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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04885829




Registration number
NCT04885829
Ethics application status
Date submitted
3/05/2021
Date registered
13/05/2021

Titles & IDs
Public title
Comparative Study of 3 Tocilizumab Products in Normal Healthy Volunteeers
Scientific title
A Single Dose, Double-Blind, Two-Period, Crossover, Comparative Pharmacokinetic Study of Three Tocilizumab Products Administered by the Subcutaneous Route to Normal Healthy Volunteers
Secondary ID [1] 0 0
TC-01-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Giant Cell Arteritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Neurological 0 0 0 0
Other neurological disorders
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

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

Experimental: DRL_TC - Subcutaneous injection of DRL's Tocilizumab

Active comparator: RP and RMP - Subcutaneous injection of Actemra and RoActemra (Commercially available Tocilizumab)


Treatment: Drugs: Tocilizumab Prefilled Syringe
0.9ml Subcutaneous pre-filled syringes containing 162mg of Tocilizumab.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To demonstrate the PK (Pharmacokinetics) similarity of DRL_TC vs RP, DRL_TC vs RMP and RP vs RMP.
Timepoint [1] 0 0
Period I pre-dose (1hour prior to drug administration), Days 1, 2, 3, 4, 5, 6, 7, 9, 11, 15, 18, 22, 29, 36, 43 and Period II - Day 1 (dosing), 2 ,3 , 4 , 5 , 6, 7, 9, 11, 15, 18, 22, 29 , 36 , 43 (-2 to +4 days)
Primary outcome [2] 0 0
To demonstrate the PK (Pharmacokinetics) similarity of DRL_TC vs RP, DRL_TC vs RMP
Timepoint [2] 0 0
Period I pre-dose (1hour prior to drug administration), Days 1, 2, 3, 4, 5, 6, 7, 9, 11, 15, 18, 22, 29, 36, 43 and Period II - Day 1 (dosing), 2 ,3 , 4 , 5 , 6, 7, 9, 11, 15, 18, 22, 29 , 36 , 43 (-2 to +4 days)
Secondary outcome [1] 0 0
Safety assessment
Timepoint [1] 0 0
Screening (Days -28 to -2), Day -1, predose (within 1hour before dosing), post dose (10 minutes, 60 minutes, 4 hours, 8 hours, 12 hours on day 1 and 43) and 24hours, 36hours, 48hours, 60 hours, 72 hours and 84hours after dosing
Secondary outcome [2] 0 0
Safety assessment
Timepoint [2] 0 0
Screening (Days -28 to -2), Day -1, predose (within 1hour before dosing), post dose (10 minutes, 60 minutes, 4 hours, 8 hours, 12 hours on day 1 and 43) and 24hours, 36hours, 48hours, 60 hours, 72 hours and 84hours after dosing
Secondary outcome [3] 0 0
Safety assessment
Timepoint [3] 0 0
Screening (Days -28 to -2), Day -1, predose (within 1hour before dosing), post dose (10 minutes, 60 minutes, 4 hours, 8 hours, 12 hours on day 1 and 43) and 24hours, 36hours, 48hours, 60 hours, 72 hours and 84hours after dosing
Secondary outcome [4] 0 0
Safety assessment
Timepoint [4] 0 0
Screening (Days -28 to -2), Day -1, predose (within 1hour before dosing), post dose (10 minutes, 60 minutes, 4 hours, 8 hours, 12 hours on day 1 and 43) and 24hours, 36hours, 48hours, 60 hours, 72 hours and 84hours after dosing
Secondary outcome [5] 0 0
Safety assessment
Timepoint [5] 0 0
Screening (Day -28 to -2) to EOS visit
Secondary outcome [6] 0 0
Safety assessment
Timepoint [6] 0 0
2,24,36,48,60,72 and 84 hours post dosing.
Secondary outcome [7] 0 0
Safety assessment
Timepoint [7] 0 0
Period I - Screening (Days -28 to -2), Day -1 (check- in), 1 (dosing),4, 5 and Period II - Day 1 (check- in), 1 (dosing) 4, 5 , 43 (-2 to +4 days)
Secondary outcome [8] 0 0
Safety assessment
Timepoint [8] 0 0
Period I - Screening (Days -28 to -2), check-in (day -1), 2, 5, 9, 15 and 29 and Period II - Day 1 (check- in), 2 , 5 , 9, 15, 29, 43 (-2 to +4 days)
Secondary outcome [9] 0 0
Safety assessment
Timepoint [9] 0 0
Period I - Screening (Days -28 to -2), check-in (day -1), 2, 5, 9, 15 and 29 and Period II - Day 1 (check- in), 2 , 5 , 9, 15, 29, 43 (-2 to +4 days)
Secondary outcome [10] 0 0
Safety assessment
Timepoint [10] 0 0
Period I - Screening (Days -28 to -2), check-in (day -1), 2, 5, 9, 15 and 29 and Period II - Day 1 (check- in), 2 , 5 , 9, 15, 29, 43 (-2 to +4 days)
Secondary outcome [11] 0 0
Safety assessment
Timepoint [11] 0 0
Period I - Screening (Days -28 to -2), check-in (day -1), 2, 5, 9, 15 and 29 and Period II - Day 1 (check- in), 2 , 5 , 9, 15, 29, 43 (-2 to +4 days)
Secondary outcome [12] 0 0
Safety assessment
Timepoint [12] 0 0
Period I - Screening (Days -28 to -2), check-in (day -1), 2, 5, 9, 15 and 29 and Period II - Day 1 (check- in), 2 , 5 , 9, 15, 29, 43 (-2 to +4 days)
Secondary outcome [13] 0 0
Safety assessment
Timepoint [13] 0 0
Period I - Screening (Days -28 to -2), check-in (day -1), 2, 5, 9, 15 and 29 and Period II - check-in (day -1), 2, 5, 9, 15, 29 ,43 (-2 to +4 days)
Secondary outcome [14] 0 0
IL-6 assessment
Timepoint [14] 0 0
Period I - Day-1, 2, 5, 15 and Period II - Day -1 , 2 , 5 , 15
Secondary outcome [15] 0 0
hsCRP assessment
Timepoint [15] 0 0
Period I - Day-1, 2, 5, 15 and Period II - Day -1 , 2 , 5 , 15
Secondary outcome [16] 0 0
Neutrophil assessment
Timepoint [16] 0 0
Period I - Day-1, 2, 5, 15 and Period II - Day -1 , 2 , 5 , 15
Secondary outcome [17] 0 0
Lipid parameters assessment
Timepoint [17] 0 0
Period I - Day-1, 2, 5, 15 and Period II - Day -1 , 2 , 5 , 15
Secondary outcome [18] 0 0
Immunogenicity assessment
Timepoint [18] 0 0
Period I - On Day 1 (Randomization), 15, 29 and Period II - On day 1(Dosing)), 15, 29

Eligibility
Key inclusion criteria
1. Healthy male and female volunteers, 18 to 50 years of age at the time of signing informed consent.
2. In general good health as determined by a qualified physician based on a comprehensive medical history, physical examination including vital signs, laboratory haematology, clinical chemistry, urinalysis and 12-lead ECG during screening.
3. BMI between 18.5 - 30.0 kg/m2 and body weight between 50 and 100 kg (both inclusive).
4. Screening parameters (vital signs, physical examination, clinical laboratory tests, 12-lead ECG, chest X-ray, thyroid function etc.) are within the normal range or if outside the normal range, assessed as clinically non-significant by the Investigator (unless the value constitutes an explicit exclusion criterion).
5. Male volunteers must be willing to abstain from sexual intercourse, sperm donation or willing to use in all relationships with a partner from the opposite sex a condom for the male partner and another effective method of contraception (such as an intra-uterine device, vaginal ring, oral contraceptive, injectable progesterone, or sub-dermal implant) for the female partner from the time of dosing until 3 months after the last dosing date, unless one of the partners is medically confirmed to be either infertile or surgically sterile.
6. Female volunteers should be either post-menopausal or surgically sterile. Note: ("Postmenopausal" is defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone levels > 40 mIU/ml or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy)
7. Capable, and amenable, to provide written informed consent to the study requirements.
8. Willing to abide by study restrictions for the entire study duration.
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Positive test result for Quantiferon-TB Gold test, syphilis, hepatitis B, hepatitis C, or HIV-1 or 2.
2. Any prior exposure to tocilizumab or to any other agent directly acting on interleukin-6 or on its receptors including investigational products (e.g. siltuximab, sarilumab etc.).
3. Live virus vaccination within 3 months prior to screening or intention to receive live virus vaccination during the trial or up to 3 months after the administration of the study drug.
4. Administration of immunoglobulins for anti-tetanus and antirabies post-exposure prophylaxis within 3 weeks prior to administration of study drug.
5. History of immunodeficiency or other clinically significant immunological disorders, or auto-immune disorders, ongoing or frequent/ recurring infection defined as more than 3 per year requiring treatment or prior herpes zoster not fully healed (including the post-herpetic neuralgia period if occurring) within one year prior to randomization or history of systemic fungal infection at any time.
6. Allergy, or hypersensitivity to any recombinant human, or humanized antibodies, other therapeutic proteins, or any excipients in the study formulations.
7. Current manifestation of clinically significant (in the opinion of the Investigator) atopic allergy (e.g., asthma including childhood asthma currently showing clinical manifestations, urticaria, angioedema, eczematous dermatitis), hypersensitivity, or allergic reactions.
8. Non-suitable skin for dosing or post-dosing evaluations of upper arm (same arm to be used as the injection site in the both periods) for any reasons (including presence of tattoos, skin pigmentation disorders, scarring etc., which may obscure the injection site).
9. Blood donation, participation in any study requiring repeated blood sampling or haemorrhage requiring treatment or any transfusion in the past 3 months.
10. Screening blood pressure higher than 140 mm Hg (systolic) or higher than 90 mm Hg (diastolic) or volunteers currently on anti-hypertensive drugs. Up to two repeats on different days are allowed and, in this case, the mean of the measurements will be used to decide on eligibility. Screening blood pressure is to be measured in the sitting position after 5 minutes rest.
11. History of relevant orthostatic hypotension, fainting spells, or blackouts deemed in the opinion of the Investigator to pose clinical risk to the subjects.
12. QTc (Fridericia correction) longer than 450 milliseconds or other clinically relevant ECG abnormalities such as atrial fibrillation, atrial flutter, Wolf-Parkinson-White syndrome, or presence of a cardiac pacemaker.
