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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03522012




Registration number
NCT03522012
Ethics application status
Date submitted
11/04/2018
Date registered
29/04/2018
Date last updated
2/11/2018

Titles & IDs
Public title
Phase I, Pharmacokinetic, Safety and Tolerability Study in Healthy Volunteers
Scientific title
Phase I, Double-Blind, Randomized, Three-Arm, Parallel-Group, Pharmacokinetic, Safety and Tolerability Study in Healthy Volunteers to Evaluate Bioequivalence of LusiNEX and Tocilizumab (EU and US)
Secondary ID [1] 0 0
LusiNEX-HV-PK-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pharmacokinetics 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tocilizumab

Experimental: LusiNex - 4 mg/kg, single-dose IV infusion (Mycenax tocilizumab)

Active Comparator: RoActemra - 4 mg/kg, single-dose IV infusion (RoActemra; tocilizumab marketed in EU )

Active Comparator: Actemra - 4 mg/kg, single-dose IV infusion (Actemra; tocilizumab marketed in US)


Treatment: Drugs: Tocilizumab
Tocilizumab is a recombinant human monoclonal antibody of the immunoglobulin G1 subclass, directed against the IL-6 ligand specific receptor. By preventing the binding of IL-6 to its receptor, tocilizumab inhibits the biological activity of IL-6. Tocilizumab was approved by the US Food and Drug Administration (4 mg/kg with an increase to 8 mg/kg based upon clinical response) for the treatment of adult patients with moderate to severe active rheumatoid arthritis, who have had inadequate response to one or more tissue necrotizing factor (TNF) antagonist therapies. Tocilizumab is currently approved in 95 countries for the treatment of adult onset moderate to severe rheumatoid arthritis.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pharmacokinetics - Area under concentration-time curve from time 0 (predose) extrapolated to infinity (AUC(0-8)).
Timepoint [1] 0 0
2 months
Secondary outcome [1] 0 0
Cmax - Maximum concentration (Cmax)
Timepoint [1] 0 0
2 months
Secondary outcome [2] 0 0
tmax - Time to reach maximum concentration (tmax)
Timepoint [2] 0 0
2 months
Secondary outcome [3] 0 0
AUC(0-t) - Area under concentration-time curve from time 0 (predose) to the last quantifiable data point (AUC(0-t))
Timepoint [3] 0 0
2 months
Secondary outcome [4] 0 0
t1/2 - Terminal half-life (t1/2)
Timepoint [4] 0 0
2 months
Secondary outcome [5] 0 0
Vss - Volume of distribution at steady-state
Timepoint [5] 0 0
2 months
Secondary outcome [6] 0 0
Vd - Volume of distribution (Vd)
Timepoint [6] 0 0
2 months
Secondary outcome [7] 0 0
CL - Systemic clearance (CL)
Timepoint [7] 0 0
2 months
Secondary outcome [8] 0 0
Kel - Elimination rate constant (Kel)
Timepoint [8] 0 0
2 months
Secondary outcome [9] 0 0
AEs - The Investigator will carefully monitor each subject throughout the study for any AEs (coded to preferred term and system organ class using the Medical Dictionary for Regulatory Activities [MedDRA])
Timepoint [9] 0 0
2 months
Secondary outcome [10] 0 0
antidrug antibodies - means of the occurrence of antidrug antibodies (ADA)
Timepoint [10] 0 0
2 months

Eligibility
Key inclusion criteria
1. Willing to provide written informed consent prior to performing study-related
procedures.

2. Healthy male or female aged between 18 to 55 years, inclusive.

3. A body mass index between 18 to 30 kg/m2, inclusive.

4. Medically healthy with clinically insignificant results (e.g., medical history,
electrocardiograms [ECGs], and physical examination) as judged by the Principal
Investigator at Screening/Day 1 (admission to study center).

5. All laboratory results including, but not restricted to, complete blood counts, liver
function, and lipid profile should be within the normal range or clinically
insignificant as judged by the Investigator at Screening/Day 1 (admission to study
center). An abnormal laboratory result considered to be erroneous, may be repeated
once during Screening at the discretion of the Investigator.

6. Have systolic blood pressure =140 and =90 mmHg, diastolic blood pressure =90 and =50
mmHg, and a heart rate =40 and =100 beats per minute at Screening/Day 1 (admission to
study center).

7. Has to agree to abstain from alcohol intake 48 hours before administration of the
study drug and during the inpatient period of the study.

8. Negative urine drug screen/alcohol breathylzer test at Screening/Day 1 (admission to
study center).

9. Non-smokers or social smokers (defined as less than 10 cigarettes per week). No
current use of any nicotine containing product. Cotinine levels =5 ng/mL.

10. Willing to abstain from sexual intercourse or use 2 methods of contraception (both
male and female partners) as defined in the protocol for 3 months after study drug
administration.

Female subjects who are using oral hormonal contraceptives must be willing to use,
with their partner, 2 methods of contraception as defined as defined in the protocol.

11. Has to agree to not donate sperm or ova for at least 3 months after study drug
administration.

12. Subjects who are negative for hepatitis B surface antigen, hepatitis B core antibody,
hepatitis C antibodies, human immunodeficiency virus I and II, as well as tuberculosis
(TB) tests at Screening.

13. Did not receive a blood transfusion within 4 weeks prior to study drug administration,
donate 400 mL or more blood within 8 weeks prior to study drug administration or
donate plasma within 4 weeks prior to study drug administration and agrees to not make
blood donations, including red blood cells, plasma, platelets, or whole blood for the
duration of the study and for 3 months after study drug administration.

14. Able to be compliant with the protocol and attend all scheduled visits.

15. Has to agree to not consume any caffeine and/or xanthine products from 24 hours before
admission to the study center until 48 hours after study drug administration.

16. Not have consumed grapefruit and/or grapefruit containing products, Seville oranges or
quinine (tonic water) from 24 hours before admission to the study center until after
the last sample has been collected for the study.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Volunteers with any known active current or history of recurrent bacterial, viral,
fungal, mycobacterial or other infections.

2. Have been treated with IV antibiotics for an infection within 8 weeks or oral
antibiotics within 2 weeks prior to Screening.

3. History of TB infection, active TB or latent TB infection, or recent exposure to a
person with active TB.

4. Previous exposure to therapeutic monoclonal antibodies in the past 6 months prior to
Screening.

5. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
antibodies.

6. A history of clinically significant gastrointestinal, renal, hepatic, cardiovascular,
or allergic disease.

7. Evidence of active malignant disease, malignancies diagnosed within the previous 2
years (except basal cell carcinoma of the skin that has been excised and cured), or
breast cancer diagnosed within the previous 2 years.

8. Impaired liver function as determined by:

• Serum alanine aminotransferase and/or aspartate aminotransferase >1.5 x upper limit
of normal (ULN) at Screening or admission to the study center. Subjects with values
between ULN and 1.5 x ULN may be included in the study if considered not clinically
significant by the Investigator.

9. Current or past history of diverticulitis or biliary obstruction.

10. Presence of proteinuria (other than trace amounts i.e., +, ++/+++) at Screening or
admission to the study center.

11. Administration of an investigational product in another study within 30 days or 5
half-lives of the investigational drug (whichever is longer) prior to screening, 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.

12. Use of any prescription or over-the-counter medication (with the exception of
contraceptive medication in females and paracetamol) within 7 days of Screening and
for the duration of participation in the study. This includes the use of any NSAIDs
(including aspirin) within 28 days before study drug administration and for the
duration of participation in the study.

13. Intake of herbal drugs or dietary supplements excluding routine vitamins but including
megadose (intake of 20 to 600 times the recommended daily dose) vitamin therapy within
28 days prior to study drug administration, unless agreed as not clinically relevant
by the Investigator and Sponsor.

14. Regular alcohol consumption of >14 (female subjects) or >21 (male subjects) units of
alcohol per week at the time of Screening (1 unit = 150 mL of wine or 360 mL of beer
or 45 mL of 40% alcohol).

15. Failure to satisfy the Principal Investigator of fitness to participate for any other
reason.

16. Female subjects who are pregnant, trying to become pregnant, or lactating.

17. Subjects who have a history of relevant drug hypersensitivity or hypersensitivity to
the active substance or to any of the excipients.

18. Inability to undergo venipuncture and/or tolerate venous access.

19. Subjects who do not agree to use medically acceptable methods of contraception (as
defined in the protocol).

20. Involvement in the planning and/or conduct of the study (applies to the Sponsor,
Contract Research Organizations, and study center staff, etc.).

21. Subjects who are unlikely to co-operate with the requirements of the study.

22. Any live virus vaccination or planned vaccination within 28 days before Screening and
for the duration of participation 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)
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 analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
VIC
Recruitment hospital [1] 0 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Mycenax Biotech Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a randomized, double-blind, 3-arm, parallel-group single-dose study to compare the
PK, PD, safety, tolerability, and immunogenicity of LusiNEX (Mycenax tocilizumab) versus
RoActemra (EU tocilizumab) and Actemra (US tocilizumab) after a single IV infusion of 4 mg/kg
in healthy volunteers (hereafter referred to as subjects). The therapeutic dose of
tocilizumab starts with 4 mg/kg and ranges to 12 mg/kg, considering 4 mg/kg is the lowest
dose, the same has been selected for the study.
Trial website
https://clinicaltrials.gov/show/NCT03522012
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Oscar Walsh, Dr.
Address 0 0
Nucleus Network Ltd
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Other publications