CD19 CAR-T (PTOC1) therapy for refractory systemic lupus erythematosus

Study of Autologous CD19-Targeted Chimeric Antigen Receptor T (CAR- T) Therapy for Refractory Systemic Lupus Erythematosus

This study will try a fast-made CD19 CAR-T cell treatment called PTOC1 in people aged 5 and older whose lupus has not improved with high-dose steroids and multiple immunosuppressive drugs.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 5 Years and up
• Sex: All
• Sponsor: Chongqing Precision Biotech Co., Ltd (Industry-sponsored)
• Drugs / interventions: belimumab, rituximab, CAR-T, methotrexate, cyclophosphamide, prednisone
• Locations: 1 site (Chongqing)
• Trial ID: NCT07403097 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, investigator-initiated interventional trial testing PTOC1, a CD19-targeted CAR-T product manufactured with an accelerated process, in patients with refractory systemic lupus erythematosus. Eligible participants have active moderate-to-severe disease (SLEDAI-2K ≥ 8) despite high-dose glucocorticoids, hydroxychloroquine, and at least two immunosuppressants or biologics, and must meet basic cardiac, renal, hepatic, and pulmonary function criteria. Participants will receive PTOC1 cell infusion and be followed for safety, tolerability, and signals of clinical benefit using standard disease activity measures and organ function monitoring. The trial is led by Chongqing Precision Biotech and conducted at the Children's Hospital of Chongqing Medical University in Chongqing, China.

Who should consider this trial

Good fit: People aged 5 years and older with SLE meeting the 2019 EULAR/ACR criteria who remain in moderate-to-severe activity (SLEDAI-2K ≥ 8) despite ≥3 months of high-dose steroids plus hydroxychloroquine and at least two immunosuppressants or biologics, and who meet required cardiac, renal, hepatic, and pulmonary function thresholds are ideal candidates.

Not a fit: Patients with mild or well-controlled SLE, those who do not meet the organ function or disease-activity criteria, or those with other contraindications to cellular therapy are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, PTOC1 could deplete disease-causing B cells and produce durable remission, potentially reducing or eliminating the need for lifelong immunosuppression in some patients.

How similar studies have performed: Early clinical reports and small case series of CD19-targeted CAR-T in refractory autoimmune diseases including SLE have shown promising remissions, but larger controlled data remain limited.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 5 years, no gender limitation;
* Diagnosed with SLE according to the 2019 EULAR/ACR classification criteria, and still in moderate to severe disease activity despite ≥ 3 months of high dose glucocorticoids(prednisone≥1mg/kg/d or other equivalent amount of other steroid), combined with hydroxychloroquine, and at least 2 Immunosuppressants or biologics (including cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, cyclosporin, tacrolimus, sirolimus, leflunomide, telitacicept, belimumab, and rituximab) or intolerant to standard treatments;
* SLEDAI-2K score ≥ 8 points;
* The functions of vital organs must meet the following requirements:

  1. cardiac function: left ventricular ejection fraction (LVEF) ≥ 50%, with no obvious abnormalities on electrocardiogram (ECG);
  2. renal function: eGFR ≥ 30 mL/min/1.73m2;
  3. hepatic function: AST and ALT ≤ 3.0×ULN, total bilirubin ≤ 2.0×ULN;
  4. pulmonary function: no severe pulmonary lesions; blood oxygen saturation ≥ 92% under non-oxygen supplementation conditions.
* Meet the criteria of leukapheresis or intravenous blood collection, and no contraindication for leukapheresis;
* Negative pregnancy test for female subjects of childbearing age, and agree to take effective contraceptive measures until one year after infusion;
* Participant or his/her guardians agree to participate in the clinical trial and sign the informed consent form indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.

Exclusion Criteria:

* Central nervous system (CNS) diseases: presence of CNS lupus symptoms requiring intervention within 60 days, including epilepsy, confusion, cerebrovascular events, etc;
* Congenital heart disease or severe arrhythmia before screening: Including multifocal and frequent supraventricular tachycardia, ventricular tachycardia, etc.; or complicated with moderate to large pericardial effusion, severe myocarditis, etc.; or patients with unstable vital signs who require vasopressors to maintain blood pressure;
* Presence of active infections requiring systemic treatment or uncontrolled infections within 3 months prior to screening;
* Having received solid organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening; or having grade 2 or above acute graft-versus-host disease (GVHD) within 2 weeks prior to screening;
* Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood hepatitis B virus (HBV) DNA level exceeding the normal range; positive for hepatitis C virus (HCV) antibody with peripheral blood hepatitis C virus (HCV) RNA level exceeding the normal range; positive for human immunodeficiency virus (HIV) antibody; positive for treponema pallidum antibody;
* History of macrophage activation syndrome within 1 month prior to screening (except for those for whom the investigator has determined that safety risks are excluded after treatment);
* History of previous CAR-T therapy (except for those for whom the investigator has determined that safety risks are excluded after treatment);
* Presence of active pulmonary tuberculosis at the time of screening;
* Having received any vaccination within 4 weeks prior to screening;
* Positive result of blood pregnancy test;
* A confirmed diagnosis of malignant diseases such as tumors prior to screening;
* Participation in other clinical trials within 3 months prior to enrollment;
* Other circumstances that the investigator deems inappropriate for participation in this study.

Where this trial is running

Chongqing

• Children's Hospital of Chongqing Medical University — Chongqing, China (Recruiting)

Study contacts

• Study coordinator: Xiaodong Zhao

Conditions Systemic Lupus Erythematosus; CD19; CAR-T