Clinical trial NCT06497491: An Efficacy and Safety Study of GNR-086 (canakinumab Biosimilar) and Ilaris® in Patients with Adult-onset Still&#39;s Disease
Official title: 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&#39;s Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Still's Disease Adult Onset
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
Lead sponsor: AO GENERIUM
Sponsor class: INDUSTRY
First posted: 2024-07-11
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

Primary outcomes:
measure: 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)
timeFrame: Week 12
Secondary outcomes:
measure: Change in DAS28-ESR/C-reactive protein (CRP) score
timeFrame: Week 24
measure: 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
timeFrame: Week 24
measure: Area under the curve (AUC) of the disease activity rate (ACR)
timeFrame: Week 24
measure: Proportion of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
timeFrame: Week 24
measure: Area under the curve (AUC) of CRP concentration
timeFrame: Week 24
measure: Area under the curve (AUC) of ESR
timeFrame: Week 24
measure: Area under the curve (AUC) of ferritin levels
timeFrame: Week 24
measure: 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
timeFrame: Week 24
measure: Proportion of patients with fever associated with the underlying disease during 24 weeks of treatment
timeFrame: Week 24
measure: Proportion of patients who had exacerbations
timeFrame: Week 24
Other outcomes:
Locations:
city: Chelyabinsk
country: Russian Federation
facility: State budgetary healthcare institution &#34;Chelyabinsk Regional Clinical Hospital&#34;
state: Chelyabinsk region
city: Volgograd
country: Russian Federation
facility: State health care institution city clinical hospital №25
state: Volgograd region
city: Kemerovo
country: Russian Federation
facility: Limited Liability Company &#34;Medical Center &#34;Revma-Med&#34;
city: Moscow
country: Russian Federation
facility: Limited Liability Company &#34;OLLA-MED&#34;
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution &#34;Research Institute of Rheumatology named after V.A. Nasonova&#34;
city: Moscow
country: Russian Federation
facility: State budgetary healthcare institution of the city of Moscow &#34;City Clinical Hospital No. 52 of the Moscow Health Department&#34; (GBUZ &#34;City Clinical Hospital No. 52 DZM&#34;)
city: Moscow
country: Russian Federation
facility: Federal State Autonomous Educational Institution of Russian National Research Medical University named after. N. I. Pirogova
city: Moscow
country: Russian Federation
facility: 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"
city: Novosibirsk
country: Russian Federation
facility: Limited Liability Company &#34;Medical Center &#34;Healthy Family&#34;
city: Orenburg
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education Orenburg State Medical University of the Ministry of Health of Russia
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company &#34;Medical Technologies&#34; LLC &#34;Medical Technologies&#34;
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company &#34;Ex Seven Clinical Research&#34;
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company &#34;Interleukin&#34;
city: Saint Petersburg
country: Russian Federation
facility: State Budgetary Healthcare Institution Leningrad area Clinical Hospital
city: Smolensk
country: Russian Federation
facility: Private foundation &#34;RZD-Medicine&#34; Smolensk&#34;
city: Vladimir
country: Russian Federation
facility: Limited Liability Company &#34;BioMed&#34;
city: Yaroslavl
country: Russian Federation
facility: State Budgetary Healthcare Institution "Clinical Hospital No. 2"
Study officials:
affiliation: JSC GENERIUM
name: Oksana A. Markova, MD
role: STUDY_CHAIR
References: