Comparative Study of 3 Tocilizumab Products in Normal Healthy Volunteeers

NCT04885829 | Completed Phase 1 FDA Drug

• 1 other identifier: TC-01-002
• Study Type: interventional
• Target: 300
• Locations: 3 countries
• Sites: 4

Brief Summary

A single dose, two period trial where participants will be given either of 3 Tocilizumab product on Day 1 during period 1 and either one of the remaining 2 Tocilizumab products on Day 1 period 2. There will be at least 6 weeks (42 days) of wash out between subsequent two period dosing. The maximum flexibility allowed between subsequent periods will be up to 9 weeks (63 days). Names of the 3 tocilizumab products are DRL\_TC, RP and RMP. So if a participant receives DRL\_TC on Day 1 Period 1 then he/she will either receive RP/RMP on Day 1 Period 2.

Conditions

Rheumatoid Arthritis; Giant Cell Arteritis

Outcome Measures

Primary Outcomes (2)

• To demonstrate the PK (Pharmacokinetics) similarity of DRL_TC vs RP, DRL_TC vs RMP and RP vs RMP.

  AUC0-∞ and AUC0-t will be calculated

  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)

• To demonstrate the PK (Pharmacokinetics) similarity of DRL_TC vs RP, DRL_TC vs RMP

  Cmax will be calculated

  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 Outcomes (18)

• Safety assessment

  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

• Safety assessment

  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

• Safety assessment

  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

• Safety assessment

  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

• Safety assessment

  Screening (Day -28 to -2) to EOS visit

Study Arms (2)

DRL_TC

EXPERIMENTAL

Subcutaneous injection of DRL's Tocilizumab

Drug: Tocilizumab Prefilled Syringe

RP and RMP

ACTIVE COMPARATOR

Subcutaneous injection of Actemra and RoActemra (Commercially available Tocilizumab)

Drug: Tocilizumab Prefilled Syringe

Interventions

Tocilizumab Prefilled Syringe DRUG

0.9ml Subcutaneous pre-filled syringes containing 162mg of Tocilizumab.

Also known as: Actemra, RoActemra

DRL_TC; RP and RMP

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female volunteers, 18 to 50 years of age at the time of signing informed consent.
• 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.
• BMI between 18.5 - 30.0 kg/m2 and body weight between 50 and 100 kg (both inclusive).
• 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.
• 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)
• Capable, and amenable, to provide written informed consent to the study requirements.
• Willing to abide by study restrictions for the entire study duration.

You may not qualify if:

• Positive test result for Quantiferon-TB Gold test, syphilis, hepatitis B, hepatitis C, or HIV-1 or 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.).
• 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.
• Administration of immunoglobulins for anti-tetanus and antirabies post-exposure prophylaxis within 3 weeks prior to administration of study drug.
• 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.
• Allergy, or hypersensitivity to any recombinant human, or humanized antibodies, other therapeutic proteins, or any excipients in the study formulations.
• 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.
• 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).
• Blood donation, participation in any study requiring repeated blood sampling or haemorrhage requiring treatment or any transfusion in the past 3 months.
• 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.
• History of relevant orthostatic hypotension, fainting spells, or blackouts deemed in the opinion of the Investigator to pose clinical risk to the subjects.
• 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.
• 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.
• 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.
• ALT or AST higher than 1.25 times the ULN at screening.

Sponsors & Collaborators

• Syneos Health: lead
• Dr. Reddy's Laboratories Limited: collaborator

Study Sites (4)

Nucleus Network, Brisbane

Brisbane, 4006, Australia

Location

Syngene International Ltd

Bangalore, Karnataka, 560100, India

Location

Auckland Clinical Studies Ltd (NZCR OpCo Limited)

Grafton, Auckland, 1010, New Zealand

Location

Christchurch Clinical Studies Trust Ltd (NZCR OpCo Limited)

Christchurch, 8011, New Zealand

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Giant Cell Arteritis

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2021
• First Posted: May 13, 2021
• Study Start: May 31, 2021
• Primary Completion: May 4, 2023
• Study Completion: May 4, 2023
• Last Updated: January 5, 2024

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); IN (1); NZ (2)