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A Study of CSL112 in Adults With Moderate Renal Impairment and Acute Myocardial Infarction

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ClinicalTrials.gov Identifier: NCT02742103
Recruitment Status : Completed
First Posted : April 18, 2016
Last Update Posted : June 20, 2018
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Brief Summary:
This study is a phase 2, multicenter, double-blind, randomized, placebo controlled, parallel-group study to investigate the renal safety and tolerability of multiple dose intravenous (IV) administration of CSL112 compared with placebo in subjects with moderate renal impairment (RI) and acute myocardial infarction (AMI).

Condition or disease Intervention/treatment Phase
Acute Myocardial Infarction Moderate Renal Impairment Biological: CSL_112 Other: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 83 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group, Study to Investigate the Safety and Tolerability of Multiple Dose Administration of CSL112 in Subjects With Moderate Renal Impairment and Acute Myocardial Infarction
Study Start Date : August 2016
Actual Primary Completion Date : June 2017
Actual Study Completion Date : June 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

Arm Intervention/treatment
Experimental: CSL_112
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
Biological: CSL_112
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 will be administered at the same frequency, volume and duration as the CSL112 infusion.
Other: Placebo
0.9% weight/volume sodium chloride solution (ie, normal saline)




Primary Outcome Measures :
  1. Incidence of treatment-emergent renal serious adverse event (SAE) [ Time Frame: From the start of the first infusion to the end of the subject's participation in the study, up to approximately 9 weeks ]
    The incidence rate is based on the number of subjects with at least one occurrence of a renal SAE defined as follows. A renal SAE is defined as any SAE with a MedDRA preferred term (PT) included in the Acute Renal Failure narrow Standard MedDRA Query (SMQ) or a PT of renal tubular necrosis, renal cortical necrosis, renal necrosis, or renal papillary necrosis.

  2. Incidence of treatment-emergent acute kidney injury (AKI) [ Time Frame: From baseline (before infusion) through the active treatment period, approximately 1 month. ]
    The incidence rate is based on the number of subjects with at least one occurrence of an AKI defined as follows. Acute kidney injury is defined as an absolute increase in serum creatinine from baseline ≥ 0.3 mg/dL during the Active Treatment Period that is sustained upon repeat measurement by the central laboratory no earlier than 24 hours after the elevated value. If no repeat value is obtained, a single serum creatinine value that is increased from baseline ≥ 0.3 mg/dL (26.5 μmol/L) during the Active Treatment Period would also fulfil the definition of AKI.


Secondary Outcome Measures :
  1. Number of subjects with treatment-emergent AEs (TEAEs) [ Time Frame: From the start of the first infusion to the end of the safety follow-up period, approximately 9 weeks for each subject ]
  2. Percentage of subjects with TEAEs [ Time Frame: From the start of the first infusion to the end of the safety follow-up period, approximately 9 weeks for each subject ]
  3. Total number of TEAEs [ Time Frame: From the start of the first infusion to the end of the safety follow-up period, approximately 9 weeks for each subject ]
  4. Number of subjects with treatment-emergent adverse drug reaction (ADR) or suspected ADR [ Time Frame: From the start of the first infusion to the end of the safety follow-up period, approximately 9 weeks for each subject ]

    Adverse drug reactions or suspected adverse drug reactions are defined as:

    1. All TEAEs, including local tolerability events, that begin during or within 1 hour after the end of an infusion; or
    2. Those TEAEs that the investigator or sponsor indicate may be causally related to product administration; or
    3. All TEAEs for which the Investigator's causality assessment is missing or indeterminate; or
    4. All TEAEs for which the incidence 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.

  5. Percentage of subjects with treatment-emergent adverse drug reaction (ADR) or suspected ADR [ Time Frame: From the start of the first infusion to the end of the safety follow-up period, approximately 9 weeks for each subject ]

    Adverse drug reactions or suspected adverse drug reactions are defined as:

    1. All TEAEs, including local tolerability events, that begin during or within 1 hour after the end of an infusion; or
    2. Those TEAEs that the investigator or sponsor indicate may be causally related to product administration; or
    3. All TEAEs for which the Investigator's causality assessment is missing or indeterminate; or
    4. All TEAEs for which the incidence 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.

  6. Number of subjects with change in renal status [ Time Frame: From baseline (before infusion) through the active treatment period, up to approximately 1 month ]

    Number of subjects with changes in renal status defined as:

    • Absolute increases from baseline in serum creatinine as follows:

      i. ≤ baseline value ii. > 0 to < 0.3 mg/dL iii. ≥ 0.3 to ≤ 0.5 mg/dL iv. > 0.5 mg/dL

    • Increases in serum creatinine that are sustained for ≥ 24 hours upon repeat measurement that are greater than or equal to 1.5 x, 2 x, or 3.0 x the baseline value, or serum creatinine ≥ 4.0 mg/dL
    • Initiation of renal replacement therapy
    • Decrease in eGFR ≥ 25% from baseline starting during the active treatment period and that is sustained at the final study visit

  7. Percentage of subjects with change in renal status [ Time Frame: From baseline (before infusion) through the active treatment period, up to approximately 1 month ]

    Percentage of subjects with changes in renal status defined as:

    • Absolute increases from baseline in serum creatinine as follows:

      i. ≤ baseline value ii. > 0 to < 0.3 mg/dL iii. ≥ 0.3 to ≤ 0.5 mg/dL iv. > 0.5 mg/dL

    • Increases in serum creatinine that are sustained for ≥ 24 hours upon repeat measurement that are greater than or equal to 1.5 x, 2 x, or 3.0 x the baseline value, or serum creatinine ≥ 4.0 mg/dL
    • Initiation of renal replacement therapy
    • Decrease in eGFR ≥ 25% from baseline starting during the active treatment period and that is sustained at the final study visit

  8. Number of subjects with change in hepatic status [ Time Frame: From baseline (before infusion) through the active treatment period, up to approximately 1 month ]

    Number of subjects with a change from baseline in hepatic status and that is sustained for ≥ 24 hours upon repeat measurement, defined as:

    1. Alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
    2. ALT > 5 x ULN
    3. ALT > 10 x ULN
    4. Serum total bilirubin > 1.5 x ULN
    5. Serum total bilirubin > 2 x ULN
    6. Possible Hy's law cases, as defined in the FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation (July 2009).

  9. Percentage of subjects with change in hepatic status [ Time Frame: From baseline (before infusion) through the active treatment period, up to approximately 1 month ]

    Percentage of subjects with a change from baseline in hepatic status and that is sustained for ≥ 24 hours upon repeat measurement, defined as:

    1. Alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
    2. ALT > 5 x ULN
    3. ALT > 10 x ULN
    4. Serum total bilirubin > 1.5 x ULN
    5. Serum total bilirubin > 2 x ULN
    6. Possible Hy's law cases, as defined in the FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation (July 2009).

  10. Number of subjects with treatment-emergent bleeding events [ Time Frame: From the start of the first infusion to the end of the safety follow-up period, approximately 9 weeks for each subject ]
    Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).

  11. Percentage of subjects with treatment-emergent bleeding events [ Time Frame: From the start of the first infusion to the end of the safety follow-up period, approximately 9 weeks for each subject ]
    Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).

  12. Number of subjects with clinically significant changes in routine safety assessments [ Time Frame: For the duration of the subject's participation in the study, up to approximately 9 weeks ]
    The number of subjects with clinically significant changes in clinical laboratory tests, physical examinations, body weight, electrocardiograms and vital signs.

  13. Percentage of subjects with clinically significant changes in routine safety assessments [ Time Frame: For the duration of the subject's participation in the study, up to approximately 9 weeks ]
    The percentage of subjects with clinically significant changes in clinical laboratory tests, physical examinations, body weight, electrocardiograms and vital signs.

  14. Occurrence of binding antibodies [ Time Frame: For the duration of the subject's participation in the study, up to approximately 9 weeks ]
    The percentage of subjects with binding antibodies specific to apolipoprotein A-I (apo-A1) and/or CSL112

  15. Baseline-corrected plasma apoA-I and phosphatidylcholine (PC) concentrations [ Time Frame: Before and at the end of the first infusion (day 1) and before and at the end of the fourth infusion (approximately 22 days), and within 48 hours after the start of the first infusion. ]
  16. Plasma apoA-I and PC concentration [ Time Frame: Before and at the end of the first infusion (day 1) and before and at the end of the fourth infusion (approximately 22 days), and within 48 hours after the start of the first infusion. ]
    Concentration in plasma at End-of-Infusion for apoA-I and PC

  17. Plasma apoA-I and PC accumulation ratio [ Time Frame: Before and at the end of the first infusion (day 1) and before and at the end of the fourth infusion (approximately 22 days) ]
    The plasma apoA-I and PC accumulation ratio will be determined for CSL112-treated subjects.



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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 moderate renal impairment (an eGFR ≥ 30 and <60 mL/min/1.73 m2) and myocardial necrosis in a clinical setting consistent with a type I (spontaneous) acute myocardial infarction (AMI).

Exclusion Criteria:

  • Symptoms, biomarker elevation or electrocardiogram (ECG) changes other than those of the index event that are consistent with a diagnosis of AMI but are likely not due to primary myocardial ischemia
  • Ongoing hemodynamic instability
  • Planned coronary artery bypass surgery
  • Evidence of hepatobiliary disease
  • History of acute kidney injury (AKI) after previous exposure to an intravenous contrast agent.
  • History of nephrotic range proteinuria.
  • Known history of allergy to soy beans or peanuts, immunoglobulin A (IgA) deficiency, antibodies to IgA , or hypersensitivity 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): NCT02742103


  Show 31 Study Locations
Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Danielle Duffy, MD CSL Behring

Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT02742103     History of Changes
Other Study ID Numbers: CSL112_2001
2015-003017-26 ( EudraCT Number )
First Posted: April 18, 2016    Key Record Dates
Last Update Posted: June 20, 2018
Last Verified: August 2017

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Renal Insufficiency
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Kidney Diseases
Urologic Diseases