HiSCs in the Treatment of Rheumatoid Arthritis

This trial is a single-center, single-arm exploratory clinical study aimed at assessing the safety, tolerability, and preliminary efficacy of a single intra-articular injection of hiSCs for the treatment of rheumatoid arthritis.

In this trial, participants who have given informed consent will be screened to determine their eligibility according to the inclusion and exclusion criteria. The study intervention consists of a single injection of hiSCs, and the primary endpoint will be assessed during the 24-week follow-up visit after the cell injection.

Inclusion criteria

Subjects must meet all of the following inclusion criteria

• Voluntarily sign the informed consent;
• Male or female aged 18-65 years (inclusive) at the time of signing the informed consent;
• Diagnosis of RA for ≥3 months according to the ACR/EULAR 2010 Rheumatoid Arthritis Classification Criteria at the screening visit;
• At the screening visit, presence of recurrent swelling and pain in at least one knee, with a WOMAC pain score ≥4, synovial inflammation confirmed by joint ultrasound, and no significant improvement following 3 months of anti-RA treatment (including prior use of MTX standard therapy, biologics, or small molecule targeted drugs);
• Subjects must have received csDMARD therapy for ≥3 months, with a stable dose for ≥4 weeks prior to screening;
• Background treatment with stable-dose MTX standard therapy, biologics, or small molecule targeted drugs, either alone or in combination, is permitted;
• The following csDMARDs, either alone or in combination, are permitted as background treatment, provided the dose has been stable for ≥4 weeks prior to screening: oral or IV MTX (10-25 mg/week; for subjects intolerant to doses ≥10 mg/week, the dose should be ≥7.5 mg/week), SAS (≤3 g/day), hydroxychloroquine (≤400 mg/day), and LEF (≤20 mg/day);
• Stable-dose NSAIDs are permitted, provided the dose has remained stable for ≥2 weeks prior to screening;
• All females of childbearing potential must have a negative blood pregnancy test within 7 days prior to treatment initiation and must not be breastfeeding. Females not of childbearing potential may be exempt from the pregnancy test and contraception. All enrolled patients (regardless of gender) must use at least one highly effective method of contraception, including adequate barrier methods, throughout the study duration;
• Subjects must be in good overall health, able to ambulate independently (excluding those requiring a wheelchair, walker, or crutches);
• Willingness and ability to adhere to scheduled visits, treatment regimens, laboratory tests, and other study-related procedures.

Exclusion criteria

Subjects who meet any of the following exclusion criteria will be excluded from this study：

• Presence of other immune-mediated disorders at the baseline visit that may interfere with the administration or efficacy evaluation of the study intervention;
• History or current evidence of clinically significant cardiovascular, neuropsychiatric, renal, hepatic, immune, or endocrine disorders (including uncontrolled diabetes or thyroid disease), abnormal laboratory findings, or conditions requiring medications prohibited by the study protocol. "Clinically significant" refers to conditions that, in the investigator's judgment, may jeopardize subject safety or impact efficacy or safety analyses if the disease/condition exacerbates during the study;
• Subjects with positive test results for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or syphilis (refer to laboratory tests for details);
• Evidence of active tuberculosis (TB) or a history of active TB without adequate documented treatment;
• Any other acute or chronic disorder leading to coagulation dysfunction that, in the investigator's judgment, may compromise patient safety and/or interfere with the evaluation of target knee outcomes;
• Clinically significant infection within 1 month prior to the screening visit (requiring hospitalization and parenteral administration of antibiotics, antivirals, antifungals, etc., for ≥3 days) or active infection being treated during the screening period;
• Infection in the target knee within 3 months before baseline;
• Intra-articular corticosteroid or other drug injections in the target knee within 3 months before baseline;
• History of knee injury or prior knee surgery in the target knee within 1 year prior to the baseline visit;
• Serum transaminase (ALT or AST) levels ≥2 times the upper limit of normal (ULN) during screening;
• Creatinine clearance (Ccr) <45 mL/min (based on the Cockcroft-Gault formula) during screening;
• Evidence of hematopoietic dysfunction during screening:

• Hemoglobin level <9.0 g/dL or hematocrit <30%;
• White blood cell count <3.0×10⁹/L or absolute neutrophil count (ANC) <1.2×10⁹/L;
• Platelet count <100×10⁹/L;
• Abnormal 12-lead ECG findings at screening or baseline that, in the investigator's judgment, may increase the safety risk of the study intervention or affect the interpretation of study results;
• Uncontrolled hypertension with systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥90 mmHg at screening/baseline;
• Body mass index (BMI) >30 kg/m² during screening;
• Contraindications to MRI, including but not limited to the presence of cardiac pacemakers, stents, artificial heart valves, etc.;
• Subjects with a current psychiatric disorder such as anxiety or depression, or a history of such disorders, and who are deemed by the investigator to be unsuitable for participation in the study;
• Subjects with a history of malignancy (except for adequately treated or excised non-metastatic basal cell or squamous cell carcinoma of the skin);
• Pregnant or breastfeeding women, women planning to become pregnant during the study, and men planning to donate sperm during the study;
• Use of high-dose corticosteroids (i.e., intravenous or intramuscular corticosteroids or oral prednisone equivalent >10 mg/day) or unstable doses (regardless of treatment for rheumatoid arthritis or other conditions) within 28 days prior to the baseline visit;
• Subjects with a history of hypersensitivity to any component of the study intervention or similar compounds;
• Participation in another interventional clinical study within 4 weeks prior to the baseline visit or within 5 half-lives of the last dose of the investigational drug at baseline;
• History of alcohol or drug abuse within 6 months prior to the start of study intervention treatment, deemed by the investigator to hinder study participation;
• Receipt of any live virus vaccination within 8 weeks prior to the baseline visit;
• Subjects classified as legally disabled according to the April 2008 version of the "Law of the People's Republic of China on the Protection of Persons with Disabilities";
• Subjects with potential health, mental, or social conditions that, in the investigator's judgment, may prevent or hinder compliance with the study protocol;
• Peripheral or central nervous system disorders that, in the investigator's judgment, may interfere with the assessment of knee pain and function, such as fibromyalgia, significant low back pain, hip pain, sciatica, lumbar disc herniation, etc.;
• Any other condition that is deemed by the investigator to be unsuitable for participation in the study.