQWDU\V\VWHPV
x 9LWDOVLJQV
CCI
CCI
C
C
I


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
x %OHHGLQJHYHQWDVVHVVPHQWLIDEOHHGLQJHYHQWRFFXUVWKHEOHHGLQJHYHQWVKRXOGEH
UHFRUGHGDVDQ$(DQGD%$5&VFRUHDVVLJQHG$SSHQGL[,9WKH%OHHGLQJ(YHQWH&5)
SDJHZLWKVXSSRUWLQJVRXUFHGRFXPHQWDWLRQVKRXOGEHFRPSOHWHG
x $(DVVHVVPHQW
x %ORRGFROOHFWLRQIRU
 6HUXPELRFKHPLVWU\E\FHQWUDOODERUDWRU\


 +HPDWRORJ\E\FHQWUDOODERUDWRU\
 9LURORJ\VDPSOH
 ,PPXQRJHQLFLW\WHVWLQJ








 $UFKLYDOEORRGVDPSOHIRUFHQWUDOODERUDWRU\
x 8ULQHFROOHFWLRQIRU
 3UHJQDQF\WHVW5HTXLUHGIRUDOOZRPHQRIFKLOGEHDULQJSRWHQWLDO
 8ULQDO\VLVLQFOXGLQJGLSVWLFNDQGPLFURVFRSLFH[DPLQDWLRQE\FHQWUDOODERUDWRU\


 $UFKLYDOXULQHVDPSOHIRUFHQWUDOODERUDWRU\IRUSRVVLEOHIXWXUHELRPDUNHUDQDO\VLV

 6DIHW\)ROORZXS3HULRG
7KHGD\VDIWHU9LVLWLVWKH6DIHW\)ROORZXS3HULRG9LVLW6WXG\'D\GD\VLV
WKHHQGRIVWXG\7KHIROORZLQJDVVHVVPHQWVZLOOEHPDGHDW9LVLW
x &RQFRPLWDQWPHGLFDWLRQUHYLHZ
x %RG\ZHLJKWLQNJ
x OHDG(&*
C
C
I
CCI
CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
x 3K\VLFDOH[DPLQDWLRQLQFOXGHVH[DPLQDWLRQRIKHDGDQGQHFN&9UHVSLUDWRU\*,
PXVFXORVNHOHWDOQHXURORJLFDQGLQWHJXPHQWDU\V\VWHPV
x 9LWDOVLJQV
x %OHHGLQJHYHQWDVVHVVPHQWLIDEOHHGLQJHYHQWRFFXUVWKHEOHHGLQJHYHQWVKRXOGEH
UHFRUGHGDVDQ$(DQGD%$5&VFRUHDVVLJQHG$SSHQGL[,9WKH%OHHGLQJ(YHQWH&5)
SDJHZLWKVXSSRUWLQJVRXUFHGRFXPHQWDWLRQVKRXOGEHFRPSOHWHG
x $(DVVHVVPHQW
x %ORRGFROOHFWLRQIRU
 6HUXPELRFKHPLVWU\E\FHQWUDOODERUDWRU\
 +HPDWRORJ\E\FHQWUDOODERUDWRU\
 9LURORJ\VDPSOH
 ,PPXQRJHQLFLW\7HVWLQJ







 $UFKLYDOEORRGVDPSOHIRUFHQWUDOODERUDWRU\
x 8ULQHFROOHFWLRQIRU
 3UHJQDQF\WHVW5HTXLUHGIRUDOOZRPHQRIFKLOGEHDULQJSRWHQWLDO


$'9(56((9(176

'(),1,7,216
 $GYHUVH(YHQW
$VSHUWKH,&+JXLGHOLQHVDQ$(LVDQ\XQWRZDUGPHGLFDORFFXUUHQFHLQDSDWLHQWRUFOLQLFDO
LQYHVWLJDWLRQVXEMHFWDGPLQLVWHUHGDSKDUPDFHXWLFDOSURGXFWDQGZKLFKGRHVQRWQHFHVVDULO\
KDYHDFDXVDOUHODWLRQVKLSZLWKWKLVWUHDWPHQW$Q$(FDQWKHUHIRUHEHDQ\XQIDYRUDEOHDQG
XQLQWHQGHGVLJQLQFOXGLQJDQDEQRUPDOFOLQLFDOO\VLJQLILFDQWODERUDWRU\ILQGLQJV\PSWRP
C
C
I
CCI

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 108 of 137 
CRD-TPL-077 
Confidential 
or disease temporally associated with the use of a medicinal (investigational) product, 
whether or not considered related to the medicinal (investigational) product.  
The period of observation for AEs extends from the time the subject gives informed consent 
until the end of study (see Section 9.4 for further details). 
Adverse events may include: 
• Exacerbation (ie, an increase in the frequency or severity) of a pre-existing condition.  
Illness present before study entry should be recorded in the medical history section of the 
eCRF and only be reported as an AE if there is an increase in the frequency or severity of 
the condition during the study.  
• A clinical event occurring after consent but before investigational product administration. 
• Intercurrent illnesses with an onset after administration of investigational product. 
Adverse events do not include: 
• Events identified at screening that meet exclusion criteria 
• Medical or surgical procedures (the condition that leads to the procedure is the AE) 
• Situations where an untoward medical occurrence has not taken place. For example: 
o Planned hospitalizations due to pre-existing conditions, which have not worsened. 
o Hospitalizations that occur for procedures not due to an AE (eg, cosmetic surgery). 
o Hospitalizations for a diagnostic procedure where the hospital stay is less than 
24 hours in duration or for normal management procedures (eg, chemotherapy). 
• Overdose of investigational product or any concomitant therapy that does not result in 
any adverse signs or symptoms.  
 
For laboratory safety parameters, any instances of absolute values being outside the reference 
range or changes at any visit after study start that are considered by the Investigator as 
clinically significant must recorded in the eCRF as AEs. In addition, at the Investigator’s 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 109 of 137 
CRD-TPL-077 
Confidential 
discretion, any changes or trends over time in laboratory parameters can be recorded in the 
eCRF as AEs if such changes or trends are considered to be clinically relevant, even if the 
absolute values are within the reference range. 
Laboratory findings do not need to be reported as AEs in the following cases: 
• Laboratory parameters already beyond the reference range at screening, unless a further 
increase/decrease can be considered an exacerbation of a pre-existing condition.  
• Abnormal laboratory parameters caused by mechanical or physical influences on the 
blood sample (eg, in vitro hemolysis) and flagged as such by the laboratory in the 
laboratory report. 
• Abnormal parameters that are obviously biologically implausible (eg, values that are 
incompatible with life or outside the measuring range). 
• An abnormal laboratory value that cannot be confirmed after repeat analysis, preferably 
in the same laboratory (ie, the previous result could be marked as not valid and should not 
necessarily be reported as an AE).  
9.1.2 Serious Adverse Event 
A SAE is defined as any untoward medical occurrence that at any dose: 
• Results in death – The event must be the cause of death for the SAE to meet this serious 
criterion. 
• Is life-threatening – The term “life-threatening” refers to an event in which the subject 
was at risk of death at the time of the event; it does not refer to an event that 
hypothetically might have caused death if it had been more severe. 
• Requires in-patient hospitalization or prolongation of existing hospitalization – 
CSLB considers “hospitalization or prolongation of existing hospitalization” for at least 
24 hours as the defining criterion for an SAE. Hospital admissions for planned surgery or 
for normal disease management procedures (eg, chemotherapy) are not considered as 
defining criteria for SAEs.  

