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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
Results First Posted : June 11, 2020
Last Update Posted : June 11, 2020
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

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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. Percent of Participants With at Least One Occurrence of Treatment-emergent Renal Serious Adverse Events (SAEs) (SAF) [ Time Frame: Up to 9 weeks ]
    A renal SAE is defined as any SAE with a MedDRA preferred term included in the Acute Renal Failure narrow Standard MedDRA Query or a preferred term of renal tubular necrosis, renal cortical necrosis, renal necrosis, or renal papillary necrosis.

  2. Percent of Participants With Treatment-emergent Acute Kidney Injury (AKI ) [ Time Frame: Up to 4 weeks ]
    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 Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to 9 weeks ]
  2. Percentage of Participants With TEAEs [ Time Frame: Up to 9 weeks ]
  3. Total Number of TEAEs [ Time Frame: Up to 9 weeks ]
  4. Number of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR [ Time Frame: Up to 9 weeks ]

    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 Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR [ Time Frame: Up to 9 weeks ]

    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 Participants With Change in Renal Status [ Time Frame: Baseline and up to 4 weeks ]

    Number of participants 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 Participants With Change in Renal Status [ Time Frame: Baseline and up to 4 weeks ]

    Percentage of participants 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 Participants With Change in Hepatic Status [ Time Frame: Baseline and up to 4 weeks ]

    Number of participants 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 Participants With Change in Hepatic Status [ Time Frame: Baseline and up to 4 weeks ]

    Percentage of participants 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 Participants With Treatment-emergent Bleeding Events [ Time Frame: Up to 9 weeks ]
    Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).

  11. Percentage of Participants With Treatment-emergent Bleeding Events [ Time Frame: Up to 9 weeks ]
    Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).

  12. Percentage of Participants With Binding Antibodies Specific to Apolipoprotein A-I (Apo-A1) and CSL112 [ Time Frame: Up to 9 weeks ]
  13. Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 1 for apoA-I and PC [ Time Frame: Immediately after end of infusion ]
  14. Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 4 for apoA-I and PC [ Time Frame: Immediately after end of infusion ]
  15. Plasma apoA-I and Phosphatidylcholine (PC) Accumulation Ratio After Infusion 4 [ Time Frame: Immediately after end of infusion ]
    The plasma apoA-I and PC accumulation ratio will be determined for CSL112-treated subjects.



Information from the National Library of Medicine

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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


Locations
Show Show 31 study locations
Sponsors and Collaborators
CSL Behring
Investigators
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Study Director: Danielle Duffy, MD CSL Behring
  Study Documents (Full-Text)

Documents provided by CSL Behring:
Study Protocol  [PDF] June 6, 2016
Statistical Analysis Plan  [PDF] August 3, 2017

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT02742103    
Other Study ID Numbers: CSL112_2001
2015-003017-26 ( EudraCT Number )
First Posted: April 18, 2016    Key Record Dates
Results First Posted: June 11, 2020
Last Update Posted: June 11, 2020
Last Verified: May 2020
Additional relevant MeSH terms:
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Renal Insufficiency
Myocardial Infarction
Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Kidney Diseases
Urologic Diseases