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Trial registered on ANZCTR


Registration number
ACTRN12619000220167
Ethics application status
Approved
Date submitted
8/02/2019
Date registered
14/02/2019
Date last updated
11/02/2020
Date data sharing statement initially provided
14/02/2019
Date results information initially provided
11/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to establish biosimilarity of HD201 to Herceptin when administered to healthy male participants
Scientific title
A Phase 1, Double-Blind, Randomised, Parallel Group Study to Demonstrate the Equivalent Pharmacokinetic Properties of a Single Intravenous Dose of HD201 and Herceptin in Healthy Male Subjects
Secondary ID [1] 297065 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast cancer 311071 0
Condition category
Condition code
Cancer 309708 309708 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: HD201 (trastuzumab) 150 mg powder formulated as a solution (in 0.9 percent sodium chloride solution) for intravenous infusion, to be administered as a single-dose of 6 mg/kg over a period of approximately 90 minutes.
Intervention code [1] 313338 0
Treatment: Drugs
Comparator / control treatment
Arm 2: EU-Herceptin (EU-licensed trastuzumab) 150 mg powder formulated as a solution (in 0.9 percent sodium chloride solution) for intravenous infusion, to be administered as a single-dose of 6 mg/kg over a period of approximately 90 minutes.
Arm 3: US-Herceptin (US-licensed trastuzumab) 150 mg powder formulated as a solution (in 0.9 percent sodium chloride solution) for intravenous infusion, to be administered as a single-dose of 6 mg/kg over a period of approximately 90 minutes.
Control group
Active

Outcomes
Primary outcome [1] 318670 0
To determine the pharmacokinetic profile of HD201 following a single intravenous administration of each drug in healthy male subjects. PK parameters determined are to include AUC(0-inf), AUC(0-t), C(max), residual area, T(max), T(1/2 el), K(el), Cl and V(d).
Timepoint [1] 318670 0
Blood PK samples will be collected for analysis during the treatment period at: pre-dose (0-hour), 1.5 (within 5 minutes before end of infusion), 3 (1.5 hours post-end of infusion), 8, 24, 48 (Day 3), 96 (Day 5), 168 (Day 8), 336 (Day 15), 504 (Day 22), 672 (Day 29), 1008 (Day 43), and 1272 (Day 54) hours post-dose.
Primary outcome [2] 319070 0
To assess the pharmacokinetic profile of EU-Herceptin following a single intravenous administration of each drug in healthy male subjects. PK parameters determined are to include AUC(0-inf), AUC(0-t), C(max), residual area, T(max), T(1/2 el), K(el), Cl and V(d).
Timepoint [2] 319070 0
Blood PK samples will be collected for analysis during the treatment period at: pre-dose (0-hour), 1.5 (within 5 minutes before end of infusion), 3 (1.5 hours post-end of infusion), 8, 24, 48 (Day 3), 96 (Day 5), 168 (Day 8), 336 (Day 15), 504 (Day 22), 672 (Day 29), 1008 (Day 43), and 1272 (Day 54) hours post-dose.
Primary outcome [3] 319071 0
To assess the pharmacokinetic profile of US-Herceptin following a single intravenous administration of each drug in healthy male subjects. PK parameters determined are to include AUC(0-inf), AUC(0-t), C(max), residual area, T(max), T(1/2 el), K(el), Cl and V(d).
Timepoint [3] 319071 0
Blood PK samples will be collected for analysis during the treatment period at: pre-dose (0-hour), 1.5 (within 5 minutes before end of infusion), 3 (1.5 hours post-end of infusion), 8, 24, 48 (Day 3), 96 (Day 5), 168 (Day 8), 336 (Day 15), 504 (Day 22), 672 (Day 29), 1008 (Day 43), and 1272 (Day 54) hours post-dose.
Secondary outcome [1] 365638 0
To assess the safety and tolerability after a single intravenous infusion of HD201 is administered to healthy male subjects. Safety and tolerability will be assessed by observation of the incidence, severity, causality and seriousness of adverse events (previously encountered adverse events of the study drug may include blocked or runny nose, nose bleed, headache, and fever); vital signs (blood pressure, heart rate, respiratory rate, and oral temperature); laboratory tests (drug and alcohol screening, hematology and coagulation, and biochemistry); infusion site evaluation; and medical surveillance by clinical site staff.
Timepoint [1] 365638 0
Safety and tolerability information will be recorded from the first date of admission to the study unit for a period of 54 days following study drug administration.
Secondary outcome [2] 365639 0
To compare immunogenicity after a single intravenous infusion of HD201, EU-Herceptin or US-Herceptin is administered to healthy male subjects. Immunogenicity will be assessed using an ELISA assay to test blood samples for anti-drug antibodies, with further assessment for neutralizing antibodies in samples with positive readings.
Timepoint [2] 365639 0
Blood samples will be drawn for anti-drug antibody and neutralizing antibody detection at: pre-dose (0-hour), Day 15, Day 29, Day 43 and Day 54 following study drug administration.

