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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02108262
Recruitment Status : Completed
First Posted : April 9, 2014
Results First Posted : March 15, 2021
Last Update Posted : March 15, 2021
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Acute Myocardial Infarction Biological: CSL112 Biological: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1267 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official 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.
Study Start Date : August 2014
Actual Primary Completion Date : December 2015
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

Arm Intervention/treatment
Experimental: CSL112 - low dose
CSL112 (low dose) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks.
Biological: CSL112
CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.

Experimental: CSL112 - high dose
CSL112 (high dose) is to be administered as an IV infusion once weekly for 4 consecutive weeks.
Biological: CSL112
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 Comparator: Placebo
Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion.
Biological: Placebo
0.9% weight/volume sodium chloride solution (ie, normal saline)




Primary Outcome Measures :
  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 Outcome Measures :
  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 ]


Information from the National Library of Medicine

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Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02108262


Locations
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Sponsors and Collaborators
CSL Behring
Investigators
Layout table for investigator information
Study Director: Dr. Denise D'Andrea CSL Behring
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT02108262    
Other Study ID Numbers: CSLCT-HDL-12-77
2013-003458-26 ( EudraCT Number )
First Posted: April 9, 2014    Key Record Dates
Results First Posted: March 15, 2021
Last Update Posted: March 15, 2021
Last Verified: February 2021
Additional relevant MeSH terms:
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Myocardial Infarction
Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases