an efficacy and safety study of gnr-086 (canakinumab biosimilar) and ilaris® in patients with adult-onset still&#39;s disease

Conditions: Still's Disease Adult Onset

Summary: this is a randomized single-blind comparative parallel group study of the efficacy and safety of canakinumab biosimilar gnr-086 (jsc \&#34;generium\&#34;, russia) and ilaris® (novartis pharma stein ag, switzerland) in the treatment of patients with adult-onset still\&#39;s disease. participants will receive a subcutaneous canakinumab 4 mg/kg every 4 weeks. the treatment duration is 24 weeks following with the study extension.

gnr-086 is being developed as a proposed biosimilar to ilaris®, a lyophilisate for the preparation of a solution for subcutaneous administration. canakinumab is a fully human monoclonal antibody of the immuniglobulin g1 (igg1(kappa)) isotype that binds specifically and with high affinity to interleukin-1β (il-1β). canakinumab, by binding to human il-1β, blocks the interaction of this cytokine with its receptors, thereby functionally neutralizing the biological activity of this cytokine, without preventing either the binding of the natural inhibitor il-1ra, or the binding of il-1α to il-1 receptors. il-1β is recognized as one of the main pro-inflammatory cytokines in various inflammatory conditions. this iii phase study is aimed to compare the efficacy, safety and immunogenicity of gnr-086 and ilaris®. the study will enroll patients with the confirmed diagnosis of adult-onset still\&#39;s disease in accordance with the classification criteria of yamaguchi m. et al. (j. rheumatology, 1992), and the duration of the disease at least 2 months before inclusion into the study. 148 paitnts will be randomised 2:1 to receive either gnr-098 or ilaris®. participants will receive canakinumab 4 mg/kg suncutaneously every 4 weeks for 24 weeks following the study extension.

Eligibility criteria:
inclusion criteria: * availability of written informed consent obtained from the patient before the start of any procedures related to the study. * male and female patients aged 18-75 years, inclusive, at the time of signing the informed consent form. * patients with a documented diagnosis of adult still's disease in accordance with the classification criteria of yamaguchi m. et al. (j. rheumatology, 1992) and the duration of the disease is at least 2 months before signing the informed consent form. * disease activity ≥2.6 according to das28-esr. * no change in the dosing regimen of methotrexate (maximum 20 mg/m2/week) or other immunosuppressive agent for at least 6 weeks before randomization and/or no change in the dosing regimen of one nonsteroidal anti-inflammatory drug (nsaid) as treatment for adult still's disease for at least 14 days before randomization and/or no change in the dosage regimen of the glucocorticosteroid drug for at least 7 days before randomization. * negative result of intradermal test with tuberculosis allergen / igra test at screening or within 6 months before screening. patients with missing screening data can only be included in the study if they undergo immunodiagnosis of tuberculosis infection and the result is negative. * agreement to adhere to adequate methods of contraception throughout the study and for 3 months after the end of canakinumab therapy. exclusion criteria: * diagnosis of macrophage activation syndrome (mas) within the last 3 months. * history of hypersensitivity to the active substance or other components of the study or reference drug. * acute infectious diseases within 14 days before randomization. * immunization with any live vaccine within 3 months before randomization. * concomitant diseases and conditions that, in the opinion of the investigator and/or sponsor, jeopardize the safety of the patient during participation in the study, or which will influence the analysis of safety data. * blood donation or blood loss (450 ml of blood or more) less than 2 months before the start of the study. * pregnancy or breastfeeding. * history of tuberculosis (except for successfully treated primary tuberculosis complex no later than 6 months before randomization). * use of the following treatments before randomization: anakinra within 1 week before randomization; etanercept within 6 weeks before randomization; tocilizumab within 8 weeks before randomization; sarilumab within 6 weeks before randomization; olokizumab for 8 weeks before randomization; adalimumab within 10 weeks before randomization; golimumab within 16 weeks before randomization; rituximab within 26 weeks before randomization; leflunomide within 6 weeks before randomization; cyclosporine within 4 weeks before randomization; intravenous immunoglobulin within 8 weeks before randomization; growth hormone within 4 weeks before randomization; intra-articular, periarticular, intravenous, intramuscular administration of glucocorticosteroids within 4 weeks before randomization; any other unapproved drugs within 5 half-lives before randomization. * drug dependence on drugs and potent drugs and/or alcohol dependence. * positive test results for hepatitis b or c, hiv or syphilis. * unwillingness or inability to comply with the recommendations prescribed by this protocol. * identification during screening of other diseases/conditions not listed above that, in the opinion of the physician-researcher, prevent the inclusion of the patient in the study.

Keywords: canakinumab humanized monoclonal antibodies safety still's disease adult onset equivalence biosimilar american college of rheumatology (acr) das28 disease-modifying anti-rheumatic drugs (dmards) european league against rheumatism (eular) immunogenicity