Acute Myocardial Infarction
Conditions
Brief summary
This is a phase 1 multicenter, randomized, double-blind, placebo-controlled, ascending dose study to investigate the pharmacokinetics (PK), safety, and tolerability of CSL112 in adult subjects with moderate renal impairment and in healthy adult subjects with normal renal function.
Interventions
BIOLOGICALCSL112
CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OTHERPlacebo
0.9% weight/volume sodium chloride solution (ie, normal saline)
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Men or women aged 18 to 85 years (inclusive) of age, with body weight 50 kg or more. * Subjects with renal impairment (RI) must have stable chronic moderate RI (estimated glomerular filtration rate \[eGFR\] ≥ 30 and \< 60 mL/min/1.73 m2) * Healthy subjects must have normal renal function (eGFR ≥ 90 mL/min/1.73 m2)
Exclusion criteria
* Evidence of a clinically significant medical condition, disorder or disease * Evidence of hepatobiliary disease * Any clinically relevant abnormal laboratory test result * Known history of allergies, hypersensitivity or deficiencies 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, including: history of cancer, low platelet count, bleeding disorder or coagulopathy, significantly altered electrocardiogram waveform, unstable glycemia control in subjects with diabetes, acute renal failure, recent donation or loss of blood * Evidence or history of alcohol or substance abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma apolipoprotein A-I (apoA-I) and phosphatidylcholine (PC) area under the curve (AUC) | Before and at up to 10 time points (during up to 7 days) after infusion | Baseline corrected plasma apoA-I and PC AUC0-infinity |
| Plasma apoA-I and PC AUC0-last and AUC 0-t | Before and at up to 10 time points (during up to 7 days) after infusion | AUC from time point zero to the last quantifiable time point before the analyte first returns to baseline (AUC0-last) and/or a partial AUC from baseline to time point t (AUC0-t) with and without baseline correction |
| Plasma apoA-I and PC Cmax | Before and at up to 10 time points (during up to 7 days) after infusion | — |
| Plasma apoA-I and PC Tmax | Before and at up to 10 time points (during up to 7 days) after infusion | — |
| Plasma apoA-I and PC Volume of distribution during terminal phase | Before and at up to 10 time points (during up to 7 days) after infusion | — |
| Plasma apoA-I and PC clearance | Before and at up to 10 time points (during up to 7 days) after infusion | — |
| Plasma apoA-I and PC t1/2 | Before and at up to 10 time points (during up to 7 days) after infusion | — |
| Urinary excretion of apoA-I (Ae0-t) | Before and up to 48 hours after infusion | Amount excreted (Ae) of apoA-I over a collection interval 0-t. |
| Urinary excretion of apoA-I (%fe0-t) | Before and up to 48 hours after infusion | Percent fraction excreted (%fe) of apoA-I in urine over time interval 0-t, calculated as Ae0-t/Dose x 100. |
| Renal clearance of apoA-I | Before and up to 48 hours after infusion | Renal clearance of apoA-I, calculated as Ae0-48/AUC0-48 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma sucrose Tmax | Before and at up to 7 time points (during up to 2 days) after infusion | — |
| Plasma sucrose Volume of distribution during terminal phase | Before and at up to 7 time points (during up to 2 days) after infusion | — |
| Plasma sucrose Clearance | Before and at up to 7 time points (during up to 2 days) after infusion | — |
| Urinary excretion of sucrose(Ae0-t) | Before and up to 48 hours after infusion | Amount of sucrose excreted over a collection interval 0-t. |
| Adverse drug reaction (ADR) or suspected ADR frequency | Up to approximately 127 days | The overall number of participants with adverse reactions or suspected adverse reactions: 1. That begin during or within 1 hour of an infusion; or 2. That may be causally related to the administration of the investigational product; or 3. For which the Investigator's causality assessment is missing or indeterminate; or 4. 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 subjects with AEs | After the start of infusion up to approximately 127 days | — |
| Plasma sucrose t1/2 | Before and at up to 7 time points (during up to 2 days) after infusion | — |
| Urinary excretion of sucrose (%fe0-t) | Before and up to 48 hours after infusion | Percent fraction excreted sucrose in urine over time interval 0-t, calculated as Ae0-t/Dose x 100. |
| Urinary excretion of sucrose (clearance) | Before and up to 48 hours after infusion | Renal clearance of sucrose, calculated as Ae0-48/AUC0-48 |
| Adverse drug reaction (ADR) or suspected ADR frequency (%) | Up to approximately 127 days | The overall percentage of participants with adverse reactions or suspected adverse reactions: 1. That begin during or within 1 hour of an infusion; or 2. That may be causally related to the administration of the investigational product; or 3. For which the Investigator's causality assessment is missing or indeterminate; or 4. 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. |
| Clinically significant changes in routine safety assessments | Up to approximately 97 days | The number of participants with clinically significant changes in any of the following assessments: clinical laboratory tests, physical examinations, body weight, electrocardiograms, vital signs, immunogenicity testing, serology, nucleic acid testing or proteinuria findings. |
| Clinically important change in drug-induced liver injury | From baseline (before infusion) up to Day 16. | A clinically important change in drug-induced liver injury is defined as a change (from baseline) in alanine aminotransferase (ALT) greater than 3 times the upper limit of normal (ULN) or a change in total bilirubin greater than 2 times ULN, that is confirmed upon repeat measurement. |
| Clinically important change in renal status | From baseline (before infusion) up to Day 16. | A clinically important change in renal status is defined as a serum creatinine (Cr) increase to ≥ 1.5 x the baseline value that is confirmed upon repeat measurement, or the need for renal replacement therapy. |
| Plasma sucrose AUC | Before and at up to 7 time points (during up to 2 days) after infusion | Baseline corrected plasma sucrose AUC0-infinity |
| Plasma sucrose AUC0-last and AUC 0-t | Before and at up to 7 time points (during up to 2 days) after infusion | AUC from time point zero to the last quantifiable time point before the analyte first returns to baseline (AUC0-last) and/or a partial AUC from baseline to time point y (AUC0-t) with and without baseline correction |
| Plasma sucrose Cmax | Before and at up to 7 time points (during up to 2 days) after infusion | — |
Countries
Germany, United Kingdom
Outcome results
None listed