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

Phase 2

Completed

Conditions: Moderate Renal Impairment
Acute Myocardial Infarction

Interventions: Other: Placebo
Biological: CSL_112

Registration Number: NCT02742103

Lead Sponsor: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 83

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.

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
CSL_112	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).

Primary Outcome Measures

Name	Time	Method
Percent of Participants With at Least One Occurrence of Treatment-emergent Renal Serious Adverse Events (SAEs) (SAF)	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.
Percent of Participants With Treatment-emergent Acute Kidney Injury (AKI )	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

Name	Time	Method
Total Number of TEAEs	Up to 9 weeks
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Up to 9 weeks
Percentage of Participants With TEAEs	Up to 9 weeks
Number of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR	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.
Percentage of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR	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.
Number of Participants With Change in Renal Status	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
Percentage of Participants With Change in Renal Status	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
Number of Participants With Change in Hepatic Status	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).
Percentage of Participants With Treatment-emergent Bleeding Events	Up to 9 weeks	Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).
Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 1 for apoA-I and PC	Immediately after end of infusion
Plasma apoA-I and Phosphatidylcholine (PC) Accumulation Ratio After Infusion 4	Immediately after end of infusion	The plasma apoA-I and PC accumulation ratio will be determined for CSL112-treated subjects.
Percentage of Participants With Change in Hepatic Status	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).
Number of Participants With Treatment-emergent Bleeding Events	Up to 9 weeks	Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).
Percentage of Participants With Binding Antibodies Specific to Apolipoprotein A-I (Apo-A1) and CSL112	Up to 9 weeks
Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 4 for apoA-I and PC	Immediately after end of infusion

Trial Locations

Locations (31): Study Site 16168
🇺🇸
Concord, California, United States
Study Site 16135
🇺🇸
Danbury, Connecticut, United States
Study Site 19005
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Haifa, Israel
Study Site 19002
🇮🇱
Nahariya, Israel
Study Site 18005
🇭🇺
Budapest, Hungary
Study Site 16018
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Rapid City, South Dakota, United States
Study Site 17005
🇩🇪
Berlin, Germany
Study Site 16003
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Jacksonville, Florida, United States
Study Site 16208
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Alexandria, Louisiana, United States
Study Site 18009
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Szeged, Hungary
Study Site 17014
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Frankfurt, Hessen, Germany
Study Site 17006
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Hamburg, Germany
Study Site 16061
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Petoskey, Michigan, United States
Study Site 17001
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Freiburg, Baden Wuerttemberg, Germany
Study Site 16130
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Littleton, Colorado, United States
Study Site 16112
🇺🇸
Boise, Idaho, United States
Study Site 18003
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Pecs, Hungary
Study Site 16101
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Birmingham, Alabama, United States
Study Site 16078
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Huntsville, Alabama, United States
Study Site 18007
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Nyiregyhaza, Hungary
Study Site 21001
🇳🇱
Alkmaar, Netherlands
Study Site 21017
🇳🇱
Amsterfoort, Netherlands
Study Site 21008
🇳🇱
Nijmegen, Netherlands
Study Site 18001
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Budapest, Hungary
Study Site 19008
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Safed, Israel
Study Site 16014
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High Point, North Carolina, United States
Study Site 21006
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Amsterdam, Netherlands
Study Site 16056
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Durham, North Carolina, United States
Study Site 16241
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Wichita Falls, Texas, United States
Study Site 17009
🇩🇪
Berlin, Germany
Study Site 17003
🇩🇪
Berlin, Germany

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

Recruitment & Eligibility

Study & Design

Trial Locations

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