adult patients with severe, active rheumatoid arthritis patients treated with methotrexate (MTX) MedDRA version: 14.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Teva Pharmaceutical Industries
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 18-80 years (inclusive) at screening. 2. Rheumatoid arthritis for at least 6 months, as defined by the Revised Criteria ACR 1987 (adult onset RA). 3. Severe, active, seropositive (plasma RF level of at least 20 IU/mL and/or ACPA/anti-CCP positive) disease as defined by the following, revealed in screening tests: • Active disease defined as presence of at least 8 swollen and 8 tender joints (at the screening visit). • A serum CRP level of >=15 mg/L (>=1.5 mg/dL) and/or an ESR (Westergren method) of >= 28 mm per hour at screening. 4. Inadequate response or intolerance DMARDs other than MTX and/or TNFi therapies (1 or more). 5. Treatment with MTX (10 to 25 mg/week) for at least 12 weeks prior to screening, with at least 4 weeks before screening at a stable dosage that will remain stable throughout the study period (up to Week 48). 6. Willing and able to provide written informed consent prior to performing study procedures. 7. Women or men of reproductive potential must use (or have his/her partner use) effective contraceptive methods starting from screening and until 12 months following the last infusion (acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partner’s vasectomy or double-barrier method [condom or diaphragm with spermicide]). 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 354 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 190
Exclusion criteria
Exclusion criteria: 1. Documented rheumatic autoimmune disease or inflammatory joint disease other than RA (eg, psoriatic arthritis or ankylosing spondylitis). 2. Significant systemic involvement secondary to RA (eg, vasculitis, pulmonary fibrosis, or Felty’s syndrome) or American Rheumatism Association (ARA) functional class IV disease. 3. Hypersensitivity to active ingredients, excipients (sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid, water for injections) and murine proteins. 4. Active uncontrolled infection (viral, bacterial or fungal infection) requiring systemic therapy or clinically significant infection, at screening and/or at Day 1 (baseline), or a history of recurring or chronic infections or with underlying conditions that may, according to the Investigator’s judgment, further predispose subjects to serious infection. 5. Known immunodeficiency syndrome, including total immunoglobulins (IgG, IgA and IgM) lower than the lower limit of normal (LLN). 6. Positive human immunodeficiency virus (HIV) serology (in case of positive result an additional HIV RNA test should be performed), positive hepatitis B surface antigen or positive hepatitis C antigen (in case of positive result an additional hepatitis C virus [HCV] RNA test should be performed). 7. History of cancer in the past 5 years prior to screening (except 8. Immunization with live viral vaccines less than 4 weeks prior to Day 1 (baseline) and/or planned live viral vaccination during the core 9. Use of oral/intravenous/intramuscular systemic corticosteroids • Oral corticosteroids at a dose higher than 10 mg prednisone daily (or an equivalent dose of other oral steroids) within the 4 weeks prior to screening and between screening and Day 1 (baseline) OR • Oral corticosteroids at a dose equal to or lower than 10 mg prednisone daily (or an equivalent dose of other oral steroids) that were not kept at a stable dose within 4 weeks prior to screening and between screening and Day 1 (baseline). • Use of intravenous/intramuscular/intra-articular or parenteral glucocorticoids <4 weeks prior to screening. 10. Use of any cytotoxic therapies and immunosuppressants, (except for allowed dosage of MTX) or other DMARDs within the 4 weeks prior to screening or between screening and Day 1 (baseline). 11. Prior use of MabThera (rituximab) and/or participation in a previous clinical trial with the investigational study drug TL011. 12. Use of TNFi and any other biological agent for the treatment of autoimmune diseases less than 8 weeks prior to Day 1 (baseline) or use of etanercept and anakinra less than 4 weeks prior to Day 1. 13. Participation in a previous clinical trial and/or use of an investigational drug within 90 days of screening. 14. Clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation based on the Investigator’s judgment. Conditions may include cardiovascular disease (including severe heart failure of New York Heart Association [NYHA] class IV or severe, uncontrolled cardiac disease) pulmonary, hepatic, renal, or neurological disease as determined by medical history, physical examination, laboratory tests, chest X-ray, or ECG. 15. Likely to be non-compliant or uncooperative during the study in the judgment of the Investigator. 16. History of tuberculosis, latent tuberculosis tested as required by the local regulations, and/or positive chest X-ray for tuberculosis at screening or within the prev
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to demonstrate equivalence of the efficacy of TL011 in comparison with the reference product MabThera® (rituximab) in subjects with severe, active RA treated with MTX;Secondary Objective: To assess the pharmacodynamics (PD), immunogenicity, safety, and tolerability of TL011 in comparison with MabThera® (rituximab) in subjects with severe, active RA treated with MTX;Primary end point(s): Determination of therapeutic equivalence of TL011 to rituximab (MabThera®) Primary efficacy endpoint: proportion of subjects (%) who meet the ACR criteria for 20% improvement (ACR20) from baseline ;Timepoint(s) of evaluation of this end point: At week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ACR20, ACR50, ACR70;Timepoint(s) of evaluation of this end point: At week 24 and 48 | — |
Countries
Bulgaria, Czech Republic, Georgia, Germany, Hungary, Macedonia, the former Yugoslav Republic of, Netherlands, Poland, Romania, Russian Federation, Serbia, Spain, Ukraine
Contacts
Public ContactDr. Ronit Haviv
Teva Pharmaceutical Industries
Outcome results
None listed