A Single-arm, Open-label Study of the Safety and Reduction of Signs and Symptoms During Treatment With Tocilizumab in Combination With Methotrexate, in Patients With Moderate to Severe Active Rheumatoid Arthritis

Not Applicable

• Conditions: -M05; M05

• Registration Number: PER-129-08
• Lead Sponsor: PRODUCTOS ROCHE Q.F.S.A.,

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-12-24
• Last Update Posted: 4 September 2023

Recruitment & Eligibility

• Status: Complete
• Sex: Not specified
• Target Recruitment: 20

Inclusion Criteria

• Ability and willingness to grant informed written consent and comply with the requirements of the study protocol;
• Age> 18 years;
• Patients with RA of> 6 months duration, diagnosed according to the 1987 Revised Version of the Classification Criteria for Rheumatoid Arthritis of the American Rheumatism Association (ACR; formerly American Rheumatism Association) (Appendix 1);
• Swollen joint count (SJC)> 6 (66 joints) and painful joint count (TJC)> 8 (68 joints) in the scrutiny (Appendix 2);
• DAS28 of> 3.2 (Appendix 3);
• Functional Status I-III according to the revised 1991 version of the Criteria for Classifying Functional Capacity in Rheumatoid Arthritis of the ACR (Appendix 4);
• Receive treatment as an outpatient;
• Have received MTX for at least 12 weeks immediately before baseline, of which the last 8 weeks prior to baseline should have been at stable doses between 15 and 25 mg / week (oral or parenteral).
• Patients who have responded insufficiently to prior treatment with stable doses (> 8 weeks) of MTX therapy.
• All DMARDS other than MTX should be removed at least 4 weeks before enrollment, except in the following cases: 2 weeks for etanercept, 3 weeks for adalimumab, 8 weeks for infliximab and abatacept, and 12 weeks for leflunomide (8 weeks if used cholestyramine or activated carbon to accelerate the removal of leflunomide).
• C-reactive protein (CRP)> 0.6 mg / dL at screening;
• Oral corticosteroids (<10 mg / day of prednisone or equivalent) and NSAIDs (up to the maximum recommended dose) are allowed if the dose has remained stable for at least 4 weeks before baseline;
• Patients who are willing to receive oral folic acid;
• Women of reproductive age can participate in this study if they use a reliable method of contraception;
• If she is a woman of reproductive age, the patient must obtain a negative pregnancy test for blood pHCG three weeks before the baseline;
• Men with female partners of reproductive age may participate in this trial only if the patient or his partner uses a reliable method of contraception.

Exclusion Criteria

• Autoimmune rheumatic disease other than RA (including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma or variants, or polymyositis) or significant systemic involvement, secondary to RA (eg, vasculitis, pulmonary fibrosis or Felty´s syndrome); patients with interstitial pulmonary fibrosis who can tolerate MTX therapy are allowed, secondary Sjogren syndrome with RA is allowed.
• Functional class IV, defined in accordance with the revised version of the Criteria for Classifying Functional Capacity in Rheumatoid Arthritis of the ACR (Appendix 4);
• Diagnosis of juvenile idiopathic arthritis (JIA) or juvenile rheumatoid arthritis (JRA) and / or RA before 16 years of age;
• History or current inflammatory joint disease other than RA (including, without limitation: gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease);
• Unsuccessful treatment with a biological agent (that is, due to important safety issues or lack of efficacy); Patients who have completed a previous biological treatment due to the cost or discomfort of subcutaneous injections may participate in this study (see the Inclusion Criteria for biological agent washing);
• Previous / concurrent treatment with any cell depletion therapy, as agents under investigation (for example, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and antLCD20);
• Treatment with daily oral / systemic corticosteroids at doses of> 10 mg of prednisone equivalents;
• Intraarticular or parenteral corticosteroids within six weeks prior to baseline;
• Treatment with intravenous gamma globulin, plasmapheresis or Prosorba® spine within six months prior to baseline;
• Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil or with total lymphoid irradiation;
• Treatment with any investigating agent within 4 weeks prior to scrutiny (or five half-lives of the investigational drug, whichever is greater);
• Immunization with a live / attenuated vaccine of the four weeks prior to baseline;
• History of severe or anaphylactic allergic reactions to human, humanized or murine monoclonal antibodies;
• In patients with a history and diverticulitis or diverticulosis that require antibiotic treatment, the attending physician needs to consider the risk-benefit ratio;
• History of lower gastrointestinal, ulcerative and chronic disease, ulcerative colitis and other lower gastrointestinal conditions that could predispose the patient to perforations;
• Evidence of significant concomitant and / or uncontrolled diseases such as cardiovascular disease or nervous, respiratory, renal, hepatic, endocrine or gastrointestinal disorders;
• Current active infection known or a history of recurrence of bacterial, fungal, mycobacterial or other infections (including, without limitation, tuberculosis and atypical mycobacterial disease, clinically important abnormalities in CXR determined by the researcher, hepatitis B and C and herpes zoster , and excluding onychomycotic infections) and any infectious episode that requires hospitalization or intravenous antibiotics within 4 weeks before randomization or treatment with oral antibiotics within 2 weeks prior to scrutiny.
• Chronic active hepatitis B (identified by tests of central antibody, surface antigen or viral DNA) or C (identified by serology).
• Known HIV infection;
• Active tuberculosis (TB) that

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br>Outcome name:ACR50 is defined as 50 percent (%) improvement in: a) Swollen Joints Count (SJC) and Tender Joints Count (TJC) and b) Three of the following 5 assessments: Participants global assessment of pain by Visual Analog Scale (VAS), Participants global assessment of disease activity (VAS), Investigator/Physicians global assessment of disease activity (VAS), Participants assessment of disability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI)<br>Acute phase reactant levels - Erythrocyte Sedimentation Rate or C-Reactive Protein (ESR or CRP)<br>Measure:Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24<br>Timepoints:Week 24<br>