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Trial registered on ANZCTR


Registration number
ACTRN12618000868280
Ethics application status
Approved
Date submitted
27/10/2017
Date registered
22/05/2018
Date last updated
5/12/2018
Date data sharing statement initially provided
5/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 Study to Evaluate the Safety of CBL-514 Injection on Convexity or Fullness of Abdominal Subcutaneous Fat in Healthy Volunteers
Scientific title
A Phase 1 Study to Evaluate the Safety and Tolerability of CBL-514 Injection on Convexity or Fullness of Abdominal Subcutaneous Fat in Healthy Volunteers
Secondary ID [1] 293223 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy to overweight subjects with undesirable subcutaneous fat thickness in belly 305243 0
Condition category
Condition code
Skin 304547 304547 0 0
Dermatological conditions
Diet and Nutrition 305174 305174 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
CBL-514 will be administered via injection into the abdominal subcutaneous adipose layer. The intervention will be administered in a single dose escalation scheme with 9 sequential cohorts. The design of dose escalation is 2, 10, 20, 40, 40, 80, 160, 240, and 320 mg of CBL-514-active pharmaceutical ingredient in these sequential cohorts. In each cohort, one single dose of CBL-514 comprises a number of administered injections which varies with the study design. The amount of CBL-514 per injection is 0.4 mL in the first 3 cohorts and 0.8 mL in the rest of cohorts. The first 5 cohorts will receive both CBL-514 and placebo on each side of the abdomen. The treatment will be double-blind and randomized so which side of abdomen receives placebo or CBL-514 is unknown. The injection numbers of CBL-514 and placebo are 1~10 injections and 1~10 injections respectively on the different side of the abdomen. The following 4 cohorts will receive only CBL-514, respectively administered with 20, 40, 60, and 80 injections.

The intervention will be primarily conducted by the research nurse and supervised by the Principal Investigator who is a cosmetic practitioner, and the following safety monitoring will be conducted by Principal Investigator.
Intervention code [1] 299480 0
Treatment: Drugs
Comparator / control treatment
Individual placebo-controlled of saline injection
Control group
Placebo

Outcomes
Primary outcome [1] 303781 0
Safety and tolerability following a single dose of CBL-514 as assessed by recording of treatment-emergent adverse events, laboratory assessments, vital signs, electrocardiograms (ECGs) and clinical observations

Treatment-emergent adverse events will be summarized by system organ class, preferred term, severity, and suspected relationship to study drug.
The major adverse events may include localised pain, bruising, numbness, redness, swelling, edema, induration, itching, altered sensations, and skin tightness which would be around the injection sites.
Clinical laboratory test includes biochemistry, hematology, urinalysis, pregnancy status, and virology assessments. Physical examinations, vital signs, standard electrocardiogram and any other untoward medical events during the study period will also be recorded for assessment.
Timepoint [1] 303781 0
On day 1 and throughout the follow-up visits on week 2 and week 4
Secondary outcome [1] 340128 0
Pharmacokinetics parameters after single dose injection There are 9 timepoints within 24 hours after the injection to collect the plasma samples from subjects. Pharmacokinetic parameters including Cmax, Tmax, AUC0-last, AUC0-24hr, AUCinf, T1/2, CL/F and Vz/F will be analyzed by plasma assay and presented with descriptive statistics by the dose level given.
Timepoint [1] 340128 0
On day 1: Pre-dosing, 1 hr (± 5 min), 2 hrs (± 5 min), 4 hrs (± 10 min), 6 hrs (± 10 min), 8 hrs (± 10 min), 10 hrs (± 10 min), 12 hrs (± 10 min), 24 hrs (± 10 min) post-dosing

Eligibility
Key inclusion criteria
A subject can participate in the study only if all the following criteria are met:

1. Aged 18 years to 64 years old (at Screening), inclusive.

2. Body Mass Index >18.5 and <35 kg/m^2 and body weight greater than or equal to 50 kg at Screening and Day 1.

3. Has maximum waist circumference greater than or equal to 80 cm

4. Subcutaneous fat thickness of at least 3.0 cm by pinch method (measured by calibrated caliper) surrounding the navel at Screening and Day 1.

5. Voluntarily signs the informed consent form and, in the opinion of the investigators or delegates, are physically and mentally capable of participating in the study and willing to adhere to study procedures
Minimum age
18 Years
Maximum age
64 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
A subject who meets any of the following criteria will not be eligible to enter the study:

1. Female subject of childbearing potential who is not willing to commit to an acceptable contraceptive regimen (barrier method) with her partner from the time of Screening and throughout study participation until 12 weeks after the last study drug dose, or who is currently pregnant or lactating.
Females who have been surgically sterilized (hysterectomy or bilateral oophorectomy) or who are postmenopausal (e.g., defined as at least 50 years with greater than or equal to 12 months of amenorrhea with a follicle stimulating hormone >40 IU/L or at least 5 years since last regular menses) are considered to be of non-childbearing potential. Subjects who are not of childbearing potential are not required to use contraception.

2. Subject diagnosed with coagulation disorders or is receiving anticoagulant/antiplatelet therapy or medications or dietary supplements, which impede coagulation or platelet aggregation.

3. Subject has diabetes or glycated hemoglobin greater than or equal to 6.5% (48 mmol/mol) or fasting blood sugar greater than or equal to 7 mmol/L.

4. Subject has a cardiovascular disease, or shows clinically significant abnormal findings in ECG at Screening.

5. Subject with active or prior history of malignancies (except for successfully treated non invasive basal cell carcinoma) or being worked-up for a possible malignancy.

6. Subject with a history of human immunodeficiency virus (HIV)-1, hepatitis B, or hepatitis C infections or subjects with active HIV, hepatitis B, or hepatitis C infections at Screening:
a. Active HIV infection: positive HIV Ag/Ab combo test;
b. Active hepatitis B virus (HBV) infection: positive HBV surface antigen (HBsAg). Subjects with negative HBsAg but with positive HBV core antibody with or without positive HBV surface antibody will also be excluded. However, subjects with negative HBsAg, negative HBV core antibody, and positive HBV surface antibody may be included.
c. Active hepatitis C virus (HCV) infection: positive HCV antibody.

7. Subject has abnormal skin or local skin conditions, which in the opinion of Investigator is inappropriate to participate in the study, including but not limited to any of the following:
a. Skin manifestations of a systemic disease,
b. Any abnormality of the skin or soft tissues of the abdominal wall in the area to be treated,
c. Skin or superficial tissue that does not lie flat on its own when the subject is in the supine position,
d. Sensory loss or dysesthesia in the area to be treated,
e. Evidence of any cause of enlargement in the abdominal area other than localized subcutaneous fat,
f. Tattoos on the area to be treated.

8. Subject who has undergone the following procedures:
a. Previous open or laparoscopic abdominal surgery in the anticipated treatment area,
b. Cardiac pacemakers or any implantable electrical device,
c. Metal implants of any type in the area to be treated,
d. Esthetic procedure to the region to be treated within 6 months before Screening.

9. Subject is on prescription or over-the-counter weight reduction medication or weight reduction programs within 3 months before Screening.

10. Subject is undergoing chronic steroid or immunosuppressive therapy.

11. Requiring continual use of the following therapeutic agents during the study: S-mephenytoin, terfenadine, buspirone, fexofenadine, breast cancer resistance protein (BCRP) substrates (such as mitoxantrone, methotrexate, topotecan, nitrofurantoin, dipyridamole, statins, etc.), cytochrome P450 3A4 inhibitor, or non-steroidal anti-inflammatory drugs (NSAIDs).
If a subject needs to use the above mentioned therapeutic agents during the study for any reason, these therapeutic agents should not be used at least for 48 hours prior to dosing until 24 hours post-dose or the collection of the last PK sample, whichever is later.

