Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001473156
Ethics application status
Approved
Date submitted
30/09/2019
Date registered
24/10/2019
Date last updated
5/11/2019
Date data sharing statement initially provided
24/10/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 1 Single Dose Study to Assess the Pharmacokinetics and Safety of the Biosimilar Ustekinumab Healthy Volunteers
Scientific title
A Phase 1, Randomized, Three-Arm, Double-Blind, Single-Dose Study To Compare The Pharmacokinetics And Safety Of The Potential Biosimilar NeuLara With Ustekinumab In Healthy Volunteers
Secondary ID [1] 299428 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Plaque Psoriasis 314616 0
Condition category
Condition code
Inflammatory and Immune System 312955 312955 0 0
Autoimmune diseases
Skin 313107 313107 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment A: Single dose of NeuLara (ustekinumab) 45 mg/0.5 ml solution to be administered for sub cutaneous injection
Treatment B: Single dose of Stelara (EU-licensed ustekinumab) 45 mg/0.5 ml solution to be administered for sub cutaneous injection
Treatment C: Single dose of Stelara (US-licensed ustekinumab) 45 mg/0.5 ml solution to be administered for sub cutaneous injection

Each participant will undergo only one of the above mentioned treatment arms.
Intervention code [1] 315677 0
Treatment: Drugs
Comparator / control treatment
Treatment B: Single dose of Stelara (EU-licensed ustekinumab) 45 mg/0.5 ml solution to be administered for sub cutaneous injection
Treatment C: Single dose of Stelara (US-licensed ustekinumab) 45 mg/0.5 ml solution to be administered for sub cutaneous injection
Control group
Active

Outcomes
Primary outcome [1] 321539 0
To evaluate the PK similarity of Neulara with Stelara-EU and Stelara-US reference products following single SC injection of 45 mg/0.5 ml in healthy volunteers
Timepoint [1] 321539 0
Total 16 blood samples will be collected to assess PK similarity at: Pre-dose and 12, 24, 48 (Day 3), 72 (Day 4), 96 (Day 5), 144 (Day 7), 192 (Day 9), 240 (Day 11), 312 (Day 14),
480 (Day 21), 648 (Day 28), 984 (Day 42), 1488 (Day 63), 1992 (Day 84), and
2496 (Day 105) hours post-dose. PK parameters for all the blood samples will be calculated by standard non-compartmental method for AUC, Cmax, Tmax , T1/2, CL/F (total clearance)
Secondary outcome [1] 375281 0
To evaluate the safety and tolerability of NeuLara compared to Stelara-EU and Stelara-US reference products, by assessing AE’s, use of concomitant medications, physical examination (respiratory,cardiovascular, and gastrointestinal systems, weight, and BMI), vital signs (blood pressure, heart rate,respiratory rate, and body temperature), clinical lab sampling (hematology and chemistry), urine (urinalysis), Injection site evaluation and 12-lead ECGs.
Timepoint [1] 375281 0
Adverse Events will be recorded from time of informed consent until Day 108. AE will be recorded throughout the conduct of study at following specified visits:
Screening Day -1, Day 1 to 5, 7, 9 , 11, 14, 21, 28, 42, 63, 84, 105, 108.
Vital signs, 12 lead ECG will be performed at Screening, Day 1 to 5, 7, 9 , 11, 14, 21, 28, 42, 63, 84, 105, 108. Hematology & Biochemistry, Urinalysis will be performed at Screening, Day -1, Day 14, Day 28, Day 105 (Study exit or early termination visit).
Secondary outcome [2] 375282 0
To evaluate the PK similarity between the Stelara-EU and Stelara-US reference products, following a single SC injection of 45 mg/0.5 mL in healthy volunteers.
Timepoint [2] 375282 0
Total 16 blood samples will be collected to assess PK similarity at: Pre-dose and 12, 24, 48 (Day 3), 72 (Day 4), 96 (Day 5), 144 (Day 7), 192 (Day 9), 240 (Day 11), 312 (Day 14),
480 (Day 21), 648 (Day 28), 984 (Day 42), 1488 (Day 63), 1992 (Day 84), and
2496 (Day 105) hours post-dose. PK parameters for all the blood samples will be calculated by standard non-compartmental method for AUC, Cmax, Tmax , T1/2, CL/F (total clearance
Secondary outcome [3] 375283 0
To evaluate the immunogenicity of NeuLara compared to Stelara-EU and Stelara-US reference products, following a single SC injection of 45 mg/0.5 mL in healthy volunteers.
Timepoint [3] 375283 0
A total of 5 blood samples will be collected for anti-drug antibodies (ADA)
detection: pre-dose and approximately 312 (Day 14), 648 (Day 28), 1488
(Day 63), and 2496 (Day 105) hours post-dose.
Any positive sample for ADA will be further analyzed for neutralizing
antibodies (NAb).

