A Multiple Ascending Dose Study of CSL112 in Healthy Volunteers
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Objective
- 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]
Timeline
Start Date
June 2010
End Date for Final Data Collection for Primary Outcomes
December 2010
Study Completion Date
January 2011
Methods
- Phase I study
- Adaptive, randomized, placebo-controlled, double-blinded, sponsor-unblinded, multiple ascending dose clinical trial
- Patients enrolled: 36 healthy subjects
Inclusion Criteria
- Healthy individual
- Age: 18-55 year old
- Weight ≥ 5 kg
- BMI between 18-42 kg/m2
Exclusion Criteria
- Clinically significant medical condition or disease
- Abnormal lab test result
- History of alcohol or other substance abuse
Study Arms
- Intravenous placebo infusions composed of 0.9% normal saline
- Single escalating intravenous doses of CSL112 composed of reconstituted HDL. There are 3 dosing groups: 4 once-weekly infusions of 3.4 g, 4 once-weekly infusions of 6.8 g, and 8 twice-weekly infusions of 3.4 g.[1]
Biomarkers of cholesterol movement - cholesterol efflux capacity, serum preBeta1-HDL and HDL were measured.[1]
Outcomes
Primary Outcomes
Safety and tolerability defined as rate of clinically associated adverse events that occur within 14 days of CSL112 infusion.[1]
Secondary Outcomes
Evaluation of lipoprotein pharmacokinetics during a time frame of 10 days following CSL112 infusion and measurement of plasma levels of lipoprotein.[1]
Results
- Infusions of CSL-112 caused immediate and profound elevation in all the biomarkers.[1]
- Serum preBeta1-HDL elevation was up to 20-fold.[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 causes a greater efflux of cholesterol from tissues to HDL when compared with a single infusion.[1]
- No observed changes in the baseline of other lipoproteins.[1]
Conclusion
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]