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 110 of 137 
CRD-TPL-077 
Confidential 
• Results in persistent or significant disability or incapacity. 
• Is a congenital anomaly or birth defect. 
• Is medically significant – A medically significant event is defined as an event that does 
not necessarily meet any of the SAE criteria, but which is judged by a physician to 
potentially jeopardize the subject or require medical or surgical intervention to prevent 1 
of the above outcomes listed as an SAE criterion. 
Adverse events that do not fall into the above categories are defined as nonserious AEs. 
9.1.3 Adverse Events of Special Interest 
The following AEs are of special interest for which ongoing monitoring and/or expedited 
reporting by the Investigator is required as per Section 9.5.1: 
9.1.3.1 Stage 3 Acute Kidney Injury 
Acute kidney injury for this purpose will be defined as an elevation in serum creatinine 
during the Active Treatment Period to ≥ 3 x the baseline value or a serum creatinine of 
≥ 4.0 mg/dL (353.6 μmol/L, Kidney Disease Improving Global Outcomes [KDIGO] March 
2012) that is confirmed by repeat assessment by the central laboratory. 
9.1.3.2 Drug Hypersensitivity 
Drug hypersensitivity will be as assessed by the Investigator. Assessments should be 
performed as described in Section 8.2.3.6. 
9.1.3.3 Potential Hy’s Law Case 
Potential Hy’s Law cases for this purpose will be defined as elevation in ALT > 3 x ULN 
with a concomitant increase in total bilirubin that is > 2 x ULN that is confirmed by repeat 
assessment by the central laboratory. AST is not being used in this definition since there may 
be increases in AST that are due to the index AMI event. Hy’s Law is defined as an elevation 
in AST or ALT > 3 x ULN with a concomitant increase in total bilirubin that is > 2 x ULN 
without initial findings of cholestasis (elevated alkaline phosphatase), and with no other 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 111 of 137 
CRD-TPL-077 
Confidential 
reason found to explain the combination of these increased AST/ALT and total bilirubin 
findings (Guidance for Industry: Drug-induced Liver Injury: Premarketing Clinical 
Evaluation 2009). Additional assessments should be performed as described in Section 8.2.2. 
9.1.3.4 Hemolysis 
Hemolysis will be defined as a decrease in hemoglobin during the Active Treatment Period of 
≥ 2 g/dL from baseline that is not explained by overt blood loss. Additional assessments 
should be performed as described in Section 8.2.3.7.2.  
9.1.3.5 Bleeding Events 
Bleeding events will be assessed according to the BARC definition for bleeding (see 
Appendix IV). 
9.2 
SEVERITY OF ADVERSE EVENTS 
The severity of each AE (ie, nonserious and serious AEs) is to be assessed by the Investigator 
using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events 
(CTCAE) criteria as follows: 
NCI Grade 
Definition 
Grade 0 
Grade 0 is universally defined as absence of AE or within normal limits or values. 
Grade 1 
An AE that is asymptomatic; or involves mild or minor symptoms; or is of marginal 
clinical relevance; or consists of clinical or diagnostic observations alone; or for 
which intervention is not indicated; or for which only non-prescription intervention is 
indicated. 
Grade 2 
An AE for which only minimal, local, or noninvasive intervention (eg, packing, 
cautery) is indicated; or that limits instrumental activities of daily living (ADLs, eg, 
shopping, laundry, transportation or ability to conduct finances). 
Grade 3 
An AE that is medically significant but not life-threatening; or for which inpatient 
care or prolongation of hospitalization are indicated; or that is an important medical 
event that does not result in hospitalization, but may jeopardize the patient or may 
require intervention either to prevent hospitalization, to prevent the AE from 
becoming life-threatening or causing death; or that is disabling; or that results in 
persistent or significant disability, incapacity, or limitation of self-care activities of 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 112 of 137 
CRD-TPL-077 
Confidential 
NCI Grade 
Definition 
daily living (ADLs, eg, getting in and out of bed, dressing, eating, getting around 
inside, bathing, or using the toilet). 
Grade 4 
An AE that has life-threatening consequences; for which urgent intervention is 
indicated; that puts the patient at risk of death at the time of the event if immediate 
intervention is not undertaken; or that causes blindness or deafness. 
Grade 5 
The termination of life as a result of an AE.  
ADLs = activities of daily living; AE = adverse event; NCI = National Cancer Institute 
Note: Definitions provided here correspond to: NCI Common Terminology Criteria for Adverse Events V4.0.  
 
If an AE is reported that is not part of the CTCAE criteria, the following criteria will be 
used:  
Severity 
Definition 
Mild 
A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual ADLs. 
Moderate 
A type of AE that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual ADLs, causing discomfort but poses no 
significant or permanent risk of harm to the subject. 
Severe 
A type of AE that interrupts usual ADLs, or significantly affects clinical status, or 
may require intensive therapeutic intervention. 
ADLs = activities of daily living; AE = adverse event  
Note: definitions are based on the Clinical Data Interchange Standards Consortium (CDISC) Study Data 
Tabulation Model (SDTM) Severity Intensity Scale for Adverse Event Terminology  
 
9.3 
CAUSALITY OF ADVERSE EVENTS 
The causal relationship of an AE to investigational product must always be assessed by the 
Investigator. All AEs will be classified as either related or not related to investigational 
product. If a causality assessment is not provided for an AE (including an SAE) that AE will 
be considered related to investigational product.  
The degree of certainty with which an AE is attributed to investigational product or an 
alternative cause (eg, natural history of the underlying disease, concomitant therapy) will be 
determined by how well the event can be understood in terms of: 
• Known pharmacology of investigational product. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 113 of 137 
CRD-TPL-077 
Confidential 
• Clinically and / or pathophysiologically plausible context. 
• Reaction of a similar nature previously observed with similar products, or reported in the 
literature for similar products as being product related (eg, headache, facial flushing, 
pallor). 
• Plausibility supported by the temporal relationship (eg, the event being related by time to 
administration or termination of treatment with investigational product, drug withdrawal 
or reproduced on rechallenge). 
9.4 
OBSERVATION PERIOD FOR ADVERSE EVENTS 
The observation period for AE (and SAE) reporting in an individual subject will start at the 
time of giving written informed consent for participation in the current study and finish with 
the end of study visit (Visit 8).   
If the Investigator becomes aware of an SAE that has started after the observation period has 
finished, and there is at least a possible causal relationship to investigational product, the 
event must be reported to CSLB (see Section 9.6). 
9.5 
ADVERSE EVENT REPORTING 
At each clinical evaluation, the Investigator (or medically-qualified delegate) will determine 
whether any AEs have occurred. Adverse events will be recorded in the AE page of the 
eCRF. If known, the medical diagnosis of an AE should be recorded in preference to the 
listing of individual signs and symptoms. The Investigator must follow up on the course of an 
AE until resolution or stabilization. If an AE is ongoing after the end of study visit, the AE 
will continue to be followed up until resolution, stabilization. 
If, during the study period, a subject presents with a preexisting condition that was not noted 
at the time of study entry, the condition should be retrospectively recorded in the Medical 
History section of the eCRF. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 114 of 137 
CRD-TPL-077 
Confidential 
For AE reporting, the study period is defined as that time period from the signature of the 
informed consent form (ICF) through Visit 8. Therefore, events that occur before the initial 
screening visit will be recorded in the medical history and events that occur after the signing 
of the ICF will be recorded as an AE. 
9.5.1 
Adverse Events of Special Interest 
9.5.1.1 Stage 3 Acute Kidney Injury 
Any elevation in serum creatinine of  ≥ 3 x the baseline value or a serum creatinine of 
≥ 4.0 mg/dL (353.6 μmol/L) that is confirmed by repeat assessment by the central laboratory 
should be reported as an SAE as described in Section 9.6. In addition, the increased value 
should be confirmed by repeat assessment by the central laboratory and followed until 
resolution or stabilization. 
9.5.1.2 Drug Hypersensitivity Reaction 
If a drug hypersensitivity reaction is suspected, it should be reported as an AE as described in 
Section 9.1. Assessments should be performed as described in Section 8.2.3.6. 
9.5.1.3 Potential Hy’s Law Case 
An elevation in ALT > 3 x ULN with a concomitant increase in total bilirubin that is 
> 2 x ULN should be should be reported as an SAE as described in Section 9.6 as this could 
be an indicator of a potential Hy’s Law case. See Section 9.1.3.3 for definition of Hy’s Law.  
Additional assessments should be performed as described in Section 8.2.2. 
9.5.1.4 Hemolysis 
Hemolysis as defined in Section 9.1.3 should be reported as an AE as described in 
Section 9.1. Additional assessments should be performed as described in Section 8.2.3.7.2. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 115 of 137 
CRD-TPL-077 
Confidential 
9.5.1.5 Bleeding Events 
Bleeding events should be reported as AEs (see Sections 3.6.4 and 9.1) and the Bleeding 
Event eCRF page must be completed for each suspected bleeding event. 
9.6 
SERIOUS ADVERSE EVENT REPORTING 
This study will comply with all applicable regulatory requirements and adhere to the full 
requirements of ICH Topic E2A (Clinical Safety Data Management: Definitions and 
Standards for Expedited Reporting). 
All SAEs that occur during the course of the study, whether or not causally related to 
the investigational product, must be reported and entered into the eCRF immediately 
(within 24 hours of the Investigator becoming aware of the event). 
Adverse events occurring in the period between the time that the subject gave written 
informed consent and the first exposure to investigational product that meet 1 or more of the 
seriousness criteria for AEs must be entered immediately (within 24 hours of the Investigator 
becoming aware of the event) in the clinical study database in the same manner as other 
SAEs.  
Any SAE that occurs after the end of study visit that is considered to be causally related to 
investigational product must be immediately (ie, within 24 hours of the Investigator 
becoming aware of the event) reported to the sponsor. 
If access to the clinical database is not available (eg, system or internet access problem, or the 
clinical study database is locked), a handwritten SAE report must be completed, signed and 
dated by the Investigator and sent to CSLB Global Clinical Safety and Pharmacovigilance via 
facsimile or email. 
If and/or when the system becomes available post outage, the SAE must be entered in to the 
clinical study database immediately. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 116 of 137 
CRD-TPL-077 
Confidential 
9.6.1 Requirements for Immediate Reporting of Serious Adverse Events 
The minimum reporting requirements for immediate entry of SAEs in the eCRF include: 
• Identifiable subject. 
• Suspected medicinal product and / or procedure. 
• Event term. 
• Identifiable reporting source. 
In addition, the Investigator must: 
• Report all SAEs to the relevant IRB / IEC within the timeframe specified by the 
IRB / IEC. 
• Enter relevant follow-up information in the eCRF until the SAE has resolved, or, in the 
case of permanent impairment, until stabilized. 
• Ensure that the causality assessment for all SAEs is entered in the eCRF. 
If the minimum requirements for reporting are fulfilled, the Investigator should not wait to 
receive additional information to fully document the event before entering the information 
into the clinical study database.  
When submitting SAE reports and any other related reports (eg, discharge summaries) to 
CSLB, subjects should be identified only by their subject number and study number. The 
Investigator should not include the subject’s name, date of birth, or address. 
In cases of death, the Investigator should supply CSLB and the IRB / IEC (as applicable) 
with any additional information as it becomes available (eg, autopsy reports). When 
submitting medical reports to CSLB, the subject should be identified only by their subject 
identification number and study number. 
The procedure to be followed if an ongoing AE becomes an SAE after the end of the 
observation period for AEs is described in Section 9.9. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 117 of 137 
CRD-TPL-077 
Confidential 
9.7 
OTHER SIGNIFICANT EVENT REPORTING 
9.7.1 Overdose 
Details (ie, volume, location of infusions, infusion rate) of overdose of investigational 
product or any concomitant therapy must be recorded in the eCRF. Any overdose that is 
considered by the Investigator to be medically significant (ie, occurs in association with an 
event and meets any seriousness criteria) must be entered as an SAE (see Section 9.5.1). An 
overdose that does not result in any adverse signs or symptoms should not be considered an 
AE (see Section 9.1.1). 
9.7.2 Pregnancy and Lactation  
A female subject or female partner of a male subject who becomes pregnant while 
participating in the study, or up to and including 3 months after the last dose of 
investigational product, must notify the Investigator immediately.   
If a female subject becomes pregnant, she must discontinue treatment with investigational 
product, but may continue other study procedures at the discretion of the Investigator. If the 
female subject is in the Active Treatment Period of the study, her participation will be 
discontinued and the procedure for discontinuation of a subject will be followed, as described 
in Section 4.1.4). Every effort will be made to ensure that the relevant safety assessments for 
early termination Visit 7 are completed (telephone documentation is allowed). 
CSLB must be notified within 5 days of the Investigator becoming aware of the pregnancy.  
Whenever possible, a pregnancy in a subject or in a female partner of a male subject exposed 
to investigational product should be followed to term so as to assess any potential occurrence 
of congenital anomalies or birth defects. Any follow-up information, including premature 
termination and the status of the mother and child after delivery, should be reported by the 
Investigator to CSLB using a Pregnancy Reporting / Outcome Form.  

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 118 of 137 
CRD-TPL-077 
Confidential 
If the outcome of the pregnancy meets the criteria for classification as an SAE (eg, 
spontaneous abortion, stillbirth, neonatal death or congenital anomaly) then the Investigator 
should follow the procedure for reporting an SAE (Section 9.6.1).  
9.8 
INSTITUTIONAL REVIEW BOARD / INDEPENDENT ETHICS COMMITTEE 
REPORTING REQUIREMENTS 
The time frame within which an IRB / IEC must be notified of deaths and investigational 
product-related unexpected SAEs is stipulated by each IRB / IEC. It is the Investigator’s 
responsibility to comply with the requirements for IRB / IEC notification. CSLB will provide 
Investigators with all details of all SAEs reported to regulatory authorities. 
9.9 
FOLLOW-UP OF ADVERSE EVENTS 
Every effort should be made to follow-up subjects who continue to experience an AE, AE of 
special interest, or an SAE on completion of the study until either the AE resolves or 
stabilizes. All follow-up information (and attempted follow-up contacts) should be 
documented in the subject’s medical records. Relevant details of the subject’s progress 
should also be entered in the eCRF. 
10. STATISTICS 
10.1 SAMPLE SIZE ESTIMATION 
This is a randomized, placebo-controlled, multi-dose safety study in subjects with moderate 
RI and AMI. Subjects are to be randomized to CSL112 or placebo treatment in a 2:1 ratio. 
The co-primary endpoints are: 
• Renal SAEs (defined as any SAE with a MedDRA PT included in the Acute Renal 
Failure narrow SMQ or a PT of renal tubular necrosis, renal cortical necrosis, renal 
necrosis, or renal papillary necrosis), and  
• AKI, defined as an absolute increase in serum creatinine from baseline of ≥ 0.3 mg/dL 
(26.5 μmol/L) during the Active Treatment Period that is sustained upon repeat 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 119 of 137 
CRD-TPL-077 
Confidential 
measurement by the central laboratory no earlier than 24 hours after the elevated value. If 
no repeat value is obtained [due, for example, to loss of follow-up or protocol violation], 
a single serum creatinine value that is increased from baseline ≥ 0.3 mg/dL (26.5 μmol/L) 
during the Active Treatment Period would also fulfil the definition of AKI. Baseline for 
determination of AKI is defined as the pre-infusion central laboratory serum creatinine 
level on Study Day 1. 
With a sample size of 81 (54 active: 27 placebo), the study will detect with 80% probability a 
treatment-emergent event with a frequency of 3% in the active group and 2% overall. A total 
of 81 subjects, 27 placebo and 54 CSL112, is planned for this study to meet regulatory 
considerations for treatment-emergent renal event characterization; it is not powered for 
statistical testing of the co-primary endpoints.  
10.2 STUDY POPULATIONS 
10.2.1 Screened Population 
The Screened Population will comprise all subjects who provided written informed consent to 
undergo study screening procedures.   
10.2.2 Intent-to-Treat Population 
The Intent-to-Treat (ITT) Population will comprise all subjects in the Screened Population 
who were randomized to 1 of the 2 treatment groups. This population will be analyzed using 
the treatment to which the subject was randomized regardless of the treatment actually 
received.  
10.2.3 Safety Population 
The Safety Population will comprise all subjects in the ITT Population who received at least 
a partial dose of investigational product, and will be based on the actual treatment received.   


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
 3KDUPDFRNLQHWLF3RSXODWLRQ
7KH3.$QDO\VLV3RSXODWLRQZLOOFRPSULVHDOOVXEMHFWVLQWKH6DIHW\3RSXODWLRQZKRKDYHDW
OHDVWPHDVXUDEOHSODVPDFRQFHQWUDWLRQRIDSR$,RU3&




 67$7,67,&$/$1$/<6(6$1'0(7+2'6
$FRPSOHWHGHVFULSWLRQRIWKHVWDWLVWLFDODQDO\VHVDQGPHWKRGVZLOOEHDYDLODEOHLQD
6WDWLVWLFDO$QDO\VLV3ODQ6$3ZKLFKZLOOEHILQDOL]HGEHIRUHWKHGDWDEDVHLVORFNHG
 6XEMHFW'LVSRVLWLRQ'HPRJUDSKLFVDQG%DVHOLQH&KDUDFWHULVWLFV
7KHQXPEHURIVXEMHFWVZKRZHUHVFUHHQHGIDLOHGVFUHHQLQJUDQGRPL]HGWUHDWHGDQG
FRPSOHWHGWKHVWXG\ZLOOEHSUHVHQWHGLQVXPPDU\WDEOHVE\WUHDWPHQWJURXSDQGRYHUDOO7KH
UHDVRQIRUGLVFRQWLQXLQJVWXG\WUHDWPHQWRUZLWKGUDZDOIURPWKHVWXG\ZLOOEHVXPPDUL]HG
DQGOLVWHGE\VXEMHFW
'HPRJUDSKLFVDQGEDVHOLQHFKDUDFWHULVWLFVRIVXEMHFWVLQWKH6DIHW\3RSXODWLRQZLOOEH
VXPPDUL]HGXVLQJGHVFULSWLYHVWDWLVWLFVE\WUHDWPHQWJURXSDQGRYHUDOO&RQWLQXRXVGDWDZLOO
EHVXPPDUL]HGE\GHVFULSWLYHVWDWLVWLFVDQGFDWHJRULFDOGDWDZLOOEHVXPPDUL]HGE\
IUHTXHQFLHVDQGSURSRUWLRQV$JHZLOOEHGHVFULEHGDVERWKDFRQWLQXRXVDQGDFDWHJRULFDO
YDULDEOH6XSSRUWLYHGDWDZLOOEHOLVWHGE\VXEMHFW
 6DIHW\$QDO\VHV
&R3ULPDU\(QGSRLQWV
)RUWKHFRSULPDU\VDIHW\HQGSRLQWVRIWUHDWPHQWHPHUJHQWUHQDO6$(VDQG$.,HYHQWV
LQFLGHQFHUDWHVZLOOEHEDVHGRQWKHQXPEHURIVXEMHFWVZLWKDWOHDVWRFFXUUHQFHRIWKHHYHQW
CCI
CCI

