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Trial registered on ANZCTR


Registration number
ACTRN12618001597280
Ethics application status
Approved
Date submitted
19/09/2018
Date registered
26/09/2018
Date last updated
20/11/2018
Date data sharing statement initially provided
20/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Compare the Pharmacokinetics, Safety, Tolerability and Immunogenicity of JHL1188 versus Herceptin (EU and US sourced) in Healthy Male subjects
Scientific title
A Randomized, Double-Blind, 3-Arm, Parallel-Controlled Clinical Study to Compare the Pharmacokinetics, Safety, Tolerability and Immunogenicity of JHL1188 versus Herceptin (EU and US sourced) in Healthy Male subjects
Secondary ID [1] 296059 0
NIL
Universal Trial Number (UTN)
U1111-1220-6223
Trial acronym
Protocol number: JHL -CLIN -1188 -01
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 309702 0
Condition category
Condition code
Cancer 308510 308510 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
JHL1188, single dose of 6 mg/kg via intravenous infusion
Intervention code [1] 312452 0
Treatment: Drugs
Comparator / control treatment
EU sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion
US sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion
Control group
Active

Outcomes
Primary outcome [1] 307482 0
Pharmacokinetic similarity between JHL1188, EU-Herceptin and US-Herceptin after a single IV infusion of 6 mg/kg in healthy male subjects detected using serum samples to calculate the primary PK parameter - Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf)
Timepoint [1] 307482 0
Blood samples will be collected at the following timepoints: predose (within -30min prior to dose), prior to end of infusion (within 10min prior to end of infusion), 3h (± 10 min), 6h (± 10 min), 12h (± 10 min) and 24h (± 10 min) after the start of infusion, 48h ± 2h (Day 3), 72h ± 2h (Day 4), 96h ± 2h (Day 5), 168h ± 2h (Day 8), 336h (Day 15 ± 1d), 504h (Day 22 ± 1d), 672h (Day 29 ± 1d), 1008h (Day 43 ± 2d) and 1680h (Day 71 ± 2d) after the start of infusion.
Secondary outcome [1] 352031 0
Pharmacokinetic similarity between JHL1188, EU-Herceptin and US-Herceptin after a single IV infusion of 6 mg/kg in healthy male subjects detected using serum samples to calculate the pK parameter - Area under the serum drug concentration - time curve from 0 to the last quantifiable concentration (AUC0-last)
Timepoint [1] 352031 0
Blood samples will be collected at the following timepoints: predose (within -30min prior to dose), prior to end of infusion (within 10min prior to end of infusion), 3h (± 10 min), 6h (± 10 min), 12h (± 10 min) and 24h (± 10 min) after the start of infusion, 48h ± 2h (Day 3), 72h ± 2h (Day 4), 96h ± 2h (Day 5), 168h ± 2h (Day 8), 336h (Day 15 ± 1d), 504h (Day 22 ± 1d), 672h (Day 29 ± 1d), 1008h (Day 43 ± 2d) and 1680h (Day 71 ± 2d) after the start of infusion.
Secondary outcome [2] 352145 0
Pharmacokinetic similarity between JHL1188, EU-Herceptin and US-Herceptin after a single IV infusion of 6 mg/kg in healthy male subjects detected using serum samples to calculate the pK parameter - Maximum concentration (Cmax)
Timepoint [2] 352145 0
Blood samples will be collected at the following timepoints: predose (within -30min prior to dose), prior to end of infusion (within 10min prior to end of infusion), 3h (± 10 min), 6h (± 10 min), 12h (± 10 min) and 24h (± 10 min) after the start of infusion, 48h ± 2h (Day 3), 72h ± 2h (Day 4), 96h ± 2h (Day 5), 168h ± 2h (Day 8), 336h (Day 15 ± 1d), 504h (Day 22 ± 1d), 672h (Day 29 ± 1d), 1008h (Day 43 ± 2d) and 1680h (Day 71 ± 2d) after the start of infusion.
Secondary outcome [3] 352146 0
Pharmacokinetic similarity between JHL1188, EU-Herceptin and US-Herceptin after a single IV infusion of 6 mg/kg in healthy male subjects detected using serum samples to calculate the pK parameter - Time to Cmax (Tmax)
Timepoint [3] 352146 0
Blood samples will be collected at the following timepoints: predose (within -30min prior to dose), prior to end of infusion (within 10min prior to end of infusion), 3h (± 10 min), 6h (± 10 min), 12h (± 10 min) and 24h (± 10 min) after the start of infusion, 48h ± 2h (Day 3), 72h ± 2h (Day 4), 96h ± 2h (Day 5), 168h ± 2h (Day 8), 336h (Day 15 ± 1d), 504h (Day 22 ± 1d), 672h (Day 29 ± 1d), 1008h (Day 43 ± 2d) and 1680h (Day 71 ± 2d) after the start of infusion.
Secondary outcome [4] 352147 0
Pharmacokinetic similarity between JHL1188, EU-Herceptin and US-Herceptin after a single IV infusion of 6 mg/kg in healthy male subjects detected using serum samples to calculate the pK parameter - Apparent volume of terminal phase distribution (Vz)
