An Efficacy and Safety Study of GNR-086 (Canakinumab Biosimilar) and Ilaris® in Patients With Adult-onset Still's Disease

A Single-blind Randomized Study of the Efficacy and Safety of the GNR-086 (Canakinumab Proposed Biosimilar) in Comparison With the Ilaris®, Conducted in Parallel Groups of Patients With Adult-onset Still's Disease

This is a randomized single-blind comparative parallel group study of the efficacy and safety of canakinumab biosimilar GNR-086 (JSC "GENERIUM", Russia) and Ilaris® (Novartis Pharma Stein AG, Switzerland) in the treatment of patients with adult-onset Still'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'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.

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.