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 121 of 137 
CRD-TPL-077 
Confidential 
of interest; eg, a subject with 2 treatment-emergent renal SAEs will be counted once. 
Baseline for determination of AKI is defined as the pre-infusion central laboratory serum 
creatinine level from Study Day 1. Acute kidney injury events will be identified using central 
laboratory results. Treatment-emergent is defined as occurring at or after the start of the first 
infusion. The difference in incidence rates will be computed by subtracting the rate in the 
placebo arm from the incidence rate in the CSL112 arm so that a positive difference indicates 
a higher incidence rate in the CSL112 arm. For each co-primary endpoint, Newcombe-
Wilson 2-sided 95% confidence intervals around the difference in incidence rates will be 
calculated if at least 1 event occurs. Otherwise, an exact, 1-sided, upper 97.5% confidence 
interval will be reported for the incidence rate in each treatment arm. 
A sensitivity analysis of the renal SAE co-primary endpoint will use independently 
adjudicated results and the same methods as the primary study analysis. A sensitivity analysis 
of the AKI co-primary endpoint will use local laboratory results and the same methods as the 
primary study analysis. 
Acute kidney injury rates will be compared among subjects whose dosing eligibility was 
determined in part based on serum creatinine determinations performed 12 to 24 hours after 
radiographic contrast exposure versus those whose dosing eligibility was determined in part 
based on serum creatinine determinations performed 48± 6 hours after radiographic contrast 
exposure. If data on subjects with serum creatinine determinations performed 12 to 24 hours 
after radiographic contrast are insufficient to perform this analysis, an analysis comparing the 
AKI rates among subjects whose dosing eligibility was determined in part based on serum 
creatinine determinations performed 12 to 48 hours after radiographic contrast exposure 
versus those whose dosing eligibility was determined in part based on serum creatinine 
determinations performed > 48 hours after radiographic contrast exposure will be performed. 
For either analysis, the difference in placebo-corrected rates between the 2 time-period 
subgroups will be calculated, along with a 2-sided 95% confidence interval. 
All primary endpoint analyses will use the Safety population. 


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
2WKHU6DIHW\$QDO\VHV
$OOVXEMHFWVLQWKH6DIHW\3RSXODWLRQZLOOEHHYDOXDWHGIRUVDIHW\7UHDWPHQWJURXS
FODVVLILFDWLRQZLOOEHDFFRUGLQJWRWKHWUHDWPHQWDFWXDOO\UHFHLYHG7UHDWPHQWHPHUJHQW$(V
ZLOOEHVXPPDUL]HGE\WUHDWPHQWJUDGHUHODWLRQVKLSWRVWXG\WUHDWPHQWDQGVHULRXVQHVV
&KDQJHVIURPEDVHOLQHSUHLQIXVLRQRQ6WXG\'D\LQFOLQLFDOODERUDWRU\DVVHVVPHQWVYLWDO
VLJQPHDVXUHPHQWV(&*LQWHUYDOPHDVXUHPHQWVLPPXQRJHQLFLW\DQGSURWHLQXULDZLOOEH
VXPPDUL]HGE\WUHDWPHQWDQGFKDQJHVRISRWHQWLDOFOLQLFDOVLJQLILFDQFHZLOOEHLGHQWLILHG
'HVFULSWLYHVWDWLVWLFVZLOOEHXVHGWRVXPPDUL]HWKHH[SRVXUHWRVWXG\WUHDWPHQWDQGWKH
VDIHW\DVVHVVPHQWV1RQODERUDWRU\YDOXHEDVHG$(VRIVSHFLDOLQWHUHVWK\SHUVHQVLWLYLW\DQG
EOHHGLQJHYHQWV6HFWLRQZLOOEHVXPPDUL]HGDQGOLVWHG7KHVXPPDU\RIEOHHGLQJ$(V
RIVSHFLDOLQWHUHVWZLOOXVHWKRVHDGMXGLFDWHGE\WKH&(&XVLQJ%$5&FULWHULD%OHHGLQJ
HYHQWVZLOOEHOLVWHGVHSDUDWHO\E\VRXUFH,QYHVWLJDWRUUHSRUWHGDQG&(&DGMXGLFDWHG
/DERUDWRU\YDOXHEDVHG$(VRIVSHFLDOLQWHUHVW$.,KHPRO\VLVDQGSRWHQWLDO+\¶V/DZ
FDVHVZLOOEHUHSRUWHGXVLQJVHUXPELRFKHPLVWU\DQGKHPDWRORJ\ODERUDWRU\YDOXHV
 3KDUPDFRNLQHWLF
$QDO\VHV
0HDVXUHGSODVPDFRQFHQWUDWLRQVRIDSR$,DQG3&DQGEDVHOLQHFRUUHFWHGFRQFHQWUDWLRQVLH
FKDQJHIURPEDVHOLQHZLOOEHOLVWHGDQGVXPPDUL]HGE\WLPHSRLQW3ODVPD3.SDUDPHWHUV
IRUDSR$,DQG3&ZLOOEHVXPPDUL]HGGHVFULSWLYHO\7KHIROORZLQJSDUDPHWHUVZLOOEH
FDOFXODWHG
x 0D[LPXPFRQFHQWUDWLRQLQSODVPD&PD[
x $FFXPXODWLRQ5DWLR
1RQOLQHDUPL[HGHIIHFWVPRGHOLQJZLOOEHSHUIRUPHGWRDVVHVVWKH3.GDWDIRUDSR$,DQG
3&7KLVSRSXODWLRQEDVHGDSSURDFKZLOOEHXVHGWRH[SORUHDQGTXDQWLI\FOLQLFDOO\UHOHYDQW
FRYDULDWHVVXFKDVDJHVH[DQGUHQDOIXQFWLRQRQSRSXODWLRQ3.SDUDPHWHUV

CCI
CCI


6WXG\1XPEHU
&6/BB$P
6WXG\3URGXFW
&6/

)LQDO9
-XQH
3DJHRI
&5'73/
&RQILGHQWLDO
 6DIHW\5HYLHZ
$QH[WHUQDOSURJUDPOHYHO'60%ZLOOLQGHSHQGHQWO\UHYLHZVDIHW\GDWDDIWHUHYHU\
VXEMHFWVKDYHUHFHLYHGLQIXVLRQVRILQYHVWLJDWLRQDOSURGXFWDQGKDYHSUHLQIXVLRQVDIHW\
GDWDDYDLODEOHEHIRUHWKHWKLUGLQIXVLRQDW9LVLW7KHVHUHYLHZVZLOOFRQWLQXHXQWLODWOHDVW
VXEMHFWVDSSUR[LPDWHO\RIVXEMHFWVFRPSOHWH9LVLW,QDGGLWLRQWKHLQGHSHQGHQW
'60%ZLOOKDYHLQWHULPVDIHW\UHYLHZVZKHQDSSUR[LPDWHO\RIVXEMHFWVKDYH
FRPSOHWHGWKH$FWLYH7UHDWPHQW3HULRG9LVLWDSSUR[LPDWHO\RIVXEMHFWVKDYH
FRPSOHWHG9LVLWDQGDSSUR[LPDWHO\RIVXEMHFWVKDYHFRPSOHWHGWKH$FWLYH
7UHDWPHQW3HULRG9LVLW$WDOOSODQQHGUHYLHZVWKH'60%ZLOODVVHVVIRUDQ\VDIHW\VLJQDO
WKDWKDVHPHUJHGDQGWKDWZRXOGZDUUDQWDFKDQJHLQWKHFRQGXFWRIWKHVWXG\RUSURYLGH
UHFRPPHQGDWLRQVUHJDUGLQJVXEVHTXHQWGRVLQJDQGRUVWXG\SURJUHVVLRQVWRSSLQJ7KH
'60%ZLOODOVREHFRQYHQHGWRUHYLHZDOODYDLODEOHGDWDLIRUPRUHRIWKHVWXG\OHYHO
VWRSSLQJUXOHVLVDUHPHWVHH6HFWLRQ
,IDQ\RIWKHVDIHW\VWRSSLQJUXOHVLVPHWRURWKHUVDIHW\FRQFHUQVDUHLGHQWLILHGDWWKHVH
UHYLHZVFRQWLQXDWLRQRIWKHVWXG\ZLWKRXWDOWHUDWLRQVKRXOGEHTXHVWLRQHGDVLWPD\EHDQ
HDUO\LQGLFDWLRQRIDQXQDFFHSWDEOHVDIHW\SURILOHLQWKHEURDGHUSRSXODWLRQ7KH'60%PD\
UHFRPPHQGDFKDQJHWRWKHSURWRFROWRDPHOLRUDWHDQ\VDIHW\FRQFHUQV
 2WKHU$QDO\VHV
$SRSXODWLRQ3.DQDO\VLVWRH[SORUHWKHUHODWLRQVKLSEHWZHHQWKH3.RIDSR$,DQG3&DQG
GHPRJUDSKLFDQGFOLQLFDOIHDWXUHVRIWKHVXEMHFWSRSXODWLRQZLOOEHGHWDLOHGDQGUHSRUWHG
VHSDUDWHO\





CCI
C
C
I

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 124 of 137 
CRD-TPL-077 
Confidential 
11. QUALITY ASSURANCE 
Before a site enrolls subjects, the Study Monitor will conduct a Site Initiation Visit. The 
purpose of the Site Initiation Visit is to provide the staff with training on the following: 
• Study protocol procedures to ensure high quality and consistent data collection 
• Maintenance of the Investigator site files 
• Responsibilities of site staff and Investigators, under ICH GCP, to ensure that the rights 
and well-being of subjects are protected. 
Representatives of the sponsor will visit all study sites periodically to assess the data quality, 
site conduct and study integrity. On site, they will review study data and directly compare 
them with source documents, discuss the conduct of the study with the Investigator, and 
verify that the facilities remain acceptable. Further information regarding data quality 
assurance is found in Section 13.5.2. 
The study may be subject to an audit by CSLB, an authorized representative(s) of CSLB, 
and/or inspections by an authorized regulatory authority (eg, US Food and Drug 
Administration [FDA]). Regulatory authorities may request access to all study 
documentation, including source documents for inspection and copying, in keeping with local 
regulations. CSLB will immediately notify the Investigator of an upcoming audit / inspection. 
In the event of an audit, all pertinent study-related documentation must be made available to 
the auditor(s). If an audit or inspection occurs, the Investigator at each study site will permit 
the auditor / inspector direct access to all relevant documents and allocate their time as well 
as the time of relevant staff to discuss the findings and any relevant issues. 
12. REGULATORY AND ETHICS CONSIDERATIONS 
12.1 REGULATORY CONSIDERATIONS 
CSLB or its agents will submit the appropriate documents to the local regulatory agencies 
and will await approval before study start. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 125 of 137 
CRD-TPL-077 
Confidential 
This study will be conducted under an FDA IND application and documented in accordance 
with the applicable regulatory guidelines and requirements. 
The procedures set out in this study protocol are designed to ensure that CSLB and the 
Investigator abide by the principles of the current ICH GCP guideline on the conduct, 
evaluation and documentation of this study, as described in ICH Topic E6 (Guideline for 
GCP). The study will also be carried out according to all applicable international and national 
regulatory requirements. 
12.2 Institutional Review Board / Independent Ethics Committee 
The Investigator must submit the protocol and ICFs for review by an authorized and properly 
constituted (according to local guidelines) IRB / IEC. Written approval must be received 
from the IRB / IEC before commencement of the study. 
12.3 SUBJECT INFORMATION AND INFORMED CONSENT 
The principles of informed consent in the Declaration of Helsinki must be implemented in 
this clinical study before protocol-specified procedures are carried out. Information should be 
given in both oral and written form whenever possible and deemed appropriate by the 
IRB / IEC. Subjects, their relatives (or if necessary, legally acceptable representatives) must 
be given ample opportunity to inquire about details of the study. 
Should there be any amendments to the protocol that would directly affect the subject’s 
participation in the study (eg, a change in any procedure), the ICF must be amended to 
incorporate this modification. Subjects must be informed of the change and they must sign 
the amended ICF indicating that they re-consent to participate in the study. 
12.4 SUBJECT IDENTIFICATION AND CONFIDENTIALITY 
All subject names and contact details will be kept confidential. Subjects will be identified 
throughout documentation and evaluation by the number allotted to them during the study.  
Each subject will be told that all study findings will be handled in the strictest confidence. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 126 of 137 
CRD-TPL-077 
Confidential 
The Investigator at the study site will be responsible for retaining sufficient information about 
each subject (eg, name, address, phone number and identity in the study) so that regulatory 
agencies or CSLB may access this information should the need arise. These records should be 
retained in a confidential manner as long as legally mandated according to local 
requirements. 
Subject medical records pertaining to the study may be inspected / audited at any time by 
CSLB employees or their duly authorized representatives, a regulatory authority or the 
IRB / IEC. All records accessed will be strictly confidential. Consent to participate in the 
study includes consent to these inspections / audits. 
12.5 INDEMNITY AND COMPENSATION 
It is CSLB policy that persons who participate in CSLB’s clinical studies should be no worse 
off for their having been involved in the study. These persons include the subjects / 
volunteers, the Investigator, the hospital and the IRB / IEC.   
CSLB has taken out insurance to cover its obligations under both the Indemnity and the 
Compensation guidelines for injury to subjects involved in the study. 
Other details regarding compensation and the obligations of the Investigator / CSLB are 
provided in the Clinical Trial Agreement for the study (see Section 13.1). 
13. ADMINISTRATIVE CONSIDERATIONS 
13.1 CLINICAL TRIAL AGREEMENT 
This study will be conducted under a Clinical Trial Agreement between CSLB (“Sponsor”) 
and the institution(s) representing the investigational study site(s) (“Authority”). Financial 
support to the investigational site(s) will be detailed in the Clinical Trial Agreement. The 
Clinical Trial Agreement must be signed before the commencement of the study and will 
clearly delineate the responsibilities and obligations of Investigator and CSLB, and will form 
the contractual basis under which the clinical study will be conducted.  

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 127 of 137 
CRD-TPL-077 
Confidential 
13.2 CLINICAL STUDY REGISTRATION AND RESULTS DISCLOSURE  
CSLB will provide the relevant study protocol information in public database(s) before or at 
commencement of the study. CSLB may also provide study information for inclusion in 
national registries according to local regulatory requirements. 
Results of this study will be disclosed according to the relevant regulatory requirements. All 
publications in peer-reviewed medical journals resulting from this study will be listed in the 
original study protocol registration record. 
13.3 IMPLEMENTATION OF THE PROTOCOL / PROTOCOL AMENDMENT(S) 
With the exception of medical emergencies, no changes or deviations in the conduct of the 
signed protocol will be permitted without documented approval of the CSLB Medical 
Monitor and the IRB / IEC. In the event of a medical emergency, the Investigator at the study 
site will institute any medical procedures deemed appropriate. However, all such procedures 
must be promptly reported to the CSLB Medical Monitor and the IRB / IEC.   
Modifications to the protocol that may affect subject safety or the way the study is to be 
conducted will be documented in a protocol amendment, which must be approved by the 
IRB / IEC.   
Administrative changes to the protocol, defined as minor corrections and / or clarifications 
that have no effect on the way the study is to be conducted, will not require IRB / IEC 
approval, but will be submitted to the IRB / IEC for their information. 
13.4 PROTOCOL DEVIATIONS 
All instances where the requirements of the study protocol were not complied with will be 
tracked. Corresponding subjects may be withdrawn from the study at the discretion of the 
Investigator and / or CSLB. Study protocol deviations arise when subjects who have been 
entered in the study deviate from the IRB / IEC -approved study protocol.  

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 128 of 137 
CRD-TPL-077 
Confidential 
If a major protocol deviation (ie, a deviation that could have a significant effect on the 
subject’s safety, rights, or welfare and / or on the integrity of the study data) occurs, the 
Investigator must notify CSLB and the appropriate IRB / IEC as soon as possible or as per 
local requirements.  
13.5 DOCUMENTATION AND RECORD KEEPING  
13.5.1 Data Collection 
The Investigator (or delegate) will maintain individual records for each subject. These 
records should include dates when a subject visited the study site, records of vital signs, 
medical history, or physical examinations, administration of investigational product or 
concomitant therapy, any AEs experienced, and other notes as appropriate. These records 
constitute source data.   
An eCRF will be provided by CSLB (or delegate) for each subject enrolled into the study. 
The Investigator is responsible for ensuring accurate and proper completion of the eCRF in a 
timely manner so that it always reflects the latest observations on the subjects enrolled in the 
study. All entries on the eCRF must be backed up by source data unless there is prior 
agreement that the eCRF is the source data.   
All source data will be kept according to all applicable regulatory requirements. Source data 
must be completed legibly for each subject enrolled into the study and signed by the 
Investigator (or delegate). 
13.5.2 Data Quality Assurance 
Data generated throughout the study will be monitored and the eCRFs checked against the 
subject records for completeness and accuracy. CSLB’s study monitor will perform this 
function. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 129 of 137 
CRD-TPL-077 
Confidential 
After completion of eCRF pages and entry of the data into a database, the data will be 
checked electronically for consistency and plausibility. Queries will be generated for 
questionable data and clarification sought from the Investigator. These data queries must be 
resolved in a timely manner by the Investigator (or delegate). 
13.5.3 Record Retention 
An investigator study file prepared by CSLB (or delegate), containing all applicable 
documents for use at the study site, will be made available to the Investigator before the start 
of the study. All study documentation and materials maintained in the investigator study file 
must be kept in conformance with applicable national laws and regulations.   
All study documentation and materials maintained in the investigator study file at the study 
site must be available for inspection by the CSLB’s study monitor (or delegate) to determine 
that all required documentation is present and correct.  
The study may be audited or inspected by qualified delegates from CSLB or a competent 
regulatory authority. 
After completion of the study, the Investigator is responsible for archiving the Investigator’s 
study file, the subject’s records and the source data according to applicable regulatory 
requirements.  
13.6 STUDY AND SITE CLOSURE 
CSLB reserves the right to prematurely discontinue or suspend the study either at a particular 
site or at all study sites at any time and for any reason. If such action is taken, the CSLB 
Study Monitor (or delegate) will discuss this with the Investigator at each study site at that 
time and notify the Investigators in writing. If the study is suspended or terminated for safety 
reasons, all Investigators, and the relevant regulatory agencies, will be immediately notified 
of the action as well as the reason for it. The Investigator at each study site will advise the 
IRB / IEC overseeing the study at their site. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 130 of 137 
CRD-TPL-077 
Confidential 
13.7 CLINICAL STUDY REPORT 
A clinical study report will be written after the completion of the study. CSLB or its agent 
will write the report in consultation with the Investigator or, if applicable, a nominated 
coordinating Investigator (or delegate). It is required by CSLB that the coordinating 
Investigator will sign the clinical study report.  
Progress reports may be provided to the relevant regulatory bodies in accordance with their 
requirements. 
13.8 USE OF DATA AND PUBLICATIONS 
The rights and obligations of Investigators and CSLB concerning any formal presentation or 
publication of data collected as a direct or indirect result of this study will be addressed 
specifically in the Clinical Trial Agreement for the study. 
14. REFERENCES 
Anderson WAD, Bethea WR. Renal lesions following administration of hypertonic solutions 
of sucrose. JAMA. 1940;114(20):1983–7. 
Bhandari S, Jain P. Management of acute coronary syndrome in chronic kidney disease. J 
Assoc Physicians India. 2012;60:48–51.  
Epstein JS, Zoon KC. Important drug warning: Immune Globulin Intravenous (human) 
(IGIV) products. Neonatal Network. 2000;19:60–2.  
Fox KAA, Dabbous OH, Goldberg RJ, et al. Prediction of risk of death and myocardial 
infarction in the six months after presentation with acute coronary syndrome: prospective 
multinational observational study (GRACE). BMJ. 2006;333:1091–4.  
Fox CS, Muntner P, Chen AY, et al. Use of evidence-based therapies in short-term outcomes 
of ST-segment elevation myocardial infarction and non–ST-segment elevation myocardial 
infarction in patients with chronic kidney disease: A report from the National Cardiovascular 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 131 of 137 
CRD-TPL-077 
Confidential 
Data Acute Coronary Treatment and Intervention Outcomes Network Registry. Circulation. 
2010;121:357–65.  
Gibson CM., Dumaine RL, Gelfand EV, et al. Association of glomerular filtration rate on 
presentation with subsequent mortality in non-ST-segment elevation acute coronary 
syndrome; observations in 13307 patients in five TIMI trials. Eur Heart J. 2004; 25:1998–
2005.  
Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation. July 
2009 http://www.fda.gov/downloads/Drugs/.../Guidances/UCM174090.pdf 
KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney International 
Supplements 2012; 2(1) doi:10.1038/kisup.2012.1 
www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO%20AKI%20Guideline.pdf 
Killip T, Kimball JT. Treatment of myocardial infarction  in a coronary care unit – a two year 
experience with 250 patients. Am J Cardiol. 1967;20:457–64. 
Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration 
rate. Ann Intern Med. 2009;150(9):604–12.  
Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular 
clinical trials. A consensus report from the Bleeding Academic Research Consortium. 
Circulation. 2011;123:2736–47.  
Nabais S, Rocha S, João C, et al. Prognostic impact of moderate renal dysfunction in acute 
coronary syndrome. Rev Port Cardiol. 2008;27(3):303–12.  
Remaley AT, Amar M, Sviridov D. HDL-replacement therapy: mechanism of action, types of 
agents and potential clinical indications. Expert Rev Cardiovasc Ther. 2008;6(9):1203-15.  
Stevens LA, Schmid CH, Greene T, et al. Comparative performance of the CKD 
epidemiology collaboration (CKD-EPI) and the modification of diet in renal disease (MDRD) 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 132 of 137 
CRD-TPL-077 
Confidential 
study equations for estimating GFR levels above 60 mL/minute/1.73 m2. American Journal of 
Kidney Diseases. 2010;56(3):486–95.  
Tall AR. An overview of reverse cholesterol transport. Eur Heart J. 1998;19:A31–5. 
Tardif JC, Gregoire J, L’Allier PL, et al. Effects of reconstituted high-density lipoprotein 
infusions on coronary atherosclerosis. JAMA. 2007; 297: (doi:10.1001/ 
jama.297.15.jpc70004).  
Tardif J-C, Heinonen T, Noble S. High-density lipoprotein/ apolipoprotein A-I infusion 
therapy. Current Atherosclerosis Reports. 2009;11:58–63.  
Thygesen K, Alpert J, Jaffe A, . et al. Third Universal Definition of Myocardial Infarction. 
Circulation. 2012;126:2020–35.  
Tsai TT, Patel UD, Chang TL, et al.. Contemporary incidence, predictors, and outcomes of 
acute kidneyi in patients undergoing percutaneous coronary interventions: insights from the 
NCDR Cath-PCI Registry. J Am Coll Cardiol Intv. 2014;7:1–9. 
 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 133 of 137 
CRD-TPL-077 
Confidential 
 
Appendix I:Calculation of Estimated Glomerular Filtration Rate by the 
Chronic Kidney Disease Epidemiology Collaboration Equation 
 
eGFR = 141 X min(Scr/κ,1)α X max(Scr/κ,1)-1.209 X 0.993Age X 1.018 [if female] X 1.159 
[if black]) or if subject is receiving dialysis (Levey et al, 2009; Stevens et al, 2010) 
An eGFR calculator can be found on the National Kidney Foundation’s website at the 
following address: http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm 
Estimated glomerular filtration rate will be determined automatically via IRT at the 
randomization visit. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 134 of 137 
CRD-TPL-077 
Confidential 
 
Appendix II: 
Third Universal Definition of Myocardial Infarction 
 
 
Reference: 
Thygesen K, Alpert J, Jaffe A, et al. Third Universal Definition of Myocardial Infarction. Circulation. 
2012;126:2020-35. 

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 135 of 137 
CRD-TPL-077 
Confidential 
 
Appendix III: 
 
Killip Classification 
 
• 
Killip class I includes individuals with no clinical signs of heart failure. 
• 
Killip class II includes individuals with rales or crackles in the lungs, an S3 heart 
sound, and elevated jugular venous pressure. 
• 
Killip class III describes individuals with frank pulmonary edema. 
• 
Killip class IV describes individuals in cardiogenic shock or hypotension (measured 
as systolic blood pressure lower than 90 mmHg), and evidence of peripheral 
vasoconstriction (oliguria, cyanosis or sweating). 
Reference:   
Killip T, Kimball JT. Treatment of myocardial infarction  in a coronary care unit – a two year experience with 
250 patients. Am J Cardiol. 1967;20:457-64.

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 136 of 137 
CRD-TPL-077 
Confidential 
 
Appendix IV: 
Assessment of Bleeding Events by Bleeding Academic 
Research Consortium (BARC) Definition for Bleeding 
Type 0: no bleeding 
Type 1: bleeding that is not actionable and does not cause the patient to seek unscheduled performance of 
studies, hospitalization, or treatment by a healthcare professional; may include episodes leading to self-
discontinuation of medical therapy by the patient without consulting a healthcare professional 
Type 2: any overt, actionable sign of hemorrhage (eg, more bleeding than would be expected for a clinical 
circumstance, including bleeding found by imaging alone) that does not fit the criteria for type 3, 4, or 5 but 
does meet at least 1 of the following criteria: (1) requiring nonsurgical, medical intervention by a healthcare 
professional, (2) leading to hospitalization or increased level of care, or (3) prompting evaluation 
Type 3 
Type 3a  
• 
Overt bleeding plus hemoglobin drop of 3 to < 5 g/dLa (provided hemoglobin drop is related to 
bleed)  
• 
Any transfusion with overt bleeding 
Type 3b  
• 
Overt bleeding plus hemoglobin drop ≥ 5 g/dLa (provided hemoglobin drop is related to 
bleed)  
• 
Cardiac tamponade  
• 
Bleeding requiring surgical intervention for control (excluding 
dental/nasal/skin/hemorrhoid)  
• 
Bleeding requiring intravenous vasoactive agents 
Type 3c  
• 
Intracranial hemorrhage (does not include microbleeds or hemorrhagic transformation, does 
include intraspinal)  
Subcategories confirmed by autopsy or imaging or lumbar puncture  
• 
Intraocular bleed compromising vision 
Type 4: CABG-related bleeding : 
• 
Perioperative intracranial bleeding within 48 h  
• 
Reoperation after closure of sternotomy for the purpose of controlling bleeding  
• 
Transfusion of ≥5 U whole blood or PRBCs within a 48-h periodb  
• 
Chest tube output ≥2L within a 24-h period 
Type 5: fatal bleeding 
Type 5a  
Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious 
Type 5b  
Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation 
CABG = coronary artery bypass graft h = hour; PRBCs = packed red blood cells  
a. 
Corrected for transfusion (1 U PRBCs or 1 U whole blood = 1 g/dL hemoglobin).  
b. 
Cell saver products are not counted. 
NOTE: Platelet transfusions should be recorded and reported but are not included in these definitions until 
further information is obtained about the relationship to outcomes.  If a CABG-related bleed is not adjudicated 
as at least a type 3 severity event, it will be classified as not a bleeding event. If a bleeding event occurs with a 
clear temporal relationship to CABG (ie, within a 48-h time frame) but does not meet type 4 severity criteria, it 
will be classified as not a bleeding event.  

 
Study Number: 
CSL112_2001_Am1 
Study Product: 
CSL112 
 
Final V2.0  
6 June 2016 
Page 137 of 137 
CRD-TPL-077 
Confidential 
 
 
Reference:  
Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials. A 
consensus report from the Bleeding Academic Research Consortium. Circulation. 2011;123:2736-47.