CD19/CD22/BCMA CAR‑T (BZE2204) for relapsed or refractory autoimmune diseases

An Exploratory Clinical Study to Evaluate the Safety and Efficacy of BZE2204 CD19/CD22/BCMA CAR-T Cells in Subjects With Relapsed or Refractory Active Autoimmune Diseases

This will test whether a personalized CAR‑T cell therapy (BZE2204) targeting CD19, CD22, and BCMA can help adults with relapsed or refractory IIM, ITP, or SLE.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Shanghai Cell Therapy Group Co.,Ltd (Industry-sponsored)
• Drugs / interventions: CAR-T, chimeric antigen receptor
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07174843 on ClinicalTrials.gov

What this trial studies

This is a single‑arm, open‑label dose‑escalation and expansion trial of autologous CAR‑T cells (BZE2204) that targets CD19, CD22, and BCMA in adults with active relapsed or refractory autoimmune diseases. The primary goal is to characterize safety, tolerability, and to determine a maximum tolerated or recommended dose. Participants undergo screening, apheresis to collect their cells, lymphodepletion and a single CAR‑T infusion on Day 0, followed by close safety monitoring through Month 6 and long‑term follow‑up to Month 12. Secondary measures include pharmacokinetics, pharmacodynamics, and preliminary signals of clinical benefit.

Who should consider this trial

Good fit: Adults aged 18–70 with relapsed or refractory active idiopathic inflammatory myopathies, immune thrombocytopenia, or systemic lupus erythematosus who have adequate organ function and prior treatment failure are the intended candidates.

Not a fit: Patients with stable disease, uncontrolled infections, inadequate bone marrow/organ function, or who cannot tolerate lymphodepletion are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, the therapy could produce sustained reductions in autoimmune activity and reduce or eliminate the need for ongoing immunosuppression in some patients.

How similar studies have performed: Early reports of CD19‑targeted CAR‑T in refractory autoimmune conditions have shown promising remissions, but a triple‑target CD19/CD22/BCMA CAR‑T approach in this population is novel and largely untested.

Eligibility criteria

Major Inclusion Criteria:

1. Males or females, aged 18-70 years old
2. Adequate bone marrow, hepatic, renal, coagulation and pulmonary function defined as:

   * Bone marrow reservation: absolute neutrophil count (ANC) ≥1 ×10\^9/L; absolute lymphocyte count (ALC)≥ 0.5 ×10\^9/L; hemoglobulin ≥80 g/L; platelets ≥50 ×10\^9/L(except for ITP);
   * Hepatic function: i: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 5 upper limit of normal(ULN) (except for elevations are evaluated to be related to autoimmune disease by investigators)and ii: total bilirubin ≤ 2 ULN, (except for Gilbert's syndrome patients, those with total bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN can be enrolled).
   * Renal function: serum creatinine ≤ 1.5 ULN , or estimated glomerular filtration rate(eGFR) ≥ 60 mL/min/1.73m2 \[eGFR=186×age\^-0.203×SCr\^-1.154（mg/dl）,female×0.742\]
   * Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤1.5 ULN
   * Pulmonary function: Have the minimum level of pulmonary reserve, defined as ≤ CTCAE (Common Terminology Criteria for Adverse Events) grade 1 dyspnea and the SaO2(oxygen saturation)≥ 91% on room air
3. Life expectancy \> 6 months
4. Subjects with relapsed or refractory active IIM also need meet following criteria:

   * Subjects with suspected or confirmed dermatomyositis(DM), polymyositis(PM), anti-synthetase syndrome(ASS) and immune-mediated necrotizing myopathy(IMNM, need to be assessed by the investigator that the patient has no safety instability) based on the 2017 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria
   * Positive (+ or above) for at least one myositis-specific antibody (MSA) or myositis-associated antibody (MAA), including anti-TIF-1γ, NXP-2, Mi-2α, Mi-2β, MDA-5, SAE-1/2, SRP, HMGCR, Jo-1, PL-7, PL-12, HA, EJ, OJ, KS, Zo, Tyr, PM-Scl100, PM-Scl75, SSA/Ro-52, SSB/LA, Ku, RNA-PIII, cN1A, etc
   * At screening, the subject must have moderate to severe IIM, defined as manual muscle testing (MMT) ≤ 141 and 2 of the following criteria are met; or CT suggests active interstitial lung disease(ILD)

