Rheumatoid arthritis MedDRA version: 18.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: RGB-03
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Current Sponsor code: RGB-03
Concentration unit: mg/ml milligram(
Sponsors
Gedeon Richter Plc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for the study entry patients MUST satisfy all of the following criteria at Screening: 1. Age: 18-75 years, inclusive; 2. Gender: male or female; 3. Rheumatoid arthritis (RA) as defined by the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria; 4. Active disease, defined as a. at least 6 swollen joints (66 joints assessed), AND b. at least 6 tender joints (68 joints assessed), AND c. elevated acute phase protein (serum C-reactive protein [CRP] =10 mg/L OR an erythrocyte sedimentation rate [ESR] =28 mm/hour), AND d. Disease activity score [DAS]28-ESR >3.2; 5. Inadequate response to adequate treatment with at least one anti-tumour necrosis factor (TNF) drug (infliximab [=3 mg/kg, =4 infusions {i.e. =14 weeks}], adalimumab [40 mg every other week =3 months], etanercept [25 mg twice weekly or 50 mg weekly =3 months], certolizumab pegol [400 mg every 2 weeks {given 3 times}, then 200 mg every 2 weeks, total administration =3 months], or golimumab [50 mg every 4 weeks =4 months]), and discontinued the biological treatment due to lack of efficacy or due to being intolerant to at least one administration of these agents; 6. Treatment with oral or parenteral methotrexate (MTX) (10 to 25 mg/week) for 12 weeks prior to Screening, at a stable dose at least in the last 4 weeks; 7. Adequate screening with documented negative results for latent tuberculosis using state-of-the art interferon gamma release assay test (QuantiFERON® TB Gold) and other assessments if deemed necessary based on the local requirements and/or according to the Investigator’s discretion (e.g. chest radiograph); 8. Female patients of childbearing potential must have a negative serum pregnancy test (serum beta-human chorionic gonadotropin) at Screening unless they are surgically sterile (documentation should be available) or have been postmenopausal for =1 year (12 consecutive months without period); 9. Women of childbearing potential must use medically acceptable means of birth control and agree to continue its use and perform regular pregnancy tests during the study and up to 12 months following the last IMP infusion; - be abstinent (true abstinence in line with the preferred and usual lifestyle of the subject) or be using one of the following acceptable birth control methods: a. implants, injectables, combined oral contraceptives, and intrauterine devices; b. combination of 2 barrier methods (condom, diaphragm) with spermicide; c. sole male partner of the subject has been sterilised (documentation should be available); 10. Male patients should be surgically sterile (documentation should be available), be abstinent (true abstinence in line with the preferred and usual lifestyle of the subject) or agree together with their partner to use one of the following medically acceptable means of birth control during the study and up to 12 months following the last IMP infusion: a. implants, injectables, combined oral contraceptives, and intrauterine devices; b. combination of 2 barrier methods (condom, diaphragm) with spermicide; c. sole female partner of the subject is surgically sterile (documentation should be available) or has been postmenopausal for =1 year (12 consecutive months without period); 11. Patients must be able to understand and provide written informed consent to participate in the study and understand that they are free to withdraw from the study at any time. Are the trial s
Exclusion criteria
Exclusion criteria: If any of the following apply at Screening, the patient MUST NOT enter the study: 1. Rheumatoid arthritis patients with functional status class IV classified according to the revised ACR criteria (see Appendix 17.3); 2. Patients with significant systemic manifestations of RA (e.g. vasculitis, pulmonary fibrosis, or Felty's syndrome); 3. Patients seropositive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) on screening assay; 4. Previous treatment with rituximab; 5. Concurrent treatment with any synthetic DMARDs other than MTX within 28 days prior to Screening; 6. Chronic and/or recurrent infections, which according to the Investigator’s discretion might pose a risk to the patient's safety; 7. Major surgery 8 weeks prior to Screening; 8. Other investigational drug administration within 12 weeks or 5-times the terminal serum half-life, whichever is longer prior to Screening; 9. Participation in other interventional clinical study (including follow-up and/or study extension) within 12 weeks prior to Screening; 10. Hypersensitivity to the active substance or to any of the excipients or to murine proteins; 11. Female patients nursing (women should not breastfeed for 12 months following rituximab treatment); 12. Any condition or circumstance which in the opinion of the Investigator may make the patient unlikely to complete the study or comply with study procedures and requirements or may pose a risk to the patient's safety; 13. Any patient who has a disease state or condition that in the opinion of the Investigator could confound the results of the study;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the pharmacokinetics of RGB-03 and its reference product MabThera® in a comparative manner in rheumatoid arthritis patients to establish biosimilarity.;Secondary Objective: To evaluate the efficacy, pharmacodynamics and safety characteristics of RGB-03 and its reference product MabThera® in a comparative manner rheumatoid arthritis patients to establish biosimilarity.;Primary end point(s): Pharmacokinetic Parameter: Area under the serum concentration versus time curve, from time 0 to last data point above the limit of quantitation during the Treatment Period (AUC)0-tlast.;Timepoint(s) of evaluation of this end point: This endpoint will be evaluated during the treatment period on visits Baseline, day 3, day 15, day 17, day 29, day 57, day 85 and day 169. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): A. Pharmacokinetic Parameters: 1. Maximum measured serum concentration over the Treatment Period 2. Serum AUC(0-inf) during the Treatment Period 3. Apparent terminal elimination half-life after the second IMP administration, during the Treatment Period 4. Apparent terminal elimination rate constant after the second IMP administration, during the Treatment Period 5. Total volume of distribution during the Treatment Period 6. Total body clearance during the Treatment Period B. Pharmacodynamic parameters: 7. CD19+ B-cell count 8. IgM levels 9. IgG, IgA levels 10. RF, anti-CCP levels C. Efficacy Parameters: 11. Change in disease activity compared to Baseline, as measured by change in DAS28 12. Change in disease activity compared to Baseline, as measured by change in Clinical Disease Activity Index value 13. Change in disease activity compared to Baseline, as measured by change in Simplified Disease Activity Index value 14. EULAR response 15. Proportion of patients achieving low disease activity 16. Proportion of patients achieving remission 17. ACR20, ACR50, and ACR70 response D. Safety parameters: 18. Adverse events 19. Immunogenicity: serum anti-rituximab antibody 20. Other safety parameters;Timepoint(s) of evaluation of this end point: Endpoints will be assessed during the whole study till Day 169 of the third retreatment course (days 1, 3, 8, 15, 17, 29, 57, 85, 113, 141 and 169 of the treatment period and days 15, 85 and 169 of each retreatment course). Please note not all endpoints will be assessed on each of the visits. | — |
Countries
Austria, Belgium, Czech Republic, Estonia, Germany, Hungary, Israel, Poland, Romania, Russian Federation, Spain, Ukraine
Contacts
Public ContactGedeon Richter Plc
Gedeon Richter Plc
Outcome results
None listed