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Completed

NCT Number: NCT02108262

A Phase 2b Study of CSL112 in Subjects With Acute Myocardial Infarction.

This is a multicenter randomized, double-blind, placebo-controlled, parallel-group, dose-ranging phase 2b study to investigate the hepatic and renal safety and tolerability of multiple dose administration of two dose levels of CSL112 compared with placebo in subjects with acute myocardial infarction (AMI).

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Key information

Conditions

Acute Myocardial Infarction

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Study Site 10002, Herston, Queensland, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Men or women, at least 18 years of age, with evidence of myocardial necrosis in a clinical setting consistent with a type I (spontaneous) acute myocardial infarction (AMI), in the last week.

Exclusion criteria

  • Ongoing hemodynamic instability
  • Evidence of hepatobiliary disease
  • Evidence of chronic kidney disease (CKD) (Stage III, IV, or V), defined as moderate or severe renal impairment or if subject is receiving dialysis
  • Evidence of unstable renal function
  • History of acute kidney injury after previous exposure to an intravenous contrast agent.
  • Known history of allergies, hypersensitivity or deficiencies to CSL112 or any of its components
  • Other severe comorbid condition, concurrent medication, or other issue that renders the subject unsuitable for participation in the study

Treatment and study plan

CSL112

Biological

CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.

Placebo

Biological

0.9% weight/volume sodium chloride solution (ie, normal saline)

Primary outcomes

  1. Percent of Participants With Clinically Important Change in Drug-induced Liver Injury

    Time frame: From baseline (before first infusion) to Day 29.

    A clinically important change in drug-induced liver injury is defined as a change (from baseline) in alanine aminotransferase (ALT) greater than 3 times the upper limit of normal (ULN) or a change in total bilirubin greater than 2 times ULN, that is confirmed upon repeat measurement.

  2. Percent of Participants With Clinically Important Change in Renal Status

    Time frame: From baseline (before first infusion) to Day 29.

    A clinically important change in renal status is defined as a serum creatinine (Cr) increase to ≥ 1.5 x the baseline value that is confirmed upon repeat measurement.

Secondary outcomes

  1. The Percentage of Participants With a Time-to-first Major Adverse Cardiovascular Event (MACE)

    Time frame: From the start of the first infusion up to approximately 382 days

    The MACE is a 4-component composite comprised of the time to the first of the following events: CV death, nonfatal myocardial infarction, ischemic stroke (non-hemorrhagic), and hospitalization for unstable angina.

  2. Change From Baseline in Concentrations of Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) at End of First Infusion for All Participants

    Time frame: Before first infusion and end of first infusion

    Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) are analytes of CSL112

  3. Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for All Participants

    Time frame: Before first infusion and end of fourth infusion

  4. Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion and end of first infusion

    apoA-I and PC are analytes of CSL112

  5. Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion and end of fourth infusion

    apoA-I and PC are analytes of CSL112

  6. Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion and end of first infusion

    apoA-I and PC are analytes of CSL112

  7. Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion and end of fourth infusion

    apoA-I and PC are analytes of CSL112

  8. Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for All Participants

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

    Cmax is the maximal plasma concentration.

  9. Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for All Participants

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

    Cmax is the maximal plasma concentration.

  10. Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

    Cmax is the maximal plasma concentration.

  11. Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

    Cmax is the maximal plasma concentration.

  12. Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

    Cmax is the maximal plasma concentration.

  13. Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

    Cmax is the maximal plasma concentration.

  14. Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for All Participants

    Time frame: Before and for 7 days after the first infusion

    Tmax is time to maximal plasma concentration

  15. Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for All Participants

    Time frame: Before and for 7 days after the fourth infusion

    Tmax is time to maximal plasma concentration

  16. Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function

    Time frame: Before and for 7 days after the first infusion

    Tmax is time to maximal plasma concentration

  17. Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function

    Time frame: Before and for 7 days after the fourth infusion

    Tmax is time to maximal plasma concentration

  18. Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment

    Time frame: Before and for 7 days after the first infusion

    Tmax is time to maximal plasma concentration

  19. Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment

    Time frame: Before and for 7 days after the fourth infusion

    Tmax is time to maximal plasma concentration

  20. Change From Baseline in Plasma Area Under the Curve (AUC) AUC0 - Last for apoA-I and PC After First Infusion for All Participants

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

    Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline [AUC0 - last]

  21. Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for All Participants

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

    Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline [AUC0 - last]

  22. Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

    Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline [AUC0 - last]

  23. Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

    Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline [AUC0 - last]

  24. Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Subjects With Mild Renal Impairment

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

    Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline [AUC0 - last]

  25. Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

    Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline [AUC0 - last]

  26. Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

    AUC from baseline to time point t (AUC0-t)

  27. Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

    AUC from baseline to time point t (AUC0-t)

  28. Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

    AUC from baseline to time point t (AUC0-t)

  29. Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

    AUC from baseline to time point t (AUC0-t)

  30. Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

    AUC from baseline to time point t (AUC0-t)

  31. Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

    AUC from baseline to time point t (AUC0-t)

  32. Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for All Participants

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

    AUC0-∞ is plasma area under the curve (AUC0-infinity)

  33. Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for All Participants

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

    AUC0-∞ is plasma area under the curve (AUC0-infinity)

  34. Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

    AUC0-∞ is plasma area under the curve (AUC0-infinity)

  35. Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

    AUC0-∞ is plasma area under the curve (AUC0-infinity)

  36. Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

    AUC0-∞ is plasma area under the curve (AUC0-infinity)

  37. Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

    AUC0-∞ is plasma area under the curve (AUC0-infinity)

  38. Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for All Participants

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

  39. Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for All Participants

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

  40. Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

  41. Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

  42. Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

  43. Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

  44. Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for All Participants

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

  45. Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for All Participants

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

  46. Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

  47. Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

  48. Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

  49. Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

  50. Change From Baseline in Plasma Volume of Distribution at Steady State (Vss) for apoA-I and PC After First Infusion for All Participants

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

  51. Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for All Participants

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

  52. Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

  53. Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

  54. Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion

  55. Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment

    Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

  56. Percent of Participants With the Occurrence of Suspected Adverse Drug Reactions

    Time frame: From the start of first infusion, up to approximately Day 382

    The overall percentage of subjects:

    • with adverse events (AEs), including local tolerability events, that begin during or within 1 hour of an infusion; or
    • with AEs considered to be causally related to the test product; or
    • who experience an AE for which the incidence rate in an active treatment arm exceeds the exposure-adjusted incidence rate in the placebo arm by 30% or more, provided the difference in incidence rates is 1% or more.

  57. Percent of Participants With Any Adverse Event (AE)

    Time frame: From the start of first infusion, up to approximately Day 382

  58. Percent of Participants Who Experience Bleeding Events

    Time frame: From the start of first infusion, up to approximately Day 112

    The number of subjects who experience bleeding events as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al, 2011)

  59. Change From Baseline in Serum Antibodies to CSL112 and apoA-I

    Time frame: Before first infusion, up to approximately Day 112

  60. Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19

    Time frame: Study Day 112

  61. Number of Participants With Parvovirus B19 DNA in Serum

    Time frame: Study Day 112

Sponsors and collaborators

Lead sponsor

CSL Behring

Industry

Registry information

Official study title

A Phase 2b, Multi-center, Randomized, Placebo-controlled, Dose-ranging Study to Investigate the Safety and Tolerability of Multiple Dose Administration of CSL112 in Subjects With Acute Myocardial Infarction.

Important dates

Study start
2014
Primary completion
2015
Study completion
2016
First posted
Apr 9, 2014
Registry last updated
Mar 15, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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