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
Overview
- Phase
- Phase 3
- Intervention
- GNR-086
- Conditions
- Still's Disease Adult Onset
- Sponsor
- AO GENERIUM
- Enrollment
- 118
- Locations
- 17
- Primary Endpoint
- Proportion of patients with a clinically significant (>1.2 points) decrease in the Disease Activity Score-28 for Rheumatoid Arthritis with Erythrocyte Sedimentation Rate (DAS28-ESR)
- Status
- Completed
- Last Updated
- 8 months ago
Overview
Brief Summary
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 Still's disease adult onset. Participants received a subcutaneous dose of canakinumab 4 mg/kg once 4 weeks. The time on study treatment was 24 weeks.
Detailed Description
GNR-086 developed as a 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 effectiveness, safety and immunogenicity of GNR-086 and Ilaris®. The study included patients aged 18-75 years at the time of signing the informed consent form with a confirmed diagnosis 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 inclusion in the study, which is indicated for therapy with canakinumab, who meet all criteria for participation in the study. The study included a screening period and a treatment period. Allocation of patients to treatment groups was carried out by randomization in a ratio of 2:1. 148 patients were randomized. Participants received a subcutaneous dose of canakinumab 4 mg/kg once 4 weeks. The time on study treatment was 24 weeks.
Investigators
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.
Arms & Interventions
GNR-086
canakinumab biosimilar
Intervention: GNR-086
Ilaris®
canakinumab
Intervention: Ilaris®
Outcomes
Primary Outcomes
Proportion of patients with a clinically significant (>1.2 points) decrease in the Disease Activity Score-28 for Rheumatoid Arthritis with Erythrocyte Sedimentation Rate (DAS28-ESR)
Time Frame: Week 12
A composite index and takes into account the following items: Tender joint count (number of tender joints; 0-28); swollen joint count (number of swollen joints; 0-28); ESR (mm/h) and Global Health (Patient's Global Assessment of Disease Activity; from 0=best to 100=worst). Thus, given the reliability, validity, and ability of DAS28 to discriminate the severity of joint involvement, this index has been used in other rheumatic diseases characterized by rheumatoid artritis (RA)-like poly-articular involvement. Of note, a DAS28 score \> 5.1 implies active disease, ≤3.2 low disease activity, and \<2.6 remission. Moderate/high disease activity is defined as a DAS28 higher than 3.2.
Secondary Outcomes
- Proportion of patients with an American College of Rheumatology score (ACR) 30/50/70/90/100 response without fever associated with the underlying disease during the 7 days preceding the day of assessment(Week 24)
- Proportion of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28(Week 24)
- Proportion of patients with fever associated with the underlying disease during 24 weeks of treatment(Week 24)
- Area under the curve (AUC) of ferritin levels(Week 24)
- Change in DAS28-ESR/C-reactive protein (CRP) score(Week 24)
- Area under the curve (AUC) of the disease activity rate (ACR)(Week 24)
- Area under the curve (AUC) of ESR(Week 24)
- Area under the curve (AUC) of CRP concentration(Week 24)
- Proportion of patients with no rash within 24 hours before the end of the 1st week of treatment; and within 7 days before all subsequent visits(Week 24)
- Proportion of patients who had exacerbations(Week 24)