Clinical trial NCT06475508: Comparison of Complarate® (Tocilizumab Biosimilar) and Actemra® in Patients With Rheumatoid Arthritis
Official title: Double-blind Multicenter Randomized Study of the Effectiveness and Safety of Tocilizumab Biosimilar (Complarate®) and Actemra® in Parallel Groups in Patients With Rheumatoid Arthritis With Repeated Intravenous Administration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: tocilizumab
humanized monoclonal antibodies
safety
rheumatoid arthritis
equivalence
biosimilar
American College of Rheumatology (ACR)
DAS28
disease-modifying anti-rheumatic drugs (DMARDs)
rheumatic autoimmune disease
European League Against Rheumatism (EULAR)
immunogenicity
Clinical Disease Activity Index (CDAI)
Simplified Disease Activity Index (SDAI)
Lead sponsor: AO GENERIUM
Sponsor class: INDUSTRY
First posted: 2024-06-26
Enrollment: 465
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 double-blind comparative parallel group study of the efficacy and safety of tocilizumab biosimilar Complarate® and Actemra® in the treatment of patients with rheumatoid arthritis with moderate to high disease activity. Participants received an intravenous dose of tocilizumab 8 mg/kg once 4 weeks. The time on study treatment was 24 weeks.

Detailed description: Complarate® (INN: tocilizumab) is being developed as a biosimilar to the drug Actemra®, a concentrate for the preparation of a solution for infusion.

Tocilizumab is a recombinant humanized monoclonal antibody to the human interleukin-6 (IL-6) receptor from the immunoglobulin G1 (IgG1) subclass of immunoglobulins. Tocilizumab binds to and inhibits both soluble and membrane IL-6 receptors.

This III phase study is aimed to compare the effectiveness, safety and immunogenicity of Complarate® and Actemra®. The study included patients aged 18-75 years at the time of signing the informed consent form with a documented diagnosis of rheumatoid artritis, established according to the 2010 ACR/EULAR classification criteria, at least 6 months before screening, with moderate or high degree of disease activity and insufficient response to methotrexate monotherapy (preservation of moderate/high disease activity for at least 3 months) and/or poor tolerability of methotrexate (including the subcutaneous form of the drug) and/or insufficient response to or intolerance to other synthetic disease-modifying anti-inflammatory drugs (sDMARDs) with or without methotrexate inclusive, 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 to the study drug (Complarate®) and comparator drug (Actemra®). 465 patients (310 to the study drug group and 155 to the comparator drug group) were randomized.

Eligibility criteria: Inclusion Criteria:

* Availability of written informed consent obtained from the patient before the start of any procedures related to the study.
* Men and women 18-75 years of age, inclusive, at the time of signing the informed consent form.
* Patients with a documented diagnosis of rheumatoid artritis (RA), established according to the 2010 ACR/EULAR classification criteria at least 6 months before screening, with moderate to high disease activity and an insufficient response to methotrexate monotherapy (maintaining moderate/high disease activity for at least 3 months) and/or poor tolerability of methotrexate (including the subcutaneous form of the drug) and/or insufficient response to or intolerance to other synthetic disease-modifying anti-inflammatory drugs (sDMARDs) in combination with methotrexate or without methotrexate.
* The number of swollen and/or painful joints is 6 or more.
* No changes in the dosage regimen of standard RA therapy with oral glucocorticosteroids and NSAIDs for ≥ 4 weeks before screening.
* No changes in the dosing regimen of standard RA sDMARD therapy for ≥ 4 weeks before screening.
* Agreement to adhere to adequate methods of contraception throughout the study and for 3 months after the end of tocilizumab therapy.

Exclusion Criteria:

* A history of rheumatic autoimmune disease other than rheumatoid arthritis.
* Functional Class IV according to the ACR Functional Status Classification or wheelchair/bedridden.
* Development of pronounced extra-articular (systemic) manifestations of the disease and complications (rheumatoid vasculitis, amyloidosis, Felty's syndrome, neuropathy, damage to the organ of vision).
* Use of oral corticosteroids in doses greater than \>10 mg daily prednisolone equivalent, or change in oral corticosteroid dose within 4 weeks before or during screening.
* Use of injectable corticosteroids (including intra-articular corticosteroids) or intra-articular hyaluronic acid injections within 4 weeks before or during screening.
* Therapy with tumor necrosis factor-alfa (TNF-alpha) inhibitors or any other genetically engineered biological drugs within 1 month before screening.
* History of tocilizumab therapy.
* Major surgery (including joint surgery) within 8 weeks before the start of the study or elective surgery within 6 months after the start of the study.
* A history of an adverse drug reaction to any of the components of the study drug or a reference drug.
* Immunization with any live or live attenuated vaccine within 1 month before the first dose of the study or comparator drug.
* A history of a disease associated with the accumulation of immune complexes (including serum sickness).
* 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.
* Active systemic infection (bacterial, viral or fungal) within 14 days before signing the informed consent form or at the time of screening.
* 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 demyelinating disease of the central nervous system.
* History of diverticulosis/intestinal diverticulitis or chronic ulcerative diseases of the lower gastrointestinal tract, such as Crohn's disease, ulcerative colitis.
* History of tuberculosis.
* Positive/doubtful test with tuberculosis allergen.
* Participation in clinical trials of drugs less than 3 months before signing the informed consent form.
* Positive tests 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 Participants with an American College of Rheumatology 20% (ACR20) response
timeFrame: week 24
Secondary outcomes:
measure: Proportion of Participants with an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
timeFrame: week 24
measure: Time to ACR20 response
timeFrame: week 24
measure: Change in Disease Activity Score Based on 28-Joints Count (DAS28)
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 the disease activity index (DAS28)
timeFrame: week 24
measure: Change in Simplified Disease Activity Index (SDAI)
timeFrame: week 24
measure: Change in Clinical Disease Activity Index (CDAI)
timeFrame: week 24
measure: Proportion of Participants who achieved remission in accordance with the ACR remission criteria
timeFrame: week 24
measure: Proportion of Participants who dropped out of the study due to insufficient treatment effectiveness
timeFrame: week 24
Other outcomes:
Locations:
city: Korolev
country: Russian Federation
facility: Limited Liability Company "Family Clinic No. 4"
state: Moscow Region
city: Kazan
country: Russian Federation
facility: Limited Liability Company Research Medical Complex "Your Health"
state: Republic Of Tatarstan
city: Volgograd
country: Russian Federation
facility: State health care institution city clinical hospital №25
state: Volgograd Region
city: Chelyabinsk
country: Russian Federation
facility: State Budgetary Healthcare Institution Chelyabinsk area Clinical Hospital
city: Ekaterinburg
country: Russian Federation
facility: JSC "TsSM"
city: Kemerovo
country: Russian Federation
facility: Limited Liability Company "Medical Center "Revma-Med"
city: Moscow
country: Russian Federation
facility: Limited Liability Company "OLLA-MED"
city: Moscow
country: Russian Federation
facility: State Budgetary Healthcare Institution MKSC named after A.S. Loginova Moscow Health Department
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution "Research Institute of Rheumatology named after V.A. Nasonova"
city: Moscow
country: Russian Federation
facility: Federal State Autonomous Educational Institution of Higher Education First Moscow State Medical University named after I.M. Sechenov Ministry of Health of Russia
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education Moscow State University of Medicine and Dentistry
city: Moscow
country: Russian Federation
facility: Federal State Autonomous Educational Institution of Russian National Research Medical University named after. N. I. Pirogova
city: Novosibirsk
country: Russian Federation
facility: Limited Liability Company "Ersi Medical"
city: Novosibirsk
country: Russian Federation
facility: Limited Liability Company "Medical Center "Healthy Family"
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: Medical center, clinic "Medical Technologies"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Ex Seven Clinical Research"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Interleukin"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Strategic Medical Systems"
city: Saint Petersburg
country: Russian Federation
facility: State Budgetary Healthcare Institution Leningrad area Clinical Hospital
city: Saint Petersburg
country: Russian Federation
facility: JSC "North-West Center for Evidence-Based Medicine"
city: Saratov
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education Saratov State Medical University named after. V.I.Razumovsky Ministry of Health of Russia
city: Smolensk
country: Russian Federation
facility: Private foundation "RZD-Medicine" Smolensk"
city: Tula
country: Russian Federation
facility: State Budgetary Healthcare Institution Tula area Clinical Hospital
city: Ulyanovsk
country: Russian Federation
facility: State Budgetary Healthcare Institution Ulyanovsk area Clinical Hospital
city: Yaroslavl
country: Russian Federation
facility: Limited Liability Company "CMKI-PRACTIKA"
city: Yaroslavl
country: Russian Federation
facility: State Budgetary Healthcare Institution "Clinical Hospital No. 2"
city: Yaroslavl
country: Russian Federation
facility: Central City Hospital
Study officials:
affiliation: JSC GENERIUM
name: Oksana A. Markova, MD
role: STUDY_CHAIR
References: