CD19 CAR-T (JY231) for hard-to-treat autoimmune diseases

An Exploratory Clinical Study of the Safety, Tolerability, and Initial Efficacy of Targeted Cluster of Differentiation 19 (CD19) CAR-T Therapy for Refractory Autoimmune Diseases

This project will try a CD19 CAR-T treatment called JY231 in adults whose autoimmune diseases haven't improved with standard therapies.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shenzhen Genocury Biotech Co., Ltd. (Industry-sponsored)
• Drugs / interventions: CAR-T, Chimeric Antigen Receptor, cyclophosphamide, fludarabine
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT07059169 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm, single-center study will give an in vivo CD19-directed CAR-T product (JY231) to adults with refractory autoimmune diseases and follow them for safety and early signs of efficacy. Some participants will undergo leukapheresis and lymphodepleting chemotherapy (fludarabine and cyclophosphamide) before receiving JY231 plus autologous PBMCs, while others will receive JY231 without lymphodepletion. Infusions are delivered intravenously and patients will be monitored closely with clinical and laboratory assessments for up to 24 months. The primary focus is on safety and tolerability with exploratory measures of disease control across conditions such as SLE, Sjögren's, systemic sclerosis, dermatomyositis, and ANCA-associated vasculitis.

Who should consider this trial

Good fit: Adults (≥18) with SLE, Sjögren's syndrome, systemic sclerosis with interstitial lung disease, dermatomyositis, or ANCA-associated vasculitis who have failed at least two immunosuppressive agents or require ≥15 mg of glucocorticoids to maintain stability and who meet the protocol's disease-activity thresholds are the intended participants.

Not a fit: Patients with mild or well-controlled disease or who do not meet the specified activity or treatment-failure thresholds are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could provide longer-lasting disease control or remission for patients whose autoimmune conditions have failed standard treatments.

How similar studies have performed: Small case series and early-phase reports of CD19-targeted CAR-T in refractory autoimmune diseases have shown promising responses, but larger controlled data are still limited.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years old, regardless of gender, signed with informed consent (ICF).
2. Diagnosed as one of the following diseases: Systemic lupus erythematosus (SLE)；Sjogren's syndrome (SS) ; Systemic Scleroderma (SSc); Dermatomyositis (DM); Anti neutrophil cytoplasmic antibody associated vasculitis (ANCA-AAV).
3. Patients who have been treated with ≥ 2 immunosuppressive agents for 3 months, or require ≥ 15mg glucocorticoids to maintain stable condition, or are intolerant to standard treatment, or have relative contraindications, and whose disease activity meets the following criteria:

   1. For SLE patients, SLEDAI ≥ 8 points;
   2. For SS patients, Sjogren's syndrome disease activity index(ESSDAI )≥ 14 points;
   3. For SSc patients, the modified skin score (mRSS) score ranges from 10 to 35 (including cutoff values) and is associated with interstitial pneumonia (ILD);
   4. For DM patients, diagnosed for at least 1 year;
   5. For ANCA-AAV patients, Birmingham Vasculitis Activity Score(BVAS) score ≥ 15 and ANCA antibodies.
4. Eastern Cooperative Oncology Group(ECOG) 0-1 points;
5. The evaluation of important organ functions meets the following conditions:

   1. Blood count: hemoglobin ≥ 60g/L, platelet count ≥ 30 × 109/L;
   2. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 55%, no significant abnormalities observed on electrocardiogram;
   3. Renal function: estimated glomerular filtration rate(eGFR) ≥ 30 mL/min/1.73m2;
   4. Liver function: Aspartate Aminotransferase(AST) and Alanine Transaminase(ALT) ≤ 3.0 upper limit of normal(ULN), total bilirubin ≤ 2.0 ULN;
   5. Pulmonary function: diffusion capacity of the lung for carbon monoxide(DLCO) ≥ 40% expected value; forced vital capacity(FVC) ≥ 50% of expected value;
   6. Having single or intravenous blood collection standards and no other contraindications for cell collection;
6. The urine pregnancy test results of subjects of childbearing age are negative, and they agree to take effective contraceptive measures during the trial period, until one year after infusion;
7. The patient or their guardian agrees to participate in this clinical trial and signs an informed consent form, indicating their understanding of the purpose and procedures of this clinical trial and willingness to participate in the study.

Exclusion Criteria:

1. Previously received Chimeric Antigen Receptor T cell(CAR-T) therapy;
2. Suffering from severe diseases of the heart, liver, lungs, blood system, and endocrine system, the researcher has determined that the risk of participating in the trial is higher than the benefit;
3. Active or uncontrollable infections that require systemic treatment within the first week of screening;
4. Previously received hematopoietic stem cell transplantation or solid organ transplantation (excluding corneal and hair transplantation), or screened for acute graft-versus-host disease (GVHD) with grade 2 or above in the first two weeks;
5. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) is positive and the hepatitis B virus(HBV) DNA titer in peripheral blood is greater than the normal reference value; Or hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA titer detection greater than the normal reference range; Or positive for human immunodeficiency virus (HIV) antibodies; Or those who test positive for syphilis; Or positive for cytomegalovirus (CMV) DNA detection;
6. Received live vaccine within 4 weeks prior to screening;
7. Pregnancy test positive individuals;
8. Patients with malignant tumors and other malignant diseases before screening, in addition to fully treated cervical cancer in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and ductal carcinoma in situ after radical surgery;
9. Screening patients who have participated in other clinical trials within the first three months;
10. Other researchers believe that it is not suitable to participate in this study.

Where this trial is running

Wuhan, Hubei

• Wuhan No.1 Hospital — Wuhan, Hubei, China (Recruiting)

Study contacts

• Study coordinator: Liang Zou, Doctor

Conditions Autoimmune Diseases