13. History or presence of any clinically relevant nervous system disease including, but not restricted to any stroke/TIA (Transient Ischemic Attack), or of seizures other than febrile seizures before the age of 5 years.
14. History of and/or current gastrointestinal, renal endocrine, pulmonary, hepatic, cardiovascular (including history of or presence of angina, exertional dyspnoea, orthopnoea, congestive heart failure or myocardial infarction and thrombotic or embolic episode requiring treatment), hematological (including pancytopenia, aplastic anemia or blood dyscrasia and coagulopathies, or an INR higher than 1.5), metabolic (including known diabetes mellitus) considered as significant by the Investigator. This criterion includes any disorder or condition that, in the Investigator's opinion, may interfere with the safety of the subject, the study evaluations or the subject compliance to the study procedures and limitations.
15. ALT or AST higher than 1.25 times the ULN at screening.
16. Neutrophil count below 2 x 109/liter (2,000 per mm3) or platelet count below 100 x 109/liter (100,000 per mm3) at screening.
17. Clinically relevant hyperlipidemia (fasting serum LDL-cholesterol higher than 190 mg/dL or fasting serum triglycerides higher than 200 mg/dL or subject currently on antihyperlipidemic drugs).
18. Any active infection, even if minor, ongoing at the time of screening or dosing.
19. Presence of any non-healed wound or bone fracture of a clinically relevant size (in the Investigator's opinion).
20. Participation in an interventional or Phase I study in the last three months, or on, or participation in more than 3 studies of experimental drug products in the past 12 months, or intake of an investigational drug in another trial within 3 months or 5 half-lives (whichever is longer) prior to intake of study drug in this trial or planned intake of an investigational drug (any drug administered in a clinical trial setting is considered an investigational drug) or follow up visit scheduled from any study during the course of this trial or intake for any reason in the last 6 months of some specific long body residence drugs such as any immunoglobulin or antibody drug (except for post-exposure prophylaxis of tetanus or rabies given more than 3 weeks before the date of the first study drug dose) pirimethamine, teicoplanin, systemic retinoids, mefloquine and hydroxychloroquine.
21. History of any cancer, including carcinoma in situ, lymphoma or leukemia.
22. History of, or current intestinal ulceration or diverticulitis.
23. Major surgery within the past 12 months, major surgery planned within 12 months of study enrolment or any surgery including dental interventions planned within 3 months of study enrolment.
24. Intake of any medication including herbal products within 3 weeks prior to dosing other than for the exceptions detailed in Section 10.2-Prior and Concomitant Medications.
25. Current smokers or those who gave up smoking less than 3 months prior to screening, (thus 3 months cessation required at screening time), including alternative tobacco products such as chewing tobacco and vaping, or positive urine cotinine test at screening.
26. Positive test for alcohol in breath or drugs of abuse (including benzodiazepines, amphetamines, barbiturates, cocaine, methadone, phencyclidine 3,4-methylenedioxymethamphetamine [MDMA/ecstasy], tetrahydrocannabinol, and opiates) in urine.
27. Any history of difficulty in blood sampling or any vasovagal attack during blood sampling which in the opinion of the Investigator may relevantly interfere with the study sampling.

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 assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/05/2023
Sample size
Target
Accrual to date
Final
300
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Nucleus Network, Brisbane - Brisbane
Recruitment postcode(s) [1] 0 0
4006 - Brisbane
Recruitment outside Australia
Country [1] 0 0
India
State/province [1] 0 0
Karnataka
Country [2] 0 0
New Zealand
State/province [2] 0 0
Auckland
Country [3] 0 0
New Zealand
State/province [3] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Other
Name
Syneos Health
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Dr. Reddy's Laboratories Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04885829