Clinical Research Details

A Phase 3, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Investigate the Efficacy and Safety of CSL112 in Subjects with Acute Coronary Syndrome –the AEGIS-II Study

Study Description

The purpose of this study is to find out how effective and safe CSL112 is at reducing the risk of dying from heart related events, having another heart attack, or having a stroke.

If you agree to join the study, screening tests will be performed while you are in the hospital to assess your eligibility for the study. If you are eligible to take part in the study, you will be randomized to receive either the study drug or placebo. “Randomized” means that you will be assigned by chance, like flipping a coin, to take the study drug (CSL112) or the placebo. You will have a 50/50 chance of receiving either CSL112 or placebo.

Inclusion/Exclusion Criteria


1. Capable of providing written informed consent and willing and able to adhere to all
protocol requirements.
2. Male or female at least 18 years of age at the time of providing written informed consent.
3. Evidence of myocardial necrosis in a clinical setting consistent with type 1 (spontaneous)
MI (STEMI or NSTEMI) caused by atherothrombotic coronary artery disease (4th
Universal Definition of MI [Thygesen et al, 2019]) 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.

b. Any 1 or more of the following:
i. Symptoms of acute myocardial ischemia (ie, resulting from a primary coronary
artery event).
ii. New (or presumably new) significant ST/T wave changes or left bundle branch
iii. Development of pathological Q waves on electrocardiogram.
iv. Imaging evidence of new loss of viable myocardium or regional wall motion
abnormality in a pattern consistent with an ischemic etiology.
v. Identification of intracoronary thrombus by angiography.
Note: Electrocardiograms obtained as part of standard of care can be used to support or
confirm the index MI.
4. No suspicion of AKI at least 12 hours after IV contrast agent administration (subjects
who have undergone angiography) or after FMC for the index MI (subjects who have not
undergone angiography). There must be documented evidence of stable renal function
defined as no more than an increase in serum creatinine < 0.3 mg/dL (27 μmol/L) from
pre-contrast serum creatinine value.
5. Evidence of multivessel coronary artery disease defined as meeting 1 or more of the
following criteria:
a. At least 50% stenosis of the left main coronary artery or at least 2 epicardial coronary
artery territories (left anterior descending, left circumflex, right coronary artery) on
catheterization performed during the index hospitalization.
b. Prior cardiac catheterization documenting at least 50% stenosis of the left main
coronary artery or at least 2 epicardial coronary artery territories (left anterior
descending, left circumflex, right coronary artery).
c. Prior PCI and evidence of at least 50% stenosis of at least 1 epicardial coronary artery
territory different from prior revascularized artery territory.
d. Prior multivessel coronary artery bypass grafting.
6. Presence of established cardiovascular risk factor(s), defined as:
a. Diabetes mellitus on pharmacotherapy.
b. 2 or more of the following:

i. Age ≥ 65 years.
ii. Prior history of MI.
iii. Peripheral arterial disease defined as meeting at least 1 of the following criteria:
1. Current intermittent claudication or resting limb ischemia AND an ankle
brachial index ≤ 0.90.
2. History of peripheral revascularization (surgical or percutaneous).
3. History of limb amputation due to peripheral arterial disease.
4. Angiographic evidence (using computed tomographic angiography, magnetic
resonance angiography, or invasive angiography) of a peripheral artery
stenosis ≥ 50%.
7. Female subjects must be postmenopausal or with a negative urine pregnancy test prior to
randomization. If the urine test cannot be confirmed as negative, a serum pregnancy test
will be required. This pregnancy test must be negative for the subject to be eligible.
a. Postmenopausal status is defined as subjects over the age of 60 years, subjects
aged 45 to 60 years (inclusive) with amenorrhea for at least 1 year with
documented evidence of follicle-stimulating hormone level > 30 IU/L, or
subjects who are surgically sterile for at least 3 months before randomization.
If the follicle-stimulating hormone value is not available prior to
randomization, a urine pregnancy test is required.
b. Females of childbearing potential must be willing to use an acceptable method
of contraception to avoid pregnancy while receiving treatment with CSL112
(ie, during the Active Treatment Period) and for 30 days after receipt of the
last dose of investigational product; and, if currently breastfeeding a child,
willing to cease breastfeeding.
NOTE: Acceptable methods of contraception are:
i. 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, postovulation methods),
withdrawal (coitus interruptus), spermicides only, and lactational
amenorrhoea method are not acceptable definitions of abstinence.
ii. Surgical sterilization (more than 3 months before randomization) of
subject or subject's partner.

iii. Use of intrauterine device (placed more than 3 months before
iv. Injectable combined hormonal or contraceptive medication implant
v. Injectable single hormone, oral hormonal contraceptive (eg, combined
or progesterone only), contraceptive medication patch, or
estrogen/progestin vaginal ring plus an acceptable barrier method as
outlined below.
Acceptable barrier methods include: female or male condoms, with spermicidal
foam or spermicidal jelly, or diaphragm, with spermicidal foam or spermicidal
jelly, all of which must be used with an additional method of contraception
outlined above. Female condom and male condom should not be used together.
8. Investigator believes that the subject is willing and able to adhere to all protocol
9. Willing to not participate in another investigational study until completion of their final
study visit.



1. Ongoing hemodynamic instability defined as any of the following:
a. A history of New York Heart Association Class III or IV HF within the last year.
b. Killip Class III or IV.
c. Sustained and / or symptomatic hypotension (systolic blood pressure < 90 mmHg).
d. Known left ventricular ejection fraction < 30%.
2. Evidence of hepatobiliary disease as indicated by any 1 or more of the following at
a. Current active hepatic dysfunction or active biliary obstruction.
b. Chronic or prior history of cirrhosis or of infectious / inflammatory hepatitis.

Note: If a subject has a 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 negative).
c. ALT > 3 × upper limit of normal (ULN) or total bilirubin > 2 × ULN at time of
randomization. Subjects with a known or suspected history of Gilbert's syndrome are
not eligible for study participation if their direct bilirubin is > 2 × ULN.
3. Evidence of severe chronic kidney disease with an estimated glomerular filtration rate of
< 30 mL/min/1.73 m2 (as calculated by the Chronic Kidney Disease Epidemiology
Collaboration equation) [Levey et al, 2009; Stevens et al, 2010] or if subject is receiving
4. Plan to undergo scheduled coronary artery bypass graft surgery as treatment for the index
5. Body weight < 50 kg.
6. Known history of allergies, hypersensitivity, or deficiencies as follows:
a. Allergy to soy bean or peanuts (Section 7.1)
b. Known or suspected hypersensitivity to the investigational product, or to any
excipients of the investigational product or placebo (albumin) (Section 5.1.1 and
Section 5.1.2, respectively).
c. A known history of IgA deficiency or antibodies to IgA.
7. 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 at the time of
b. Women who are pregnant or breastfeeding at the time of randomization.
c. Participated in another interventional clinical study within 30 days of consent or has
plans to participate in another interventional clinical study at the time of consent.
d. Known 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) is permissible. Hormonal therapy or anti-hormonal therapy is
also allowed; however, a subject’s life expectancy must be > 24 months at the time of
f. Previously randomized or participated 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 through end of the study,
and / or unwilling to allow review of medical records in accordance with local
regulatory requirements at time of consent.
j. Investigator determines that the subject is not suitable for study participation for any
other reason.
8. Involved in the planning and / or conduct of the study (applies to CSLB staff, staff at the
study site, and third-party vendors).