Eligibility
Key inclusion criteria
1) Male or female, light smoker or non-smoker, greater than or equal to 18 and less than or equal to 55 years of age, with BMI greater than or equal to 17.0 and less than or equal to 32.0 kg/m2 and body weight greater than or equal to 50.0 kg and less than or equal to 100 kg.
2) Healthy as defined by:
a) the absence of clinically significant illness and surgery within 4 weeks prior to drug
administration.
b) the absence of clinically significant history of neurological (including seizures),
endocrine, cardiovascular (including unstable angina, heart failure, and myocardial
infarction), pulmonary (including chronic obstructive pulmonary disease [COPD]),
hematological, immunological, psychiatric, gastrointestinal, renal, hepatic,
dermatological (including eczema and allergic dermatitis), and metabolic diseases.
c) the absence of clinically significant active or chronic infection.
d) values for hematology and for biochemistry tests of blood and urine within the reference
ranges or showing no clinically relevant deviations as judged by the Investigator.
3) Females of childbearing potential who are sexually active with a non-sterile male partner
must be willing to use one of the following acceptable contraceptive methods throughout the study and for at least 105 days after drug administration
4) Females of non-childbearing potential defined as post-menopausal and surgically sterile
5) Male subjects who are not vasectomized for at least 6 months, and who are sexually active
with a female partner of childbearing potential must be willing to use one of
the following acceptable contraceptive methods throughout the study until at least 105 days
after drug administration
6) Male subjects with a pregnant partner must agree to use a condom throughout the study until at least 105 days after drug administration.
7) Male subjects must be willing not to donate sperm throughout the study until at least
105 days following drug administration.
8) Capable of consenting and complying with study requirements and procedures.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) Any clinically significant abnormality at physical examination or clinically significant
abnormal laboratory test results at screening or Day -1.
2) Positive test for HIV, hepatitis B, or hepatitis C found during medical screening.
3) Positive pregnancy test at screening or Day -1.
4) History of allergic reactions to ustekinumab or other related drugs, or to any excipient in the
formulation.
5) History of previous exposure to ustekinumab or other anti-IL12/23 molecules for a medical
condition or in the context of another clinical research study.
6) Clinically significant 12-lead ECG abnormalities or vital sign abnormalities at screening.
7) History of significant drug abuse within 1 year prior to screening or positive urine drug
screen
8) History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol
within 6 months prior to the screening visit
9) Participation in a clinical research study involving the administration of an investigational or
marketed drug or device within 30 days or 5 half-lives of the previous drug
10)Use of medications for the timeframes specified below, with the exception of medications
exempted by the Investigator on a case-by-case basis because they are judged unlikely to
affect the PK profile of the study drug or subject safety (e.g., topical drug products without
significant systemic absorption) and hormonal contraceptives
11)Have received a live attenuated vaccine within 1 month prior to screening or plan to receive
such vaccination during the study.
12)Donation of plasma within 7 days prior to dosing. Donation or loss of blood of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to drug administration.
13) Breast-feeding subject.
14)History of cancer, including any form of skin cancer, or strong family history of cancer
15)History of relevant anaphylactic reactions, drug, or food allergies.
16) Self or any first degree relative history with known disturbance of coagulation or blood disorder which would be cause for anemia or excess bleeding Inclusion of subjects with first degree relative history of thalassemia will be at the discretion of the
Investigator.
17)Any confirmed or suspected immunosuppressive or immunodeficient condition based on
medical history, family history, and physical examination.
18)History of clinically significant opportunistic infection
19)History of serious local infection or systemic infection within 3 months prior to screening.
20)History of recurrent infections, including recurring sinus and respiratory infections.
21) Presence of fever within 2 weeks prior to drug administration.
22)History of active tuberculosis or presence of active or latent tuberculosis, or positive
QuantiFERON®-TB test indicating possible tuberculosis infection.
23)Have resided or travelled in regions where tuberculosis or mycosis is endemic within
1 month prior to screening, or plan to visit such a region during the study.
24)Any reason which, in the opinion of the Investigator, would prevent the subject from
participating in the study.

