Active Rheumatoid Arthritis MedDRA version: 17.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: MabionCD20
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Rituximab
Current Sponsor code: MabionCD20
Concentration unit: mg/ml milligram(s)/millilitre
Co
Sponsors
Mabion S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each patient/subject must meet all of the following inclusion criteria to be enrolled in the study: 1. Able to provide written informed consent after receiving information about benefits and potential risks of the trial, as well as details of the insurance covering the subjects participating in the study 2. Caucasian males and females ³ 18 up to 80 years old 3. Body Surface Area (BSA) between 1.5 – 2.2 m2 calculated according to the DuBois & DuBois formula : BSA in m2 = (Weight (kg) 0.425 x Height (cm) 0.725) x 0.007184 4. Patients with active rheumatoid arthritis diagnosed according to revised 1987 American Rheumatism Association criteria (Appendix 3), with disease duration minimum 6 months prior to screening visit, who are naive to tumor necrosis factor (TNF) antagonists or any other monoclonal antibody therapies and who have had an inadequate response to an adequate regimen of methotrexate or/and other disease modifying anti-rheumatic drugs (DMARDs); 5. Patients with moderate to severe active RA defined as the presence of the following: · ³ 8 swollen joints and ³ 8 tender joints, observed by a physician at the screening · radiographic evidence of ³ 1 joint with define erosion attributable to RA and 2 or more of the following: · serum C-reactive protein (CRP) ³ 6 mg/L · erythrocyte sedimentation rate (ESR) ³ 28 mm/hr · morning stiffness in and around joints lasting longer than 45 minutes 6. Patients on methotrexate treatment receiving 10-25 mg /week for at least 12 weeks, with the last 4 weeks at a stable dose 7. Negative serum pregnancy test for women of childbearing potential 8. Female and male (or her/his partner) of childbearing potential willing to use acceptable forms of contraception (e.g., hormonal contraceptive, contraceptive patch, intrauterine device, double- barrier method (condom or diaphragm with spermicide, surgical sterilization, partner’s vasectomy) starting from screening and until 12 months following the last infusion. 9. Ability and willingness to comply with the requirements of the study protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 647 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 216
Exclusion criteria
Exclusion criteria: Patients meeting any of the following exclusion criteria [12] are not to be enrolled: 1. History of or current rheumatic autoimmune disease other than RA eg. Juvenile Idiopathic Arthritis (except concurrent Sjogren’s syndrome) 2. History of or current inflammatory joint disease other than RA 3. American College for Rheumatology functional Class IV disease 4. History of significant systemic involvement secondary to RA like severe vasculitis, pulmonary fibrosis, Felty’s syndrome or other immunological disorders eg. systemic lupus erythematosus [SLE], scleroderma, inflammatory bowel disease, 5. Inability to understand the written and verbal instructions, in particular the risks connected with the study 6. History of psychiatric disorder that would interfere with normal participation in this protocol 7. Subject has known positive tests for HIV, hepatitis B surface antigen (HBsAg) Anti-HBc antibody, hepatitis C antibody 8. Serious and uncontrolled coexisting diseases which, in the Investigator's opinion, would preclude subject participation. These may include but are not limited to: · Known cardiopulmonary disease, e.g. coronary artery disease, significant cardiac arrhythmias or severe congestive heart failure, i.e. satisfying criteria for the New York Heart Association [NYHA] classes III or IV · Serious and uncontrolled pulmonary diseases (chronic, latent and acute infections of the lung, obstructive pulmonary disease) · History of or currently treated serious central nervous system/neurological disorders · Any neurological (congenital or acquired), vascular or systemic disorder that might affect any of the efficacy assessments, in particular, joint pain and swelling (e.g., neuropathies and neurovasculopathies, Parkinson’s disease, cerebral palsy, diabetic neuropathy) · Serious disorders of the renal, hepatic, endocrine, or gastrointestinal system · Active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis, sepsis, opportunistic infections) but excluding fungal infections of nail beds · History of recurrent clinically significant infection · History of tuberculosis or latent tuberculosis tested and confirmed according to the local standards and regulations and/or positive result of Chest X-ray for tuberculosis at screening or within last 6 months prior to screening. · History of cancer including solid tumors, haematologic malignancies, without recovery /remission within 5 years prior to screening, except basal cell and squamous cell carcinoma of the skin that have been excised and cured and treated cervical cancer in situ. · History of significant cytopenia or other serious bone marrow disorders · Primary or secondary immunodeficiency · History of drug, alcohol, or chemical abuse within 2 years prior to screening · Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications 9. Serious abnormal laboratory findings, specifically: · Neutrophil count 2.5 times upper limit of normal · Hemoglobin <8.0 g/dL · IgG below 5.0 mg/mL or IgM below 0.4 mg/mL · Any other serious laboratory abnormality 10. Prior tre
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate biosimilarity between Test Product: MabionCD20® and the Reference Product: MabThera® (rituximab) in patients with active rheumatoid arthritis (RA), based on the percentage of patients in each treatment group achieving the primary efficacy endpoint of a ³ 20% improvement on the American College of Rheumatology score (ACR20) at Week 24;Secondary Objective: 1.To assess biosimilarity between Test Product: MabionCD20 and the Reference Product: rituximab. 2. To demonstrate comparative safety and tolerability of a single course of treatment (two infusions spaced two weeks apart) of MabionCD20 and rituximab in patients with moderate to severe active RA. 3. To demonstrate bioequivalence in pharmacokinetic (PK) characteristics between MabionCD20 and rituximab. 4. To demonstrate safety of MabionCD20 as second cycle treatment after initial rituximab treatment.;Primary end point(s): Primary PK Endpoints: · AUC(0-t): area under the plasma concentration-time curve from the first administration to final time point at Week 24. The area under the plasma concentration will be calculated by the linear trapezoidal method up to Cmax and by log-linear approximation after Cmax · Cmax - second: maximum measured plasma concentration after the second infusion of the treatment cycle Efficacy Endpoints: - Percentage of patients who achieved an ACR20 at Week 24. ;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary PK Endpoints: - Cmax - first: maximum measured plasma concentration after the first infusion of the treatment cycle. - Ctrough: plasma concentration just before second study treatment infusion on Day 15 - AUC(0-8): The area under the plasma concentration versus time curve from time 0 to infinity. AUC(0-8) is calculated as the sum of AUC(0-t) plus the ratio of the last measurable plasma concentration to Kel - t½ - after second infusion: apparent first-order terminal elimination half life will be calculated as ln(2)/ Kel - Volume of distribution at steady state - Plasma clearance Efficacy secondary endpoints: - Percentage of patients who achieved an ACR20 - Percentage of patients who achieved an ACR50 - Percentage of patients who achieved an ACR70 - Mean change from baseline in Disease Activity Score (DAS28 – ESR) - Percent of patients with moderate response on the European League Against Rheumatism (EULAR) scale - Percent of patients with good response on the European League Against Rheumatism (EULAR) scale;Timepoint(s) of evaluation of this end point: Weeks 4, 8, 12, 16, 20, 24, 48 | — |
Countries
Croatia, Georgia, Lithuania, Poland, Romania, Russian Federation, Serbia, Ukraine
Contacts
Public ContactClinical Trial Contact Point
Mabion Research&Development Centre
Outcome results
None listed