Skip to main content
OpenTrials
Completed

NCT Number: NCT02742103

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

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).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Acute Myocardial Infarction Moderate Renal Impairment

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Study Site 17001, Freiburg im Breisgau, Baden-Wurttemberg, Germany

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

CSL_112

Biological

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

Other

0.9% weight/volume sodium chloride solution (ie, normal saline)

Primary outcomes

  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 outcomes

  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:

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

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

    • Alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
    • ALT > 5 x ULN
    • ALT > 10 x ULN
    • Serum total bilirubin > 1.5 x ULN
    • Serum total bilirubin > 2 x ULN
    • 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:

    • Alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
    • ALT > 5 x ULN
    • ALT > 10 x ULN
    • Serum total bilirubin > 1.5 x ULN
    • Serum total bilirubin > 2 x ULN
    • 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.

Sponsors and collaborators

Lead sponsor

CSL Behring

Industry

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2017
Study completion
2017
First posted
Apr 18, 2016
Registry last updated
Jun 11, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.