active rheumatoid arthritis
Conditions
Interventions
Experimental group:treatment with Methotrexate Injection (Prefilled) for 12 weeks:Subcutaneously, 15 mg/ week, once a week, until W12
Control group:treatment with Moderate for 12 weeks:Orally, 15 mg/ week, once a week, until W12
Sponsors
Peking Union Medical college Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1.Fully understand the purpose and requirements of the trial, participate in the clinical trial voluntarily and sign the written informed consent form, so as to complete the whole trial process as required by the trial; 2.18=12 weeks according to the American Rheumatology Society (ACR1987) revised criteria or the American Rheumatology Society/European Anti-Rheumatology Alliance (ACR/EULAR) 2010 classification criteria; 4.Moderate to severe active RAs at screening, defined as tenderness or pain with at least 6/68 joints in motion and swelling of at least 6/66 joints (note: If a joint has undergone major surgical treatment, for screening in this study, this joint cannot be included in the TJC and SJC evaluations); 5.Erythrocyte sedimentation rate (ESR) >28 mm/h; 6.Any of the following is required for prior treatment of RA: a) No anti-rheumatic agents were used to improve the disease before screening; b) screening before 4 weeks stop using traditional improve rheumatism disease drugs (mitt to fluorine must be stopped for at least 8 weeks before random, but if have been treated with standard test to enamine or activated carbon after elution, is must be stopped at least 4 weeks before random), 4 weeks before the screening stop using the proprietary Chinese medicine for the treatment of RA or Chinese herbal medicine (such as tripterygium wilfordii, radix paeoniae alba, total glycosides, sinomenine, etc.), Discontinue biologics that ameliorate rheumatism or radiopharmological agents for RA (e.g., technetium [99mTc] methylene diphosphonate injection) 12 weeks before screening; 7.If the subject takes oral NSaids and/or glucocorticoids, the NSAID dose must be stable at least 2 weeks before screening and the glucocorticoid dose must be stable at least 4 weeks before screening (for glucocorticoids, a dose equivalent to 10mg or less prednisone per day); 8.Subjects receiving non-contraindicated concomitant medications for any reason must remain in a stable treatment regimen, defined as not starting a new drug or changing dose within 7 days or 5 half-lives, whichever is longer, prior to screening; 9.Laboratory tests at screening met the following criteria: Blood routine Neutrophil count (NEUT#) >=1.0× 10^9/L; Lymphocyte count (LYMPH#) >=0.5× 10^9/L; Total white blood cell count >=3.5× 10^9/L; Hemoglobin (HGB) >=80.0 g/L; Platelet count (PLT) >=80× 10^9/L; Liver Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)<=1.5-fold ULN; Total bilirubin (TBIL) <=1.5-fold ; Kidney Serum creatinine is not higher than the upper limit of normal, and the investigator judges that the renal function is normal based on the medical history and other auxiliary examinations; 10.Fertile men and women of reproductive age must agree to have no reproductive plans and to voluntarily use reliable contraception from the time of signing the informed consent until 6 months after the last administration of the study drug. Women of childbearing age include premenopausal women and women within 2 years after menopause. Females of childbearing potential must have a negative blood pregnancy test result within <=7 days prior to the first dose of study drug.
Exclusion criteria
Exclusion criteria: 1.Patients with autoimmune disorders other than RA, including but not limited to psoriatic arthritis (PsA) patients with primary Sjogren's syndrome, ankylosing spondylitis, systemic lupus erythematosus or Lyme disease, mixed connective tissue disease, scleroderma, etc; 2.Patients with or history of malignancy, including solid tumours and hematologic malignancies within the last 5 years (except for fully treated or resected non-metastatic basal or squamous cell carcinoma or cervical carcinoma in situ); 3.Has an uncontrolled cardiovascular, respiratory, digestive, endocrine, haematological, immune, cutaneous, neurological, or psychiatric disorder or any other serious and/or unstable condition or medical history that, in the opinion of the investigator, poses a risk to the administration of the study drug or interferes with the interpretation of the data; 4.Inability to tolerate subcutaneous injection, dysphagia, or any history of gastrointestinal disease or surgery that may affect the absorption of oral medications; 5.Those who have had surgery that has an impact on this trial (e.g. joint surgery) within 3 months prior to Screening or are scheduled for surgery during the study; 6.Patients with active fibromyalgia who present difficulties to the investigator in accurately evaluating RA activity in this study; 7.Patients with a history of infection and still in situ prosthesis, or who have received intra-articular corticosteroid therapy within 3 months prior to screening; 8.Patients with any of the following cardiac disorders: Screening QTc>= 450 ms (male), >= 460 ms (female); The presence of uncontrolled hypertension despite drug treatment during the screening period (systolic blood pressure>=160 mm Hg, diastolic pressure >= 100 mm Hg); History of myocardial infarction within 6 months prior to screening; Known unstable angina; Known severe or uncontrolled ventricular arrhythmias; 9.A history of any lymphoproliferative disorder, such as a history of EBV-related lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorders, multiple myeloma, or evidence of active tuberculosis (TB) suggestive of current signs and symptoms of lymphoid disease, or prior evidence of active TB without appropriate documented treatment; Patients with occult tuberculosis who have not completed 4 weeks of preventive intervention or active tuberculosis (judged by the investigator based on chest X-ray, tuberculin skin test results, or other necessary examinations); 10.Those with severe acute or chronic infection (e.g., requiring hospitalization or parenteral antimicrobial therapy or opportunistic infection) or a history of severe herpes zoster (e.g., Hunter's syndrome or ulcerative disease), a history of disseminated herpes zoster, a history of multiple relapses of local herpes zoster (at least 2 times), any infection that the investigator otherwise determines may have worsened due to participation in the study, or any infection requiring antimicrobial therapy within 4 weeks of screening and the researcher judged it unsuitable for methotrexate treatment; 11.Virology tests meet any of the following: Hepatitis B virus infection (subjects with hepatitis B surface antigen [HBsAg] positive or hepatitis B core antibody [HBcAb] positive may be enrolled if HBV- DNA<1× 103 copies/ml and ALT and AST = ULN); Hepatitis C virus infection (defined as HCV antibody positive); Human immunodeficiency virus infection (defined as H
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Reduction of DAS28-ESR from baseline at week 12; | — |
Secondary
| Measure | Time frame |
|---|---|
| Response rate of ACR20, ACR50 and ACR70 at week 4, 8 and 12;Change of DAS28-ESR score from baseline at week 4 and 8;Changes in DAS28-CRP scores from baseline at weeks 4, 8, and 12;Proportion of subjects who achieved clinical remission (judged by DAS28-CRP and DAS28-ESR = 2.6 respectively) at weeks 4, 8 and 12;Proportion of subjects with low disease activity (judged by DAS28-CRP and DAS28-ESR = 3.2) at week 4, 8 and 12;Change of tenderness joint count (TJC) from baseline at week 4, 8 and 12;Changes in Swelling Joint Count (SJC) from Baseline at Weeks 4, 8, and 12;Changes in VAS from baseline at weeks 4, 8 and 12;Changes from baseline in the investigator's assessment of overall illness (PGA) at weeks 4, 8 and 12;Changes from baseline in subjects' assessment of overall condition (SGA) at weeks 4, 8 and 12;Change of disability index (HAQ-DI) of health assessment questionnaire from baseline at week 4, 8 and 12;Good response rate of clinical disease activity index (CDAI) at week 4, 8 and 12 (defined as improvement of CDAI = 50% or CDAI = 2.8); | — |
Countries
China
Contacts
Public ContactXiaofeng Zeng
Peking Union Medical college Hospital
Outcome results
None listed