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Trial registered on ANZCTR


Registration number
ACTRN12616000283471
Ethics application status
Approved
Date submitted
2/03/2016
Date registered
4/03/2016
Date last updated
4/03/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A study assessing the similarity of Avastin (Registered Trademark) and the trial drug BAT1706.
Scientific title
Randomized, double-blind, single-dose, 3-arm parallel design comparative pharmacokinetic and safety Phase I study of BAT1706 versus EU-sourced Avastin (Registered Trademark) and US-sourced Avastin (Registered Trademark) administered in healthy subjects
Secondary ID [1] 288674 0
BAT-1706-001-CR
Universal Trial Number (UTN)
U1111-1177-1427
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-squamous non-small cell lung cancer 297876 0
Metastatic breast cancer 297877 0
Metastatic colorectal cancer 297878 0
Condition category
Condition code
Cancer 298046 298046 0 0
Breast
Cancer 298047 298047 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 298048 298048 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Three Bevacizumab Preperations

Arm 1:BAT1706
100 mg in 4 mL - 1mg/kg
Recombinant humanised monoclonal antibody - bevacizumab
1 time only Intravenous infusion.

Arm 2: Avastin (Registered Trademark) United States-licenced (bevacizumab)
100 mg in 4 mL- 1mg/kg
Recombinant humanised monoclonal antibody - bevacizumab
1 time only Intravenous infusion.

Arm 3: Avastin (Registered Trademark) European Approved (bevacizumab)
100 mg in 4 mL- 1mg/kg
Recombinant humanised monoclonal antibody - bevacizumab
1 time only Intravenous infusion.

As the Infusion will be administered while the participants are inpatients of the facility, no strategy for adherence is required.
Intervention code [1] 294094 0
Treatment: Drugs
Comparator / control treatment
Avastin (Registered Trademark) United States-licenced (bevacizumab)
100 mg in 4 mL- 1mg/kg
Recombinant humanised monoclonal antibody - bevacizumab
1 time only Intravenous infusion.

Avastin (Registered Trademark) European Approved (bevacizumab)
100 mg in 4 mL- 1mg/kg
Recombinant humanised monoclonal antibody - bevacizumab
1 time only Intravenous infusion
Control group
Active

Outcomes
Primary outcome [1] 297566 0
To establish pairwise pharmacokinetic (PK) similarity between BAT1706, EU Avastin and US-Avastin after a single intravenous (IV) infusion in healthy male subjects.
The primary PK parameters will consist of:
Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf).
Timepoint [1] 297566 0
Blood samples for analysis of serum concentrations of the study drugs will be collected at the following specified times to perform a comparison of PK similarity.

Pre infusion - 0 hour or within 1 hour prior to the start of the infusion.
Mid infusion - at 45 minutes - relative to the start of infusion.
End of infusion - 1 hour, 2 hours, 5 hours, 8 hours, 12 hours from the end of infusion, and 24 hours (Day 2), 48 hours (Day 3), 96 hours (day 5), 168 hours (day 8), 240 hours (Day 11), 336 hours (Day 15), 504 hours (day 22), 672 hours (Day 29), 840 hours (Day 36), 1008 hours (Day 43), 1344 hours (Day 57), 1680 hours (Day 71), 2016 hours (Day85) and 2352 hours (Day 99) post start of infusion.
Secondary outcome [1] 321410 0
To evaluate the safety and tolerability of BAT1706 in healthy male subjects.

The expected adverse reactions for this study are asthenia, headache, nausea, or low grade fever, gastro-intestinal symptoms and increased blood pressure. The exclusion criteria has been selected to preclude the inclusion of subjects with a predictable predisposition to any of these conditions. It is expected that the dose will be well tolerated.
The subjects will be dosed in a sequential manner, 3, subjects then 6 subjects and then 9 subjects and for each subject enrolled, prolonged clinical and laboratory surveillance will take place.
Timepoint [1] 321410 0
The following assessments will be reviewed:
Vital Signs: Pre Dose, 30 mins and 60 mins post start of infusion. 15 mins, 30 mins,1 hour, 2 hour, 4 hour, 5 hour, 6 hour, 8 hour and 12 hour post end of infusion, Day 2 and Day 3, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, Day 43, Day 57, Day 71, Day 85 and Day 99.
Full Physical Examination: screening, Day -1, day 3, day 15, Day 99.
Infusion site check: day 1
If clinically indicated a physical examination will be conducted at Day 29, Day 43, Day57 and Day 71.
ECG: screening, Day -1, Pre Dose 45 mins, 1 hour post start of infusion, 4 hour and 12 hours post end of infusion, Day 5, Day 15, Day 43 and Day 99.
Adverse Events will be collected at each and every visit throughout the trial
Clinical Laboratory Tests: Screening, Day -1, Day 3, Day 5, Day 15, Day 43, Day 71 and Day 99.
Secondary outcome [2] 321421 0
To evaluate the immunogenicity of BAT1706, EU-Avastin and US-Avastin after a single IV infusion in healthy male subjects.

Immunogenicity will be assessed by means of the occurrence of ADA, ADA titres, and the occurrence of neutralising antibodies.
ADA positive samples with be analysed anti-bevacizumab antibodies.
Serum will also be tested for anti-VEGF antibodies.
Timepoint [2] 321421 0
Blood Samples taken at screening, Day 1, Day 15, Day 43, Day 71 and Day 99 will be assessed.
After the End-of-Study visit, subjects who are confirmed positive for anti-bevacizumab antibodies will be followed for 12 months after study drug administration.
Blood Sampling will be collected at 6, 9, and 12 months after study drug administration or until 2 consecutive samples have been negative for ADA, whichever comes first.
At screening subjects will also be tested for anti-VEGF antibodies.
Secondary outcome [3] 321422 0
To further characterize the PK of BAT1706, EU-Avastin and US-Avastin after a single IV infusion in healthy male subjects.

The secondary PK parameters will consist of:
Area under the concentration-time curve from time 0 to the last quantifiable data point (AUC0-t);
Maximum measured concentration (Cmax).
Time to maximum measured concentration (tmax);
Terminal half-life (t½);

These outcomes will be assessed using serum samples.
Timepoint [3] 321422 0
Blood samples for analysis of serum concentrations of the study drugs will be collected at the following specified times:.

Pre infusion - 0 hour or within 1 hour prior to the start of the infusion.
Mid infusion - at 45 minutes - relative to the start of infusion.
End of infusion - 1 hour, 2 hours, 5 hours, 8 hours, 12 hours from the end of infusion, and 24 hours (Day 2), 48 hours (Day 3), 96 hours (day 5), 168 hours (day 8), 240 hours (Day 11), 336 hours (Day 15), 504 hours (day 22), 672 hours (Day 29), 840 hours (Day 36), 1008 hours (Day 43), 1344 hours (Day 57), 1680 hours (Day 71), 2016 hours (Day85) and 2352 hours (Day 99) post start of infusion.

Eligibility
Key inclusion criteria
1. Adult males aged 18 to 50 years inclusive and between 19 and 28 kg/m2 body mass index (BMI) and body weight greater than and equal to 65 and less than and equal to 100 kg.
2. Subjects who are healthy as determined by pre-study medical history, physical examination, vital signs and 12-lead electrocardiogram (ECG).
3. Subjects whose clinical laboratory test results are normal, or where outside the reference range are judged as not clinically relevant.
4. Subjects who are non-smokers and have not regularly used tobacco or nicotine containing products for at least 3 months preceding screening and have a <10 pack year smoking history.
5. Must be willing to abstain from sexual intercourse or willing to use a condom in addition to having their female partner use another form of contraception such as an intra-uterine device, barrier method with spermicide, oral contraceptive, injectable progesterone, sub-dermal implant, or a bilateral tubal ligation, unless their partners are infertile from the time of the administration of investigational product (IP) until completion of study procedures.
6. Must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures including standardised meals.
Minimum age
18 Years
Maximum age
50 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Have a history of and/or current clinically significant gastrointestinal (including diverticulitis, stomach ulcers), renal, hepatic, cardiovascular, haematological (including pancytopenia, aplastic anaemia or blood dyscrasia), pulmonary, neurologic, metabolic (including known diabetes mellitus), psychiatric or allergic disease excluding mild asymptomatic seasonal allergies.
2. Subject with a psychiatric disorder or considered unsuitable for inclusion by the investigator (e.g., inability to understand and/or comply with study requirements or presence of any condition which, in the opinion of the investigator, would not allow safe participation in the study).
3. History or current clinically significant (in the opinion of the Investigator) allergy, excluding mild asymptomatic seasonal allergies, hypersensitivity or allergic reactions including known or suspected drug hypersensitivity to any component of the study drug formulations (e.g. hypersensitivity to any recombinant human or humanized antibodies) or comparable drugs.
4. Any inherited predisposition to bleeding or to thrombosis or history of non-traumatic hemorrhage (i.e. any hemorrhage requiring medical intervention), thromboembolic event or any condition which may increase bleeding risk including clotting disorders, thrombocytopenia (platelet count <150, 000 per micro Litre) or an international normalized ratio higher than 1.5 at screening.
5. History of cancer including lymphoma, leukemia and skin cancer.
6. Intended participation in contact/collision sports from admission until Day 30.
7. Live virus vaccination within 12 weeks prior to screening or intention to receive live virus vaccination during the study until the final follow-up visit.
8. Prior exposure to any Investigational drug in any clinical trial within 3 months of study drug administration or are currently participating in another clinical study of an investigational drug, or intending to participate in another clinical study of an investigational drug before completion of all scheduled evaluations in this clinical study.
9. Any prior exposure to bevacizumab or VEGF targeted treatment.
10. Any biological drug within 3 months or monoclonal antibodies within 9 months of study drug administration.
11. Intake of prescribed or over-the-counter drugs including non-steroidal anti-inflammatory drugs (NSAID) within 14 days or 5 half-lives (whichever is longer) prior to study drug administration. Any dose of aspirin in the last 14 days before administration of the study drug and for the duration of the study is not allowed.
12. Intake of herbal remedies within 14 days prior to study drug administration.
13. Blood or blood product donation >500 mL in the 1 month before screening or the intention to donate blood or blood products during the study (through Day 99).
14. Abnormal and clinically relevant (in the opinion of the Investigator) ECG or corrected QT value (Bazett correction) longer than 450 ms.
15. Subjects with abnormal blood pressure (systolic blood pressure less than and equal to 90 and greater than and equal to 140 mmHg, diastolic blood pressure less than and equal to 50 and greater than and equal to 90 mmHg) or pulse rate less than and equal to 45 and greater than and equal to 100 bpm at screening or admission to the clinical center (Day -1).
16. Subjects with known hypertension or relevant family history of hypertension, or history of relevant orthostatic hypotension, fainting spells, or blackouts as judged by the Investigator.
17. Total cholesterol >7.5 mmol/L at screening or glucose >7.7 mmol/L at screening or admission.
18. Impaired liver function at screening or admission as determined by:
? Serum alanine aminotransferase and/or aspartate aminotransferase >1.5 x upper limit of normal (ULN) at screening or admission. Subjects with values between ULN and 1.5 x ULN may be included in the study if considered not clinically significant by the Investigator.
19. Any clinically significant chronic or acute infection ongoing at screening or admission to the clinical center or subjects who are positive for hepatitis B surface antigen (HBsAg), hepatitis C ribonucleic acid (RNA) or human immunodeficiency virus (HIV) 1 and 2 tests at screening.
20. Major injuries and/or surgery or bone fracture within 4 weeks of trial inclusion, or planned surgical procedures during the trial period.
21. Poor oral hygiene that may require surgical intervention during the study or any planned dental surgical interventions during the clinical trial.
22. History of alcohol abuse or a positive alcohol test on screening or admission to the clinical center.
23. No alcoholic beverages from 48 prior to drug administration until discharge from the study center on Day 3.
24. History of drug abuse or positive drug test at screening or admission to the clinical center as indicated by a positive urinary drug test. Subjects are to refrain from drugs of abuse for the duration of the study.
25. Inability to refrain from smoking during days of confinement at the study center and for the duration of the study (through Day 99).
26. Any persons who are:
an employee of the Principal Investigator, clinical center, clinical research organisation (CRO) or Sponsor
a relative of an employee of the clinical center, the Investigators, CRO or the 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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised 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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/03/2016
Actual
Date of last participant enrolment
Anticipated
29/07/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
129
Accrual to date
Final
Recruitment outside Australia
Country [1] 7637 0
New Zealand
State/province [1] 7637 0

Funding & Sponsors
Funding source category [1] 293032 0
Commercial sector/Industry
Name [1] 293032 0
Bio-Thera Solutions Ltd
Country [1] 293032 0
China
Primary sponsor type
Commercial sector/Industry
Name
Quintiles Pty Ltd
Address
4th Floor, Symonds Centre, 49-51 Symonds Street, Auckland 1010
Country
New Zealand
Secondary sponsor category [1] 291819 0
None
Name [1] 291819 0
not applicable
Address [1] 291819 0
not applicable
Country [1] 291819 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294543 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 294543 0
Ministry of Health Ethics Department
20 Aitken Street
Thorndon
WELLINGTON, 6011
Ethics committee country [1] 294543 0
New Zealand
Date submitted for ethics approval [1] 294543 0
03/12/2015
Approval date [1] 294543 0
23/12/2015
Ethics approval number [1] 294543 0
15/NTA/217

Summary
Brief summary
Avastin (Registered Trademark) is currently used in many countries for the treatment of certain cancers.
The primary purpose of this study is to investigate the similarities in the manner in which a new drug, BAT1706 is distributed around the body compared with European approved and USA licensed Avastin. Who is it for? You may be eligible to join this study if you are a healthy male adult from 18 to 50 years of age with a BMI of 19.0 to 29.0 kg/m2 and body weight of 65 to 100kg. Participants enrolled in this study will be randomly allocated (by chance) to receive either the new BAT1706 drug, USA licensed Avastin or European approved Avastin. All participants will receive a single dose which is adjusted for their weight. Participants will have a number of blood samples taken until Day 99 after the dose and will be monitored for side effects for 99 Days. It is hoped that the findings of this study will provide information regarding the similarity of drug distribution and safety of the new drug BAT1706 compared to currently used Avastin for the treatment of certain types of cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 64078 0
Dr Chris Wynne
Address 64078 0
Christchurch Clinical Studies Trust
PO Box 2856
Christchurch
8140
Country 64078 0
New Zealand
Phone 64078 0
+64 3 372 9477
Fax 64078 0
+64 3 372 9478
Email 64078 0
[email protected]
Contact person for public queries
Name 64079 0
Jo Sanders
Address 64079 0
Christchurch Clinical Studies Trust
PO Box 2856
Christchurch
8140
Country 64079 0
New Zealand
Phone 64079 0
+64 3 372 9477
Fax 64079 0
+64 3 372 9478
Email 64079 0
[email protected]
Contact person for scientific queries
Name 64080 0
Chris Wynne
Address 64080 0
Christchurch Clinical Studies Trust
PO Box 2856
Christchurch
8140
Country 64080 0
New Zealand
Phone 64080 0
+64 3 372 9477
Fax 64080 0
+64 3 372 9478
Email 64080 0
[email protected]

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