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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-005520-10 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low | Experimental | A low dose of either CSL112 or placebo is to be administered as a single intravenous (IV) infusion. The placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. |
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| High | Experimental | A high dose of either CSL112 or placebo is to be administered as a single intravenous (IV) infusion. The placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CSL112 | 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| Plasma apolipoprotein A-I (apoA-I) and phosphatidylcholine (PC) area under the curve (AUC) | Baseline corrected plasma apoA-I and PC AUC0-infinity | Before and at up to 10 time points (during up to 7 days) after infusion |
| Plasma apoA-I and PC AUC0-last and AUC 0-t | 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 | Before and at up to 10 time points (during up to 7 days) after infusion |
| 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) | Amount excreted (Ae) of apoA-I over a collection interval 0-t. |
| Measure | Description | Time Frame |
|---|---|---|
| Urinary excretion of sucrose(Ae0-t) | Amount of sucrose excreted over a collection interval 0-t. | Before and up to 48 hours after infusion |
| Urinary excretion of sucrose (%fe0-t) | Percent fraction excreted sucrose in urine over time interval 0-t, calculated as Ae0-t/Dose x 100. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Denise D'Andrea, M.D. | CSL Behring | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Study Site - 17101 | Berlin | 13353 | Germany | |||
| Study Site - 17102 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33217027 | Derived | Zheng B, Duffy D, Tricoci P, Kastrissios H, Pfister M, Wright SD, Gille A, Tortorici MA. Pharmacometric analyses to characterize the effect of CSL112 on apolipoprotein A-I and cholesterol efflux capacity in acute myocardial infarction patients. Br J Clin Pharmacol. 2021 Jun;87(6):2558-2571. doi: 10.1111/bcp.14666. Epub 2020 Dec 23. | |
| 30240132 |
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| ID | Term |
|---|---|
| C584257 | CSL112 |
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| Placebo | Other | 0.9% weight/volume sodium chloride solution (ie, normal saline) |
|
| Before and up to 48 hours after infusion |
| Urinary excretion of apoA-I (%fe0-t) | Percent fraction excreted (%fe) of apoA-I in urine over time interval 0-t, calculated as Ae0-t/Dose x 100. | Before and up to 48 hours after infusion |
| Renal clearance of apoA-I | Renal clearance of apoA-I, calculated as Ae0-48/AUC0-48 | Before and up to 48 hours after infusion |
| Before and up to 48 hours after infusion |
| Urinary excretion of sucrose (clearance) | Renal clearance of sucrose, calculated as Ae0-48/AUC0-48 | Before and up to 48 hours after infusion |
| Adverse drug reaction (ADR) or suspected ADR frequency (%) | The overall percentage of participants with adverse reactions or suspected adverse reactions:
| Up to approximately 127 days |
| Clinically significant changes in routine safety assessments | 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. | Up to approximately 97 days |
| Clinically important change in drug-induced liver injury | 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. | From baseline (before infusion) up to Day 16. |
| Clinically important change in renal status | 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. | From baseline (before infusion) up to Day 16. |
| Plasma sucrose AUC | Baseline corrected plasma sucrose AUC0-infinity | Before and at up to 7 time points (during up to 2 days) after infusion |
| Plasma sucrose AUC0-last and AUC 0-t | 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 | Before and at up to 7 time points (during up to 2 days) after infusion |
| Plasma sucrose Cmax | Before and at up to 7 time points (during up to 2 days) after infusion |
| 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 |
| Plasma sucrose t1/2 | Before and at up to 7 time points (during up to 2 days) after infusion |
| Adverse drug reaction (ADR) or suspected ADR frequency | The overall number of participants with adverse reactions or suspected adverse reactions:
| Up to approximately 127 days |
| Number of subjects with AEs | After the start of infusion up to approximately 127 days |
| Munich |
| D-81241 |
| Germany |
| Study Site - 24101 | London | SE1 1YR | United Kingdom |
| Study Site - 24102 | Manchester | M13 9WL | United Kingdom |
| Tortorici MA, Duffy D, Evans R, Feaster J, Gille A, Mant TGK, Wright SD, D'Andrea D. Pharmacokinetics and Safety of CSL112 (Apolipoprotein A-I [Human]) in Adults With Moderate Renal Impairment and Normal Renal Function. Clin Pharmacol Drug Dev. 2019 Jul;8(5):628-636. doi: 10.1002/cpdd.618. Epub 2018 Sep 21. |