Back to resultsA Study of CSL112 in Healthy Adults and in Adults With Moderate Renal Impairment
Primary Purpose
Acute Myocardial Infarction
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CSL112
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myocardial Infarction
Eligibility Criteria
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
Sites / Locations
- Study Site - 17101
- Study Site - 17102
- Study Site - 24101
- Study Site - 24102
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Low
High
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Plasma apolipoprotein A-I (apoA-I) and phosphatidylcholine (PC) area under the curve (AUC)
Baseline corrected plasma apoA-I and PC AUC0-infinity
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
Plasma apoA-I and PC Cmax
Plasma apoA-I and PC Tmax
Plasma apoA-I and PC Volume of distribution during terminal phase
Plasma apoA-I and PC clearance
Plasma apoA-I and PC t1/2
Urinary excretion of apoA-I (Ae0-t)
Amount excreted (Ae) of apoA-I over a collection interval 0-t.
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.
Renal clearance of apoA-I
Renal clearance of apoA-I, calculated as Ae0-48/AUC0-48
Secondary Outcome Measures
Urinary excretion of sucrose(Ae0-t)
Amount of sucrose excreted over a collection interval 0-t.
Urinary excretion of sucrose (%fe0-t)
Percent fraction excreted sucrose in urine over time interval 0-t, calculated as Ae0-t/Dose x 100.
Urinary excretion of sucrose (clearance)
Renal clearance of sucrose, calculated as Ae0-48/AUC0-48
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.
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.
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.
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.
Plasma sucrose AUC
Baseline corrected plasma sucrose AUC0-infinity
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
Plasma sucrose Cmax
Plasma sucrose Tmax
Plasma sucrose Volume of distribution during terminal phase
Plasma sucrose Clearance
Plasma sucrose t1/2
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.
Number of subjects with AEs
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02427035
Brief Title
A Study of CSL112 in Healthy Adults and in Adults With Moderate Renal Impairment
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
May 2015 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
February 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myocardial Infarction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low
Arm Type
Experimental
Arm Description
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.
Arm Title
High
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
CSL112
Intervention Description
CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
0.9% weight/volume sodium chloride solution (ie, normal saline)
Primary Outcome Measure Information:
Title
Plasma apolipoprotein A-I (apoA-I) and phosphatidylcholine (PC) area under the curve (AUC)
Description
Baseline corrected plasma apoA-I and PC AUC0-infinity
Time Frame
Before and at up to 10 time points (during up to 7 days) after infusion
Title
Plasma apoA-I and PC AUC0-last and AUC 0-t
Description
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
Time Frame
Before and at up to 10 time points (during up to 7 days) after infusion
Title
Plasma apoA-I and PC Cmax
Time Frame
Before and at up to 10 time points (during up to 7 days) after infusion
Title
Plasma apoA-I and PC Tmax
Time Frame
Before and at up to 10 time points (during up to 7 days) after infusion
Title
Plasma apoA-I and PC Volume of distribution during terminal phase
Time Frame
Before and at up to 10 time points (during up to 7 days) after infusion
Title
Plasma apoA-I and PC clearance
Time Frame
Before and at up to 10 time points (during up to 7 days) after infusion
Title
Plasma apoA-I and PC t1/2
Time Frame
Before and at up to 10 time points (during up to 7 days) after infusion
Title
Urinary excretion of apoA-I (Ae0-t)
Description
Amount excreted (Ae) of apoA-I over a collection interval 0-t.
Time Frame
Before and up to 48 hours after infusion
Title
Urinary excretion of apoA-I (%fe0-t)
Description
Percent fraction excreted (%fe) of apoA-I in urine over time interval 0-t, calculated as Ae0-t/Dose x 100.
Time Frame
Before and up to 48 hours after infusion
Title
Renal clearance of apoA-I
Description
Renal clearance of apoA-I, calculated as Ae0-48/AUC0-48
Time Frame
Before and up to 48 hours after infusion
Secondary Outcome Measure Information:
Title
Urinary excretion of sucrose(Ae0-t)
Description
Amount of sucrose excreted over a collection interval 0-t.
Time Frame
Before and up to 48 hours after infusion
Title
Urinary excretion of sucrose (%fe0-t)
Description
Percent fraction excreted sucrose in urine over time interval 0-t, calculated as Ae0-t/Dose x 100.
Time Frame
Before and up to 48 hours after infusion
Title
Urinary excretion of sucrose (clearance)
Description
Renal clearance of sucrose, calculated as Ae0-48/AUC0-48
Time Frame
Before and up to 48 hours after infusion
Title
Adverse drug reaction (ADR) or suspected ADR frequency (%)
Description
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.
Time Frame
Up to approximately 127 days
Title
Clinically significant changes in routine safety assessments
Description
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.
Time Frame
Up to approximately 97 days
Title
Clinically important change in drug-induced liver injury
Description
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.
Time Frame
From baseline (before infusion) up to Day 16.
Title
Clinically important change in renal status
Description
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.
Time Frame
From baseline (before infusion) up to Day 16.
Title
Plasma sucrose AUC
Description
Baseline corrected plasma sucrose AUC0-infinity
Time Frame
Before and at up to 7 time points (during up to 2 days) after infusion
Title
Plasma sucrose AUC0-last and AUC 0-t
Description
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
Time Frame
Before and at up to 7 time points (during up to 2 days) after infusion
Title
Plasma sucrose Cmax
Time Frame
Before and at up to 7 time points (during up to 2 days) after infusion
Title
Plasma sucrose Tmax
Time Frame
Before and at up to 7 time points (during up to 2 days) after infusion
Title
Plasma sucrose Volume of distribution during terminal phase
Time Frame
Before and at up to 7 time points (during up to 2 days) after infusion
Title
Plasma sucrose Clearance
Time Frame
Before and at up to 7 time points (during up to 2 days) after infusion
Title
Plasma sucrose t1/2
Time Frame
Before and at up to 7 time points (during up to 2 days) after infusion
Title
Adverse drug reaction (ADR) or suspected ADR frequency
Description
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.
Time Frame
Up to approximately 127 days
Title
Number of subjects with AEs
Time Frame
After the start of infusion up to approximately 127 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Denise D'Andrea, M.D.
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
Study Site - 17101
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Study Site - 17102
City
Munich
ZIP/Postal Code
D-81241
Country
Germany
Facility Name
Study Site - 24101
City
London
ZIP/Postal Code
SE1 1YR
Country
United Kingdom
Facility Name
Study Site - 24102
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
33217027
Citation
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.
Results Reference
derived
PubMed Identifier
30240132
Citation
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.
Results Reference
derived
Learn more about this trial
A Study of CSL112 in Healthy Adults and in Adults With Moderate Renal Impairment
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