     1. Physician global activity assessment (PGA) ≥ 2 cm (Visual analogue scale VAS 10 cm);
     2. Patient global activity assessment (PtGA) ≥ 2 cm ( VAS 10 cm scale);
     3. Extramuscular global assessment (Myositis Disease Activity Assessment Tool \[MDAAT\]) ≥ 2.0 cm (VAS 10 cm scale);
     4. Health assessment questionnaire (HAQ) \> 0.25;
     5. Elevation in one or more muscle enzymes (CK, LDH, AST, ALT) is ≥ 1.5 ULN;
   * Lack of efficacy or intolerance to corticosteroids and at least 1 immunosuppressant or biologic agents
5. Subjects with relapsed or refractory active ITP also need meet following criteria

   * Diagnosed with ITP for more than 3 months, including primary ITP and ITP secondary to autoimmune diseases
   * Platelets \<50 ×10\^9/L with at least twice tests(≥24h interval)
   * At least one platelet glycoprotein specific autoantibody positive
   * Lack of efficacy for first line of therapy, or lack of efficacy/relapse post splenectomy
6. Subjects with relapsed or refractory active SLE also need meet following criteria

   * Diagnosed with SLE according to the 2019 EULAR/ACR classification criteria for at least 6 months
   * Positive autoantibodies: antinuclear antibody (ANA) and/or anti-double strand-DNA(dsDNA) antibody and/or anti-Smith(Sm) antibody
   * SLEDAI-2K scores ≥8 at screening. If the scores for low complement and/or anti-ds-DNA antibody are available, the SLEDAI-2K scores for clinical symptoms (except low complement and/or anti-ds-DNA antibody) should be ≥6
   * Proliferative class III or IV , or class III+V or IV+V lupus nephritis(LN) confirmed by biopsies within 12 months; urine protein \> 1.0g/24h or urine protein creatinine ratio (UPCR) \>1000mg/g and PGA\>1
   * Lack of efficacy or intolerance to at least one immunosuppressant and/or one biologic in medical history; for LN patients, relapse during maintenance post induction therapy is also eligible.

Major Exclusion Criteria:

1. A history of severe hypersensitivity or allergic reactions, or contraindications or hypersensitivity to any component of the investigational drug
2. Presence of any serious heart diseases defined in the protocol
3. A medical history of severe central nervous system or symptoms within 6 months
4. Any concurrent malignancy or a history of malignancy with exceptions indicated in the protocol
5. Clinically significant hemorrhage symptoms or definite bleeding tendencies (except for events caused by ITP) within 6 months prior to screening; arteriovenous thrombosis events within 6 months prior to screening
6. Any positive results of contagious diseases as following:

   * Human immunodeficiency virus (HIV) antibody positive;
   * HBsAg positive; or HBcAb/HBeAb positive (subjects with HBV DNA copy numbers below the lower limit of detection can be enrolled);
   * hepatitis C antibody (HCV-Ab) positive (the subjects with HCV RNA below the lower limit of detection can be enrolled) or a known medical history of hepatitis C;
   * Treponema pallidum antibody (TP-Ab) positive
   * Epstein-Barr virus(EBV), cytomegalovirus(CMV) antibody positive and copy number is above the limit
7. Active tuberculosis or latent tuberculosis that has not been adequately treated
8. Evidenced viral, bacterial or fungal infection that is uncontrolled or requires systemic antimicrobial therapy
9. Requirements of wash-out period for specific treatment are not met(detailed in protocol)
10. Subjects with relapsed or refractory active IIM will be excluded in the following situations:

    * Inclusion body myositis, amyopathic dermatomyositis or secondary myositis with documented medical history
    * Severe muscle damage
    * Uncontrolled extra muscle damage relating to PM or DM
11. Subjects with relapsed or refractory active ITP will be excluded if platelet \< 10x10\^9/L with active bleeding or bleeding score ≥5
12. Subjects with relapsed or refractory active SLE will be excluded if the subject has lupus crisis within 3 month, active CNS lupus, severe hemolytic anemia, severe thrombocytopenic purpura etc
13. Any situations evaluated by investigators that may prevent the subjects from participating in the study, or may confound the study results, or participation in this study is not in the best interests of the subjects.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Mengchao Cancer Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Jinxing Lou

Conditions Idiopathic Inflammatory Myopathies; Immune Thrombocytopenia; Systemic Lupus Erythematosus; Autoimmune diseases; SLE; IIM; ITP; CAR-T