Moderately to severely active Rheumatoid Arthritis MedDRA version: 23.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Fresenius Kabi SwissBioSim GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Are =18 years of age. 2. Diagnosis of rheumatoid arthritis according to the revised 1987 ACR/EULAR Classification 2010 criteria with disease duration of =6 months. 3. Have moderately to severely active rheumatoid arthritis as defined by: a.Swollen Joint Count =6 (66 joint count) and Tender Joint Count =6 (68 joint count) 4. Must have been treated with methotrexate for at least 12 consecutive weeks immediately prior to randomization and are on a stable dose between 10 and 25 mg/week methotrexate for the last 8 weeks prior to screening. 5. Have had previous inadequate clinical response to at least one XML File Identifier: yzY3ZiiM+wPVagTihKoX+xNzGD0= Page 16/27 modifying anti rheumatic drug. 6. Women of childbearing potential (i.e., considered fertile following menarche and until becoming postmenopausal unless permanently sterile) can participate only if they have a negative serum pregnancy test at screening and a negative urine pregnancy test at Day -1 before randomization. Women of childbearing potential must have used and agree to use a highly effective contraception (i.e., methods with a failure rate of less than 1% per year), for 4 weeks before randomization and must agree to continue to practice adequate contraception for 3 months after the last study drug administration. Note: A separate ICF will be provided to and signed by each patient to provide information on the general risks of study participation related to COVID-19 and to document that it is understood by the patient. Another separate Informed Consent Form will be required to be understood and signed by partners of male participating patients who become pregnant during the study or within 10 weeks after the participating patient's last dose of study drug. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 298 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 244
Exclusion criteria
Exclusion criteria: 1. American College of Rheumatology functional class IV as defined by the ACR classification of functional status or heelchair/bedbound. 2. Rheumatic autoimmune disease or history of/current inflammatory joint disease other than rheumatoid arthritis or significant systemic involvement secondary to rheumatoid arthritis. Sjögren's syndrome secondary to rheumatoid arthritis is allowed. 3. Previously received tocilizumab, an investigational or licensed biosimilar of tocilizumab or any interleukin-6 acting drugs (approved or investigational). 4. Prior use of targeted synthetic disease-modifying anti-rheumatic drugs like janus kinase inhibitors 5. Prior use of any biological agent for a condition other than rheumatoid arthritis (e.g., ranibizumab, denosumab). 6. Prior use of more than two biologic treatments for rheumatoid arthritis. 7. Prior use of biologic investigational drugs (excluding biosimilars) for the treatment of rheumatoid arthritis. 8. Received any investigational drugs within 12 weeks or five drug half lives prior to screening or planned intake of an investigational drug during the course of this trial including the Follow-Up Period. 9. Previous treatment with any alkylating agents or cell-depleting therapies including investigational drugs or approved biosimilars, or has previously undergone total lymphoid irradiation. 10. Use of non-steroidal anti-inflammatory drugs not at a stable dose for at least 4 weeks prior to randomization or exceeding the maximum recommended dose. Note: Patients are permitted to take aspirin at a dose of =325 mg daily for cardiac prophylaxis. 11. Use of oral corticosteroids >10 mg/day prednisone or equivalent if the dose has not been stable for at least 6 weeks prior to randomization. 12. Intra-articular or parenteral corticosteroids within 4 weeks prior to randomization. 13. Use of high potency opioid analgesics 14. Has been treated with intravenous gamma globulin or plasmapheresis within 6 months of randomization. 15. Received a live or attenuated vaccine within 4 weeks prior to randomization. 16. History of hypersensitivity or severe allergic reactions to monoclonal antibodies, any components of the study drug formulations, comparable drugs, or latex. 17. Patient is considered by the Investigator, for any reason, to be anunsuitable candidate for the study. Investigator should specifically evaluate the patient's eligibility taking into consideration COVID-19 risk factors and situation. 18. Has a serious and/or unstable and/or poorly controlled medical condition that, in the opinion of the Investigator, would put the patient at risk by participation in the study. 19. History of diverticulosis requiring antibiotic treatment or any other GI condition that might predispose the patient to gastrointestinal perforations. 20. Uncontrolled medical conditions for which flares are commonly treated with corticosteroids or systemic corticosteroid treatment for these conditions within the last 12 months prior to randomization. 21. Major surgery within 8 weeks prior to screening or planned major surgery during the study. 22. History of, or current myeloproliferative or lymphoproliferative disease or malignancy. 23. Medical evidence of current or history of primary or secondary immunodeficiency as per Investigator's judgment. 24. Pre-existing or recent-onset central or peripheral nervous system demyelinating disorder, or symptoms suggestive of such a disorder as per Investigator's judgment. 25. Confirmed or, based
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to demonstrate equivalent efficacy of proposed biosimilar tocilizumab MSB11456 and EU-approved RoActemra both administered subcutaneously to patients with moderately to severely active rheumatoid arthritis.;Secondary Objective: To compare the safety, immunogenicity and long-term efficacy of MSB11456 to EU-approved RoActemra.;Primary end point(s): The primary efficacy endpoint is the mean absolute change from baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24.;Timepoint(s) of evaluation of this end point: From baseline to Week 24. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: - DAS28-ESR mean absolute change from baseline at all assessment visits (except Week 1) - ACR20 (20% improvement in ACR Core Set Measurements) response rate at Week 24. Safety: - Occurrence of treatment-emergent adverse events - Occurrence of serious adverse events Immunogenicity: - Antidrug antibody incidence - Antidrug antibody titer - Neutralizing antibody incidence;Timepoint(s) of evaluation of this end point: DAS28-ESR mean absolute change from baseline at all assessment visits excl. Week 1 and 24. ACR20 response rate at Week 24. Occurrence of treatment-emergent AEs up to Week 24, Week 30, Week 55 and Week 63. Occurrence of SAEs up to Week 24, Week 30, Week 55 and Week 63. Antidrug antibody incidence at Weeks 2, 12, 24, 30, 52 and 55. Antidrug antibody titer at Weeks 2, 12, 24, 30, 52 and 55. Neutralizing antibody incidence at Weeks 2, 12, 24, 30, 52 and 55. | — |
Countries
Bulgaria, Czechia, Czech Republic, Georgia, Germany, Hungary, Moldova, Republic of, Poland, Russian Federation, Serbia, Slovakia
Contacts
Public ContactClinical Development
Fresenius Kabi SwissBioSim GmbH
Outcome results
None listed