A phase III, randomised, double-blind, multicentre study comparing the efficacy, safety, and immunogenicity of proposed tocilizumab biosimilar (DRL_Tocilizumab) with tocilizumab reference product (RoActemra®) administered by the subcutaneous route as an add-on to methotrexate in the treatment of patients with moderate to severe rheumatoid arthritis
- Conditions
- Adult patients of either gender with active moderate to severe rheumatoid arthritis (1987 revised ACR criteriaArnett et al. 1987) of at least 6 months duration, with an inadequate response to cDMARDs and currently on treatment with stable doses of MTX for at least 8 weeks prior to randomisation will be eligible for the study. Up to 25% of patients might have also been previously exposed to bDMARDs.Patients with previous exposure to other cDMARD and bDMARD would enter the study after an adequate washout period.Patients previously exposed to JAK pathway inhibitors will not be allowed in the study.MedDRA version: 21.0Level: PTClassification code: 10039073Term: Rheumatoid arthritis Class: 100000004859MedDRA version: 21.1Level: LLTClassification code: 10039074Term: Rheumatoid arthritis aggravated Class: 10028395MedDRA version: 21.1Level: LLTClassification code: 10066578Term: Progression of rheumatoid arthritis Class: 10028395MedDRA version: 20.0Level: HLTClassification code: 10039075Term: Rheumatoid arthritis and associated conditions Class: 10021428Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- CTIS2022-501361-44-00
- Lead Sponsor
- Dr. Reddy's Laboratories Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 448
1. Male or female patient aged = 18 years and = 80 years and willing to voluntarily provide informed consent for participation as per the locally applicable regulations., 10. Patient must be able to self-administer or must have help to administer the study treatment by caregiver., 11. Patient must be able to comply with all study requirements in the opinion of the Investigator., 2. Patient with active moderate to severe rheumatoid arthritis of at least 6 months duration, as per ACR 1987 revised criteria for the classification of Rheumatoid Arthritis., 3. Patients with: a. Swollen Joint Count (SJC) = 6 b. Tender Joint Count (TJC) = 8 c. Erythrocyte Sedimentation Rate (ESR) = 28 mm/ hour, 4. Patient must have been treated with stable doses of MTX (at least 15 mg/ week, not exceeding allowed maximum dose in the country-specific label; at least 6 mg/ week for patients from other Eastern Asia countries) for at least 8 weeks prior to randomisation. a. Patients who cannot tolerate higher dose of MTX should be on stable dose of tolerable dose of MTX for 8 weeks prior to study entry (there should be documented evidence of intolerance to MTX)., 5. Patient taking MTX must be on a stable dose of folic acid (= 5 mg per week) or equivalent. Patient must have received folic acid or equivalent for at least 2 months and at a stable dose for 4 weeks prior to randomisation., 6. If the patient is on any of these cDMARDs or bDMARDs, an adequate washout period needs to be completed before first dose of study drug: hydroxychloroquine, chloroquine, azathioprine, leflunomide, sulfasalazine, cyclophosphamide, TNF inhibitors, abatacept, rituximab. Refer Section 10.3 for further details on washout periods., 7. Patient on glucocorticoids should not be receiving more than 10 mg oral prednisone/ prednisolone or equivalent per day, and those receiving should be using stable dose for at least 6 weeks prior to randomisation., 8. For patient receiving NSAIDs, a stable dose not higher than the maximum recommended dose for the agent in the Prescribing Information of the country where the centre is located for the last 4 weeks prior to randomisation., 9.Woman of childbearing potential should have a negative pregnancy test and should agree to use reliable means of contraception and not to donate or cryopreserve ova during the course of the study and for at least 6 months after the last dose of the study drug. OR Male patient permanently sterile by bilateral orchidectomy or agree to use appropriate contraception methods (see list in the Note below) and not to donate or cryopreserve sperm during the study and for at least 6 months after the last dose of study drug.
1. Patients who have received prior treatment with tocilizumab (even if tocilizumab was used for COVID-19 treatment, patient should be excluded), or other agents directly acting on the IL-6 signalling axis (e.g. sirukumab, olokizumab etc.)., 18. Patients with active tuberculosis, unrecovered hepatitis B, herpes zoster including the period of post-herpetic neuralgia within 1 year of randomisation, or any other ongoing clinically relevant active infection, even if localised., 10. Patients with any history or current presence of known demyelinating disease., 11. Patients with any history of or presence of an active neoplasia except for successfully treated (at least five years in advance) non-metastatic cutaneous squamous cell or basal cell carcinoma and /or localised carcinoma in situ of the cervix., 12. Patients with renal impairment (Cockcroft-Gault creatinine clearance < 60 ml/ min) or liver function impairment (bilirubin > 1.25 x ULN, albumin < 3.5 g/ dL, INR > 1.25, ALT or AST > 1.5 x ULN) at screening., 13. Patients with any disorder or treatment that, in the Investigator’s opinion, may interfere with the safety of the patient, the study evaluations, or the patient compliance to the study procedures and limitations, such as history of chronic alcohol or drug abuse, or significant (for the purposes of the study in the opinion of the Investigator) endocrinological, cardiac, respiratory, mental, or nervous disorder or other diseases. Special focus should be given to lung conditions to ensure it is sufficiently close to normal to avert excessive risks upon study participation., 14. Patients with absolute neutrophil count (ANC) < 2 x 109/ L or platelet count < 100 x 109/ L at the time of screening., 15. Patients with clinically relevant hyperlipidaemia (fasting serum LDL cholesterol higher than 190 mg/ dL or fasting serum triglycerides higher than 200 mg/ dL despite treatment with antihyperlipidemic drugs) at the time of screening. Note: Repeat tests up to two times are allowed as per Investigator’s discretion., 2. Patients who have received treatment with IV gamma globulin or plasmapheresis within 6 months of randomisation., 3. Patients with known contraindication to treatment with tocilizumab, including, but not restricted to hypersensitivity to tocilizumab, other monoclonal antibodies, or any excipients (L-arginine hydrochloride, L-histidine, L-histidine hydrochloride monohydrate, L-methionine, polysorbate 80)., 19. Patients who received live virus vaccination within 3 months prior to randomization or intention to receive live virus vaccination during the trial or up to 3 months after the end of administration of the study drug., 4. Patients who need concomitant rheumatoid arthritis therapies other than a. methotrexate with folic acid (at a dose of at least 5 mg per week [or equivalent]) (methotrexate and folic acid will be kept at a stable dose during the study); b. nonsteroidal anti-inflammatory drugs at approved doses kept at stable doses during the study; c. corticosteroids at a maximum daily dose of 10 mg of oral prednisone or equivalent; or d. an analgesics-free period of appropriate duration (12 hr for analgesics in general; 24 hr for oxicams and other single daily or less frequently administered drugs) cannot be maintained before patient evaluation visit. Note: Aspirin at anti-aggregant doses (up to 325 mg per day) is not considered an analgesic., 20. Patients with positive screening for hepatitis B, hepatitis C or HIV., 21. P
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method