Clinical Trials List
Protocol NumberCSL112_3001
NCT Number(ClinicalTrials.gov Identfier)NCT03473223
2018-03-20 - 2024-03-31
Phase III
Recruiting7
Terminated3
ICD-10I20.0
Unstable angina
ICD-9411.1
Intermediate coronary syndrome
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
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Trial Applicant
COVANCE TAIWAN SERVICES LIMITED
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Sponsor
CSL Behring LLC
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
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The Actual Total Number of Participants Enrolled
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The Actual Total Number of Participants Enrolled
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The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Shih-Sheng Chang 未分科
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Completed
The Actual Total Number of Participants Enrolled
0 Completed
The Actual Total Number of Participants Enrolled
0 Completed
Condition/Disease
Acute Coronary Syndrome
Objectives
Primary Objective(s)
The primary objective of this study is to evaluate the efficacy of
CSL112 on reducing the risk of MACE (CV death, MI, or stroke) from
the time of randomization through 90 days in subjects with ACS
(diagnosed with STEMI or NSTEMI).
Key Secondary Objective(s)
1. To evaluate the efficacy of CSL112 on reducing the total number
of hospitalizations for coronary, cerebral, or peripheral ischemia.
2. To evaluate the efficacy of CSL112 on reducing the risk of MACE
(CV death, MI, or stroke) through 180 and 365 days in subjects
with ACS (diagnosed with STEMI or NSTEMI).
Other Secondary Objectives
1. To further evaluate the efficacy of CSL112 on reducing the risk of
MACE (CV death, MI, or stroke) and all-cause death in subjects
with ACS (diagnosed with STEMI or NSTEMI).
2. To evaluate the safety of CSL112 in subjects with ACS (diagnosed
with STEMI or NSTEMI).
Test Drug
CSL112
Active Ingredient
Apolipoprotein A-I [ApoA-I]
Dosage Form
injection
Dosage
2g
Endpoints
Primary Endpoint(s)
The primary endpoint is the time to first occurrence of any component
of the composite MACE, defined as CV death, MI, or stroke from the
time of randomization through 90 days.
Key Secondary Endpoint(s)
1. Total number of hospitalizations for coronary, cerebral, or
peripheral ischemia from the time of randomization through
90 days.
2. Time to first occurrence of CV death, MI, or stroke from the time
of randomization through 180 days.
3. Time to first occurrence of CV death, MI, or stroke from the time
of randomization through 365 days.
Other Secondary Endpoints
1. The time to first occurrence of each individual component of the
composite primary efficacy endpoint from the time of
randomization through 90 days:
• CV death.
• MI.
• Stroke.
2. Time to occurrence of all-cause death from the time of
randomization through 365 days
The primary endpoint is the time to first occurrence of any component
of the composite MACE, defined as CV death, MI, or stroke from the
time of randomization through 90 days.
Key Secondary Endpoint(s)
1. Total number of hospitalizations for coronary, cerebral, or
peripheral ischemia from the time of randomization through
90 days.
2. Time to first occurrence of CV death, MI, or stroke from the time
of randomization through 180 days.
3. Time to first occurrence of CV death, MI, or stroke from the time
of randomization through 365 days.
Other Secondary Endpoints
1. The time to first occurrence of each individual component of the
composite primary efficacy endpoint from the time of
randomization through 90 days:
• CV death.
• MI.
• Stroke.
2. Time to occurrence of all-cause death from the time of
randomization through 365 days
Inclution Criteria
Inclusion Criteria
To be enrolled into the study, subjects must meet all of the following inclusion 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 I (spontaneous)
MI 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 (ie, resulting from a primary coronary artery event).
ii. New (or presumably new) significant ST/T wave changes or left bundle branch block.
iii. Development of pathological Q waves on electrocardiogram.
iv. Imaging evidence of new loss of viable myocardium or regional wall motion abnormality.
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 on > 1 epicardial artery or left main artery on catheterization
performed during the index hospitalization.
b. Prior cardiac catheterization with at least 50% stenosis on > 1 epicardial artery or left main artery.
c. Prior PCI and evidence of at least 50% stenosis of at least 1 epicardial artery different
from prior revascularized artery.
d. Prior multivessel coronary artery bypass grafting.
6. At least 1 of the following established risk factors:
a. Age ≥ 65 years.
b. Prior history of MI.
c. On pharmacological treatment for diabetes mellitus.
d. Peripheral arterial disease defined as meeting at least 1 of the following criteria:
i. Current intermittent claudication or resting limb ischemia AND an ankle brachial index ≤ 0.90.
ii. History of peripheral revascularization (surgical or percutaneous).
iii. History of limb amputation due to peripheral arterial disease.
iv. 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 during the study and for 30 days after receipt of the
last dose of investigational product; and, if currently breastfeeding a child, willing to cease breastfeeding.
8. Investigator believes that the subject is willing and able to adhere to all protocol requirements.
9. Willing to not participate in another investigational study until completion of their final study visit.
To be enrolled into the study, subjects must meet all of the following inclusion 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 I (spontaneous)
MI 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 (ie, resulting from a primary coronary artery event).
ii. New (or presumably new) significant ST/T wave changes or left bundle branch block.
iii. Development of pathological Q waves on electrocardiogram.
iv. Imaging evidence of new loss of viable myocardium or regional wall motion abnormality.
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 on > 1 epicardial artery or left main artery on catheterization
performed during the index hospitalization.
b. Prior cardiac catheterization with at least 50% stenosis on > 1 epicardial artery or left main artery.
c. Prior PCI and evidence of at least 50% stenosis of at least 1 epicardial artery different
from prior revascularized artery.
d. Prior multivessel coronary artery bypass grafting.
6. At least 1 of the following established risk factors:
a. Age ≥ 65 years.
b. Prior history of MI.
c. On pharmacological treatment for diabetes mellitus.
d. Peripheral arterial disease defined as meeting at least 1 of the following criteria:
i. Current intermittent claudication or resting limb ischemia AND an ankle brachial index ≤ 0.90.
ii. History of peripheral revascularization (surgical or percutaneous).
iii. History of limb amputation due to peripheral arterial disease.
iv. 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 during the study and for 30 days after receipt of the
last dose of investigational product; and, if currently breastfeeding a child, willing to cease breastfeeding.
8. Investigator believes that the subject is willing and able to adhere to all protocol requirements.
9. Willing to not participate in another investigational study until completion of their final study visit.
Exclusion Criteria
Exclusion Criteria
Subjects must not be enrolled into the study if they meet any of the following exclusion
criteria:
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
screening:
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
dialysis.
4. Plan to undergo scheduled coronary artery bypass graft surgery after randomization, as
determined at the time of screening.
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
consent.
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 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
consent.
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).
Subjects must not be enrolled into the study if they meet any of the following exclusion
criteria:
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
screening:
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
dialysis.
4. Plan to undergo scheduled coronary artery bypass graft surgery after randomization, as
determined at the time of screening.
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
consent.
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 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
consent.
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).
The Estimated Number of Participants
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Taiwan
200 participants
-
Global
17400 participants
