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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- CSL Behring
- Enrollment
- 83
- Locations
- 62
- Primary Endpoint
- Percent of Participants With at Least One Occurrence of Treatment-emergent Renal Serious Adverse Events (SAEs) (SAF)
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Outcomes
Primary Outcomes
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.
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
- 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)
- Percentage of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR(Up to 9 weeks)
- Number of Participants With Change in Renal Status(Baseline and up to 4 weeks)
- Percentage of Participants With Change in Renal Status(Baseline and up to 4 weeks)
- Number of Participants With Change in Hepatic Status(Baseline and up to 4 weeks)
- Percentage of Participants With Treatment-emergent Bleeding Events(Up to 9 weeks)
- 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)
- Percentage of Participants With Change in Hepatic Status(Baseline and up to 4 weeks)
- Number of Participants With Treatment-emergent Bleeding Events(Up to 9 weeks)
- 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)