ESAR-814 Study

INTERVENTION: CIGB‐814 Group I (control): Placebo + Methotrexate + Prednisone + Folic Acid Group II (experimental): CIGB 814 (0,5 mg) + Methotrexate + Prednisone + Folic Acid Group III (experimental): CIGB 814 (1,0 mg) + Methotrexate + Prednisone + Folic Acid Group IV (experimental): CIGB 814 (2,5 mg) + Methotrexate + Prednisone + Folic Acid The experimental treatment/placebo will receive by subcutaneous route (deltoid region) once a week for the first four weeks, and often the remaining five months of treatment monthly. The Methotrexate (12.5 mg) will receive by subcutaneous route (deltoid region), once a week for the first four weeks, and frequently monthly for the remaining five months of treatment. This subcutaneous injection will be independent of the experimental treatment. The Prednisone (5 mg) will receive 2 tablets daily by oral route for 24 weeks The Folic Acid (5 mg tablet) will receive by oral route once a week for 24 weeks. Peptides CONDITION: Arthritis, Rheumatoid Rheumatoid arthritis with moderate activity PRIMARY OUTCOME: ACR clinical response (ACR20, ACR50 or ACR70. ACR20 decrease at least 20% in the number of painful joints and in the number of inflamed joints, and a 20% improvement in 3 of 5 following parameters: 1‐Assessment of pain by the patient; 2‐Overall evaluation of the patient's disease activity; 3‐Overall assessment of disease activity by the physician; 4‐Evaluation of the patient's physical function, through a self‐assessment instrument; 5‐Determination of acute phase reactants (C‐reactive protein, erythrocyte sedimentation). ACR50 decrease at least 50% in the number of painful joints and in the number of inflamed joints, and a 50% improvement in 3 of 5 parameters. ACR70 decrease at least 70% in the number of painful joints and in the number of inflamed joints, and a 70% improvement in 3 of 5 parameters). Measurement time: at baseline, Weeks 1, 2, 3, 4 and, Months 2, 3, 4, 5, 6 and 9. EULAR response (Assessment of clinical activity by DAS28. DAS28 <2.6 Referral; DAS28> 2.6 and = 3.2; Light disease activity; DAS28> 3.2 e = 5.2 Moderate disease activity; DAS28> 5.2 Severe disease activity). Measurement time: at baseline, Weeks 1, 2, 3, 4 and, Months 2, 3, 4, 5, 6 and 9. SECONDARY OUTCOME: Clinical Adverse Events‐AE (Ocurrence of AE (Yes, No), Description of AE (event name), ‐AE intensity (mild, moderate, severe)). Measurement time: at baseline, in the first four weeks, and in the months 2, 3, 4, 5, 6 and 9 Laboratory test (Numerical values of hemochemical tests: hemoglobin, hematocrit, leukogram with differential, velocity of globular sedimentation and platelet count). Measurement time: at the beginning, in the first four weeks, and in the months 2, 3, 4, 5, 6 and 9. Immunological response: Quantification of inflammatory cytokine levels (IL‐17, IFN? and TNF?). Measurement time: at baseline, months 6 and 9. Determination of C‐reactive protein (values of test). Measurement time: at baseline, months 6 and 9. Citrullinated antibodies (values obtained by ELISA in patient sera). Measurement time: at baseline, months 6 and 9. Imaging response: Evaluation of the imaging changes (edema, erosion, synovitis) in the most affected hand of the patients through magnetic resonance imaging. Measurement time: at the beginning and in the months 6 and 9. Quality of life (Questionnaire SF36). Measurement time: at baseline, Weeks 1, 2, 3 and 4, Months 2, 3, 4, 5, 6 and 9. Clinical response according to SDAI (Simplified Disease Activity Index. High activity> 26, Moderate activity> 11.1 and <26, Low activity> 3.3 and <11, Remission <3.3). Measurement time: Weeks 24 and 36. Clinical response according to SDAI (Clinical Disease Activity Index. High Activity> 22, Moderate Activity> 10.0‐22, Low Activity> 2.8 ‐10, Referral 2.8). Measurement time: Weeks 24 and 36. INCLUSION CRITERIA: 1. Diagnosis of Rheumatoid Arthritis with evolution time equal to or greater than 2 years. 2. Moderate clinical activity, assessed by DAS28. 3. Have received MTX at a stable dose of 12.5 to 25 mg over a period >= 6 months prior to inclusion in the study (patient with inadequate response to treatment with Methotrexate). 4. Age between 18 and 60 years, both inclusive. 5. Laboratory parameters within normal limits or outside the limit of normality, which at the discretion of the investigator are not clinically significant. 6. Female patient of childbearing age with negative pregnancy test and using effective contraceptive methods or male patient using effective methods to prevent procreation. 7. Have received Prednisone (10‐20 mg) and Folic Acid (5 mg) for a period >= 6 months prior to inclusion in the study. 8. Have received FAME prior to inclusion in the study. 9. Expressed and written willingness by the patient to enter the study with his / her consent to participat