A Phase 2b Study of CSL112 in Subjects With Acute Myocardial Infarction.
Summary
This is a multicenter randomized, double-blind, placebo-controlled, parallel-group, dose-ranging phase 2b study to investigate the hepatic and renal safety and tolerability of multiple dose administration of two dose levels of CSL112 compared with placebo in subjects with acute myocardial infarction (AMI).
Timeline
- Start
- 2014-08
- Primary completion
- 2015-12
- Completion
- 2016-03
Outcome
Met primary endpoint
paper incidence rates for an increase in alanine transaminase or total bilirubin between both CSL112 arms and placebo was within the protocol-defined noninferiority margin of 4% PMID 27881559 ↗
paper incidence rates for an increase in serum creatinine or a new requirement for renal replacement therapy was within the protocol-defined noninferiority margin of 5% PMID 27881559 ↗
release “The AEGIS-I study met its co-primary safety endpoints, showing that CSL112 does not cause significant changes in liver or kidney function” csl.com ↗
Publications
- Didichenko SA, Velkoska E, Navdaev AV, Greene BH, Lorkowski SW, Duffy D, Mears SJ, Wright SD, Gibson CM, Smith JD, Kingwell BA. CSL112 Infusion Rapidly Increases APOA1 Exchange Rate via Specific Serum Amyloid-Poor HDL Subpopulations When Administered to Patients Post-Myocardial Infarction. Arterioscler Thromb Vasc Biol. 2023 Jun;43(6):855-869. doi: 10.1161/ATVBAHA.122.318243. Epub 2023 Mar 30.
- 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.
- Michael Gibson C, Korjian S, Tricoci P, Daaboul Y, Yee M, Jain P, Alexander JH, Steg PG, Lincoff AM, Kastelein JJ, Mehran R, D'Andrea DM, Deckelbaum LI, Merkely B, Zarebinski M, Ophuis TO, Harrington RA. Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction: The AEGIS-I Trial (ApoA-I Event Reducing in Ischemic Syndromes I). Circulation. 2016 Dec 13;134(24):1918-1930. doi: 10.1161/CIRCULATIONAHA.116.025687. Epub 2016 Nov 15.
- Gibson CM, Korjian S, Tricoci P, Daaboul Y, Alexander JH, Steg PG, Lincoff AM, Kastelein JJ, Mehran R, D'Andrea D, Merkely B, Zarebinski M, Ophius TO, Harrington RA. Rationale and design of Apo-I Event Reduction in Ischemic Syndromes I (AEGIS-I): A phase 2b, randomized, placebo-controlled, dose-ranging trial to investigate the safety and tolerability of CSL112, a reconstituted, infusible, human apoA-I, after acute myocardial infarction. Am Heart J. 2016 Oct;180:22-8. doi: 10.1016/j.ahj.2016.06.017. Epub 2016 Jul 5.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | CSL112 | Protein / enzyme biologic | 2 g | Intravenous |
| Subject | CSL112 | Protein / enzyme biologic | 6 g | Intravenous |