Study of CD19 CAR-T Therapy for Refractory SLE

Official title

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

Overview

This is an investigator-initiated trial aimed at assessing the safety and efficacy of PTOC1 cells Injection in the treatment of refractory systemic lupus erythematosus.

Detailed description

Systemic lupus erythematosus (SLE) is a serious autoimmune disease that can lead to extensive damage in multiple organs and systems, ultimately resulting in disability and even death.

Currently, the primary treatment for SLE relies on glucocorticoids and immunosuppressants to alleviate symptoms. However, due to the absence of a curative treatment, patients typically need to remain on medication indefinitely. In recent years, biological agents such as belimumab and rituximab have been introduced for the treatment of SLE, but these treatments cannot completely eliminate autoimmune B cells in the bone marrow, leading to unsatisfactory overall outcomes. In addition, discontinuing these drugs can lead to disease relapse, and patients still face the challenges of lifelong medication and an incurable disease.

CAR-T therapy is an adoptive cell therapy that uses genetic modification technology to reprogram T cells and eliminate target cells expressing disease-related antigens through antigen-specific recognition. Clinical studies have demonstrated that CD19-targeted CAR-T cells hold significant therapeutic potential for SLE. Compared with traditional CAR-T cells, PTOC1 cells Injection, relying on an innovative CAR-T manufacturing system, can be produced in an extremely short period of time (with a preparation time of only 10 minutes).

The purpose of this study is to assess the safety and efficacy of PTOC1 cells Injection in the treatment of refractory SLE.

Interventions

• Biological PTOC1
  Three dose groups (1.5×10\^5/kg, 5×10\^5/kg,1×10\^6/kg) were set up, starting from the low dose group climbing to explore the safe and effective dose.

Primary outcome measures

• The safety of PTOC1 cell therapy in patients with refractory SLE [Safety] [Time frame: 3 months]
• The changes in SLEDAI-2K from baseline [efficacy] [Time frame: 6 months]
• The changes in PGA from baseline [efficacy] [Time frame: 6 months]
• The changes in BILAG-2004 from baseline [efficacy] [Time frame: 6 months]
• The number of patients with SRI-4 response [efficacy] [Time frame: 3 months]
• The number of patients with LLDAS [efficacy] [Time frame: 6 months]
• The number of patients with DORIS [efficacy] [Time frame: 6 months]

Secondary outcome measures (9)

• Cmax of PTOC1 cells [PK parameter] [Time frame: 3 months]
• Tmax of PTOC1 cells [PK parameter] [Time frame: 3 months]
• AUC28d/90d of PTOC1 cells [PK parameter] [Time frame: 3 months]
• The degree of B cell depletion [PD parameter] [Time frame: 3 months]
• The concentration of IL-6 [PD parameter] [Time frame: 3 months]
• The concentration of CRP [PD parameter] [Time frame: 3 months]
• The concentration of ferritin [PD parameter] [Time frame: 3 months]
• The proportion of major B-cell subtypes [Time frame: 6 months]
• The correlation between the proportion of major B-cell subtypes and the reduction of disease activity [Time frame: 6 months]

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:

• cardiac function: left ventricular ejection fraction (LVEF) ≥ 50%, with no obvious abnormalities on electrocardiogram (ECG);
• renal function: eGFR ≥ 30 mL/min/1.73m2;
• hepatic function: AST and ALT ≤ 3.0×ULN, total bilirubin ≤ 2.0×ULN;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Children's Hospital of Chongqing Medical University — Chongqing

Identifiers

NCT: NCT07403097 · PBC098

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