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Trial registered on ANZCTR


Registration number
ACTRN12614000400662
Ethics application status
Approved
Date submitted
1/04/2014
Date registered
14/04/2014
Date last updated
13/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomized, Single-Blind, Single-Dose, 3-Arm, Parallel Group Study to Determine the Pharmacokinetic Equivalence of ABP 980 and Trastuzumab (Herceptin "(Registered Trademark)" ) in Healthy Male Subjects
Scientific title
A Randomized, Single-Blind, Single-Dose, 3-Arm, Parallel Group Study to Determine the Pharmacokinetic Equivalence of ABP 980 and Trastuzumab (Herceptin "(Registered Trademark)" ) in Healthy Male Subjects
Secondary ID [1] 284356 0
NIL
Universal Trial Number (UTN)
NIL
Trial acronym
Protocol Number: 20130119
Linked study record

Health condition
Health condition(s) or problem(s) studied:
To determine the safety, tolerability, and immunogenicity of ABP 980 in healthy subjects compared with FDA-licensed trastuzumab and EU-authorized trastuzumab.

Trastuzumab received marketing authorization in the EU in 2000 and is approved for use in patients with Breast Cancer and Metastatic Gastric Cancer. 291514 0
Breast Cancer 291571 0
Gastric cancer 291572 0
Condition category
Condition code
Cancer 291884 291884 0 0
Breast
Cancer 291951 291951 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: ABP 980 6 mg/kg (440 mg vial)
Arm 2: trastuzumab 6 mg/kg (FDA-licensed 440 mg vial)
Arm 3: trastuzumab 6 mg/kg (EU-authorized; 150 mg vial)

Subjects will be randomized to receive intravenous infusion of ABP 980 6 mg/kg (Treatment Arm 1), trastuzumab 6 mg/kg (FDA-licensed; Treatment Arm 2), or trastuzumab 6 mg/kg (EU-authorized; Treatment Arm 3) in a ratio of 1:1:1 stratified by ethnicity (Japanese versus non-Japanese).

Subjects will only be dosed once, on the morning of Day 1 over 90 minutes after breakfast. Weight from Day -1 will be used to calculate dose.
Intervention code [1] 289083 0
Treatment: Drugs
Comparator / control treatment
Food and Drug Administration (FDA)-licensed trastuzumab and EU-authorized trastuzumab
Control group
Active

Outcomes
Primary outcome [1] 291802 0
Primary Outcome 1: To demonstrate bioequivalence (as assessed principally by area under the serum concentration-time curve [AUC] from time 0 extrapolated to infinity [AUCinf] and the maximum serum concentration [Cmax]) of ABP 980 following a 6 mg/kg intravenous (IV) infusion relative to that from a 6 mg/kg IV infusion of Food and Drug Administration (FDA)-licensed trastuzumab and EU-authorized trastuzumab
Timepoint [1] 291802 0
Timepoint: at 64 days after randomisation
Secondary outcome [1] 307582 0
Secondary Outcome 1: To demonstrate bioequivalence (as assessed principally by AUCinf and Cmax) of a 6 mg/kg IV infusion of FDA-licensed trastuzumab relative to a 6 mg/kg IV infusion of EU-authorized trastuzumab
Timepoint [1] 307582 0
Timepoint: at 64 days after randomisation
Secondary outcome [2] 307583 0
Secondary Outcome 2: To determine the safety of ABP 980 in healthy subjects compared with FDA-licensed trastuzumab and EU-authorized trastuzumab

Safety assessments, including physical examinations, vital sign measurements, 12-lead electrocardiograms, echocardiograms, clinical laboratory tests will be performed at select time points.
Timepoint [2] 307583 0
Timepoint: at 64 days after randomisation
Secondary outcome [3] 307672 0
Secondary Outcome 3: To determine the tolerability of ABP 980 in healthy subjects compared with FDA-licensed trastuzumab and EU-authorized trastuzumab

Adverse events will be collected and evaluated as they occur throughout the study. Some possible adverse events participants may experience are Diarrhoea, Joint pain, Nose bleeds, Skin rashes, Muscle pain, Dizziness and Abdominal pain.
Timepoint [3] 307672 0
Timepoint: at 64 days after randomisation
Secondary outcome [4] 307673 0
Secondary Outcome 4: To determine the immunogenicity of ABP 980 in healthy subjects compared with FDA-licensed trastuzumab and EU-authorized trastuzumab

Immunogenicity tests will be performed at select time points and will be summarised descriptively by treatment groups and time points.
Timepoint [4] 307673 0
Timepoint: at 64 days after randomsiation

Eligibility
Key inclusion criteria
1. Subjects must sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form (ICF) before any study-specific procedures are performed.
2. Healthy adult men between 18 to 45 years of age, inclusive.
3. Body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive, for non-Japanese subjects. A BMI between 18.0 and 25.0 kg/m2, inclusive, for Japanese subjects. BMI = weight (kg)/(height [m])2
4. Normal or clinically acceptable physical examination, clinical laboratory test values, vital signs, echocardiogram, and electrocardiograms (ECGs; 12-lead ECG reporting heart rate and RR, PR, QRS, QT, and QTcF intervals) at screening (physical examination, ECGs, and vital signs will be repeated on Day -1).
5. Subjects must be able to communicate effectively with the study personnel.
6. To be enrolled as a Japanese subject, subjects must be either first- or second-generation
Japanese:
- First-generation Japanese are subjects who may be living outside of Japan but were born in Japan to parents of Japanese descent;
- Second-generation Japanese are subjects who were born outside of Japan to
first-generation Japanese parents.
Minimum age
18 Years
Maximum age
45 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Men of reproductive potential (ie, men who have not had a vasectomy), unwilling to practice a highly effective method of birth control for the duration of the study and continuing 5 months following treatment with investigational product. Highly effective methods of birth control include:
a. sexual abstinence;
b. vasectomy or a condom (men) in combination with either barrier methods, hormonal birth control, or intrauterine device (utilized by female partners).
2. Men who are unwilling to refrain from donating sperm during the study and for 5 months following treatment with investigational product.
3. Men with pregnant partners.
4. History or evidence of a clinically significant disorder (including psychiatric), condition, or disease that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
5. History or presence of conditions known to interfere with the distribution, metabolism, or excretion of drugs.
6. History of surgery or major trauma within 12 weeks of screening, or surgery planned during the study.
7. Positive screen for alcohol and/or potential drugs of abuse at screening or prior to randomization.
8. Positive screen for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), or hepatitis C virus (HCV).

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)
Participants will be recruited through radio, print and television advertising and database searches. The Nucleus Network database currently has a number of Japanese and Caucasian volunteers. If required, print advertising may be used after translation to Japanese.

Through advertising, potential participants will contact the Nucleus Network volunteer recruitment office and a brief synopsis of the study and its requirements will be discussed over the telephone. Following this initial telephone conversation, potential participants will be invited to the Centre for Clinical Studies.

The database searches will involve the volunteer recruitment officers identifying participants that are suitable for inclusion in the trial and contacting them by telephone. A brief synopsis of the study and its requirements will be discussed. Following this initial telephone conversation, potential participants will be invited to the Centre for Clinical Studies. Volunteers registered on the databases have given consent to be contacted for future studies.

Participants will be provided with the information and consent form for this study by mail or email prior to attendance at the Centre for Clinical Studies where possible. Where this is not possible the information and consent form will be provided in the privacy of a consulting room. The participant will be given the opportunity to take the information home before deciding to take part in the study or not. The information will be discussed with the potential participant and any questions answered by the investigator and / or study staff.

When the participant is satisfied that they understand what their participation in the study involves, and they have had all their questions answered to their satisfaction, they will be asked to sign the consent form to participate in research, only if they are willing to participate. The consenting process will be documented in the volunteers’ source documents.

Once the participant is deemed eligible, study treatment would be allocated by central randomisation by phone/fax/computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The treatment assigned will be decided by a code produced by a computer and will be decided at random (by chance, just like a roll of a dice). Allocation of a participant to the study will be performed by central randomisation by phone/fax/computer.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
Prior to statistical modeling, PK parameters will be loge-transformed. Point estimates and 90% confidence intervals (CIs) for the mean difference in logarithmic PK parameters will be estimated using an analysis of covariance model adjusted for treatment and ethnicity (Japanese and Non-Japanese) for comparisons of ABP 980 and FDA-licensed trastuzumab (Treatment A versus Treatment B), ABP 980 and EU-authorized trastuzumab (Treatment A versus Treatment C), and FDA-licensed trastuzumab and EU-authorized trastuzumab (Treatment B versus Treatment C). The point estimates and 90% CIs for geometric mean test-to-reference ratio will then be calculated by transforming back to original scale.
To establish bioequivalence, the 90% CI for the geometric mean test-to-reference ratio for Cmax and AUCinf should fall within the bioequivalence criteria of 0.80 and 1.25.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
19/05/2014
Actual
26/05/2014
Date of last participant enrolment
Anticipated
18/07/2014
Actual
13/08/2014
Date of last data collection
Anticipated
Actual
15/10/2014
Sample size
Target
150
Accrual to date
Final
158
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 2273 0
Alfred Health
Recruitment postcode(s) [1] 7945 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 288994 0
Commercial sector/Industry
Name [1] 288994 0
Amgen Inc, USA.
Country [1] 288994 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Amgen Inc, USA.
Address
One Amgen Center Drive
MS 28-3-D
Thousand Oaks, CA 91320
Country
United States of America
Secondary sponsor category [1] 287674 0
None
Name [1] 287674 0
NIL
Address [1] 287674 0
NIL
Country [1] 287674 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290801 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 290801 0
Commercial Road
Melbourne, 3004
Victoria
Ethics committee country [1] 290801 0
Australia
Date submitted for ethics approval [1] 290801 0
24/03/2014
Approval date [1] 290801 0
12/05/2014
Ethics approval number [1] 290801 0
128/14

Summary
Brief summary
The study is evaluating the safety, tolerability, and immunogenicity of ABP 980 in healthy subjects compared with US Food and Drug Administration (FDA)-licensed trastuzumab and European Union (EU)-authorized trastuzumab.

Who is it for?
You may be eligible to join this study if you are healthy male, aged between 18 to 45 years of age (inclusive), and have a body mass index between 18.0 and 30.0 kg/m2 (inclusive) for non-Japanese subjects. To be enrolled as a Japanese subject, subjects must be either first- or second-generation Japanese and have a body mass index between 18.0 and 25.0 kg/m2.

Trial details
Participants in this study will be randomly (by chance) divided into one of three groups. Participants in one group will receive 6mg/kg of ABP 980 (440mg vial) intravenously once only. Participants in the second group will receive 6mg/kg2 of FDA-licensed trastuzumab (440mg vial) intravenously. Participants in the third group will receive 6mg/kg2 of EU-authorised trastuzumab (440mg vial) intravenously.
All participants will be followed-up at 64 days post allocation to one of the three drugs used in this trial.

Address: Nucleus Network Limited
Centre for Clinical Studies (AMREP site)
Level 5 Burnet Building
89 Commercial Road, Melbourne, Victoria 3004
Trial website
NIL
Trial related presentations / publications
No publications released
Public notes
NIL

Contacts
Principal investigator
Name 47334 0
Dr Jason Lickliter
Address 47334 0
Nucleus Network Limited
Centre for Clinical Studies (AMREP site)
Level 5 Burnet Building
89 Commercial Road, Melbourne, Victoria 3004
Country 47334 0
Australia
Phone 47334 0
+61 3 9076 8960
Fax 47334 0
Email 47334 0
[email protected]
Contact person for public queries
Name 47335 0
Jeffery Wong
Address 47335 0
Nucleus Network Limited
Centre for Clinical Studies (AMREP site)
Level 5 Burnet Building
89 Commercial Road, Melbourne, Victoria 3004
Country 47335 0
Australia
Phone 47335 0
+61 3 9076 8909
Fax 47335 0
Email 47335 0
[email protected]
Contact person for scientific queries
Name 47336 0
Jason Lickliter
Address 47336 0
Nucleus Network Limited
Centre for Clinical Studies (AMREP site)
Level 5 Burnet Building
89 Commercial Road, Melbourne, Victoria 3004
Country 47336 0
Australia
Phone 47336 0
+61 3 9076 8960
Fax 47336 0
Email 47336 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.