A Multiple Ascending Dose Study of CSL112 in Healthy Volunteers

An adaptive, phase I, randomized, placebo-controlled, sponsor-unblinded, multiple ascending dose study to investigate the safety, tolerability and pharmacokinetics of intravenous CSL112 in healthy volunteers

• To measure the biomarkers of cholesterol movement following a single and multiple infusions of CSL-112 in healthy subjects.^[1]

• To evaluate role of CSL-112 in decreasing cholesterol-loaded plaques that contribute to cardiovascular disease.^[1]

CSL Limited

The previous information was derived from ClinicalTrials.gov on 09/19/2013 using the identification number NCT01281774.

The previous information was derived from ClinicalTrials.gov on 09/19/2013 using the identification number NCT01281774.

• Healthy individual
• Age: 18-55 year old
• Weight ≥ 5 kg
• BMI between 18-42 kg/m2

• Clinically significant medical condition or disease
• Abnormal lab test result
• History of alcohol or other substance abuse

Safety and tolerability defined as rate of clinically-associated adverse events that occur within 14 days of CSL112 infusion.^[1]

Evaluation of lipoprotein pharmacokinetics during a time frame of 10 days following CSL112 infusion and measurement of plasma levels of lipoprotein.^[1]

• Infusions of CSL-112 caused immediate and profound elevation in all the biomarkers of cholesterol transport, including preBeta1-HDL and global cholesterol efflux as measured by activity of ATP-binding cassette transporter (ABCA1) cells.^[1]

• Serum preBeta1-HDL elevation was up to 20-fold.^[1]

• The infusion of CSL112 caused a dose-dependent increase of all biomarkers. Levels were consistent in magnitude and time course following the first and last infusions.^[1]

• Serum preBeta1-HDL and cholesterol efflux capacity peaked after infusion and returned to baseline at 24 hour while there was a 72 hour sustained response for serum HDL following its peak at 24-48 hours after infusion.^[1]

• Multiple infusions of CSL112 cause a greater efflux of cholesterol from tissues to HDL when compared with a single infusion.^[1]

• There were no observed changes in the baseline of other lipoproteins.^[1]

Single and multiple infusions of CSL-112 in healthy subjects rapidly initiates the reverse cholesterol transport, and this is beneficial in rapidly lowering the risk of recurrent cardiovascular events following acute coronary syndromes.^[1]