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Trial registered on ANZCTR
Registration number
ACTRN12618000805279
Ethics application status
Approved
Date submitted
18/04/2018
Date registered
11/05/2018
Date last updated
22/11/2018
Date data sharing statement initially provided
22/11/2018
Type of registration
Prospectively registered
Titles & IDs
Public title
Assessing the pharmacokinetics, safety, and tolerability of CSL112 in healthy Japanese and Caucasian adults
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Scientific title
A phase 1, randomized, double-blind, placebo-controlled study to evaluate the pharmacokinetics, safety, and tolerability of CSL112 in healthy Japanese and Caucasian subjects
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Secondary ID [1]
294559
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None
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Universal Trial Number (UTN)
N/A
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Trial acronym
N/A
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Linked study record
N/A
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Health condition
Health condition(s) or problem(s) studied:
Acute Coronary Syndrome
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Condition category
Condition code
Cardiovascular
306444
306444
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0
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Coronary heart disease
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
CSL112 / placebo will be administered to 3 dose cohorts (each cohort receiving a different dose from the other cohorts) of subjects as a single intravenous infusion into a peripheral or central vein over 2 hours by the Investigator (or delegate). Subjects are dosed on Day 1 and are on site for observation until Day 7. Subjects are brought back to the site between day 30 and 37 for a follow-up observation.
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Intervention code [1]
300852
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Treatment: Drugs
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Comparator / control treatment
Placebo (25% albumin solution diluted to 3.2% v/v) is to be administered as a single intravenous infusion into a peripheral or central vein over 2 hours at the same volume as the CSL112 infusion.
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Control group
Placebo
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Outcomes
Primary outcome [1]
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Area under the ApoA-1 plasma concentration-time curve (AUC) from time 0 to 72 hours (AUC0-72)
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Assessment method [1]
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Timepoint [1]
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Assessed before CSL112 administration and at 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hours after the start of CSL112 administration
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Primary outcome [2]
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Maximum concentration of ApoA-1 in plasma (Cmax)
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Assessment method [2]
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Timepoint [2]
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Assessed before CSL112 administration and at 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hours after the start of CSL112 administration
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Secondary outcome [1]
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The percentage of subjects with treatment-related adverse events (AEs) overall, by severity and by causality. AEs will be assessed through evaluation of physical examinations, vital signs, electrocardiograms, clinical laboratory parameters, and monitoring of AEs. AEs will be recorded during the study and summarized by n (%) subjects overall, by severity, and by causality.
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Assessment method [1]
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Timepoint [1]
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Assessed continually for the duration of the subject's participation in the study, up to 37 days per subject.
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Secondary outcome [2]
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Clinically significant elevation in markers of liver function assessed through serum assay. Clinically significant elevations are defined as alanine aminotransferase > 3 x upper limit of normal, aspartate aminotransferase > 3 x upper limit of normal, or total bilirubin > 2 x upper limit of normal.
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Assessment method [2]
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Timepoint [2]
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Assessed before CSL112 administration and at 24, 48 and 144 hours after the start of CSL112 administration
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Secondary outcome [3]
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Serum creatinine > or = 1.5 x Baseline value
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Assessment method [3]
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Timepoint [3]
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Assessed before CSL112 administration and at 24, 48 and 144 hours after the start of CSL112 administration
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Secondary outcome [4]
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Clinically significant changes in individual clinical and / or other safety parameters:
• Clinical laboratory tests (biochemistry, hematology, urinalysis, and spot urine protein [total protein to creatinine ratio and albumin to creatinine ratio])
• ECGs
• Vital signs (supine blood pressure, pulse rate, tympanic temperature)
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Assessment method [4]
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Timepoint [4]
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Biochemistry and hematology assessed before CSL112 administration and 24, 48 and 144 hours after the start of CSL112 administration. Urinalysis and ECGs assessed before CSL112 administration and at 144 hours after the start of CSL112 administration. Spot urine assessed before CSL112 administration and 24-36, 48 and 144 hours after the start of CSL112 administration. Vital Signs assessed before CSL112 administration and 2, 4, 6, 8, 12, 24, 48, 72, 96 and 144 hours after the start of CSL112 administration.
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Secondary outcome [5]
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Clinically significant changes in individual clinical and / or other safety parameters:
• Immunogenicity (ie, presence of anti-CSL112 and / or anti-apoA-I antibodies)
• Serology (ie, presence of human immunodeficiency virus -1 and / or 2 antibodies, hepatitis A virus antibody, hepatitis B virus surface antigen, and / or hepatitis C virus antibody)
• Nucleic acid testing (ie, presence of parvovirus B19)
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Assessment method [5]
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Timepoint [5]
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Assessed before CSL112 administration. Also assessed at 144 hours and during the last visit occurring between 30 and 37 days after the start of CSL112 administration.