Timepoint [4] 352147 0
Blood samples will be collected at the following timepoints: predose (within -30min prior to dose), prior to end of infusion (within 10min prior to end of infusion), 3h (± 10 min), 6h (± 10 min), 12h (± 10 min) and 24h (± 10 min) after the start of infusion, 48h ± 2h (Day 3), 72h ± 2h (Day 4), 96h ± 2h (Day 5), 168h ± 2h (Day 8), 336h (Day 15 ± 1d), 504h (Day 22 ± 1d), 672h (Day 29 ± 1d), 1008h (Day 43 ± 2d) and 1680h (Day 71 ± 2d) after the start of infusion.
Secondary outcome [5] 352148 0
Pharmacokinetic similarity between JHL1188, EU-Herceptin and US-Herceptin after a single IV infusion of 6 mg/kg in healthy male subjects detected using serum samples to calculate the pK parameter - Terminal phase elimination rate constant
Timepoint [5] 352148 0
Blood samples will be collected at the following timepoints: predose (within -30min prior to dose), prior to end of infusion (within 10min prior to end of infusion), 3h (± 10 min), 6h (± 10 min), 12h (± 10 min) and 24h (± 10 min) after the start of infusion, 48h ± 2h (Day 3), 72h ± 2h (Day 4), 96h ± 2h (Day 5), 168h ± 2h (Day 8), 336h (Day 15 ± 1d), 504h (Day 22 ± 1d), 672h (Day 29 ± 1d), 1008h (Day 43 ± 2d) and 1680h (Day 71 ± 2d) after the start of infusion.
Secondary outcome [6] 352149 0
Pharmacokinetic similarity between JHL1188, EU-Herceptin and US-Herceptin after a single IV infusion of 6 mg/kg in healthy male subjects detected using serum samples to calculate the pK parameter - Terminal half-life (t½)
Timepoint [6] 352149 0
Blood samples will be collected at the following timepoints: predose (within -30min prior to dose), prior to end of infusion (within 10min prior to end of infusion), 3h (± 10 min), 6h (± 10 min), 12h (± 10 min) and 24h (± 10 min) after the start of infusion, 48h ± 2h (Day 3), 72h ± 2h (Day 4), 96h ± 2h (Day 5), 168h ± 2h (Day 8), 336h (Day 15 ± 1d), 504h (Day 22 ± 1d), 672h (Day 29 ± 1d), 1008h (Day 43 ± 2d) and 1680h (Day 71 ± 2d) after the start of infusion.
Secondary outcome [7] 352150 0
Pharmacokinetic similarity between JHL1188, EU-Herceptin and US-Herceptin after a single IV infusion of 6 mg/kg in healthy male subjects detected using serum samples to calculate the pK parameter - Systemic clearance (CL)
Timepoint [7] 352150 0
Blood samples will be collected at the following timepoints: predose (within -30min prior to dose), prior to end of infusion (within 10min prior to end of infusion), 3h (± 10 min), 6h (± 10 min), 12h (± 10 min) and 24h (± 10 min) after the start of infusion, 48h ± 2h (Day 3), 72h ± 2h (Day 4), 96h ± 2h (Day 5), 168h ± 2h (Day 8), 336h (Day 15 ± 1d), 504h (Day 22 ± 1d), 672h (Day 29 ± 1d), 1008h (Day 43 ± 2d) and 1680h (Day 71 ± 2d) after the start of infusion.
Secondary outcome [8] 352151 0
Serum samples will be analyzed for anti-drug antibodies (ADA) according to the following three-tiered strategy: Firstly, samples will be screened for a positive or negative signal based on a screening cut point. Samples testing positive in the screening assay then subjected to a confirmatory assay to demonstrate that ADA are specific for the drug. Samples identified as positive in the confirmatory assay should be further characterized in neutralizing assay.
Timepoint [8] 352151 0
Samples Collection: predose (within -30min), 336h (Day 15 ± 1d), 504h (Day 22 ± 1d), 1008h (Day 43 ± 2d) and 1680h (Day 71 ± 2d) after the start of infusion.
Secondary outcome [9] 352152 0
The tolerability and safety Pharmacokinetic similarity between JHL1188, EU-Herceptin and US-Herceptin after a single IV infusion of 6 mg/kg in healthy male subjects will assess the safety through vital signs, 12-lead ECG, safety clinical laboratory tests (hematology, clinical biochemistry, coagulation, and urine microscopy), adverse events (AE), serious adverse events (SAE), adverse drug reaction (ADR), physical examination, and injection site evaluations.
Timepoint [9] 352152 0
Till end of study including follow up period:
Vital signs: all visit days
12-lead ECG: screening, predose, and 6h (± 10 min), 24h (± 10 min), 48h ± 2h (Day 3), 96h ± 2h (Day 5) after the start of infusion
Safety clinical laboratory tests: screening, 48h ± 2h (Day 3), 168h ± 2h (Day 8), 672h (Day 29 ± 1d), and 1680h (Day 71 ± 2d) after the start of infusion
Physical examination: screening, 48h ± 2h (Day 3), 168h ± 2h (Day 8), 336h (Day 15 ± 1d), 504h (Day 22 ± 1d), 672h (Day 29 ± 1d), 1008h (Day 43 ± 2d) and 1680h (Day 71 ± 2d) after the start of infusion.
Injection site evaluation, AE, SAE, ADR: all days

Eligibility
Key inclusion criteria
1. Ability to understand and voluntarily give informed consent (ICF)
2. Healthy male subject
3. Age 18 to 55 years (inclusive) inclusive
4. Body Mass Index (BMI) between 19.0 and 30.0 kg per sq mtr (inclusive) and weight between 50 to 90 kg (inclusive)
5. A resting systolic blood pressure less than 140 mmHg (inclusive), a resting diastolic blood pressure less than 90 mmHg (inclusive) and heart rate between 40-100 beats/min (inclusive) in supine position
6. No clinically relevant significant finding in 12-lead electrocardiogram
7. Clinical laboratory values are within normal range
8. Left Ventricular Ejection Fraction (LVEF) falls within the normal range (>55%)
9. Male subject with female partners of child bearing potential must agree to use double barrier contraception during the study and for 90 days following completion of dosing
10. Non-smoker or smoked fewer than 5 cigarettes daily within three months prior to screening
11. Non-drinker or drink less than 14 units of alcohol weekly within six months prior to screening (1 unit of alcohol equal to 360 mL beer or 45 mL spirits with 40% alcohol content or 150 mL wine)
12. Adequate venous access
Minimum age
18 Years
Maximum age
55 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any history of clinically serious diseases
2. Previous exposure to monoclonal antibody or any biologics within six months prior to the administration of the investigational drug
3. Subject with an allergic constitution or a history of drug allergy or who are known to be allergic to the ingredients of the Investigational Medicinal Product (IMP) or Reference Medicinal Products (RMP)
4. Subjects who have several or highly significant risk factors for tuberculosis infection should have negative test for latent tuberculosis
5. Use of prescription or non-prescription medication and dietary supplements within 5 half-lives of the drug or supplement, or within 7 days prior to administration
6. Blood/plasma donation or blood loss more than 470 ml within 3 months prior to Day 1.
7. Have participated in any other clinical study within 3 months prior to Day 1
8. History of, or positive test result at screening for: Hepatitis B core antibody (HbcAb), surface antibody (HbsAb), surface antigen (HbsAg), Hepatitis C Virus (HCV) antibodies or Human Immunodeficiency Virus (HIV)
9. History of drug abuse within 12 months prior to Day 1
10. Major surgery within 3 months prior to Day 1 or anticipated surgery during the study
11. Subjects with FEV1 below the lower limit of the local reference range for age/height at screening
12. Unlikely to comply with the protocol

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet 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] 300646 0
Commercial sector/Industry
Name [1] 300646 0
JHL Biotech, Inc.
Address [1] 300646 0
PO Box 309, Ugland House, Grand Cayman, KY1-1104, Cayman Islands
Country [1] 300646 0
Cayman Islands
Primary sponsor type
Commercial sector/Industry
Name
JHL Biotech Australia Pty Ltd.
Address
Suite 6, Level 7, 122 Arthur Street North Sydney, NSW 2060, Australia
Country
Australia
Secondary sponsor category [1] 300161 0
None
Name [1] 300161 0
Address [1] 300161 0
Country [1] 300161 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301435 0
Bellberry Limited Human Research Ethics Committee
Ethics committee address [1] 301435 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 301435 0
Australia
Date submitted for ethics approval [1] 301435 0
28/09/2018
Approval date [1] 301435 0
14/11/2018
Ethics approval number [1] 301435 0

Summary
Brief summary
This is a three-arm, pharmacokinetic, safety, tolerability and immunogenicity study to compare investigational product JHL1188 versus EU and US sourced Herceptin in healthy male participants.

Who is it for?
You may be eligible to join this study if you are male aged 18 to 55 years old, healthy non-smoker and non-drinker

Study details
Approximately 159 eligible subjects will be randomized in a 1:1 ratio to receive either JHL1188 (n=53), Herceptin_EU sourced (n=64) or Herceptin_US sourced (n=53). Each subject will receive one intravenous (IV) infusions of the investigational product at the dose of 6 mg/kg on Day 1. Assessments of PK, safety, tolerability, immunogenicity will be collected over the following 70-day period.

JHl1188 is developed as a biosimilar of Herceptin, Herceptin is approved for the treatment of adult patients with HER2 positive breast cancer and metastatic gastric cancer. This clinical study is intended to study the similarity between JHL1188 and Herceptin.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 86986 0
Dr Paul Griffin
Address 86986 0
Q-Pharm Pty Limited
Level 5, 300C Herston Road, Herston QLD 4006, Australia
Country 86986 0
Australia
Phone 86986 0
+61 738 453 636
Fax 86986 0
Email 86986 0
p.griffin@qpharm.com.au
Contact person for public queries
Name 86987 0
Dr Paul Griffin
Address 86987 0
Q-Pharm Pty Limited
Level 5, 300C Herston Road, Herston QLD 4006. Australia
Country 86987 0
Australia
Phone 86987 0
+61 738 453 636
Fax 86987 0
Email 86987 0
p.griffin@qpharm.com.au
Contact person for scientific queries
Name 86988 0
Dr Rong Chen
Address 86988 0
JHL Biotech Australia Pty Ltd
Suite 6, Level 7, 122 Arthur Street North Sydney, NSW 2060, Australia
Country 86988 0
Australia
Phone 86988 0
+61 415 247 836
Fax 86988 0
Email 86988 0
ZrChen@jhlbiotech.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Not applicable