A Study of CSL112 in Healthy Adults and in Adults With Moderate Renal Impairment

Acute Myocardial Infarction Clinical Trial

Official title:

A Double-blind, Randomized, Placebo-controlled, Pharmacokinetic, Safety and Tolerability Study of CSL112 in Adult Subjects With Moderate Renal Impairment and in Healthy Adult Subjects With Normal Renal Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02427035
• Other study ID #: CSL112_1001
• Secondary ID: 2014-005520-10
• Status: Completed
• Phase: Phase 1
• First received: April 20, 2015
• Last updated: September 18, 2017
• Start date: May 2015
• Est. completion date: February 2016

Study information

• Verified date: September 2017
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: February 2016
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction
• Renal Insufficiency

Intervention

Biological:
• CSL112
CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.

Other:
• Placebo
0.9% weight/volume sodium chloride solution (ie, normal saline)

Locations

Country	Name	City	State
Germany	Study Site - 17101	Berlin
Germany	Study Site - 17102	Munich
United Kingdom	Study Site - 24101	London
United Kingdom	Study Site - 24102	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Plasma apoA-I and PC Cmax		Before and at up to 10 time points (during up to 7 days) after infusion
Primary	Plasma apoA-I and PC Tmax		Before and at up to 10 time points (during up to 7 days) after infusion
Primary	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
Primary	Plasma apoA-I and PC clearance		Before and at up to 10 time points (during up to 7 days) after infusion
Primary	Plasma apoA-I and PC t1/2		Before and at up to 10 time points (during up to 7 days) after infusion
Primary	Urinary excretion of apoA-I (Ae0-t)	Amount excreted (Ae) of apoA-I over a collection interval 0-t.	Before and up to 48 hours after infusion
Primary	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
Primary	Renal clearance of apoA-I	Renal clearance of apoA-I, calculated as Ae0-48/AUC0-48	Before and up to 48 hours after infusion
Secondary	Urinary excretion of sucrose(Ae0-t)	Amount of sucrose excreted over a collection interval 0-t.	Before and up to 48 hours after infusion
Secondary	Urinary excretion of sucrose (%fe0-t)	Percent fraction excreted sucrose in urine over time interval 0-t, calculated as Ae0-t/Dose x 100.	Before and up to 48 hours after infusion
Secondary	Urinary excretion of sucrose (clearance)	Renal clearance of sucrose, calculated as Ae0-48/AUC0-48	Before and up to 48 hours after infusion
Secondary	Adverse drug reaction (ADR) or suspected ADR frequency (%)	The overall percentage of participants with adverse reactions or suspected adverse reactions: That begin during or within 1 hour of an infusion; or; That may be causally related to the administration of the investigational product; or; For which the Investigator's causality assessment is missing or indeterminate; or; 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.	Up to approximately 127 days
Secondary	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
Secondary	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.
Secondary	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.
Secondary	Plasma sucrose AUC	Baseline corrected plasma sucrose AUC0-infinity	Before and at up to 7 time points (during up to 2 days) after infusion
Secondary	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
Secondary	Plasma sucrose Cmax		Before and at up to 7 time points (during up to 2 days) after infusion
Secondary	Plasma sucrose Tmax		Before and at up to 7 time points (during up to 2 days) after infusion
Secondary	Plasma sucrose Volume of distribution during terminal phase		Before and at up to 7 time points (during up to 2 days) after infusion
Secondary	Plasma sucrose Clearance		Before and at up to 7 time points (during up to 2 days) after infusion
Secondary	Plasma sucrose t1/2		Before and at up to 7 time points (during up to 2 days) after infusion
Secondary	Adverse drug reaction (ADR) or suspected ADR frequency	The overall number of participants with adverse reactions or suspected adverse reactions: That begin during or within 1 hour of an infusion; or; That may be causally related to the administration of the investigational product; or; For which the Investigator's causality assessment is missing or indeterminate; or; 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.	Up to approximately 127 days
Secondary	Number of subjects with AEs		After the start of infusion up to approximately 127 days