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)
Subjects eligible for the study will be randomized to receive Treatment A,
Treatment B, or Treatment C according to the randomization scheme produced.
Designated pharmacy personnel at the clinical sites not directly involved with the clinical aspects of the study will prepare, store, and dispense the study medication and will be aware of the randomization code. An envelope for each subject containing his/her treatment assignment will be available from the pharmacy personnel.
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-equivalence
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
15/10/2019
Date of last participant enrolment
Anticipated
20/12/2019
Actual
Date of last data collection
Anticipated
2/04/2020
Actual
Sample size
Target
210
Accrual to date
9
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 14885 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment hospital [2] 14886 0
Scientia Clinical Research - Randwick
Recruitment hospital [3] 14887 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 28153 0
5000 - Adelaide
Recruitment postcode(s) [2] 28154 0
2031 - Randwick
Recruitment postcode(s) [3] 28155 0
4007 - Herston

Funding & Sponsors
Funding source category [1] 303938 0
Commercial sector/Industry
Name [1] 303938 0
NeuClone Proprietary Limited
Country [1] 303938 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
NeuClone Proprietary Limited
Address
4 Cornwallis Street
Eveleigh
NSW 2015 Australia
Country
Australia
Secondary sponsor category [1] 304089 0
None
Name [1] 304089 0
None
Address [1] 304089 0
None
Country [1] 304089 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304434 0
Bellberry HREC
Ethics committee address [1] 304434 0
123 Glen Osmond Road
Eastwood
Adelaide SA 5063
Ethics committee country [1] 304434 0
Australia
Date submitted for ethics approval [1] 304434 0
10/07/2019
Approval date [1] 304434 0
18/09/2019
Ethics approval number [1] 304434 0

Summary
Brief summary
This research project is being conducted to compare the Pharmacokinetics and Safety of The Potential Biosimilar Neulara with Ustekinumab in Healthy Volunteers
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96942 0
Dr Angela Molga
Address 96942 0
Cmax Clinical Research
Level 5, 18a North Terrace
Adelaide, SA 5000 Australia
Country 96942 0
Australia
Phone 96942 0
+61 870887900
Fax 96942 0
Email 96942 0
[email protected]
Contact person for public queries
Name 96943 0
Mr Glenn Pilkington
Address 96943 0
NEUCLONE PTY LTD
AUSTRALIAN TECHNOLOGY PARK
NATIONAL INNOVATION CENTRE
4 CORNWALLIS ST, EVELEIGH NSW 2015
Country 96943 0
Australia
Phone 96943 0
+61 432 324 490
Fax 96943 0
Email 96943 0
[email protected]
Contact person for scientific queries
Name 96944 0
Mr Glenn Pilkington
Address 96944 0
NEUCLONE PTY LTD
AUSTRALIAN TECHNOLOGY PARK
NATIONAL INNOVATION CENTRE
4 CORNWALLIS ST, EVELEIGH NSW 2015
Country 96944 0
Australia
Phone 96944 0
+61 432 324 490
Fax 96944 0
Email 96944 0
[email protected]

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 Biosimilar study, only aggregate data may be posted/published


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.