A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-groupStudy to Investigate the Safety and Tolerability of Multiple Dose Administration of CSL112 in Subjects with Moderate Renal Impairment and Acute Myocardial Infarction

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
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 precontrast
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
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.

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)
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:
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