Comparison of Complarate® (Tocilizumab Biosimilar) and Actemra® in Patients With Rheumatoid Arthritis

NCT06475508 | Completed Phase 3

• 1 other identifier: TZS-RA-III
• Study Type: interventional
• Target: 465
• Locations: 1 country
• Sites: 28

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.

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)

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants with an American College of Rheumatology 20% (ACR20) response

  The ACR 20 response: greater than or equal to (\>/=) 20 percent (%) improvement in TJC and SJC (28 assessed joints), and 20% improvement in 3 of the following 5 criteria, respectively: 1) PGDA, 2) PtGDA, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP or ESR at week 24

  week 24

Secondary Outcomes (9)

• Proportion of Participants with an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response

  week 24

• Time to ACR20 response

  week 24

• Change in Disease Activity Score Based on 28-Joints Count (DAS28)

  week 24

• Proportion of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28

  week 24

• Area under the curve (AUC) of the disease activity index (DAS28)

  week 24

Study Arms (2)

Complarate® (JSC "GENERIUM", Russia)

EXPERIMENTAL

tocilizumab biosimilar

Biological: Complarate®

Actemra® (F. Hoffmann-La Roche Ltd., Switzerland)

ACTIVE COMPARATOR

tocilizumab

Biological: Actemra®

Interventions

Complarate® BIOLOGICAL

The investigational drug Complarate® was administered as an intravenous infusion at a dose of 8 mg/kg once every 4 weeks for 24 weeks.

Also known as: tocilizumab biosimilar, GNR-087

Complarate® (JSC "GENERIUM", Russia)

Actemra® BIOLOGICAL

The reference drug Actemra® was administered as an intravenous infusion at a dose of 8 mg/kg once every 4 weeks for 24 weeks.

Also known as: tocilizumab

Actemra® (F. Hoffmann-La Roche Ltd., Switzerland)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AO GENERIUM: lead

Study Sites (28)

Limited Liability Company "Family Clinic No. 4"

Korolyov, Moscow Oblast, 141060, Russia

Location

Limited Liability Company Research Medical Complex "Your Health"

Kazan', Tatarstan Republic, 420097, Russia

Location

State health care institution city clinical hospital №25

Volgograd, Volgograd Oblast, 400138, Russia

Location

State Budgetary Healthcare Institution Chelyabinsk area Clinical Hospital

Chelyabinsk, 454048, Russia

Location

Limited Liability Company "Medical Center "Revma-Med"

Kemerovo, 650070, Russia

Location

Limited Liability Company "OLLA-MED"

Moscow, 105554, Russia

Location

State Budgetary Healthcare Institution MKSC named after A.S. Loginova Moscow Health Department

Moscow, 111123, Russia

Location

Federal State Budgetary Institution "Research Institute of Rheumatology named after V.A. Nasonova"

Moscow, 115522, Russia

Location

Federal State Autonomous Educational Institution of Higher Education First Moscow State Medical University named after I.M. Sechenov Ministry of Health of Russia

Moscow, 119435, Russia

Location

Federal State Budgetary Educational Institution of Higher Education Moscow State University of Medicine and Dentistry

Moscow, 125367, Russia

Location

Federal State Autonomous Educational Institution of Russian National Research Medical University named after. N. I. Pirogova

Moscow, 129226, Russia

Location

Limited Liability Company "Ersi Medical"

Novosibirsk, 630005, Russia

Location

Limited Liability Company "Medical Center "Healthy Family"

Novosibirsk, 630099, Russia

Location

Federal State Budgetary Educational Institution of Higher Education Orenburg State Medical University of the Ministry of Health of Russia

Orenburg, 460018, Russia

Location

Medical center, clinic "Medical Technologies"

Saint Petersburg, 191025, Russia

Location

Limited Liability Company "Ex Seven Clinical Research"

Saint Petersburg, 194156, Russia

Location

Limited Liability Company "Interleukin"

Saint Petersburg, 194214, Russia

Location

Limited Liability Company "Strategic Medical Systems"

Saint Petersburg, 194291, Russia

Location

State Budgetary Healthcare Institution Leningrad area Clinical Hospital

Saint Petersburg, 194291, Russia

Location

JSC "North-West Center for Evidence-Based Medicine"

Saint Petersburg, 194355, Russia

Location

Federal State Budgetary Educational Institution of Higher Education Saratov State Medical University named after. V.I.Razumovsky Ministry of Health of Russia

Saratov, 410054, Russia

Location

Private foundation "RZD-Medicine" Smolensk"

Smolensk, 214025, Russia

Location

State Budgetary Healthcare Institution Tula area Clinical Hospital

Tula, 300053, Russia

Location

State Budgetary Healthcare Institution Ulyanovsk area Clinical Hospital

Ulyanovsk, 432063, Russia

Location

Limited Liability Company "CMKI-PRACTIKA"

Yaroslavl, 150003, Russia

Location

State Budgetary Healthcare Institution "Clinical Hospital No. 2"

Yaroslavl, 150030, Russia

Location

Central City Hospital

Yaroslavl, 150047, Russia

Location

JSC "TsSM"

Yekaterinburg, 620043, Russia

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Oksana A. Markova, MD

  JSC GENERIUM

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Throughout the study neither the investigators nor the patients knew which drug was being administered until the end of the comparative treatment study period
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2024
• First Posted: June 26, 2024
• Study Start: February 13, 2023
• Primary Completion: January 5, 2024
• Study Completion: June 11, 2024
• Last Updated: July 3, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

RU (28)