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Secondary outcome [6]
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Individual plasma PK parameters of ApoA-I including:
• AUC from time 0 to the last collection time (AUClast)
• AUC from time 0 extrapolated to time infinity (AUCinf)
• Partial AUC from time 0 to time point t (AUC0-t)
• Time to reach maximum concentration in plasma (Tmax)
• Terminal plasma half-life (t½)
• Clearance (CL)
• Volume of distribution (Vz)
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Assessment method [6]
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Timepoint [6]
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Assessed before CSL112 administration and at 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hours after the start of CSL112 administration
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Secondary outcome [7]
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Individual Plasma PK parameters (apparent values where applicable) of phosphatidylcholine including:
• AUClast
• AUCinf
• AUC0-t
• Cmax
• Tmax
• t½
• CL
• Vz
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Assessment method [7]
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Timepoint [7]
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Assessed before CSL112 administration and at 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hours after the start of CSL112 administration
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Secondary outcome [8]
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Individual Plasma PK parameters of sucrose including:
• AUClast
• AUCinf
• AUC0-t
• Cmax
• Tmax
• t½
• CL
• Vz
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Assessment method [8]
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Timepoint [8]
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Assessed before CSL112 administration and at 1, 2, 4, 6, 8, 12, 24 and 48 hours after the start of CSL112 administration
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Secondary outcome [9]
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Individual Plasma PK parameters of cholate including:
• AUClast
• AUCinf
• AUC0-t
• Cmax
• Tmax
• t½
• CL
• Vz
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Assessment method [9]
345429
0
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Timepoint [9]
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Assessed before CSL112 administration and at 1, 2, 4, 6, 8, 12 and 24 hours after the start of CSL112 administration
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Secondary outcome [10]
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Individual Urinary excretion of apoA-I including measuring:
• Cumulative amount excreted into urine from time 0 up to time point t (Ae0-t)
• Percent fraction excreted into urine from time 0 up to time point t (%fe0-t)
• Renal clearance (CLR)
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Assessment method [10]
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Timepoint [10]
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Assessed before CSL112 administration and assessed at ranges 0-4 hours, 4-8 hours, 8-12 hours, 12-24 hours, 24-36 hours and 36-48 hours after the start of CSL112 administration
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Secondary outcome [11]
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Individual Urinary excretion of sucrose including measuring:
• Ae0-t
• %fe0-t
• CLR
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Assessment method [11]
345431
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Timepoint [11]
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Assessed before CSL112 administration and assessed at ranges 0-4 hours, 4-8 hours, 8-12 hours, 12-24 hours, 24-36 hours and 36-48 hours after the start of CSL112 administration
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Secondary outcome [12]
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Individual Plasma PD parameters of cholesterol efflux capacity (total, ATP binding cassette transporter protein subfamily A member 1 [ABCA1]-independent, ABCA1-dependent [calculated]) including:
• Area under the effect curve (AUEC) from time 0 to the last collection time (AUEClast)
• AUEC from time 0 to time point t (AUEC0-t)
• Maximum response (Rmax)
• Tmax
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Assessment method [12]
345432
0
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Timepoint [12]
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Assessed before CSL112 administration and at 2, 4, 8, 24, 48, 72, 96 and 144 hours after the start of CSL112 administration
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Eligibility
Key inclusion criteria
Healthy (determined by a comprehensive clinical assessment) male or female adult Japanese or Caucasian subjects with a body weight of >= 45 kg to <= 95 kg and a body mass index of >= 18.0 to <= 29.9 kg/m2. Japanese subjects must be of Japanese descent (ie, born in Japan with 2 Japanese biologic parents and 4 Japanese biologic grandparents) and have not lived outside of Japan for >= 10 successive years. Caucasian subjects must have origins in any of the original peoples of Europe, the Middle East, or North Africa.
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Minimum age
20
Years
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Maximum age
54
Years
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Sex
Both males and females
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Can healthy volunteers participate?
Yes
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Key exclusion criteria
1. Evidence of a clinically significant medical condition, disorder or disease.
2. Evidence of hepatobiliary disease.
3. Any clinically significant abnormalities in hematology, biochemistry, or urinalysis as judged by the Investigator and / or study Medical Monitor at Screening and / or Day -1.
4. Sustained and / or symptomatic hypotension (systolic blood pressure < 90 mmHg).
5. Any major illness requiring hospitalization within the 30 days before the Screening Visit or planned hospitalization at any time during the study.
6. Known history of soy bean or peanut allergies, hypersensitivity to the investigational product, or to any excipients of the investigational product or placebo (albumin), or IgA deficiency or antibodies to IgA.
7. A positive result for HAV antibody, HBV surface antigen, HCV antibody, or HIV -1 and / or 2 antibodies at Screening.
8. Evidence or history of substance or alcohol abuse or a positive drug test or alcohol breath test at Screening or Day -1.
9. Smokers, those who have smoked or used tobacco products within 6 months before Screening
10. Plans to participate in another investigational drug study while enrolled in this study or has participated in any investigational drug study within 30 days (or 5 half-lives, whichever is longer) or more than 3 investigational drug studies within the 12 months before Day 1.
11. Clinically significant abnormalities in vital signs or physical examination at Screening or Day -1 as judged by Investigator and / or Sponsor.
12. A mean QTcF > 450 ms for male subjects or > 470 ms for female subjects at Screening.
13. Subjects who have been a recipient of an organ transplant.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Other
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Other design features
Japanese subjects enrolled in the study will be assigned to Cohorts 1, 2, or 3 in a sequential manner. Caucasian subjects will be enrolled in the study and assigned to Cohort 3 only after subject matching by weight within 15% of the median weight of Japanese subjects in Cohort 3. All subjects will be randomized to treatment (CSL112 or placebo) within their cohort and within their race (Cohort 3 only). Milestones do not need to met for the next cohort to be enrolled.
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Phase
Phase 1
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Type of endpoint/s
Pharmacokinetics / pharmacodynamics
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Date of first participant enrolment
Anticipated
12/05/2018
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Actual
16/05/2018
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Date of last participant enrolment
Anticipated
27/08/2018
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Actual
31/07/2018
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Date of last data collection
Anticipated
3/10/2018
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Actual
3/09/2018
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Sample size
Target
52
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Accrual to date
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Final
52
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Recruitment in Australia
Recruitment state(s)
NSW
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Funding & Sponsors
Funding source category [1]
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Commercial sector/Industry
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Name [1]
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CSL Limited
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Address [1]
299180
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45 Poplar Road
Parkville
VIC 3052
Australia
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Country [1]
299180
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Australia
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Primary sponsor type
Commercial sector/Industry
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Name
CSL Limited
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Address
45 Poplar Road
Parkville
VIC 3052
Australia
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Country
Australia
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Secondary sponsor category [1]
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None
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Name [1]
298439
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Address [1]
298439
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Country [1]
298439
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Ethics approval
Ethics application status
Approved
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Ethics committee name [1]
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Bellberry Limited
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Ethics committee address [1]
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129 Glen Osmond Road Eastwood SA 5063 Australia
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Ethics committee country [1]
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Australia
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Date submitted for ethics approval [1]
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07/03/2018
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Approval date [1]
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13/04/2018
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Ethics approval number [1]
300104
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2018-02-096
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Summary
Brief summary
The purpose of this study is to assess the pharmacokinetics, safety, and tolerability of single doses of CSL112 after intravenous administration in healthy Japanese and Caucasian subjects. Japanese subjects enrolled in the study will be assigned to Cohorts 1, 2, or 3 in a sequential manner. Caucasian subjects will be enrolled in the study and assigned to Cohort 3 only after subject matching by weight within 15% of the median weight of Japanese subjects in Cohort 3. All subjects will be randomized to treatment (CSL112 or placebo) within their cohort and within their race (Cohort 3 only).
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Trial website
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Trial related presentations / publications
(none)
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Public notes
N/A
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Contacts
Principal investigator
Name
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Dr Dr James Kuo
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Address
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Scientia Clinical Research Ltd
Level 5, The Bright Alliance Building
Corner Avoca & High Street
Randwick NSW 2031
Australia
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Country
82578
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Australia
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Phone
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+61-2-9382 5807
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Fax
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N/A
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Email
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charlotte.lemech@scientiaclinicalresearch.com.au
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Contact person for public queries
Name
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Dr James Kuo
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Address
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Scientia Clinical Research Ltd,
Level 5, The Bright Alliance Building
Corner Avoca & High Street
Randwick NSW 2031
Australia
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Country
82579
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Australia
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Phone
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+1800 727 874
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Fax
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N/A
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Email
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recruitment@scientiaclinicalresearch.com.au
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Contact person for scientific queries
Name
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Dr James Kuo
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Address
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Scientia Clinical Research Ltd
Level 5, The Bright Alliance Building
Corner Avoca & High Street
Randwick NSW 2031
Australia
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Country
82580
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Australia
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Phone
82580
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+61-2-9382 5807
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Fax
82580
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N/A
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Email
82580
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james.kuo@scientiaclinicalresearch.com.au
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Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
Company policy not to share data at this time
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
Documents added manually
No documents have been uploaded by study researchers.
Documents added automatically
Source
Title
Year of Publication
DOI
Embase
Pharmacometric analyses to characterize the effect of CSL112 on apolipoprotein A-I and cholesterol efflux capacity in acute myocardial infarction patients.
2021
https://dx.doi.org/10.1111/bcp.14666
Embase
A method for detection of anti-drug antibodies to a biotherapeutic (CSL112) with endogenous counterpart (apolipoprotein A-I) using a novel sample pre-treatment electrochemiluminescence assay.
2023
https://dx.doi.org/10.1016/j.jim.2022.113411
N.B. These documents automatically identified may not have been verified by the study sponsor.
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