12. Unable to receive topical anesthesia (e.g., history of hypersensitivity to lidocaine).

13. Subjects with known allergies or sensitivities to the study drug and/or excipients.

14. Subjects with inadequate liver function at Screening defined as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, or gamma-glutamyl transferase >1.5 × ULN.
A subject with an elevated liver chemistry test up to 1.5 × ULN at Screening should be evaluated by the Investigator to exclude pre-existing liver disease associated with mild elevation of liver chemistry tests. If the mild elevation is assessed by the Investigator as not clinically significant or related to non-alcoholic fatty liver, the subject may be eligible if the follow up tests show an unchanged or reducing value from the initial Screening value. A subject with marginally elevated fasting unconjugated serum bilirubin with documented Gilbert's syndrome, and no other cause for the elevated bilirubin on investigation, may be eligible.

15. Subjects with inadequate renal function, defined as normal serum creatinine, and urea >1.5 × ULN or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Subjects who are currently on dialysis should be excluded.
A subject with serum urea between 1 to 1.5 × ULN at Screening, but an eGFR >60mL/min/1.73 m2 and no other renal risk factors, should be re-tested prior to declaring the subject as eligible. The subject may be eligible if the fasting serum creatinine is not rising nor the eGFR falling, the urinary albumin/creatinine ratio remain <3 mg/mmol.

16. Use of other investigational drug or device within 4 weeks prior to Screening.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Double-blinded and individual placebo-controlled
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 297855 0
Commercial sector/Industry
Name [1] 297855 0
Caliway Biopharmaceuticals Australia Pty Ltd
Address [1] 297855 0
58 Gipps Street, Collingwood, 3066 Vic, Australia
Country [1] 297855 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Caliway Biopharmaceuticals Australia Pty Ltd
Address
58 Gipps Street, Collingwood, 3066 Vic, Australia
Country
Australia
Secondary sponsor category [1] 296905 0
None
Name [1] 296905 0
None
Address [1] 296905 0
None
Country [1] 296905 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298901 0
Bellberry Limited
Ethics committee address [1] 298901 0
Ethics committee country [1] 298901 0
Date submitted for ethics approval [1] 298901 0
20/12/2017
Approval date [1] 298901 0
22/03/2018
Ethics approval number [1] 298901 0

Summary
Brief summary
This is a Phase 1 trial to be conducted in a single center in Australia to evaluate the safety and tolerability of CBL-514 Injection on convexity or fullness of abdominal subcutaneous fat.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78598 0
Dr Ghassan Abiad
Address 78598 0
Level 5, Clive Berghofer Cancer Research Centre, 300 Herston Road, Herston, QLD 4006
Country 78598 0
Australia
Phone 78598 0
+61 4 23885371
Fax 78598 0
N/A
Email 78598 0
ghassan.abiad@bigpond.com
Contact person for public queries
Name 78599 0
Ms Shih-Chun Lu
Address 78599 0
Caliway Biopharmaceuticals Australia Pty Ltd
58 Gipps Street, Collingwood, 3066 Vic, Australia
Country 78599 0
Australia
Phone 78599 0
+61 3 9419 7607
Fax 78599 0
Email 78599 0
jessica.lu@caliway.com.tw
Contact person for scientific queries
Name 78600 0
Dr Ying-Jie Chen
Address 78600 0
Caliway Biopharmaceuticals Australia Pty Ltd
58 Gipps Street, Collingwood, 3066 Vic, Australia
Country 78600 0
Australia
Phone 78600 0
+61 3 9419 7607
Fax 78600 0
Email 78600 0
ying-jie.chen@caliway.com.tw

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Due to the commercial consideration and protection of privacy, the individual participant data for this trial will not be available.
What supporting documents are/will be available?
No other documents available
Summary results
Not applicable