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

NCT01759030 | Completed Phase 3

• 1 other identifier: BIORA (BCD-020-2)
• Study Type: interventional
• Target: 181
• Locations: 4 countries
• Sites: 40

Brief Summary

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

Conditions

Rheumatoid Arthritis

Keywords

rheumatoid arthritis, DMARDs; rituximab; biosimilar; interchangeability

Outcome Measures

Primary Outcomes (1)

• Number of patients who have reached ACR20 within 24 weeks after the treatment initiation

  week 24

Secondary Outcomes (5)

• Frequency of adverse events (AE) and serious adverse events (SAE) that is related, in Investigator's opinion, to rheumatoid arthritis therapy

  during all time of participation in the study

• Frequency of AE and SAE grade 3-4 that is related, in Investigator's opinion, to rheumatoid arthritis therapy

  during all time of participation in the study

• Number of cases of early withdrawal from the study caused by AE or SAE

  during all time of participation in the study

• Level of binding and neutralizing antibodies to rituximab in patients from both groups

  at screening, week 12, week 24

• CD19+ and CD20+ lymphocyte counts

  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

Other Outcomes (24)

• CD3+ lymphocyte count

  before infusion, after the 1st and the 2nd infusion of rituximab, on day 3,17,29, at week 12,24,48

• Number of patients in each group who have reached ACR20

  week 48

• Number of patients in each group that have reached ACR50/70

  week 24, week 48

Study Arms (2)

MabThera (F. Hoffmann-La Roche Ltd.)

ACTIVE COMPARATOR

Stage 1 (week 1 - week 24) MabThera will be administered at a dose of 1000 mg, IV (on day 1 and day 15). Stage 2 (week 24 - 48) If the disease activity remains on Week 24 the patient will undergo the second randomization (1:1 ratio): if he/she randomised into group A then he/she recieves BCD-020 at a dose f 1000 mg, IV, once in 2 weeks, 2 infusions per course (on day 1 and day 15); if he/she if he/she randomised into group B then he/she continues to recieve MabThera at a dose f 1000 mg, IV, once in 2 weeks, 2 infusions per course (on day 1 and day 15). MabThera/BCD-020 will be used in combination with methotrexate (irrespectively to study stage).

Drug: Rituximab

BCD-020 (CJSC BIOCAD)

EXPERIMENTAL

Stage 1 (week 1-week 24) BCD-020 will be administered at a dose of 1000 mg, IV (on day 1 and day 15). Stage 2 (week 24-48) If the disease activity remains on Week 24 the patient will undergo the second randomization (1:1 ratio): if he/she randomised into group A then he/she recieves MabThera at a dose f 1000 mg, IV, on day 1 and day 15; if he/she if he/she randomised into group B then he/she continues to recieve BCD-020 at a dose f 1000 mg, IV, on day 1 and day 15. MabThera/BCD-020 will be used in combination with methotrexate (irrespectively to study stage).

Drug: Rituximab

Interventions

Rituximab DRUG

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).

Also known as: MabThera, Rituxan, BCD-020

BCD-020 (CJSC BIOCAD); MabThera (F. Hoffmann-La Roche Ltd.)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients with Felty's syndrome (irrespectively to clinical 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;

Sponsors & Collaborators

• Biocad: lead

Study Sites (40)

Gomel Regional Clinical Hospital

Homyel, Belarus

Location

City Clinical Hospital №1

Minsk, Belarus

Location

City Clinical Hospital №9

Minsk, Belarus

Location

Vitebsk Regional Clinical Hospital

Vitebsk, Belarus

Location

Satellite Orthopaedic Hospital & Research Centre Pvt Ltd

Ahmadābād, India

Location

Smt NHL Medical College and SethVS General Hospital

Ahmadābād, India

Location

Government Medical College and Hospital Panchakki Road

Aurangabad, India

Location

Bangalore Medical College and Research Institute, Victoria Hospital

Bangalore, India

Location

Pristine Hospital and Research Center Pvt. Ltd

Bangalore, India

Location

Sapthagiri Institute of Medical Sciences and Research Centre#15

Bangalore, India

Location

Sri Venkateshwara Hospital

Bangalore, India

Location

Sri Ramachandra Medical Centre, No.1

Chennai, India

Location

Swami Vivekananda National Institrute of Rehabilitation Training and research

Cuttack, India

Location

Gandhi Hospital, Department of Orthopedics

Hyderabad, India

Location

Sri Sri Holistic Hospitals

Hyderabad, India

Location

Sumana Hospitals, Research Department

Hyderabad, India

Location

Yashoda Hospital

Hyderabad, India

Location

Jaipur Hospital, Lal Kothi, Near SMS Stadium

Jaipur, India

Location

SMS Medical College & Hospital

Jaipur, India

Location

Calcutta national medical college, Kolkata

Kolkata, India

Location

Bhatia Hospital, Medical Research Society

Mumbai, India

Location

Government Medical College and Hospital

Nagpur, India

Location

Jawarlal Institute of Postgraduation Medical Education and Research

Puducherry, India

Location

B.J Medical college Sassoon General Hospital, Near Pune Railway Station

Pune, India

Location

Medipoint Hospitals Pvt Ltd

Pune, India

Location

Ruby Hall Clinic

Pune, India

Location

Christian Medical College

Vellore, India

Location

Chelyabinsk Regional Clinical hospital

Chelyabinsk, Russia

Location

Clinical Hospital at Chelyabinsk Railway Station

Chelyabinsk, Russia

Location

Kursk regional hospital

Kursk, Russia

Location

Research Institute of Rheumotology

Moscow, Russia

Location

Nizhegorodskaya Regional Clinical Hospital named after N.A. Semashko

N.Novgorod, Russia

Location

Limited liability company Consultation and Diagnostic Center "Zdorovyye sustavy"

Novosibirsk, Russia

Location

North-Western State Medical University n.a. I.I.Mechnikov

Saint Petersburg, Russia

Location

Local hospital at the station Smolensk OAO RZD

Smolensk, Russia

Location

Smolensk State Medical Academy

Smolensk, Russia

Location

Novgorod regional clinical hospital

Veliky Novgorod, Russia

Location

Kharkiv City Clinical Emergency Hospital n.a. O.I.Meschaninov

Kharkiv, Ukraine

Location

National Research Center "Cardiology Institute n.a. M.D.Strazheska"

Kyiv, Ukraine

Location

Odessa Regional Cardiology Dispensary

Odesa, Ukraine

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2012
• First Posted: January 2, 2013
• Study Start: December 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: March 27, 2017

Record last verified: 2017-03

Locations

IN (23); UA (3); RU (10); BE (4)