Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001554358
Ethics application status
Approved
Date submitted
3/11/2017
Date registered
15/11/2017
Date last updated
16/09/2019
Date data sharing statement initially provided
13/12/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 1 single ascending study in healthy Caucasian and Japanese Adult subjects to evaluate the Safety, Tolerability, and Pharmacokinetics of CSL346.
Scientific title
A Phase 1, Randomized, Double-blind, Placebo-controlled Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CSL346 in Healthy Caucasian and Japanese Adult Subjects
Secondary ID [1] 293272 0
CSL346_1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Abnormal lipid accumulation 305341 0
Dyslipidemia 305342 0
Hyperglycemia 305343 0
Condition category
Condition code
Metabolic and Endocrine 304629 304629 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single intravenous infusion or subcutaneous injection of sterile solution for injection containing CSL346. Cohort A1: 0.1 mg/kg CSL346 or placebo; Cohort A2: 0.3 mg/kg CSL346 or placebo; Cohort A3: 1.0 mg/kg CSL346 or placebo; Cohort A4: 3 mg/kg CSL346 or placebo; Cohort A5: 10 mg/kg CSL346 or placebo; Cohort A6: (Optional) Additional dose, may be tested provided the dose is not expected to exceed predicted serum CSL346 Cmax of 3605 µg/mL and AUC0-168 of 297500 µg hr/mL
Cohort B1 through B4: Part B procedures will mirror Part A, but without the use of a sentinel group. Up to 4 dose levels of CSL346 will be studied in a total of approximately 32 subjects.
Cohorts C1-C2: In Part C of the study, the doses to be administered will be equivalent to doses previously administered by IV infusion. single ascending-doses of CSL346 will be administered by subcutaneous injection or infusion in up to 2 cohorts of healthy, adult, Caucasian subjects. SC administration will be evaluated at two dose levels: 'low dose' and 'high dose.' The Sponsor, in consultation with the SRC, will decide if sentinel subjects should be included in Part C.
Intervention code [1] 299530 0
Treatment: Drugs
Comparator / control treatment
Single intravenous infusion of sterile solution for injection containing placebo.
Control group
Placebo

Outcomes
Primary outcome [1] 303857 0
Frequency, nature, and severity of Adverse Events (AEs). All AEs, regardless of when they were reported, will be listed. An overview summary of AEs, including the number of subjects with any AE; AEs related to study treatment; AEs leading to discontinuation of study treatment; SAEs and deaths will be produced. Treatment emergent AEs will be summarized by preferred term and System Organ Class (SOC) as well as severity.
Timepoint [1] 303857 0
Up to 111 days
Secondary outcome [1] 340294 0
Characterize the pharmacokinetics (PK) of CSL346. PK of CSL346 in serum, including Cmax, AUC from 0 until time t (AUC0-t), AUC from 0 extrapolated to infinity (AUC0-inf), time of maximum concentration (tmax), terminal elimination half-life (t1/2), total systemic clearance (CL), and volume of distribution during the elimination phase (V), and in Part C only, bioavailability (F), apparent clearance (CL/F), and apparent volume of distribution (Vz/F) in healthy Caucasian and Japanese adult subjects.
Timepoint [1] 340294 0
At 1, 2, 3, 4, 5, 8, 15, 22, 29, 36, 57, and 85 days post drug administration
Secondary outcome [2] 340295 0
Assess if clinically significant changes from predose baseline values develop in vital signs and safety laboratory measurements after single dose IV and SC administration. Clinically significant changes from baseline in vital signs (blood pressure, pulse rate, temperature, respiratory rate), physical exam, and safety laboratory determinations including hematology, serum chemistry, Real-time and 12 lead electrocardiograms (ECGs), and urinalysis.
Timepoint [2] 340295 0
Vital Signs: -21 to -2 (screening), -1, 1, 2, 3, 4, 5, 8, 15, 22, 29, 36, 57, and 85 days post drug administration.
Physical Exam: -21 to -2 (screening), -1, 2, 5, and 85 days post drug administration
Safety Lab Measurements:
Hematology: -21 to -2 (screening), -1, 2, 3, 5, 8, 22, 36, 85 post drug administration.
Serum Chemistry: -1, 1, 2, 3, 8, 29, 57, and 85 post drug administration.
ECGs: -21 to -2 (screening), -1, 1, 2, 3, 5, and 85 post drug administration
Secondary outcome [3] 340296 0
Determine the immunogenicity of CSL346 after single ascending dose IV and SC administration in healthy Caucasian and Japanese subjects. This will be determined through the presence of anti-CSL346 antibodies in serum.
Timepoint [3] 340296 0
At 1, 29, and 85 post drug administration.
Secondary outcome [4] 354950 0
Evaluate the effect of single dose IV administration of CSL346 on cardiodynamic electrocardiogram (ECG) parameters. Electrocardiogram related endpoints from Holter Monitor:
• Change-from-baseline Corrected QT interval using Fridericia's formula (QTcF)
• Change-from-baseline heart rate, PR interval and QRS interval (HR, PR and QRS)
• Placebo-corrected HR, QTcF, PR and QRS (HR, QTcF, PR and QRS)
• Frequency of T-wave morphology changes and presence of U- waves
Timepoint [4] 354950 0
Days -21 to -2 (Screening), -1, 1, 2, 3, 6, and 85. For Holter monitor assessments, up to 10 replicate 12-lead ECGs will be extracted at 3 timepoints prior to the infusion (-45, -30 and -15 minutes) and immediately after (0 hour) and 0.5, 1, 6, 12, 24, and 48 hours after the end of the infusion.

Eligibility
Key inclusion criteria
PART A:
1. Healthy caucasian male or female subject aged 20 to 55 years.
2. Male subjects and their female partners who are of childbearing potential must be using 2 highly effective forms of birth control (1 of which must be a barrier method) starting at Screening and through 90 days after the IV infusion of IP unless (a)-The male subject has undergone effective surgical sterilization prior to entering the clinical study, and/or (b)-The female sexual partner(s) of male subject has undergone effective surgical sterilization prior to the subject entering the clinical study or is (are) post-menopausal.
3. Healthy, as judged by the investigator, with a clinical assessment to include medical history, physical examination, vital signs, ECG, and clinical laboratory tests with no clinically important findings.
4. Have a body mass index (BMI) of 18 to 30 kg/m2 and weight > 50 kg.

PART B: (In addition to inclusion criteria for PART A).1. Must be first generation Japanese, born in Japan and has not lived outside of Japan for greater than 10 years.

PART C: (In addition to inclusion criteria items 2-4 for PART A). 1. Must be Caucasian or first generation Japanese.
Minimum age
20 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History of any clinically significant disease or disorder
2. Any positive result on screening for hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (anti-HAV; IgM), hepatitis C virus antibodies (anti-HCV) or human immunodeficiency virus (HIV)-1 and/or -2 antibodies
3. Medical history of heart disease or any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG
4. History of alcohol, drug, or medication abuse within 1 year of providing informed consent
5. Smokers, those who have smoked or used tobacco products within 6 months prior to providing informed consent
6. Known or suspected hypersensitivity to CSL346, or to any excipients of CSL346
7. Women of childbearing potential
8. The subject has participated in any other investigational study drug trial within 30 days (or 5 half-lives, whichever is longer) or, has participated in more than 3 clinical studies involving the administration of an investigational agent within the last 12 months prior to the 1st dose of investigational product (IP)
9. The subject has a history of significant blood loss or has donated more than 500 mL within 90 days prior to the 1st dose of IP
10. Any clinically significant abnormalities in clinical chemistry, hematology or urinalysis results as judged by the investigator and/or sponsor.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomization by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
This will be done by means of a computer-generated randomization list and there will be no specification with respect to any of the demographic or baseline characteristics (ie, no stratification factors).
Masking / blinding
Blinded (masking used)
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
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
17/11/2017
Actual
13/11/2017
Date of last participant enrolment
Anticipated
11/03/2019
Actual
4/02/2019
Date of last data collection
Anticipated
30/06/2019
Actual
3/05/2019
Sample size
Target
116
Accrual to date
Final
82
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 18006 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 297900 0
Commercial sector/Industry
Name [1] 297900 0
CSL Limited
Country [1] 297900 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
CSL Limited
Address
45 Poplar Road
Parkville
VIC 3052 Australia
Country
Australia
Secondary sponsor category [1] 296955 0
None
Name [1] 296955 0
Address [1] 296955 0
Country [1] 296955 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298950 0
Alfred Human Research Ethics Committee
Ethics committee address [1] 298950 0
Ethics committee country [1] 298950 0
Australia
Date submitted for ethics approval [1] 298950 0
30/08/2017
Approval date [1] 298950 0
12/10/2017
Ethics approval number [1] 298950 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2274 2274 0 0
/AnzctrAttachments/373925-440-17 Certificate of Approval.pdf (Ethics approval)
Attachments [2] 2275 2275 0 0
/AnzctrAttachments/373925-CSL345_1001_Yellow Form_12Oct2017 (2).pdf (Ethics approval)

Contacts
Principal investigator
Name 78758 0
Dr Jason Lickliter
Address 78758 0
Nucleus Network - Centre for Clinical Studies
(AMREP)
Level 5, 89 Commercial Road
3004 Melbourne VIC
Country 78758 0
Australia
Phone 78758 0
+61 3 9076 8917
Fax 78758 0
Email 78758 0
[email protected]
Contact person for public queries
Name 78759 0
Diana Lanchoney
Address 78759 0
CSL Behring
1020 First Avenue
King of Prussia, PA. 19406
Country 78759 0
United States of America
Phone 78759 0
+1-610-878-4424
Fax 78759 0
Email 78759 0
[email protected]
Contact person for scientific queries
Name 78760 0
Diana Lanchoney
Address 78760 0
CSL Behring
1020 First Avenue
King of Prussia, PA. 19406
Country 78760 0
United States of America
Phone 78760 0
+1-610-878-4424
Fax 78760 0
Email 78760 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
CSL will not be sharing IPD for this Phase I study.


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
No additional documents have been identified.