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

CSL Behring83 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

Conditions

Acute Myocardial Infarction Moderate Renal Impairment

Interventions

CSL_112BIOLOGICAL

CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.

PlaceboOTHER

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (31)

Study Site 16101

Outcomes

Primary Outcomes

Percent of Participants With at Least One Occurrence of Treatment-emergent Renal Serious Adverse Events (SAEs) (SAF)

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.

Time frame: Up to 9 weeks

Percent of Participants With Treatment-emergent Acute Kidney Injury (AKI )

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.

Time frame: Up to 4 weeks

Secondary Outcomes

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Time frame: Up to 9 weeks

Percentage of Participants With TEAEs

Time frame: Up to 9 weeks

Total Number of TEAEs

Time frame: Up to 9 weeks

Number of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR

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.

Data from ClinicalTrials.gov

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Birmingham, Alabama, United States

Study Site 16078

Huntsville, Alabama, United States

Study Site 16168

Concord, California, United States

Study Site 16130

Littleton, Colorado, United States

Study Site 16135

Danbury, Connecticut, United States

Study Site 16003

Jacksonville, Florida, United States

Study Site 16112

Boise, Idaho, United States

Study Site 16208

Alexandria, Louisiana, United States

Study Site 16061

Petoskey, Michigan, United States

Study Site 16056

Durham, North Carolina, United States

...and 21 more locations

Time frame: Up to 9 weeks

Percentage of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR

Time frame: Up to 9 weeks

Number of Participants With Change in Renal Status

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

Time frame: Baseline and up to 4 weeks

Percentage of Participants With Change in Renal Status

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

Time frame: Baseline and up to 4 weeks

Number of Participants With Change in Hepatic Status

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).

Time frame: Baseline and up to 4 weeks

Percentage of Participants With Change in Hepatic Status

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).

Time frame: Baseline and up to 4 weeks

Number of Participants With Treatment-emergent Bleeding Events

Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).

Time frame: Up to 9 weeks

Percentage of Participants With Treatment-emergent Bleeding Events

Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).

Time frame: Up to 9 weeks

Percentage of Participants With Binding Antibodies Specific to Apolipoprotein A-I (Apo-A1) and CSL112

Time frame: Up to 9 weeks

Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 1 for apoA-I and PC

Time frame: Immediately after end of infusion

Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 4 for apoA-I and PC

Time frame: Immediately after end of infusion

Plasma apoA-I and Phosphatidylcholine (PC) Accumulation Ratio After Infusion 4

The plasma apoA-I and PC accumulation ratio will be determined for CSL112-treated subjects.

Time frame: Immediately after end of infusion