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Trial registered on ANZCTR


Registration number
ACTRN12618001657213
Ethics application status
Approved
Date submitted
4/10/2018
Date registered
8/10/2018
Date last updated
8/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical trial to compare the rate of blood clearance and safety of a biosimilar, to the original Herceptin drug, in healthy male volunteers.
Scientific title
A Phase 1, Randomized, Three-Arm, Double-Blind, Single Dose Study to Compare the Safety and Pharmacokinetics of the Potential Biosimilar NeuCeptin with Trastuzumab in Healthy Male Volunteers
Secondary ID [1] 295786 0
None
Universal Trial Number (UTN)
NeuCeptin-001
Trial acronym
None
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Her2 positive breast cancer 309207 0
Her2 positive gastric cancer 309208 0
Condition category
Condition code
Cancer 308083 308083 0 0
Breast
Cancer 308084 308084 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single IV infusion dose at 6 mg/kg over less than or equal to 90 minutes will be compared for the Herceptin biosimilar (NeuCeptin), EU sourced Herceptin and US sourced Herceptin. The Herceptin biosimilar is the intervention.
Intervention code [1] 312116 0
Treatment: Drugs
Comparator / control treatment
EU sourced Herceptin and US sourced Herceptin
Control group
Active

Outcomes
Primary outcome [1] 307067 0
To assess if NeuCeptin administered intravenously (IV) to healthy adult male subjects is comparable to Herceptin® (EU and/or US) in area under the concentration-time curve (AUC) from time 0 to last quantifiable concentration (AUC0-last), AUC from time 0 extrapolated to infinity (AUC0-8), and maximum plasma concentration (Cmax) (ie, within 80.00% to 125.00% for all 3 pairwise comparisons), up to 71 days post treatment.
Timepoint [1] 307067 0
Assessments will be done at day 1 (1.5, 3 and 8 hours), and days 2, 3, 8, 15, 22, 29, 43 and 71 post treatment.
Secondary outcome [1] 350537 0
To assess the safety and tolerability of NeuCeptin administered as a single dose in healthy male adult subjects through 71 days post treatment, compared to Herceptin®.(EU and/or US).
• Safety and tolerability of NeuCeptin will be compared to Herceptin-EU and Herceptin US based on occurrence, severity, timing, and relatedness of the following until 71 days post treatment:
- Infusion-related reactions (IRR) (local and systemic),
- Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs),
- Clinically significant hematological and biochemical measurements (including C-reactive protein).
• Monitoring of vital signs and heart function – electrocardiogram (ECG) and echocardiography (LVEF) assessments, until 71 days post treatment.
Timepoint [1] 350537 0
Assessments will be done at day 1 (1.5, 3 and 8 hours), and days 2, 3, 8, 15, 22, 29, 43 and 71 post treatment.. Echocardiograms will be occur at Screening, and then Day 29. Repeat tests will occur every month in those subjects where an abnormal ejection fraction is noted. The subject will be followed until the ejection fraction returns to normal.

Eligibility
Key inclusion criteria
1. Healthy male subjects 18 to 45 years of age, inclusive.
2. Body mass index of 17.5 to 30.5 kg/m2.
3. Total body weight >50 kg and <100 kg.
4. A left ventricular ejection fraction (LVEF) within the normal range as measured by an echocardiogram within 8 weeks of randomization and diastolic function within the normal range.
5. Subjects must provide a voluntary written informed consent to participate in the study and be capable of comprehending and complying with study requirements and procedures, able and willing to complete a subject diary, return for all scheduled follow-up visits, have expressed availability for the required study period, and access to a means of telephone contact, either residential land line or mobile.
6. Males with female partners of childbearing potential must agree to practice abstinence or double-method, defined as condom for males and highly effective method of contraception (with <1% failure rate) for female partners from Screening through 90 days after the last dose of study drug. Males must also refrain from sperm donations during this time period.
Minimum age
18 Years
Maximum age
45 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. A history of significant clinical disease or evidence thereof at Screening.
2. Previous exposure to trastuzumab in the past and/or administration of monoclonal antibodies or similar Fc fusion product (e.g., Enbrel®) in the past 3 6 months, or 5 half-lives, whichever is longer; or anticipation of such administration during the study period.
3. Previous history of cancer, other than adequately treated basal cell carcinoma of the skin, with confirmed clinical clearance.
4. Hypertension (>140/90 mm Hg).
5. History of significant dermatologic disease (eg, eczema, allergic dermatitis).
6. History of anaphylactic reactions.
7. Autoimmune disorders.
8. Acute illness (moderate or severe) and/or fever (oral temperature >38°C) within 14 days before randomization.
9. Use of medications including antibiotics 14 days before randomization or 5 half-lives, whichever is longer. Over-the-counter medications, such as paracetamol/ibuprofen for mild aches and pains or antihistamines for hay fever, are allowed. Medications that are deemed appropriate by the Principal Investigator as not interfering with absorption, distribution, and metabolism of the investigational product are also allowed.
10. Any confirmed or suspected immunosuppressive or immunodeficient condition based on family history, medical history, and physical examination.
11. Any screening laboratory test result outside normal parameters and deemed clinically significant by the Principal Investigator .
12. Chronic administration of immunosuppressant or other immune-modifying drugs before the administration of the study drug. For glucocorticoids (prednisolone) this will mean a dose of >0.5 mg/kg/day or equivalent. Short term administration of topical or inhaled steroids could be allowed at the Principal Investigator’s discretion if not thought to have any significant systemic immunosuppressant/immune-modifying impact.
13. Administration of vaccinations before and after dosing, especially influenza vaccine, depending on time of study enrolment.
14. Self or any first degree relative history (e.g., parent, siblings) with known disturbance of coagulation or blood disorder which would be cause for anemia or excess bleeding (eg, thalassemia, coagulation factor deficiencies, severe anemia at birth). Thalassaemia minor without prior anaemic episode is allowed.
15. History of any neurological disorder, including history of seizures; excluding migraines (i.e., migraines are acceptable).
16. Prior or current acute or chronic clinically significant pulmonary (including asthma or shortness of breath), cardiovascular (including unstable angina, heart failure, or myocardial infarction), hepatobiliary, gastrointestinal, renal, neurological, or hematological functional abnormality or major congenital defects or illness that requires medical therapy, as determined by medical history or clinical assessment before entering the study.
17. Any medical or social condition that, in the opinion of the Investigator, will interfere with the study objectives or pose a risk to the study subject or may prevent the subject from completing the study follow-up.
18. Subject is a direct descendant (child or grandchild) of a member of the Sponsor, the contract research organization, any Investigator, or study site personnel.

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)
Allocation involves contacting the holder of the allocation schedule who is "off-site" or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
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
Three arm: biosimilar, EU comparator and US comparator
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis
For PK, a sample size of at least 30 evaluable healthy male adult subjects per treatment arm will provide a >90% chance of observing AUC0-last, AUC0-8, and Cmax within 80.00% to 125.00% for all 3 pairwise comparisons. As such, at least 90 subjects are required for the PK analyses.

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)
SA,VIC
Recruitment hospital [1] 11636 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment hospital [2] 11637 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 23682 0
5000 - Adelaide
Recruitment postcode(s) [2] 23683 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 300378 0
Commercial sector/Industry
Name [1] 300378 0
NeuClone Pty Ltd
Address [1] 300378 0
ATP, 4 Cornwallis St., Eveleigh, NSW 2015
Country [1] 300378 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
NeuClone Pty Ltd
Address
ATP, 4 Cornwallis St., Eveleigh, NSW 2015
Country
Australia
Secondary sponsor category [1] 299827 0
Commercial sector/Industry
Name [1] 299827 0
Syneos Health
Address [1] 299827 0
159 Port Rd., Hindmarsh, SA 5007
Country [1] 299827 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301188 0
Bellberry Human Research Ethics Committee [EC00459]
Ethics committee address [1] 301188 0
129 Glen Osmond Road, Eastwood, South Australia 5063
Ethics committee country [1] 301188 0
Australia
Date submitted for ethics approval [1] 301188 0
08/08/2018
Approval date [1] 301188 0
03/10/2018
Ethics approval number [1] 301188 0
2018-08-626

Summary
Brief summary
The purpose of this study is to compare a new product (called Herceptin biosimilar) to two existing Herceptin products.

Who is it for?
You may be eligible for this study if you are a healthy male aged between 18 and 45 years old.

Study details
Participants in this study will be randomised (by chance) into three groups. All participants will have a single infusion of either the new product or one of the two existing products. The infusion will be delivered through a needle in the arm over 90 minutes or less. After the infusion, participants will provide a number of blood samples so the products can be compared.

It is hoped this research will be used to improve health outcomes, by providing lower priced treatments to larger numbers of cancer patients.
Trial website
Trial related presentations / publications

Public notes

Contacts
Principal investigator
Name 86154 0
Dr Angela Molga
Address 86154 0
Cmax Clinical Research
5/18a North Terrace, Adelaide
SA5000

Country 86154 0
Australia
Phone 86154 0
+61870887900
Fax 86154 0
Email 86154 0
Angela.Molga@sa.gov.au
Contact person for public queries
Name 86155 0
Dr Noelle Sunstrom
Address 86155 0
NeuClone Pty Ltd,
ATP, 4 Cornwallis St.
Eveleigh
NSW 2015
Country 86155 0
Australia
Phone 86155 0
+61292094026
Fax 86155 0
Email 86155 0
N.Sunstrom@NeuClone.com
Contact person for scientific queries
Name 86156 0
Mr Glenn Pilkington
Address 86156 0
NeuClone Pty Ltd,
ATP, 4 Cornwallis St.
Eveleigh
NSW 2015
Country 86156 0
Australia
Phone 86156 0
+61292094020
Fax 86156 0
Email 86156 0
G.Pilkington@NeuClone.com

No data has been provided for results reporting
Summary results
Not applicable