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Trial registered on ANZCTR


Registration number
ACTRN12616000509460
Ethics application status
Approved
Date submitted
18/03/2016
Date registered
20/04/2016
Date last updated
7/07/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Randomized, Double-Blind, Single-Dose, 3-Arm, Parallel Group Study to Determine the Pharmacokinetic Similarity of ABP 959 and Eculizumab (Soliris Registered Trademark) in Healthy Male Subjects
Scientific title
A Randomized, Double-Blind, Single-Dose, 3-Arm, Parallel Group Study to Determine the Pharmacokinetic Similarity of ABP 959 and Eculizumab (Soliris Registered Trademark) in Healthy Male Subjects
Secondary ID [1] 288246 0
Protocol Number: 20150164
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atypical Haemolytic Uraemic Syndrome (aHUS)
298465 0
Complement-mediated thrombotic microangiopathy 298466 0
Paroxysmal Nocturnal Haemoglobinuria (PNH) 298467 0
Haemolysis 298468 0
Condition category
Condition code
Blood 297398 297398 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: ABP 959 300 mg intravenously, final admixture concentration of 5 mg/mL
Arm 2: FDA-licensed eculizumab 300 mg intravenously, final admixture concentration of 5 mg/mL
Arm 3: EU-authorized eculizumab 300 mgintravenously, final admixture concentration of 5 mg/mL

Subjects will be randomized on Day -1 or prior to dosing on Day 1 according to a
computer-generated randomization schedule to receive either intravenous ABP 959 300 mg(treatment Arm 1) , Intravenous FDA-licensed eculizumab 300 mg (treatment Arm 2), or Intravenous EU-authorized eculizumab 300 mg (treatment arm 3) in a ratio of 1:1:1, stratified by CPU and ethnicity (Japanese versus non-Japanese).

Subjects will only be dosed once, on the morning of Day 1 over 35 minutes after breakfast.
Intervention code [1] 293533 0
Treatment: Drugs
Intervention code [2] 294527 0
Other interventions
Comparator / control treatment
Food and Drug Administration (FDA)-licensed eculizumab EU-authorized eculizumab
Control group
Active

Outcomes
Primary outcome [1] 296952 0
The primary objective of this study is to demonstrate PK similarity (as assessed principally by AUCinf) of ABP 959 following a 300 mg intravenous (IV) infusion relative to that from a 300 mg IV infusion of FDA-licensed eculizumab and EU-authorized eculizumab.

The outcome is assessed using a validated electrochemiluminescent assay.
Timepoint [1] 296952 0
Regular blood samples will be taken to measure PK at
-Screening visit (within 28 days of scheduled dosing date)
-Day - 1 ( check in)
-Day 1 /Treatment Visit, pre-dose, end of infusion, 4, 8 and 12hours post dose
-Day 2/Checkout
-Visit Days, 3, 5, 11, 15, 29, 36, 50
-Visit days 8, 22, 43
-End of Study visit day 57

Data collected will be assessed at 57 days after randomisation.
Secondary outcome [1] 319755 0
To determine PK similarity as assessed principally by AUCinf, AUC from time 0 to the time of the last observed quantifiable concentration (AUClast), Maximum observed concentration (Cmax) ,Terminal elimination half-life (t1/2) and Time of maximal concentration (tmax) of a 300 mg IV infusion of FDA-licensed eculizumab relative to a 300 mg IV infusion of EU-authorized eculizumab.

This composite outcome is assessed using a validated electrochemiluminescent assay.
Timepoint [1] 319755 0
Regular blood samples will be taken to measure PK at
-Screening visit (within 28 days of scheduled dosing date)
-Day - 1 ( check in)
-Day 1 /Treatment Visit pre-dose, end of infusion, 4, 8 and 12hours post dose
-Day 2/Checkout
-Visit Days, 3, 5, 8 11, 15,22, 29, 36, 43, 50
-End of Study visit day 57

Data collected will be assessed at 57 days after randomisation.
Secondary outcome [2] 319756 0
To assess the changes in 50% total hemolytic complement activity (CH50; as assessed by area between the effect curve [ABEC]) following a 300 mg IV infusion of ABP 959, FDA
licensed eculizumab, and EU authorized eculizumab.

The outcome is assessed using a validated electrochemiluminescent assay.
Timepoint [2] 319756 0
Regular blood samples to measure CH50 will be taken at
-Screening visit (within 28 days of scheduled dosing date)
-Day - 1 ( check in)
-Day 1 /Treatment Visit pre-dose, end of infusion, 4, 8 and 12hours post dose
-Day 2/Checkout
-Visit Days, 3, 5, 8 11, 15,22, 29, 36, 43, 50
-End of Study visit day 57

Data collected will be assessed at 57 days after randomisation.
Secondary outcome [3] 319757 0
To determine the safety and tolerability of ABP 959 in healthy male
subjects compared with FDA-licensed eculizumab and EU-authorized eculizumab.

-Safety laboratory results and vital signs will be asessed at each follow-up visit.
-ECG Review on day 2
-Self reported Adverse Events
Timepoint [3] 319757 0
Subjects will be monitored for AEs from days 1, 2, 3, 5, 8, 11, 45, 22, 29, 36, 43, 50,57 after dose administration. Clinically significant clinical or laboratory abnormalities will be followed until resolution or until considered stable.

Secondary outcome [4] 322972 0
To determine the immunogenicity of ABP 959 in healthy male subjects compared with FDA-licensed eculizumab and EU-authorized eculizumab.

- Serum assay for anti drug antibody
Timepoint [4] 322972 0
Anti Drug Antibody sampling will be taken at:
- Days , 1 (pre-dose), 29 and 57

Data collected will be assessed at 57 days after randomisation.

Eligibility
Key inclusion criteria
Subjects must meet all inclusion criteria to be eligible for study participation.
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 male subjects between 18 and 45 years of age, inclusive, at the time of
screening.
3. Non-Japanese subjects will have a BMI of 18.0 to 30.0 kg/m2, inclusive, at screening and check-in. Japanese subjects must have a BMI of 18.0 to 25.0 kg/m2, inclusive, at screening and check-in. BMI equals weight (kg)/(height [m])2
4. Subjects will have a body weight of 50.0 to 90.0 kg, inclusive.
5. 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.
6.Normal or clinically acceptable physical examination, clinical laboratory test values,
urinalysis values, vital signs, ECGs (12-lead ECG reporting heart rate and RR, PR, QRS, QT,
and QTc intervals), and body weight, as determined by the investigator, at all predose
assessments (ie, screening, Day -1, and predose on Day 1).
7.Negative urine drug screen and alcohol screen at screening and Day -1.
8.Subjects must be able to communicate effectively with the study personnel.
Minimum age
18 Years
Maximum age
45 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Men of reproductive potential (ie, men who have not had a vasectomy) who are unwilling to practice a highly effective method of birth control for the duration of the study and continuing 6 months following treatment with IP. Highly effective methods of birth control include:
*Sexual abstinence
* 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 6 months following treatment with IP.
3. Men with pregnant partners.
4. Hypertension (defined as a systolic blood pressure > 140 mmHg and/or a diastolic blood pressure > 90 mmHg confirmed by a single repeat measurement that same day) or a history of hypertension requiring intervention.
5. Proteinuria (with a urine dipstick value of 2+ or above) at screening or check-in.
6. Coagulation abnormalities (ie, international normalized ratio [INR] > 2 x upper limit of
normal) at screening or check-in.
7. Known or suspected hereditary complement deficiency.
8. Presence or suspicion of active bacterial infection, in the opinion of the investigator.
9. History of meningococcal infection.
10. History or evidence of a clinically significant disorder (including psychiatric), condition, or disease that, in the opinion of the investigator and ICON Medical Monitor or designee, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
11. History or presence of conditions known to interfere with the distribution, metabolism, or excretion of drugs.
12. Use of any over the counter (OTC) or prescription medications within the 14 days or
5 half-lives (whichever is longer), prior to receiving IP. Acetaminophen (up to 2 g per day
and not more than 4 g per week) for analgesia will be allowed. Vitamin use can be allowed per agreement between Amgen Inc and the medical monitor.
13. All herbal medicines (eg, St. John’s wort) and supplements consumed by the subject within the 30 days prior to receiving IP, and continuing use if applicable, will be reviewed by the investigator and the ICON Medical Monitor. Written documentation of this review and Amgen acknowledgment of the decision made with respect to eligibility is required for subject participation.
14. History of surgery or major trauma within 12 weeks of screening, or surgery planned during the study.
15. Receiving or has received other investigational drugs (or is currently using an investigational device) within 30 days or 5 half-lives (whichever is longer) prior to receiving IP.
16. Prior exposure to eculizumab or related compounds (ie, a monoclonal antibody that
specifically binds to the complement protein C5).
17. Known or suspected sensitivity to products derived from mammalian cell lines.
18. Donated blood (including blood products) or experienced loss of blood = 500 mL within 2 months of screening.
19. Positive screen for alcohol and/or potential drugs of abuse (urine drug screen) at screening or upon admission to the CPU (Day -1). Subject should refrain from drinking alcohol within 72 hours prior to screening and Day -1, and should not consume alcohol throughout the study.
20. Positive screen for human immunodeficiency virus (HIV1 and 2), hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (HBcAb; immunoglobulin M test only), or hepatitis C virus (HCV).
21. History of alcohol and/or substance abuse within the last 12 months prior to screening.
22. Subjects who use > 10 cigarettes per day within the last 3 months or not able to abide by the smoking policy of the site.
23. Inability or unwillingness to reside at the CPU for 2 consecutive days or inability to be
available for follow-up assessments or protocol-required procedures, including Menactra registered trademark meningococcal vaccination (if subject is unable to show documentation of prior vaccination).

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)
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)
Subjects will be randomized according to a computer-generated randomization schedule to receive either IV ABP 959 300 mg, IV FDA-licensed eculizumab 300 mg, or IV EU-authorized eculizumab 300 mg in a ratio of 1:1:1, stratified by CPU and ethnicity (Japanese versus non-Japanese).
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
Approximately 210 healthy adult male subjects will be enrolled in this study, of which a minimum of 16% of subjects enrolled will be of first- or second-generation Japanese descent [a minimum of 12 per treatment group]) are planned for dosing.
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
Approximately 210 healthy male subjects are planned for inclusion in this study, of which a minimum of 36 Japanese subjects (12 per treatment group) are required.

This sample size will provide 90% power to demonstrate similarity of the primary PK endpoint (AUCinf) based on assumptions between-subject variability (as measured by coefficient variation) of 40% for ABP 959, EU-authorized eculizumab, and FDA-licensed eculizumab, true geometric mean ratio (GMR) of 1 between ABP 959 and each eculizumab product, bioequivalence margins of (0.80, 1.25), a 5% dropout rate, and two 1-sided tests at a = 0.05.

If the observed CV of AUCinf for the pooled FDA-licensed and EU-authorized
eculizumab exceeds 40%, alternative margins will be used to assess the PK similarity
between test (ABP 959) and reference (FDA-licensed eculizumab or EU-authorized
eculizumab).

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)
SA,VIC
Recruitment postcode(s) [1] 12499 0
5000 - Adelaide
Recruitment postcode(s) [2] 12500 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 292647 0
Commercial sector/Industry
Name [1] 292647 0
Amgen Inc, USA.
Address [1] 292647 0
Amgen Inc
One Amgen Center Drive
Thousand Oaks, CA 91320
Country [1] 292647 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Amgen Inc, USA
Address
Amgen Inc
One Amgen Center Drive
Thousand Oaks, CA 91320
Country
United States of America
Secondary sponsor category [1] 291365 0
None
Name [1] 291365 0
Address [1] 291365 0
Country [1] 291365 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294124 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 294124 0
129 Glen Osmond Rd
Eastwood SA 5063
Ethics committee country [1] 294124 0
Australia
Date submitted for ethics approval [1] 294124 0
06/01/2016
Approval date [1] 294124 0
25/02/2016
Ethics approval number [1] 294124 0
2016-01-006-AA

Summary
Brief summary
The study will compare the safety, tolerability and pharmacokinetics (the levels of drug in the blood) of 3 drugs when given intravenously (into a vein). The drugs tested are:
*a new drug called ABP 959,
*a marketed drug called Eculizumab (Soliris registered trademark) approved in United States (US)
*a marketed drug called Eculizumab (Soliris registered trademar) approved in European Union (EU)

The study is to test that these drugs behave the same in the body, for example, produce the same drug levels in the blood.

who is it for?
You may be eligible to join this study if you are a healthy male 18 to 45 years of age, inclusive. Non-Japanese subjects will have a BMI of 18.0 to 30.0 kg/m2, inclusive, at screening and check-in. Japanese subjects must have a BMI of 18.0 to 25.0 kg/m2, inclusive, at screening and check-in.


Trail Details
Participants in this study will be randomly (by chance) allocated into one of three groups to receive either:
- ABP 959 300 mg intravenously once only.
- US approved Eculizumab 300 mg intravenously once only.
- EU approved Eculizumab 300 mg intravenously once only.

All participants will be followed-up at 50 days post allocation to one of the
three drugs used in this trial.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62462 0
Dr Nicholas Farinola
Address 62462 0
CMAX, A Division of IDT Australia Ltd
Royal Adelaide Hospital
Level 5, East Wing, North Terrace
Adelaide SA 5000
Country 62462 0
Australia
Phone 62462 0
+61 8 82223923
Fax 62462 0
Email 62462 0
cmax@cmax.com.au
Contact person for public queries
Name 62463 0
Ms Christina Lekkas
Address 62463 0
CMAX, A Division of IDT Australia Ltd
Royal Adelaide Hospital
Level 5, East Wing, North Terrace
Adelaide SA 5000
Country 62463 0
Australia
Phone 62463 0
+61 8 8222 3923
Fax 62463 0
Email 62463 0
cmax@cmax.com.au
Contact person for scientific queries
Name 62464 0
Dr Nicholas Farinola
Address 62464 0
CMAX, A Division of IDT Australia Ltd
Royal Adelaide Hospital
Level 5, East Wing, North Terrace
Adelaide SA 5000
Country 62464 0
Australia
Phone 62464 0
+61 8 82223923
Fax 62464 0
Email 62464 0
cmax@cmax.com.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary