Single hiSC injection into the knee for rheumatoid arthritis

A Single-arm Clinical Study Assessing the Safety, Tolerability, and Preliminary Efficacy of a Single Intra-Articular Injection of hiSCs for Rheumatoid Arthritis Treatment

This study will try a single injection of lab-made human Sertoli cells (hiSCs) into an inflamed knee to see if it helps adults with rheumatoid arthritis who still have knee swelling and pain despite standard treatment.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Shanghai Changzheng Hospital (Academic / other)
• Drugs / interventions: prednisone
• Locations: 1 site (Shanghai)
• Trial ID: NCT06947746 on ClinicalTrials.gov

What this trial studies

This is a single-center, single-arm exploratory trial that gives one intra-articular injection of hiSCs and follows participants for 24 weeks to record safety, tolerability, and early signs of benefit. Adults aged 18–65 with established RA and persistent knee swelling and pain (WOMAC pain ≥4) with ultrasound-confirmed synovitis after prior DMARD therapy are eligible. Participants undergo screening and baseline assessments, receive one knee injection of hiSCs, and return for regular follow-up visits up to the primary endpoint at week 24. The trial focuses on short-term safety and preliminary efficacy measurements rather than randomized comparison.

Who should consider this trial

Good fit: Adults 18–65 with RA for at least 3 months who have persistent knee swelling and pain (WOMAC pain ≥4) with ultrasound-confirmed synovitis despite at least 3 months of csDMARD therapy and stable background RA medications are the intended candidates.

Not a fit: People whose RA is well controlled, who lack ultrasound evidence of knee synovitis, who are outside the 18–65 age range, or who have contraindications or major comorbidities are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, the injection could reduce knee inflammation and pain and offer a new local treatment option for patients with persistent RA knee symptoms.

How similar studies have performed: Sertoli cell injections are largely untested in people with RA so this approach is novel, although other intra-articular cell therapies such as mesenchymal stromal cells have shown mixed but occasionally promising results.

Eligibility criteria

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria

1. Voluntarily sign the informed consent;
2. Male or female aged 18-65 years (inclusive) at the time of signing the informed consent;
3. Diagnosis of RA for ≥3 months according to the ACR/EULAR 2010 Rheumatoid Arthritis Classification Criteria at the screening visit;
4. 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);
5. Subjects must have received csDMARD therapy for ≥3 months, with a stable dose for ≥4 weeks prior to screening;
6. Background treatment with stable-dose MTX standard therapy, biologics, or small molecule targeted drugs, either alone or in combination, is permitted;
7. 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);
8. Stable-dose NSAIDs are permitted, provided the dose has remained stable for ≥2 weeks prior to screening;
9. 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;
10. Subjects must be in good overall health, able to ambulate independently (excluding those requiring a wheelchair, walker, or crutches);
11. 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：

1. Presence of other immune-mediated disorders at the baseline visit that may interfere with the administration or efficacy evaluation of the study intervention;
2. 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;
3. 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);
4. Evidence of active tuberculosis (TB) or a history of active TB without adequate documented treatment;
5. 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;
6. 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;
7. Infection in the target knee within 3 months before baseline;
8. Intra-articular corticosteroid or other drug injections in the target knee within 3 months before baseline;
9. History of knee injury or prior knee surgery in the target knee within 1 year prior to the baseline visit;
10. Serum transaminase (ALT or AST) levels ≥2 times the upper limit of normal (ULN) during screening;
11. Creatinine clearance (Ccr) \<45 mL/min (based on the Cockcroft-Gault formula) during screening;
12. Evidence of hematopoietic dysfunction during screening:

    1. Hemoglobin level \<9.0 g/dL or hematocrit \<30%;
    2. White blood cell count \<3.0×10⁹/L or absolute neutrophil count (ANC) \<1.2×10⁹/L;
    3. Platelet count \<100×10⁹/L;
13. 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;
14. Uncontrolled hypertension with systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥90 mmHg at screening/baseline;
15. Body mass index (BMI) \>30 kg/m² during screening;
16. Contraindications to MRI, including but not limited to the presence of cardiac pacemakers, stents, artificial heart valves, etc.;
17. 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;
18. Subjects with a history of malignancy (except for adequately treated or excised non-metastatic basal cell or squamous cell carcinoma of the skin);
19. Pregnant or breastfeeding women, women planning to become pregnant during the study, and men planning to donate sperm during the study;
20. 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;
21. Subjects with a history of hypersensitivity to any component of the study intervention or similar compounds;
22. 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;
23. 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;
24. Receipt of any live virus vaccination within 8 weeks prior to the baseline visit;
25. 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";
26. Subjects with potential health, mental, or social conditions that, in the investigator's judgment, may prevent or hinder compliance with the study protocol;
27. 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.;
28. Any other condition that is deemed by the investigator to be unsuitable for participation in the study.

Where this trial is running

Shanghai

• Shanghai ChangZheng hospital — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Huji Xu, Ph.D, MD — Shanghai Changzheng Hospital
• Study coordinator: Huji Xu, Ph.D, MD

Conditions Rheumatoid Arthritis; Sertoli cells; intra-articular injection; hiSCs