Eligibility
Key inclusion criteria
1) Male, non-smoker (no use of tobacco products within 3 months prior to screening), greater than or equal to 18 and less than or equal to 55 years of age, with BMI greater than or equal to 18.5 and less than or equal to 30.0 kg/m^2 and body weight greater than or equal to 50.0 kg.
2) Healthy as defined by:
a) the absence of clinically significant illness and surgery within 4 weeks prior to dosing. Inclusion pre-dosing is at the discretion of the Principal Investigator.
b) the absence of clinically significant history of neurological, endocrinal, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
c) a LVEF within the normal range (greater than or equal to 60 percent) as measured by echocardiogram (ECHO) within 4 weeks prior to randomization.
d) the absence of clinically significant history of anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.
3) Male subjects who are not vasectomized for at least 6 months, and who are sexually active with non-sterile female partner [sterile female partners include post-menopausal women (absence of menses for 12 months prior to drug administration) or women who have had a tubal ligation, hysterectomy, or bilateral oophorectomy (at least 6 months prior to drug administration)] must be willing to use one of the following acceptable contraceptive method throughout the study and for 90 days after the last study drug administration:
a) simultaneous use of condom, and for the female partner hormonal contraceptives (used since at least 4 weeks) or intra-uterine contraceptive device (placed since at least 4 weeks);
b) simultaneous use of male condom, and for the female partner, diaphragm with intravaginally applied spermicide.
4) Male subjects, including men who have had vasectomy, with a pregnant partner must agree to use a condom throughout the study and for 90 days after the last study drug administration.
5) Male subjects must be willing not to donate sperm until 90 days following the last study drug administration.
6) Capable of consent.
Minimum age
18 Years
Maximum age
55 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) Any clinically significant abnormality or abnormal laboratory test results found during medical screening or positive test for hepatitis B, hepatitis C, or HIV found during medical screening.
2) Positive urine drug screen at screening.
3) History of allergic reactions to trastuzumab, benzyl alcohol, murine proteins, or other related drugs.
4) Any reason which, in the opinion of the Principal Investigator, would prevent the subject from participating in the study.
5) Clinically significant ECG abnormalities (QTc greater than 450 ms) and or vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 40 or over 90 mmHg, or heart rate less than 40 or over 100 bpm) at screening.
6) History of significant alcohol abuse within one year prior to screening or regular use of alcohol within six months prior to the screening visit (more than fourteen units of alcohol per week [1 unit equates to 150 mL of wine, 360 mL of beer, or 45 mL of 40 percent alcohol]).
7) History of significant drug abuse within one year prior to screening or use of soft drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine derivatives) within 1 year prior to screening.
8) Previous use of trastuzumab or another monoclonal antibody for a medical condition or in the context of another clinical trial in the 6 months prior to screening.
9) Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.
10) Use of medication other than topical products without significant systemic absorption:
a) prescription medication within 14 days prior to dose administration; sporadic use of prescription such as benzodiazepines and codeine can be accepted at the discretion of the investigator.
b) over-the-counter products including natural health products (e.g. food supplements and herbal supplements) within 7 days prior to dosing, with the exception of the occasional use of acetaminophen (paracetamol - up to 4 g daily);
c) a depot injection or an implant of any drug within 3 months prior to dose administration.
11) Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dosing.
12) Hemoglobin less than 12.8 g/dL and hematocrit less than 0.37 L/L at screening.

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
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
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
Statistical Analysis will be performed using SAS v9.3 (SAS Institute, Cary, USA). Statistical analysis will be performed between HD201 and EU-Herceptin (to evaluate similarity between test compound and EU reference), HD201 and US-Herceptin (to evaluate similarity between test compound and US reference), and US-Herceptin and EU-Herceptin (to evaluate similarity between EU and US references).

Recruitment
Recruitment status
Completed
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
Recruitment hospital [1] 12881 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 25358 0
4007 - Herston

Funding & Sponsors
Funding source category [1] 301636 0
Commercial sector/Industry
Name [1] 301636 0
Prestige BioPharma Pte Ltd
Address [1] 301636 0
2 Science Park Drive #04-13/14 Ascent Tower B
Singapore Science Park, Singapore 118222
Country [1] 301636 0
Singapore
Primary sponsor type
Commercial sector/Industry
Name
Prestige BioPharma Australia Pty Ltd
Address
58 Gipps Street
Collingwood, VIC, 3066
Country
Australia
Secondary sponsor category [1] 301341 0
None
Name [1] 301341 0
Address [1] 301341 0
Country [1] 301341 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302359 0
Bellberry Limited HREC (EC00372)
Ethics committee address [1] 302359 0
123 Glen Osmond Road
Eastwood SA 5063
Ethics committee country [1] 302359 0
Australia
Date submitted for ethics approval [1] 302359 0
30/01/2019
Approval date [1] 302359 0
14/03/2019
Ethics approval number [1] 302359 0

Summary
Brief summary
The purpose of this study is to conduct preliminary studies of a new version of an existing medication (called Herceptin) in healthy males.

Who is this study for?
You may be eligible for this study if you are a male aged 18 to 55 and you are in good health with no existing conditions.

Study details:
Participants in this study will be randomised (by chance) into three groups. All participants will receive a single dose of breast cancer medication infused through a needle in the arm. over a period of 90 minutes. The medication will be the same, but each group will receive a different version – EU-licensed, US-licensed and a new version. Neither participants nor those giving the medication will know which is being administered. As part of this study, participants will provide blood samples and answer questions about their general health.

It is hoped this research will provide evidence the new version of the medication is equivalent to the existing licensed versions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89950 0
Dr Kristi McLendon
Address 89950 0
Q-Pharm,
300C Herston Road, Herston QLD 4006
Country 89950 0
Australia
Phone 89950 0
+61 7 37072700
Fax 89950 0
Email 89950 0
k.mclendon@nucleusnetwork.com.au
Contact person for public queries
Name 89951 0
Ms Jessica Faggian
Address 89951 0
Nucleus Network, Level 5, Burnet Tower, AMREP Precinct,
89 Commercial Road, Melbourne VIC 3004
Country 89951 0
Australia
Phone 89951 0
+61 3 9089 8243
Fax 89951 0
Email 89951 0
j.faggian@nucleusnetwork.com.au
Contact person for scientific queries
Name 89952 0
Ms Felicia Ang
Address 89952 0
Prestige BioPharma, 2 Science Park Drive, #04-13/14 Ascent Tower B,
Singapore Science Park, Singapore 118222
Country 89952 0
Singapore
Phone 89952 0
+65 6924 6535
Fax 89952 0
Email 89952 0
felicia@pbpsg.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
As this is a Phase 1 study, only aggregate data may be posted/published.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary