Study of Safety and Efficacy of BCD-020 Comparing to MabThera in Patients With Rheumatoid Arthritis (BIORA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Biocad
Sponsor:
Information provided by (Responsible Party):
Biocad
ClinicalTrials.gov Identifier:
NCT01759030
First received: December 20, 2012
Last updated: February 3, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to prove that efficacy, safety and immunogenicity of BCD-020 is equivalent to MabThera when used in combination with methotrexate for the treatment of patient with rheumatoid arthritis


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Rituximab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Double Blind Randomized Clinical Study Evaluating Efficacy and Safety of BCD-020 and MabThera in Patients With Rheumatoid Arthritis Who Had an Inadequate Response or Intolerance to Other DMARDs Including One or More TNF Inhibitor Therapies

Resource links provided by NLM:


Further study details as provided by Biocad:

Primary Outcome Measures:
  • Number of patients who have reached ACR20 within 24 weeks after the treatment initiation [ Time Frame: week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Frequency of adverse events (AE) and serious adverse events (SAE) that is related, in Investigator's opinion, to rheumatoid arthritis therapy [ Time Frame: during all time of participation in the study ] [ Designated as safety issue: Yes ]
  • Frequency of AE and SAE grade 3-4 that is related, in Investigator's opinion, to rheumatoid arthritis therapy [ Time Frame: during all time of participation in the study ] [ Designated as safety issue: Yes ]
  • Number of cases of early withdrawal from the study caused by AE or SAE [ Time Frame: during all time of participation in the study ] [ Designated as safety issue: Yes ]
  • Level of binding and neutralizing antibodies to rituximab in patients from both groups [ Time Frame: at screening, week 12, week 24 ] [ Designated as safety issue: Yes ]
  • CD19+ and CD20+ lymphocyte counts [ Time Frame: before infusion, after the 1st and the 2nd infusion of rituximab, on day 3,17,29 after the 1st infusion, at week 12,24,48 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • CD3+ lymphocyte count [ Time Frame: before infusion, after the 1st and the 2nd infusion of rituximab, on day 3,17,29, at week 12,24,48 ] [ Designated as safety issue: No ]
  • Number of patients in each group who have reached ACR20 [ Time Frame: week 48 ] [ Designated as safety issue: No ]
  • Number of patients in each group that have reached ACR50/70 [ Time Frame: week 24, week 48 ] [ Designated as safety issue: No ]
  • Number of patients in each group with low RA activity according to DAS28 [ Time Frame: week 24, week 48 ] [ Designated as safety issue: No ]
  • Number of patients in each group with RA remission according to DAS28 [ Time Frame: week 24, week 48 ] [ Designated as safety issue: No ]
  • Number of patients in each group with RA remission according to ACR/EULAR [ Time Frame: week 24, week 48 ] [ Designated as safety issue: No ]
  • X-ray characteristic of the involved joints [ Time Frame: week 24, week 48 ] [ Designated as safety issue: No ]
    1. Rate of progression in structural joint damage in Total Modified Sharp Score (erosion score, joint space narrowing score);
    2. Percentage of patients without radiologic progression (by Steinbrocker).

  • Functional ability index according to HAQ [ Time Frame: week 12, week 24, week 48 ] [ Designated as safety issue: No ]
  • Quality of life assessment by SF-36 questionnaire [ Time Frame: week 12, week 24, week 48 ] [ Designated as safety issue: No ]
  • Level of hsCRP and ESR by Westergren [ Time Frame: Day 29, weeks 8,12,16,20,24,32,40,48 ] [ Designated as safety issue: No ]
  • Serum levels of IgA, IgG, IgM [ Time Frame: Day 17,29, 46 weeks 24,48 ] [ Designated as safety issue: No ]
  • Serum level of rituximab [ Time Frame: 0 h, 3 h, 6 h after infusion, on day 3 (48 h after the 1st infusion), day 17 (48 hours after the 2nd infusion), day 29 (after 336 hours after the 2nd infusion) and day 46 (744 hours after the 2nd infusion) ] [ Designated as safety issue: No ]

Estimated Enrollment: 308
Study Start Date: December 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: MabThera (F. Hoffmann-La Roche Ltd.)

In this study MabThera will be administered at a dose of 1000 mg, drop-wise intravenously, slowly, 30 minutes after an intravenous injection of 100 mg methylprednisolone, once in 2 weeks, 2 infusions per course (on day 1 and day 15).

MabThera will be used in combination with methotrexate.

Drug: Rituximab
Patients will will receive rituximab a dose of 1000 mg , intravenously, slowly, once in 2 weeks, with 2 infusions per course (on day 1 and day 15).
Other Name: MabThera, Rituxan, BCD-020
Experimental: BCD-020 (CISC BIOCAD)

BCD-020 is a product code for rituximab biosimilar manufactured by CJSC BIOCAD, Russia. In this study BCD-020 will be administered at a dose of 1000 mg, drop-wise intravenously, slowly, 30 minutes after an intravenous injection of 100 mg methylprednisolone, once in 2 weeks, 2 infusions per course (on day 1 and day 15).

BCD-020 will be used in combination with methotrexate.

Drug: Rituximab
Patients will will receive rituximab a dose of 1000 mg , intravenously, slowly, once in 2 weeks, with 2 infusions per course (on day 1 and day 15).
Other Name: MabThera, Rituxan, BCD-020

Detailed Description:

This international multi-center, randomized, controlled, double blind study will investigate the efficacy, immunogenicity and safety of BCD-020 (NN: rituximab, CJSC Biocad) versus MabThera (INN: rituximab, F. Hoffmann La Roche, Ltd.) both administered in combination with methotrexate in patients with rheumatoid arthritis who had an inadequate response or intolerance to other DMARDs including one or more TNF inhibitor therapies.

Patients will be centrally randomized into one of the two study groups:

Patients from the first group will receive BCD-020 as 1000 mg single dose, intravenously, once in 2 weeks, with 2 infusions per course (on day 1 and day 15).

Patients from the second group will receive MabThera at the same regimen.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Having signed a written informed consent form.
  • Patients must be from 18 to 80 years of age (both ages inclusive)
  • Rheumatoid arthritis confirmed according to ACR 1987 criteria.
  • Seropositive rheumatoid arthritis.
  • Active rheumatoid arthritis during the last 3 months.
  • Disease score according to DAS28 of 3.2 or more, TJC≥8 (68), SJC≥8 (66), hsCRP≥6 mg/l, ESR≥28 mm/hr (by Westergren) at the moment of screening.
  • Patient's functional status - class I-III according to ACR classification
  • Inadequate response to DMARDs that include one or more TNF inhibitors, intolerance or contraindications to TNF inhibitors.
  • Necessity of methotrexate treatment during the last 4 weeks prior to screening period with stable/consistent dosage of 7.5 - 20 mg per week.
  • Patient's ability (in Investigator's opinion) to follow the protocol procedures;
  • Willingness to use contraception during all study period.

Exclusion Criteria:

  • Patients with Felty's syndrome complicated by severe skin vasculitis (ulcerative-necrotic form).
  • Patient's functional status - class IV according to ACR classification .
  • Rheumatoid arthritis low activity (less than 3.2 according to DAS28).
  • Concomitant therapy:

    • Previous treatment with any biological drug products causing CD20+ lymphocyte depletion, including biological investigational drugs.
    • Treatment with azathioprine within 28 days before the study initiation and with leflunomide within 8 weeks before the study's principal phase (treatment with rituximab).
    • Intra-articular glucocorticosteroids within 4 weeks before the study's principal phase (treatment with rituximab).
    • Necessity for prednisone or its equivalent administration at dose more than 10 mg per day.
    • Necessity for prednisone or its equivalent administration at dose ≤10 mg per day in cases when this dose wasn't stable/consistent during last 4 weeks.
    • Necessity for administration of non-steroidal anti-inflammatory drugs for arthritis treatment in cases when its doses were not stable/consistent during last 4 weeks.
  • Pregnancy and breast-feeding.
  • Changes of laboratory values:

    • Hemoglobin level is less than 100 g/l;
    • Leucocyte level is less than 3,0×10e9/l;
    • Absolute neutrophil count is less than 1,5×10e9/l;
    • Thrombocyte level is less than 100×10e9/l.
  • Confirmed chicken pox within 30 days before inclusion to the screening.
  • Confirmed herpes zoster infection.
  • Acute forms of any infectious diseases, history of chronic infections with severe clinical manifestations.
  • Active tuberculosis, history of latent tuberculosis.
  • Inflammatory disease of the joints (present or in anamnesis) not related to rheumatoid arthritis (including gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease and others) or other systemic autoimmune disease (including systemic lupus erythematosus, Crohn's disease, ulcerative colitis, systemic scleroderma, inflammatory myopathy, mixed forms of connective tissue inflammatory diseases, cross-syndrome and others).
  • Juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or rheumatoid arthritis developed before the age of 16.
  • Any determined immunodeficiency.
  • Pernicious anemia.
  • Confirmed cobalamine deficiency.
  • Other somatic diseases (apart from rheumatoid arthritis) that can increase the probability of adverse events during the study or can influence the estimation of symptom manifestation of RA ; mask, enhance or alter the symptoms of RA or cause clinical or laboratory symptoms similar to that of RA;
  • Positive results of serological test of Hepatitis B surface antigen (HbsAg) or presence of Hbc IgM together with positive results of HBV PCR test, presence of antibodies to Hepatitis C virus, syphilis or HIV.
  • Major surgery within 28 days prior to the trial principal phase (treatment with rituximab).
  • Any mental disorder, including major depression and/or suicidal thoughts in anamnesis that can, in Investigator's opinion, create a risk for the patient or influence the patient's ability to follow the study protocol.
  • Unstable angina pectoris.
  • Myocardial infarction within less than 1 year prior to participation in the study.
  • Severe central or peripheral nervous system diseases.
  • Drug addiction, alcoholism.
  • Known hypersensitivity to murine proteins or any other components of the medications used in the treatment, methotrexate, folic acid and any drugs used in premedication.
  • Presence of malignant neoplasm, with the exception of adequately treated basal cell carcinoma and cervical carcinoma in situ and any malignancy with complete remission of more than 5 years;
  • Simultaneous participation in any other clinical trial, as well as former participation in other clinical trials within 3 months before this study initiation; previous participation in this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01759030

Contacts
Contact: Roman Ivanov, PhD (495)992-66-28 ext 154 ivanov@biocad.ru
Contact: Andrey Biryulin, MD (812)380 49 33 ext 925 biryulin@biocad.ru

  Show 56 Study Locations
Sponsors and Collaborators
Biocad
  More Information

No publications provided

Responsible Party: Biocad
ClinicalTrials.gov Identifier: NCT01759030     History of Changes
Other Study ID Numbers: BIORA (BCD-020-2)
Study First Received: December 20, 2012
Last Updated: February 3, 2014
Health Authority: Russia: Ministry of Health of the Russian Federation

Keywords provided by Biocad:
rheumatoid arthritis, DMARDs

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 19, 2014