Moderate to severe rheumatoid arthritis
Conditions
Interventions
Experimental group:Intravenous drip HS628
control group:Intravenous drip jamelor
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Patients who sign the informed consent and can complete the trial according to the protocol; 2. Patients aged 18 to 75 years (subject to the day of signing the informed consent), male and female are not limited; 3. Patients with body weight >=30kg; 4. According to the 2010 ACR / EULAR classification and diagnosis standard, patients with rheumatoid arthritis were diagnosed and the course of disease was >=6 months; 5. In the screening period, patients with swelling joint count >=6 (based on 66 joints count) and tenderness joint count >=6 (based on 68 joints count), if the same joint has both swelling and tenderness, this joint will be included in both swelling joint and tenderness joint count (excluding artificial joint); 6. CRP >=10mg/L or ESR >28mm/HR in screening period; 7. Patients who had received DMARD for at least 3 months before the screening visit; 8. Patients who had received at least one non biological dosage form of DMARD (including methotrexate, sulfasalazine, leflunomide) before screening visit had poor efficacy; 9. Patients who had been treated with oral methotrexate for at least 12 weeks (>=7.5 mg / week) and at least 4 weeks (with a critical dose of methotrexate of 7.5-25 mg / week) before randomization; 10. All non biological dmars, except methotrexate, should be discontinued for at least 2 weeks before randomization, such as thalidomide, eramod, etc. (in addition, leflunomide should be stopped for at least 8 weeks, but if it has been treated with standard coleenamide or eluted with active carbon, it should be stopped for at least 2 weeks before randomization; sulfasalazine should be stopped for at least 4 weeks); 11. Patients who received oral folic acid treatment (at least 5 mg / week or the dose determined according to local medical practice) or equivalent drugs (combined drugs necessary for MTX treatment) throughout the study, and the dose of folic acid or equivalent drugs was stable for at least 2 weeks before random administration; 12. Patients with biologics DMARD should have been discontinued for at least 2 weeks before randomization. For example, adalimumab, cetuzumab, infliximab and gelimumumab should be stopped for more than 8 weeks; etanercept (enri, yisaipu and qiangke) should be stopped for more than 4 weeks; tolfatipu and baretinib should be stopped for more than 2 weeks; 13. Any Chinese herbal medicine, Chinese patent medicine or natural medicine for RA treatment has been stopped for at least 2 weeks before random administration; 14. Any nonsteroidal anti-inflammatory drug must be given in a stable dose for at least 2 weeks before randomization; 15. At the time of screening, if the subjects were taking prednisone or the equivalent dose of glucocorticoid, the patients who were treated with prednisone at a stable dose (prednisone dose <=10mg / day) before randomization for at least 4 weeks; 16. The blood pregnancy test of women of childbearing age was negative, and during the test period, the subjects or their spouses used appropriate and effective contraceptive measures, such as abstinence, oral contraceptives, intrauterine device or double barrier method (such as condom and contraceptive diaphragm), and they must be non pregnant women and non lactating women.
Exclusion criteria
Exclusion criteria: 1. Patients who have been previously treated with toluzumab or who are allergic to any component of toluzumab (or test drug); 2. Patients with ACR function grade IV or long-term bed / wheelchair; 3. patients with inflammatory joint diseases other than rheumatoid arthritis (such as gout, reactive arthritis, psoriatic arthritis, spinal arthritis, Lyme disease, etc.) in the past or present history; or other systemic autoimmune diseases (such as systemic lupus erythematosus, scleroderma, inflammatory myopathy, mixed connective tissue disease or other overlapping syndromes, but rheumatoid Except for patients with Sjogren's syndrome secondary to arthritis); 4. Serious patients with poor control of concomitant diseases, such as (but not limited to) nervous system, cardiovascular, renal, liver, endocrine or gastrointestinal diseases, considered clinically significant by the researchers; 5. Patients with any congenital or acquired nervous system disease, vascular disease or systemic disease (such as Parkinson's disease, cerebral palsy, diabetic neuropathy) that may affect the evaluation of the efficacy of this trial (especially joint pain and swelling), or with neuropathy or other painful diseases that may interfere with the evaluation of pain; 6. Patients with a history of severe allergic or allergic reactions to human, humanized or mouse monoclonal antibodies; 7. The chest X-ray examination conducted within 12 weeks before the screening visit or during the screening period showed the patients with malignant tumor and pulmonary infection; the tuberculosis screening results were positive and were judged as active tuberculosis by the researchers; for the patients who were judged as latent tuberculosis, they did not receive the preventive treatment or treatment less than 4 weeks from the infectious doctors before the first administration of the test; 8. Patients who received live / attenuated vaccine within the first 4 months of randomization; 9. Patients known to have the following infections: recurrent active bacteria, viruses, fungi, mycobacteria or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, granulomatosis and herpes zoster found in chest X-ray examination, but excluding fungal infection of nail bed); 10. Patients with a history of chronic infection (such as chronic pyelonephritis, bronchiectasis or osteomyelitis, etc.) in the first 6 months of screening, or any major infectious attack requiring hospitalization or intravenous antibiotic therapy within 4 weeks before screening or oral antibiotic therapy within 2 weeks before screening; 11. Any positive items of human immunodeficiency virus (HIV) antibody, Treponema pallidum antibody, hepatitis C virus antibody and hepatitis B surface antigen should be excluded, and those with hepatitis B core antibody and HBV-DNA positive should be excluded; 12. Patients with positive anti drug antibody test in screening period; 13. Patients who have received surgery (including joint surgery) that the investigator considers to have an impact on the trial within 8 weeks before randomized administration, or those who plan to perform surgery that the investigator considers to have an impact on the trial within 6 months after randomized administration; 14. Patients with a history of malignant tumor (excluding basal cell carcinoma or squamous cell carcinoma, treated cervical dysplasia or treated grade I cervical carcinoma in situ that have been removed
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of subjects who reached ACR20 at 24 weeks from baseline; | — |
Secondary
| Measure | Time frame |
|---|---|
| The proportion of subjects with ACR50 and ACR70 at baseline after 24 weeks of treatment;The proportion of subjects who reached ACR20, ACR50 and ACR70 at baseline after 12 weeks of treatment;;DAS28 (ESR, CRP) <=3.2 and DAS28 (ESR, CRP) < 2.6 at week 12 /24 of treatment;Simplified disease activity index (SDAI) and clinical disease activity index (CDAI) at 12 and 24 weeks of treatment.;Improvement of joint swelling and joint tenderness count after 24 weeks of treatment;Functional impairment index (haq-di) and summary of health status survey in health assessment questionnaire for 24 weeks of treatment(sf-36) change from baseline;Changes of CRP, ESR, VAS (ptaap-vas, ptgada-vas, phgada-vas) from baseline at 12 and 24 weeks of treatment; | — |
Countries
China
Contacts
Public ContactXiaofeng Zeng
Peking Union Medical College Hospital
Outcome results
None listed