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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
Last Update Posted : December 14, 2016
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Tracking Information
First Submitted Date  ICMJE March 31, 2014
First Posted Date  ICMJE April 9, 2014
Last Update Posted Date December 14, 2016
Study Start Date  ICMJE August 2014
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 6, 2014)
  • Clinically important change in drug-induced liver injury [ Time Frame: From baseline (before 1st 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.
  • Clinically important change in renal status [ Time Frame: From baseline (before 1st 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2015)
  • The time-to-first occurrence of a major adverse cardiovascular event (MACE) [ Time Frame: From the start of the first infusion up to 112 days after infusion ]
    MACE includes: cardiovascular death, MI, ischemic stroke and hospitalization for unstable angina.
  • Pharmacokinetic profile of apolipoprotein A-I (apoA-I) and phosphatidylcholine (PC) [ Time Frame: Before and for 7 days after the first and last infusions ]
    Baseline-corrected plasma apoA-I and PC concentrations
  • Plasma apoA-I and PC Cmax [ Time Frame: Before and for 7 days after the first and last infusions ]
  • Plasma apoA-I and PC Tmax [ Time Frame: Before and for 7 days after the first and last infusions ]
  • Plasma apoA-I and PC area under the curve (AUC) [ Time Frame: Before and for 7 days after the first and last infusions ]
    Baseline corrected plasma apoA-I and PC AUC0-infinity, AUC0 last
  • Plasma apoA-I and PC t1/2 [ Time Frame: Before and for 7 days after the first and last infusions ]
  • Plasma apoA-I and PC Clearance [ Time Frame: Before and for 7 days after the first and last infusions ]
  • Plasma apoA-I and PC Volume of distribution at steady state [ Time Frame: Before and for 7 days after the first and last infusions ]
  • The occurrence of adverse reactions plus suspected adverse reactions (percentage of subjects) [ Time Frame: From the start of the infusion, up to approximately Day 112 ]
    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.
  • Overall AEs [ Time Frame: From the start of the infusion, up to approximately Day 382 ]
    The total number of subjects with any AE
  • Bleeding events [ Time Frame: From the start of the 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)
  • Immunogenic potential of CSL112 [ Time Frame: Before infusion, up to approximately Day 112 ]
    The number of subjects with serum antibodies to CSL112
  • Change from baseline in serology [ Time Frame: Before infusion, up to approximately Day 112. ]
    Assessments (i.e., evidence of seroconversion or infection) will be conducted for parvovirus B19
  • Change from baseline in nucleic acid testing assessments [ Time Frame: Before infusion, up to approximately Day 112. ]
    Assessments (i.e., evidence of seroconversion or infection) will be conducted for parvovirus B19
Original Secondary Outcome Measures  ICMJE
 (submitted: April 6, 2014)
  • The time-to-first occurrence of a major adverse cardiovascular event (MACE) [ Time Frame: From the start of the first infusion up to 112 days after infusion ]
    MACE includes: cardiovascular death, MI, ischemic stroke and hospitalization for unstable angina.
  • Pharmacokinetic profile of apolipoprotein A-I (apoA-I) and phosphatidylcholine (PC) [ Time Frame: Before and for 7 days after the first and last infusions ]
    Baseline-corrected plasma apoA-I and PC concentrations
  • Plasma apoA-I and PC Cmax [ Time Frame: Before and for 7 days after the first and last infusions ]
  • Plasma apoA-I and PC Tmax [ Time Frame: Before and for 7 days after the first and last infusions ]
  • Plasma apoA-I and PC area under the curve (AUC) [ Time Frame: Before and for 7 days after the first and last infusions ]
    Baseline corrected plasma apoA-I and PC AUC0-infinity, AUC0 last
  • Plasma apoA-I and PC t1/2 [ Time Frame: Before and for 7 days after the first and last infusions ]
  • Plasma apoA-I and PC Clearance [ Time Frame: Before and for 7 days after the first and last infusions ]
  • Plasma apoA-I and PC Volume of distribution at steady state [ Time Frame: Before and for 7 days after the first and last infusions ]
  • Study drug-related adverse events (AEs) [ Time Frame: From the start of the infusion, up to approximately Day 112 ]
    The number of subjects with study-drug-related AEs
  • Overall AEs [ Time Frame: From the start of the infusion, up to approximately Day 112 ]
    The total number of subjects with any AE
  • Bleeding events [ Time Frame: From the start of the 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)
  • Immunogenic potential of CSL112 [ Time Frame: Before infusion, up to approximately Day 112 ]
    The number of subjects with serum antibodies to CSL112
  • Change from baseline in serology [ Time Frame: Before infusion, up to approximately Day 382. ]
    Assessments (i.e., evidence of seroconversion or infection) will be conducted for hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) 1/2, parvovirus B19
  • Change from baseline in nucleic acid testing assessments [ Time Frame: Before infusion, up to approximately Day 382. ]
    Assessments (i.e., evidence of seroconversion or infection) will be conducted for HAV, HBV, HCV, HIV 1/2, parvovirus B19
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 2b Study of CSL112 in Subjects With Acute Myocardial Infarction.
Official Title  ICMJE 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.
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Acute Myocardial Infarction
Intervention  ICMJE
  • 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.
  • Biological: Placebo
    0.9% weight/volume sodium chloride solution (ie, normal saline)
Study Arms  ICMJE
  • Experimental: CSL112 - low dose
    CSL112 (low dose) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks.
    Intervention: Biological: CSL112
  • Experimental: CSL112 - high dose
    CSL112 (high dose) is to be administered as an IV infusion once weekly for 4 consecutive weeks.
    Intervention: Biological: CSL112
  • 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.
    Intervention: Biological: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 4, 2016)
1267
Original Estimated Enrollment  ICMJE
 (submitted: April 6, 2014)
1200
Actual Study Completion Date  ICMJE March 2016
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Bulgaria,   Canada,   Czech Republic,   Denmark,   France,   Germany,   Hungary,   Israel,   Italy,   Netherlands,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02108262
Other Study ID Numbers  ICMJE CSLCT-HDL-12-77
2013-003458-26 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CSL Behring
Study Sponsor  ICMJE CSL Behring
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Dr. Denise D'Andrea CSL Behring
PRS Account CSL Behring
Verification Date March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP