Rheumatoid Arthritis
Conditions
Interventions
Autoregulatory T cell infusion (test group):Autoregulatory T cell infusion
Placebo solution infusion (placebo group):Placebo solution infusion
Sponsors
the Third Affiliated Hospital of Sun Yat-sen University
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: (1) RA was diagnosed using the definition of the American Rheumatology Association/ADR/EULAR 2010 RA classification criteria. (2) Aged 18 to 65 years. (3) The results of the pregnancy test for female subjects (child-bearing age) during the screening period should be negative and agree to use effective contraceptive measures during the study period. Menopausal, hysterectomy, bilateral tubal ligation, and/or bilateral salpingectomy, or female subjects with congenital infertility are considered to have no fertility. (4) Voluntary signing of informed consent. (5) Subjects have been taking MTX for at least 12 weeks prior to baseline visits. The dose was stable within 4 weeks prior to randomization. (6) If the subject is taking other DMARDs (except MTX) at screening, discontinue the test for at least 4 weeks prior to randomization. However, leflunomide was discontinued for at least 12 weeks before randomization of the trial. If it was less than 12 weeks, it took 11 days of cholestyramine, cholestyramine, 3 times a day, 8 grams each time. (7) If the subject is receiving corticosteroids during screening, the dose (equivalent to the dose of prednisone) must be stable at =10 mg/day for at least 4 weeks (before randomization); (8) If the subject is taking NSAIDs of non-steroidal anti-inflammatory analgesic drugs during screening, the dose is stable for at least 4 weeks (before randomization); (9) Patients with moderate to severe active RA at screening were defined as DAS28 >3.2.
Exclusion criteria
Exclusion criteria: (1) Exclusion criteria related to rheumatoid arthritis diseases: Subjects with any other inflammatory arthritis (such as juvenile chronic arthritis, Crohn's disease (Crohn's disease), ulcerative colitis, active vasculitis, gout, psoriatic arthritis or tonic Sexual spondylitis). Subjects have secondary, non-inflammatory arthritis (such as osteoarthritis or fibromyalgia), and the investigators believe that the symptoms of this arthritis can interfere with the evaluation of the efficacy of the study drug. However, secondary Sjogren's syndrome (Sj?gren) and thyroiditis need not be ruled out. The subject has a history of artificial joint infection, regardless of when the infection occurred and the artificial joint is still in the body. Subjects underwent >3 arthroplasty for RA and/or shoulder-hand syndrome grade VI. The subject's X-ray stage reached stage IV. The subject's joint function is graded to grade VI or grade V. (2) The investigator confirmed that the subject had current or recent severe, progressive and uncontrolled heart, lung, liver, kidney and other important organs and blood, endocrine system lesions and medical history. Abnormal laboratory indicators that need to be excluded from the subject include, but are not limited to: Table 3 Laboratory parameter exclusion criteria Parameter abnormal standard White blood cell count 135 µmol/L or 5 times the upper limit of the laboratory reference range (whichever is lower) Total bilirubin >1.5 times the upper limit of the laboratory reference range AST(GOT) > 2 times the upper limit of the laboratory reference range ALT(GPT) > 2 times the upper limit of the laboratory reference range Alkaline phosphatase > 2 times the upper limit of the laboratory reference range AST = aspartate aminotransferase; GOT = aspartate aminotransferase; ALT = alanine aminotransferase; GPT = alanine aminotransferase (3) HBsAg-surface antigen-positive persons are not allowed to be selected, but only anti-HBc single-positive patients are added for HBV-DNA quantitative detection. If HBV-DNA is negative, it may not be considered as exclusion. (4) Patients with positive hepatitis C antibody (anti-HCV). (5) Those infected with herpes zoster or HIV infection during the screening period. (6) Subjects at high risk of infection. For example: leg ulcers, indwelling catheters, persistent or recurrent chest infections, long-term bedridden or sedentary wheelchair subjects. (7) A history of chronic infection, serious or life-threatening infections (including herpes zoster) in the past 6 months, or any signs or symptoms during the screening period suggesting infection (eg fever, cough). Current or recent (30 days before screening) with severe viral, bacterial, fungal, or parasitic infections. (8) Pregnant women, lactating women and men or women with birth plans for nearly 6 months. (9) Allergic reactions: Allergic reactions to contrast agents and human biological products for parenteral administration. (10) Subjects receiving live/attenuated vaccines within 8 weeks prior to screening visits or subjects known to receive live/attenuated vaccines during the trial. Except for vaccination against herpes zoster.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The magnitude of DAS28 change between the two groups; | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in CRP between the two groups ;Proportion of patients with a DAS28 (CRP) score of <2.6 and a score of =3.2 between the two groups;Changes in the duration of morning stiffness relative to baseline values and percentage changes;Number of tender joints (28 joints)relative to baseline values and percentage changes;Number of tender joints (28 joints)relative to baseline values and percentage changes;Number of swollen joints (28 joints)relative to baseline values and percentage changes;Subject assessed pain VAS score relative to baseline values and percentage changes;Subject's overall disease status VAS score relative to baseline values and percentage changes;The overall status of the disease as assessed by the investigator VAS score relative to baseline values and percentage changes;Laboratory indicators (including blood routine, liver and kidney function and ESR, CRP, etc.);Changes in the number of regulatory T cells (CD3, CD4, CD25, CD127, FOXP3, Helios, CD226, CD126, TIGIT), CD4/CD8 T cells (CD3, CD4, CD8), B cells (CD19), Th1 cells (CD4, IFN-?+), Th2 cells (CD4, IL-4+), NK cells (CD3, CD56, CD16), Th17 cells (CD4, CD45RA, CCR^, CXCR5);changes in cytokines such as TNF, IL-1, IL-6 and inflammatory mediators; | — |
Countries
China
Contacts
Public ContactSongguo Zheng
the Third Affiliated Hospital of Sun Yat-sen University
Outcome results
None listed