Official Title
Multicenter Double-blind Randomized Clinical Study of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Biosimilar Drug Ritumax® Compared to Original Drug MabThera® in Patients With Rheumatoid Arthritis
Brief Summary
This is a multicenter, double-blind, randomized clinical study of safety, tolerability,<br /> pharmacokinetics and pharmacodynamics of biosimilar drug Ritumax® compared to original drug<br /> MabThera® in patients with rheumatoid arthritis, receiving stable doses of Methotrexate.<br /><br /> At Week -2, after signing the Patient Information Sheet and Informed Consent Form, patients<br /> with rheumatoid arthritis receiving stable doses of Methotrexate (10-25 mg per week orally or<br /> parenterally) will pass screening procedures.<br /><br /> Patients meeting all the inclusion/exclusion criteria will be invited to the investigational<br /> site for Visit 2 (Week 0) to be randomized into one of two treatment arms:<br /><br /> - Ritumax® 1000 mg х 2 intravenous infusions<br /><br /> - MabThera® 1000 mg х 2 intravenous infusions After being assigned to the treatment arm<br /> patients will receive a course of study treatment, including two i/v infusions at 14-day<br /> interval: at Week 0 and Week 2.<br /><br /> After that, patients will be followed up for the next 22 weeks. Safety, pharmacokinetic and<br /> pharmacodynamic parameters will be monitored at this visits.
Study Criteria
Inclusion Criteria:
1. Signed Patient Information Sheet and Informed Consent Form to participate in the
study.
2. Men and women aged 18 years and older.
3. Patient diagnosed with rheumatoid arthritis of at least 6-month duration, determined
according to classification criteria of the American College of Rheumatology (ACR) and
the European League Against Rheumatism (EULAR) (ACR-EULAR 2010) or the American
College of Rheumatology (ACR1987) (in case if the diagnosis of rheumatoid arthritis
was determined till 2010).
4. Active phase of the disease confirmed due to the combination of the following
parameters:
- DAS28 > 3,2
- 5 (of 28) of tender and 5 (of 28) of swollen joints
- CRP level ≥1,5 mg/dL and/or ESR > 28 mm/h
- positive test for rheumatoid factor and/or CCP antibodies
5. Patients with negative response to or intolerability to the DMARD therapy.
6. Current outpatient therapy of rheumatoid arthritis:
- continuous therapy with Methotrexate for at least 12 weeks prior to screening
- stable doses of Methotrexate (10-25 mg per week) within 4 weeks prior to
screening
- when currently under the corticosteroids therapy, the dose should be stable
within the last 4 weeks prior to screening and be less than 10 mg of Prednisolone
or its equivalent
- when currently under the NSAID therapy, the dose should be stable within the last
4 weeks prior to screening
Exclusion Criteria:
The patient will be deemed ineligible for the study meeting any of the following criteria:
1. Other inflammatory arthropathies apart from rheumatoid arthritis (e.g. gout, reactive
arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme desease) or
other system autoimmune diseases (e.g. systemic lupus erythematosus, inflammatory
bowel disease, pneumosclerosis or Felly's syndrome, sclerodermia, inflammatory
myopathy, mixed collagenosis or other crossed syndrome). Patients with secondary
Sjorgen's syndrome or secondary limited cutaneous vasculitis with a rheumatoid
arthritis background may participate in the study.
2. Chronic heart failure Class III or IV in New York Heart Association (NYHA)
classification and clinically significant ventricular arrhythmias (ventricular
tachycardia, ventricular fibrillation).
3. Serious chronic pulmonary diseases (COPD, bronchial asthma); functional dyspnea of
severity level III and higher (due to the Medical Science Research Council scale for
dyspnea).
4. Signs of significant uncontrolled concomitant disease, e.g. renal, hepatic,
gastrointestinal, endocrine system and nervous system disorders, which, according to
the Investigator's opinion, could prevent the patient's participation in the study.
5. Any surgical procedure, including bone and joint surgeries, or synovectomy (including
arthrodesis or endoprosthesis replacement), performed within 12 weeks prior to
screening or planned to be performed within 24 weeks after (except for small surgical
procedures, requiring a local anesthesia or no anesthesia).
6. Infectious diseases.
