Study to Investigate CSL112 in Subjects With Acute Coronary Syndrome

Overview

About this study

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 - cardiovascular (CV) death, myocardial infarction (MI), and stroke] in subjects with acute coronary syndrome (ACS) diagnosed with either ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI), including those managed with percutaneous coronary intervention (PCI) or medically managed.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Male or female least 18 years of age.
  • Capable of providing written informed consent and willing and able to adhere to all protocol requirements.
  • 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:
    • 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 acute myocardial ischemia (ie, resulting from a primary coronary artery event);
      • New (or presumably new) significant ST/T wave changes or left bundle branch block;
      • Development of pathological Q waves on electrocardiogram;
      • Imaging evidence of new loss of viable myocardium or regional wall motion abnormality in a pattern consistent with an ischemic etiology;
      • 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.
  • 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.
  • Evidence of multivessel coronary artery disease defined as meeting 1 or more of the following criteria:
    • 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;
    • 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);
    • Prior PCI and evidence of at least 50% stenosis of at least 1 epicardial coronary artery territory different from prior revascularized artery territory;
    • Prior multivessel coronary artery bypass grafting.
  • Presence of established cardiovascular risk factor(s), defined as:
    • Diabetes mellitus on pharmacotherapy; OR
    • 2 or more of the following:
      • Age ≥ 65 years;
      • Prior history of MI;
      • Peripheral arterial disease defined as meeting at least 1 of the following criteria:
        • Current intermittent claudication or resting limb ischemia AND an ankle brachial index ≤ 0.90;
        • History of peripheral revascularization (surgical or percutaneous);
        • History of limb amputation due to peripheral arterial disease;
        • 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.
  • 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.
  • Females of childbearing potential must be willing to use an acceptable method of contraception to avoid pregnancy while receiving treatment with CSL112 (i.e., during the Active Treatment Period) and for 30 days after receipt of the last dose of investigational product; and, if currently breastfeeding achild, willing to cease breastfeeding.
    • NOTE: Acceptable methods of contraception are:
      • 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.
      • Surgical sterilization (more than 3 months before randomization) of subject or subject's partner.
      • Use of intrauterine device (placed more than 3 months before randomization).
      • Injectable combined hormonal or contraceptive medication implant alone.
      • Injectable single hormone, oral hormonal contraceptive (e.g., 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.
  • Investigator believes that the subject is willing and able to adhere to all protocol requirements.
  • Willing to not participate in another investigational study until completion of their final study visit.

Exclusion Criteria:  

  • Ongoing hemodynamic instability defined as  any of the following:
    • A history of New York Heart Association Class III or IV HF within the last year;
    • Killip Class III or IV;
    • Sustained and / or symptomatic hypotension (systolic blood pressure < 90 mmHg);
    • Known left ventricular ejection fraction < 30%.
  • Evidence of hepatobiliary disease as indicated by any 1 or more of the following at screening:
    • Current active hepatic dysfunction or active biliary obstruction;
    • 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 (i.e, antigen negative).
    • 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.
  • Evidence of severe chronic kidney disease with an estimated glomerular filtration rate of < 30 mL/min/1.73 m^2 (as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation) [Levey et al, 2009; Stevens et al, 2010] or if subject is receiving dialysis.
  • Plan to undergo scheduled coronary artery bypass graft surgery as treatment for the index MI.
  • Body weight < 50 kg.
  • Known history of allergies, hypersensitivity, or deficiencies as follows:
    • Allergy to soy bean or peanuts;
    • Known or suspected hypersensitivity to the investigational product, or to any excipients of the investigational product or placebo (albumin);
    • A known history of IgA deficiency or antibodies to IgA.
  • 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 comorbid condition with an estimated life expectancy of ≤ 6 months at the time of consent.
    • Women who are pregnant or breastfeeding at the time of randomization.
    • 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.
    • Known alcohol, drug, or medication abuse within 1 year before consent to this 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 (e.g., hematologic) must be documented in the source document.
      • NOTE: Use of low-dose chemotherapy for treatment of a condition other than cancer (e.g., 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.
    • Previously randomized or participated in this study or previously exposed to CSL112.
    • 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.
    • Subjects who are incarcerated, including prisoners or subjects compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
    • 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.
    • Investigator determines that the subject is not suitable for study participation for any other reason.
  • Involved in the planning and / or conduct of the study (applies to CSLB staff, staff at the study site, and third-party vendors).

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

F Fortuin, M.D.

Open for enrollment

Contact information:

Sarah Kirkland R.N.

(480)342-2479

Kirkland.Sarah@mayo.edu

More information

Publications

Publications are currently not available
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CLS-20442904

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