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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
118
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)
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.
Time frame: Week 12
Change in DAS28-ESR/C-reactive protein (CRP) score
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) / CRP (mg/l) 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 RA-like poly-articular involvement.
Time frame: Week 24
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
The ACR30/50/70/90/100 response: greater than or equal to (\>/=) 30/50/70/90/100 percent (%) improvement in TJC and SJC (28 assessed joints), and 30/50/70/90/100 % improvement in 3 of the following 5 criteria, respectively: 1) physician's assessment Global Disease Activity (PhGDA), 2) Patients assessment Global Disease Activity (PtGDA), 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP or ESR
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
State budgetary healthcare institution "Chelyabinsk Regional Clinical Hospital"
Chelyabinsk, Chelyabinsk Oblast, Russia
Limited Liability Company "Medical Center "Revma-Med"
Kemerovo, Kemerovo Oblast, Russia
Limited Liability Company "OLLA-MED"
Moscow, Moscow, Russia
Federal State Budgetary Institution "Research Institute of Rheumatology named after V.A. Nasonova"
Moscow, Moscow, Russia
State budgetary healthcare institution of the city of Moscow "City Clinical Hospital No. 52 of the Moscow Health Department" (GBUZ "City Clinical Hospital No. 52 DZM")
Moscow, Moscow, Russia
Federal State Autonomous Educational Institution of Russian National Research Medical University named after. N. I. Pirogova
Moscow, Moscow, Russia
Federal State Autonomous Educational Institution of Russian National Research Medical University named after. N.I. Pirogov Ministry of Health of Russia Separate structural unit "Russian Gerontological Scientific and Clinical Center"
Moscow, Moscow, Russia
Limited Liability Company "Medical Center "Healthy Family"
Novosibirsk, Novosibirsk Oblast, Russia
Federal State Budgetary Educational Institution of Higher Education Orenburg State Medical University of the Ministry of Health of Russia
Orenburg, Orenburg Oblast, Russia
Limited Liability Company "Medical Technologies" LLC "Medical Technologies"
Saint Petersburg, Sankt-Peterburg, Russia
...and 7 more locations
Time frame: Week 24
Area under the curve (AUC) of the disease activity rate (ACR)
ACR response criteria measure percentage reduction in 68 painful joints, percentage reduction in 66 swollen joints, and percentage improvement in at least three of the following: Patients assessment Global Disease Activity (PtGDA), physician's assessment Global Disease Activity (PhGDA), Patient Pain Assessment , assessment according to the health assessment questionnaire disability index (HAQ-DI), CRP concentration value.
Time frame: Week 24
Proportion of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 \</=3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to \</=5.1 or change from baseline \>0.6 to \</=1.2 with DAS28 \</=5.1; non-responders: change from baseline \</=0.6 or change from baseline \>0.6 and \</=1.2 with DAS28 \>5.1
Time frame: Week 24
Area under the curve (AUC) of CRP concentration
CRP values standardized to a normal range
Time frame: Week 24
Area under the curve (AUC) of ESR
ESR values standardized to a normal range
Time frame: Week 24
Area under the curve (AUC) of ferritin levels
Ferritin values standardized to a normal range
Time frame: 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
The absence or presence of skin rash assessed based on physical exam findings including whether it is typical or atypical
Time frame: Week 24
Proportion of patients with fever associated with the underlying disease during 24 weeks of treatment
Absence of fever associated with the underlying disease during the 7 days preceding the visit day visit was assessed. Fever is defined as an increase in body temperature ≥38.0 °C
Time frame: Week 24
Proportion of patients who had exacerbations
Increasing disease activity is defined as the appearance of signs of systemic activity, defined as any of the "major" Yamaguchi M. classification criteria (fever \>39°C intermittent for ≥1 week; arthralgias ≥2 weeks; characteristic rash; white blood cells \>10,000 in mm3 (\>80% granulocytes)), as well as an increase in CRP and/or ferritin levels ≥ 3 times normal.
Time frame: Week 24