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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by CSL Behring
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT02108262
First received: March 31, 2014
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Acute Myocardial Infarction
Biological: CSL112
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • Clinically important change in drug-induced liver injury [ Time Frame: From baseline (before 1st infusion) to Day 29. ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: Yes ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Plasma apoA-I and PC Tmax [ Time Frame: Before and for 7 days after the first and last infusions ] [ Designated as safety issue: No ]
  • Plasma apoA-I and PC area under the curve (AUC) [ Time Frame: Before and for 7 days after the first and last infusions ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Plasma apoA-I and PC Clearance [ Time Frame: Before and for 7 days after the first and last infusions ] [ Designated as safety issue: No ]
  • Plasma apoA-I and PC Volume of distribution at steady state [ Time Frame: Before and for 7 days after the first and last infusions ] [ Designated as safety issue: No ]
  • Study drug-related adverse events (AEs) [ Time Frame: From the start of the infusion, up to approximately Day 112 ] [ Designated as safety issue: Yes ]
    The number of subjects with study-drug-related AEs

  • Overall AEs [ Time Frame: From the start of the infusion, up to approximately Day 112 ] [ Designated as safety issue: Yes ]
    The total number of subjects with any AE

  • Bleeding events [ Time Frame: From the start of the infusion, up to approximately Day 112 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    The number of subjects with serum antibodies to CSL112

  • Change from baseline in serology [ Time Frame: Before infusion, up to approximately Day 382. ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: Yes ]
    Assessments (i.e., evidence of seroconversion or infection) will be conducted for HAV, HBV, HCV, HIV 1/2, parvovirus B19


Estimated Enrollment: 1200
Study Start Date: July 2014
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02108262

Contacts
Contact: Clinical Trials Registration Coordinator clinicaltrials@cslbehring.com

Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Dr. Denise D'Andrea CSL Behring
  More Information

No publications provided

Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT02108262     History of Changes
Other Study ID Numbers: CSLCT-HDL-12-77, 2013-003458-26
Study First Received: March 31, 2014
Last Updated: July 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on September 15, 2014