None listed
Conditions
Interventions
GROUP 1 Type of group
This group will be treated with: Ocrelizumab Placebo, IV, in 2 doses separated by 14 days, on days 1 and 15 and in weeks 24 and 26. Methotrexate will be administered concomitantly, in tablets, at a dose of 7.5 - 25 mg, PO, QD, for 48 weeks. After this period, patients may enter an open label extension period, where they may receive 2 separate doses for 14 days of Ocrelizumab, at a dose of 500 mg, IV, at any time, the duration of this period is 48 weeks
Group name:GROUP 3 Type of group
This group will be treated with: Ocrelizumab, at a dose of 500 mg, IV, in 2 separate doses for 14 days, on days 1 and 15 and in weeks 24 and 26. Methotrexate will be administered concomitantly, in tablets, at a dose of 7.5 - 25 mg, PO, QD, for 48 weeks. After this period, patients may enter an open label extension period, where they may receive 2 separate doses for 14 days of Ocrelizumab, at a dose of 500 mg, IV, at any time, the duration of this period is 48 weeks.
Sponsors
F. HOFFMANN-LA ROCHE LTD.,
Eligibility
Inclusion criteria
Inclusion criteria: 1. Ability and willingness to grant written informed consent and comply with protocol requirements. 2. Age ≥ 18 years. 3. Have active disease. 4. Previous and current treatments: a) Current treatment for RA as outpatient. b) Patients with an inadequate clinical response to MTX taking a dose between 7.5-25 mg / week for at least 12 weeks, with the last 4 weeks prior to the baseline visit at a stable dose. c) If you are receiving current treatment with corticosteroids, the dose should not exceed 10 mg / day of prednisolone or equivalent, and at a stable dose during the four weeks prior to the baseline visit. d) If you are receiving current treatment with NSAIDs, the patient must maintain a stable dose at 4 weeks prior to the baseline visit. e) The patient must agree to receive oral or equivalent folic acid. 5. Other: a) For patients of reproductive age, reliable methods of contraception should be used for the duration of the study according to local guidelines. b) Women patients of reproductive age must have a negative urine pregnancy test.
Exclusion criteria
Exclusion criteria: 1. Autoimmune rheumatic disease other than RA, or a significant systemic condition secondary to RA. 2. Functional class IV as defined by the Classification of the ACR of Functional State in AR. 3. History of, or current inflammatory joint disease other than RA or other systemic autoimmune disorders. 4. Any surgical procedure, including bone or surgery joint / synovectomy within the previous 12 weeks or planned within 48 weeks after the baseline visit. 5. Sepsis in an articular prosthesis within the last 48 weeks or indefinitely if the prosthesis remains in situ. 6. Lack of peripheral venous access. 7. Pregnancy or lactation. 8. Known significant cardiac disease (NYHA Class III and IV). 9. Known severe chronic obstructive pneumonia (COPD). 10. Evidence of significant uncontrolled concomitant diseases of the nervous system, renal, hepatic, endocrine, or gastrointestinal disorders. 11. Any neurological, psychiatric, vascular or systemic disorder that may affect any of the efficacy evaluations. 12. Uncontrolled diseases, where the exacerbations with corticosteroids are usually treated. 13. Primary or secondary immunodeficiency. 14. Known active infection of any type or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to the baseline visit or oral antibiotics within 2 weeks prior to the baseline visit. 15. History of tissue infection / deep spaces within 48 weeks of the baseline visit. 16. Evidence of chronic hepatitis B or C, active. 17. Evidence of active tuberculosis. 18. History of recurrent or severe chronic infections. 19. Cancer history within the last 10 years. 20. Currently active alcoholism or drug abuse; or a history of alcoholism or drug abuse within 24 weeks of the baseline visit. 21. History of severe allergic reaction or anaphylactic reaction to biological agents or known hypersensitivity to any component of the ocrelizumab infusion. 22. Pre-treatment of any biological therapy used for the treatment of RA. 23. Concomitant treatment with any DMARD. 24. Treatment with any agent under investigation 12 weeks or five half lives of the investigational drug. 25. Pre-treatment with any cell-depleting therapy, including products under investigation. 26. IV treatment with y-globulin or Prosorba® column within 24 weeks prior to the baseline visit. 27. Intraarticular or parenteral corticosteroids within 6 weeks prior to the baseline visit. 28. Receiver of any vaccine within 6 weeks prior to the baseline visit. 29. Intolerance or contraindications to methylprednisolone IV. 30. A positive urine pregnancy test. 31. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)> 2.5 times the upper limit of normal. 32. Hypogammaglobulinemia. 33. Absolute neutrophil count <1500 cells / uL.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Clinical evaluation to determine if an ACR20 has been achieved, which requires at least a 20% improvement compared to baseline in both TJCs (Painful Joint Count) and SJCs (Inflamed Joint Count), as well as a 20 % improvement in three of the five additional measurements of: a) Overall assessment by the physician of the disease activity. b) Overall assessment of the patient s disease activity. c) Evaluation of the pain patient. d) Health assessment questionnaire - Disability index (HAQ-DI). e) An acute phase reactant - CRP or ESR. Measure:1) Proportion of patients with ACR20 responses at 24 weeks. 2) Proportion of patients with ACR20 responses at 48 weeks. Timepoints:Weeks 24 and 48. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Criterion 1: Clinical determination of compliance with the ACR70 criteria for> 6 months. Criteria 2 and 3: Clinical determination of DAS28, which should achieve a score of <2.6, to be considered that remission has been achieved. Criterion 4: Response in the response rates of the European League against Rheumatism (EULAR), in those patients who respond categorically DAS28. Criteria 5, 6 and 7: Clinical evaluation to determine if an ACR50, ACR70 has been achieved, which requires at least 50% or 70% improvement compared to baseline in both TJCs and SJCs, as well as a 50 % or 70% improvement in three of the five additional measurements of: a) Overall assessment of the doctor s disease activity. b) Overall assessment of the patient s disease activity. c) Evaluation of the pain patient. d) Health assessment questionnaire - Disability index (HAQ-DI). e) An acute phase reactant - CRP or ESR. Measure:Secondary Efficacy: 1) Proportion of patients with an important clinical response. 2) Proportion of patients achieving remission of the Disease Activity Score (DAS28). 3) Change in DAS28. 4) EULAR response rates. 5) Proportion of patients that achieve an ACR50 response. 6) Proportion of patients that achieve an ACR70 response. 7) Change from the initial in the individual parameters of the central group ACR. Timepoints:Criterion 1: Week 48 Criteria 2, 3, 4, 5, 6 and 7: Weeks 24 and 48. ; Outcome name:All the criteria will be evaluated in X-rays of the patients hands and feet. For this evaluation the modified Sharp scale will be used. Radiographic evolution is defined as change in the modified Sharp total scale ≤ 0.5. Measure:Radiographic Criteria: 1) Change from the baseline on the modified Sharp total scale. 2) Change in the modified erosion score and change in the narrowing score of the modified joint space. 3) Proportion of patients without radiographic evolution. 4) Proportion of patients with a reduction from baseline on | — |
Countries
Austria, Belgium, France, Germany, Greece, Spain, United Kindgdom
Outcome results
None listed