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| Name | Class |
|---|---|
| Dr. Reddy's Laboratories Limited | INDUSTRY |
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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.
The study will be conducted at 4 sites (2 in New Zealand, 1 in Australia and 1 in India) The three pairwise product comparisons (DRL_TC vs. RP; DRL_TC vs RMP and RP vs. RMP)will be performed in parallel. Each comparison will be separately considered. Study subjectswill be randomly assigned in a 1:1:1 ratio to one of the comparisons and within eachcomparison subjects will be randomized in a 1:1 ratio to one of the two possible productsequences The total duration of the individual subject study participation will be at least 12weeks. Dosing for period 1 will be on on day 1 followed by washout out period of upto 9weeks. Dosing for Period 2 will be on Day 1.
Subjects who complete the study and are found to be positive for anti-drug antibodies (ADA)on Day 29 and/or Day 43 period 2, will be followed up every 90 days for immunogenicitysampling up to approximately one year post Period II dosing, or until two consecutive sampleshave been negative for ADA, whichever is earlier. Early dropouts will be tested forimmunogenicity at the time of EOS and if they are positive for ADAs they will be followed-up ifpossible at 90 days intervals starting from the last received dose (either Period I or Period II) ina similar manner.
300 NHV (Normal Healthy Volunteers) will be included in the study as justified under samplesize justification. After the data of these 300 volunteers become available a blinded samplesize re-estimation (BSSR) will be performed to reconfirm the statistical assumptions of thestudy design and depending upon the outcome of the BSSR, study may be stopped or thesample size may be increased, as needed to attain the required statistical power.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DRL_TC | Experimental | Subcutaneous injection of DRL's Tocilizumab |
|
| RP and RMP | Active Comparator | Subcutaneous injection of Actemra and RoActemra (Commercially available Tocilizumab) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tocilizumab Prefilled Syringe | Drug | 0.9ml Subcutaneous pre-filled syringes containing 162mg of Tocilizumab. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Safety assessment | Abnormal blood pressure | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nucleus Network, Brisbane | Brisbane | 4006 | Australia | |||
| Syngene International Ltd |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| D013700 | Giant Cell Arteritis |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| C502936 | tocilizumab |
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Abnormal pulse rate |
| 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 | Abnormal respiratory rate | 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 | Abnormal aural temperature | 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 | Assessment of outcome of Adverse events | Screening (Day -28 to -2) to EOS visit |
| Safety assessment | Injection site reaction inspection (FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials to be used) | 2,24,36,48,60,72 and 84 hours post dosing. |
| Safety assessment | Normal 12 Lead ECG | 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) |
| Safety assessment | Abnormal Clinical laboratory data ((Total blood count including hemoglobin, hematocrit, mean corpuscular volume, leukocyte counts (total and differential), and platelet count) | 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) |
| Safety assessment | Abnormal Clinical lab tests (Urea, creatinine, uric acid, glucose, ALT, AST, total bilirubin (and direct if increased), sodium, potassium, chloride, calcium, total proteins, albumin, and LDH) | 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) |
| Safety assessment | Abnormal Clinical lab tests (Coagulation test (aPTT (Activated partial thromboplastin time) and INR (International Normalized Ratio)) | 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) |
| Safety assessment | Abnormal Clinical lab tests (Thyroid hormones (T3, T4 and TSH)) | 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) |
| Safety assessment | Abnormal Clinical lab tests (Lipid profile (including total, LDL and HDL Cholesterol as well as trigycerides) | 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) |
| Safety assessment | Abnormal Clinical lab tests (Urine evaluation with dipstick (confirmation with microscopic examination, if abnormalities are found)) | 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) |
| IL-6 assessment | Change from pre-dose to selected time-points post-dose | Period I - Day-1, 2, 5, 15 and Period II - Day -1 , 2 , 5 , 15 |
| hsCRP assessment | Change from pre-dose to selected time-points post-dose | Period I - Day-1, 2, 5, 15 and Period II - Day -1 , 2 , 5 , 15 |
| Neutrophil assessment | Change from pre-dose to selected time-points post-dose | Period I - Day-1, 2, 5, 15 and Period II - Day -1 , 2 , 5 , 15 |
| Lipid parameters assessment | Change from baseline to selected time-points post-dose (Total, LDL, HDL and trigylcerides) | Period I - Day-1, 2, 5, 15 and Period II - Day -1 , 2 , 5 , 15 |
| Immunogenicity assessment | Presence of anti-drug antibodies (Confirmed positive samples, will be further tested for titre and presence of neutralizing antibodies (NAb)) | Period I - On Day 1 (Randomization), 15, 29 and Period II - On day 1(Dosing)), 15, 29 |
| Bangalore |
| Karnataka |
| 560100 |
| India |
| Auckland Clinical Studies Ltd (NZCR OpCo Limited) | Grafton | Auckland | 1010 | New Zealand |
| Christchurch Clinical Studies Trust Ltd (NZCR OpCo Limited) | Christchurch | 8011 | New Zealand |
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D020293 | Vasculitis, Central Nervous System |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D001167 | Arteritis |
| D014657 | Vasculitis |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |