Study to Investigate CSL112 in Subjects With ACS
Study Details
Study Description
Brief Summary
Acute coronary syndrome is a life-threatening condition, which 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, MI, or sudden death. Even after recovery from an acute episode of ACS, patients continue to be at heightened risk.
CSL112 is a novel formulation of apoA-I, the major functional component of high-density lipoprotein. This is a phase 3, multicenter, double-blind, randomized,placebo-controlled, parallel-group study to evaluate the efficacy and safety of CSL112 on reducing the risk of major adverse CV events (MACE) in subjects with ACS (diagnosed with STEMI or NSTEMI), who are receiving evidence-based medical therapy. Subjects will be randomized 1:1 to 1 of 2 treatment groups (CSL112 6 g or placebo). Randomization at baseline will be stratified by subjects' index MI type (STEMI vs NSTEMI), management of the index MI (PCI vs medically managed), and region (North America, Latin America, Western Europe, Central and Eastern Europe, or Asia Pacific).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment
|
Drug: CSL112
CSL112 is a novel formulation of apoA-I, the major functional component of high-density lipoprotein. It is purified from human plasma, formulated to deliver exogenous apoA-I. Apolipoprotein A-I is formulated with phosphatidylcholine (PC) and stabilized with sucrose and cholate as excipients. (dose 6 g; approximately 170 mL)
|
| Placebo Comparator: Placebo
|
Drug: Placebo
30 mL of 25% albumin solution diluted with 140 mL dextrose 5% in water
|
Outcome Measures
Primary Outcome Measures
- Time to first MACE event [90 days]
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. The primary endpoint will include all MIs.
Secondary Outcome Measures
- Risk of MACE [365 days]
To evaluate the efficacy of CSL112 on reducing the total number of hospitalizations for coronary, cerebral, or peripheral ischemia and 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).
- Risk of all cause death [365 days]
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).
- Safety of CSL112 in terms of patient death [365 days]
Time to occurrence of all-cause death from the time of randomization through 365 days.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Capable of providing written informed consent and willing and able to adhere to all protocol requirements
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Male or female at least 18 years of age at the time of providing written informed consent
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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:
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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
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Any 1 or more of the following:
- 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 block. 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.
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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.
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Evidence of multivessel coronary artery disease defined as meeting 1 or more of the following criteria:
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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.
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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).
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Prior PCI and evidence of at least 50% stenosis of at least 1 epicardial coronary artery territory different from prior revascularized artery territory.
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Prior multivessel coronary artery bypass grafting.
- Presence of established cardiovascular risk factor(s), defined as:
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Diabetes mellitus on pharmacotherapy. OR
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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:
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Current intermittent claudication or resting limb ischemia AND an ankle brachial index ≤ 0.90.
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History of peripheral revascularization (surgical or percutaneous).
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History of limb amputation due to peripheral arterial disease.
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Angiographic evidence (using computed tomographic angiography, magnetic resonance angiography, or invasive angiography) of a peripheral artery stenosis ≥ 50%.
- 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.
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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.
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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.
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Investigator believes that the subject is willing and able to adhere to all protocol requirements.
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Willing to not participate in another investigational study until completion of their final study visit
Exclusion Criteria:
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- Ongoing hemodynamic instability defined as any of the following:
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A history of New York Heart Association Class III or IV HF within the last year.
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Killip Class III or IV.
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Sustained and / or symptomatic hypotension (systolic blood pressure < 90 mmHg).
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Known left ventricular ejection fraction < 30%.
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- Evidence of hepatobiliary disease as indicated by any 1 or more of the following at screening:
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Current active hepatic dysfunction or active biliary obstruction.
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Chronic or prior history of cirrhosis or of infectious / inflammatory hepatitis.
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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.
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- 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) or if subject is receiving dialysis.
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4.Plan to undergo scheduled coronary artery bypass graft surgery as treatment for the index MI.
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- Body weight < 50 kg.
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- Known history of allergies, hypersensitivity, or deficiencies as follows:
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Allergy to soy bean or peanuts (Section 7.1)
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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).
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A known history of IgA deficiency or antibodies to IgA.
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- Other severe comorbid condition, concurrent medication, or other issue that renders the subject unsuitable for participation in the study, including but not limited to:
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A comorbid condition with an estimated life expectancy of ≤ 6 months at the time of consent.
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Women who are pregnant or breastfeeding at the time of randomization.
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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.
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Known alcohol, drug, or medication abuse within 1 year before consent to this study.
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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.
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Previously randomized or participated in this study or previously exposed to CSL112.
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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.
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Subjects who are incarcerated, including prisoners or subjects compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
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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.
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Investigator determines that the subject is not suitable for study participation for any other reason.
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- Involved in the planning and / or conduct of the study (applies to CSLB staff, staff at the study site, and third-party vendors).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Chinese University of Hong Kong | Shatin | Hong Kong | 999077 |
Sponsors and Collaborators
- Chinese University of Hong Kong
Investigators
- Principal Investigator: Bryan Yan, Chinese University of Hong Kong
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2018.442