BCMA- and CD19-directed CAR-T therapy for refractory autoimmune diseases

An Exploratory Clinical Study of Enhanced Autologous CAR-T Cell Injection (ECAR01) Targeting BCMA and CD19 in the Treatment of Refractory Autoimmune Diseases

This treatment will try BCMA- and CD19-targeted CAR-T cells in adults whose autoimmune disease hasn't responded to standard therapies.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Anhui Provincial Hospital (other gov)
• Drugs / interventions: methotrexate, cyclophosphamide, fludarabine, prednisone, CART, CAR-T, chemotherapy
• Locations: 1 site (Hefei)
• Trial ID: NCT07052565 on ClinicalTrials.gov

What this trial studies

This open-label, single-center, single-arm 3+3 dose-escalation protocol will enroll up to 18 adults with refractory autoimmune diseases. After peripheral blood collection and lymphodepleting chemotherapy, participants receive a one-time intravenous infusion of ECAR01 CAR-T cells targeting BCMA and CD19 at one of three dose levels (1×10^5/kg, 3×10^5/kg, 6×10^5/kg) with a ±20% allowable variation. Investigators may adjust dosing based on individual conditions, and safety, tolerability, and clinical response are monitored through scheduled follow-up visits. Findings from this study will inform safety and preliminary efficacy for dual-target CAR-T in autoimmune disease.

Who should consider this trial

Good fit: Adults (≥18) with refractory autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, or dry syndrome (Sjӧgren-like) who have not responded to conventional and biologic DMARDs and meet organ-function and safety criteria are the intended candidates.

Not a fit: People with well-controlled disease, active infections, significant organ dysfunction, pregnancy, or who do not meet the study's inclusion/safety criteria are unlikely to receive benefit and may be excluded.

Why it matters

Potential benefit: If successful, this approach could induce durable remission or substantially reduce disease activity in patients with autoimmune conditions that have failed standard treatments.

How similar studies have performed: Early case reports and small trials of anti-CD19 CAR-T have shown promising remissions in severe autoimmune disease, but dual BCMA/CD19 targeting is relatively novel and not yet validated in larger studies.

Eligibility criteria

Inclusion Criteria:

* ( 1) At the time of signing the informed consent form, be at least 18 years of age, both male and female.

  (2) Bone marrow hematopoietic function satisfies: white blood cell count≥3×10\^9/L; Centrocyte count ≥1×10\^9/L (no colony-stimulating factor received within 2 weeks prior to screening); Hemoglobin ≥ 60g/L.

  (3)ALT≤3×ULN; AST≤3×ULN； TBIL≤3×ULN。 (4) Renal function satisfaction: creatinine clearance CrCl≥30mL/min. (5) INR≤1.5×ULN , PT≤1.5×ULN. (6)RA:Documented diagnosis of RA which fulfills the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria ; 3 months after use of 1 or more csDMARDs and 1 or more bDMARDs prior to screening: 1) DAS28-ESR\>3.2 or CDAI\>10; or 2) the dose of the hormone (prednisone or equivalent) cannot be reduced to less than 7.5 mg/day; or 3) the number of swollen and/or tender joints ≥3; Treatment with stable 1 or more cs DMARD(s) and/or bDMARDs prior to enrollment as follows: methotrexate for at least 12 weeks and at a dose of 7.5-25mg/week for at least 4 weeks; Stable use of hydroxychloroquine dose ≤ 400 mg/day for at least 4 weeks; Stable oral sulfasalazine for at least 4 weeks 1\~3 g/d; Stable oral leflunomide 10-20 mg/day for at least 4 weeks.

  (7)systemic lupus erythematosus : Diagnosis of systemic lupus erythematosus according to the SLE classification criteria of the 2019 EULAR/ACR; History of systemic lupus erythematosus for at least 6 months prior to screening and active disease for 2 months after use of standard treatment regimens prior to screening; BILAG-2004 assesses the presence of at least 1 Grade A or 2 Grade B organ scores; Positive antinuclear antibody, or positive anti-ds-DNA antibody, or positive anti-Sm antibody; SLEDAI-2000 score ≥8 during the screening period.

  (8)Sjögren's syndrome : Diagnosis of Sjögren's syndrome according to the 2002 International Classification of Primary Sjögren's Syndrome or the 2016 ACR/EULAR classification criteria; Diagnosed with pSS-TP and platelet count \< 30×10\^9/L; Sjögren's syndrome Disease Activity Index (ESSDAI) score ≥5 during the screening period; Sjögren's syndrome for at least 6 months prior to screening and active disease 2 months after use of conventional treatment regimens prior to screening. Use of immunomodulatory drugs for more than 6 months.

  (9)systemic sclerosis : Diagnosis of systemic sclerosis according to the 2013 ACR classification criteria for systemic sclerosis. Positive antinuclear antibody at screening. Presence of clear evidence of HRCT progression. History of systemic sclerosis prior to screening for at least 6 months and active disease for 2 months after use of conventional treatment regimens prior to screening.

Exclusion Criteria:

* (1) Clinically significant central nervous system diseases or pathological changes not caused by the disease itself before screening, including but not limited to: stroke, stroke, aneurysm, epilepsy, convulsions, aphasia, severe head injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome or mental disorder.(2) Those with relatively serious heart disease, such as angina, myocardial infarction, heart failure and arrhythmia.(3) History of major organ transplantation or hematopoietic stem cell/bone marrow transplantation.(4) Vaccination, B-cell targeted therapy within 4 weeks prior to screening.(5) History of any malignant neoplastic disease.(6) Patients with end-stage renal failure.(7) The presence or suspicion of uncontrollable fungal, bacterial, viral, or other infections.(8) History of severe allergy to drugs used in clinical studies or raw and excipient materials of experimental drugs, such as cyclophosphamide, fludarabine, DMSO, etc.(9) Patient has active HBV infection or HCV antibody positivity or HIV antibody positivity or syphilis positivity or CMV DNA positivity or EBV DNA positivity.(10) Pregnant or lactating females, or planning to become pregnant within 2 years after reinfusion of the trial drug; The partner of the male patient plans to become pregnant within 2 years of receiving the trial drug.(11) Evidence of active tuberculosis infection.(12) Other conditions assessed by the investigator as unsuitable for enrollment.

Where this trial is running

Hefei

• Anhui Provincial Hospital — Hefei, China (RECRUITING)

Study contacts

• Principal investigator: wang xing bing, M.D — Anhui Provincial Hospital
• Study coordinator: chen zhu, M.D

Conditions: Autoimmune Diseases, systemic sclerosis, dry syndrome, rheumatoid arthritis, systemic lupus erythematosus