Health Condition 1: M069- Rheumatoid arthritis, unspecified
Conditions
Interventions
Intervention1: DRL_Abatacept (DRL_AB): proposed abatacept biosimilar, formulated for Subcutaneous administration in Single-dose prefilled syringe containing 125 mg once-weekly
Control Intervention1: O
Sponsors
Dr. Reddys Laboratories Ltd.
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patients should provide a written informed consent as per the local regulations applicable to the study site and Good Clinical Practice (GCP) guideline. 2. Male or female patients aged = 18 years and = 80 years at the time of signing informed consent. 3. Patients with moderately to severely active rheumatoid arthritis for at least 6 months’ duration, defined as per the American College of Rheumatology (ACR) Criteria, 1987 revision. Active rheumatoid arthritis is defined as having: a. Swollen Joint Count (SJC) =10 out of the 66 joints count b. Tender Joint Count (TJC) =12 out of the 68 joints count, and c. C-Reactive Protein (CRP) of at least 1.0 mg/dl determined using a highly sensitivity assay. 4. Patients must be on methotrexate (MTX) and folic acid for at least 3 months prior to the randomization with the below requirements. a. Must have been treated with stable doses of MTX (between 20 to 25 mg/ week; at least 6 mg/ week for patients from other Eastern Asia countries, not exceeding allowed maximum dose in the country-specific label) for at least 4 weeks prior to randomisation. b. Patients who cannot tolerate higher dose of MTX should be on stable and tolerable dose of MTX for 4 weeks prior to randomisation (there should be documented evidence of intolerance to MTX). c. Patients taking MTX must be on a stable dose of folic acid (=5 mg per week) or equivalent for at least 4 weeks prior to randomisation. 5. Patients should not be on Conventional Disease-Modifying Anti-Rheumatic Drugs (cDMARDs) other than MTX for at least 4 weeks prior to randomization (4 weeks prior for azathioprine, sulfasalazine; 8 weeks for hydroxychloroquine & chloroquine; 12 weeks for leflunomide; 24 weeks for cyclophosphamide). 6. Patients should not be on bDMARDs: these agents should have been discontinued at least 4 weeks (4 weeks prior for TNF alpha inhibitors; 24 weeks for rituximab; 4 weeks or half of biological half-life for other bDMARDs whichever is longer) prior to randomization. 7. Patients 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 patients receiving Nonsteroidal Anti-inflammatory Drugs (NSAIDs) for the last 4 weeks prior to randomisation: a. Should be taking a stable dose NOT higher than the maximum recommended dose for the agent in the Prescribing Information of the country where the study centre is located. b. NSAIDs are allowed except for the 12h before the scheduled efficacy assessment visit (24h for oxicams and other single daily dose or less frequently administered agents); Details of permitted and prohibited medication in the current study has been captured at Section 6.9. 9. Women of childbearing potential should have a negative pregnancy test and should agree to use highly effective measures of contraception(as per the Clinical Trial Facilitation Group (CTFG) guidelines 2020) 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 patients should be permanently sterile by bilateral orchidectomy or agree to use appropriate contraception methods (Per the Clinical Trial Facilitation Group (CTFG) guidelines 2020) and not to donate or cryopreserve sperm during the
Exclusion criteria
Exclusion criteria: 1. Patients who have received prior treatment with abatacept. 2. Patients who have received prior treatment with JAK inhibitors within the last 16 weeks of randomization (e.g., tofacitinib, abrocitinib, baricitinib, upadacitinib, filgotinib etc.). 3. Patients who have received treatment with IV gamma globulin or plasmapheresis within 6 months of randomisation. 4. Patients with known contraindication to treatment with abatacept, including, but not restricted to hypersensitivity to abatacept or any excipients (dibasic sodium phosphate anhydrous, monobasic sodium phosphate monohydrate, L-Histidine, sodium chloride, poloxamer and sucrose) in the study formulations. 5. Patients who need concomitant rheumatoid arthritis therapies other than a. MTX with folic acid (at a dose of at least 5 mg per week [or equivalent]) (MTX and folic acid will be kept at a stable dose during the study), Folinic acid at the same dose of folic acid, can be given in place of folic acid if it is allowed by the local label. Patient should take the same folate supplementation throughout the duration of the study. b. NSAIDs 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 kept stable during the study Also, patients who cannot maintain 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) before patient evaluation visit. Note: Aspirin at anti-aggregant doses (up to 325 mg per day) is not considered as an analgesic. 6. Patients who have received any treatment with intra-articular injections (e.g., corticosteroids) required for a flare-up within 4 weeks prior to randomisation. 7. Patients with functional class IV as defined by the ACR Classification of Functional Status in RA. 8. Patients with other inflammatory diseases that might confound the evaluation of the efficacy (e.g., Crohn’s disease, ulcerative colitis). Note: Sjogren syndrome secondary to RA is allowed. 9. Patients who have received any investigational drug within 30 days or 5 times half-life, whichever is longer, prior to randomization (or longer as per the local regulation of the country). Patients participating or participated in another clinical trial evaluating a bDMARD for RA within the last year before screening are not eligible for this trial. 10. Patients with a known history of or presence of clinically significant cardiovascular (any patient with New York Heart Association (NYHA) III or IV functional status is to be excluded), haematological, renal, or liver disease. Patients with any other disorder or treatment that, in the Investigator’s opinion, may interfere with the safety of the patient, the validity of the study evaluations, or the patient compliance to the study procedures such as neurological diseases, psychiatric diseases, respiratory diseases, gastrointestinal diseases, endocrinological diseases, metabolic diseases or any other diseases. Special focus should be given to lung conditions to ensure it is sufficiently close to normal to avoid excessive risks upon study participation. 11. Patients with any history or current presence of known demyelinating disease. 12. Patients with any history of or presence of an active neoplasia except for successfully treated (at least five years i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Comparison of the incidence and prevalence of ADAs (towards whole abatacept and or CTLA 4) and NAb between Dr Reddys Abatacept and RMP in patients with active rheumatoid arthritis Comparison of titers between Dr Reddys Abatacept and RMP dosed patients with active rheumatoid arthritisTimepoint: Baseline through scheduled timepoints till Week 56 or EOS | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy: Comparison of the following evaluations in both arms: Change from Baseline in DAS28 CRP Change from Baseline in DAS28 ESR Proportion of patients achieving EULAR moderate or good response Proportion of patients achieving ACR20 or 50 or 70 response Safety: Incidence of TEAEs, SAEs and AESI Incidence of hypersensitivity reactions and Injection site reactions TMAC: To compare Population PK parameters Pharmacodynamics: Change from baseline in PD parametersTimepoint: Efficacy: Baseline, Week 13, Week 25, Week 37, and Week 53 Safety: Baseline till Week 56 or EOS. TMAC: Baseline through scheduled time points till Week 56 or EOS Pharmacodynamics: Baseline through scheduled time points | — |
Countries
India
Contacts
Public ContactNaveen Reddy
Dr Reddys Laboratories Ltd
Outcome results
None listed