Early Clinical Study of the Safety, Tolerability, Pharmacokinetics, and Effectiveness of STR-P005

Early Clinical Study of the Safety, Tolerability, Pharmacokinetics, and Effectiveness of STR-P005 for the Treatment of Relapsed/Refractory Autoimmune Diseases

This is a single-center, single-arm, open-label, investigator-initiated early exploratory clinical trial designed to evaluate the safety and efficacy of STR-P005 in participants with relapsed/refractory autoimmune diseases.

The study will employ a traditional "3+3" dose-escalation design, with 3 dose groups: XXmg/kg, XXmg/kg, XXmg/kg. Dose Group 1 is the starting dose. This group includes two cohorts, A and B, to optimize the dosing frequency of STR-P005. Cohort A will receive doses Q3D (once every 3 days) on Days 1, 4, 7 (3 doses per cycle), for up to 2 cycles. Cohort B will receive doses Q4D (once every 4 days) on Days 1, 4 (2 doses per cycle), for up to 2 cycles. Based on preliminary safety, efficacy, PK/PD data from Cohorts 1A and 1B, the superior regimen will be selected for escalation to Dose Groups 2 and 3. If no optimal dose is identified after escalating through the 3 dose groups, additional higher doses may be explored after SRC discussion based on all accumulated preliminary safety, efficacy, and PK/PD data to further evaluate the safety and efficacy of STR-P005.

Inclusion Criteria:

• 1. Voluntarily participate and sign informed consent. 2. Age 18 to 75 years (inclusive). 3. Confirmation of positive CD19 expression on peripheral blood B cells by flow cytometry.

  4. Adequate organ function:

  1. Hematology: Absolute neutrophil count (ANC) ≥1.0×10^9^/L, absolute lymphocyte count (ALC) ≥0.1×10^9^/L, hemoglobin ≥80 g/L, platelet count (PLT) ≥50×10^9^/L. Transfusion and growth factors cannot be used within 7 days prior to screening to meet these requirements.

  2. Coagulation: International normalized ratio (INR) ≤1.5 × upper limit of normal (ULN), and activated partial thromboplastin time (APTT) ≤1.5 × ULN.

  3. Liver function: Serum AST, ALT ≤3.0 × ULN, total bilirubin ≤1.5 × ULN (for participants with Gilbert's syndrome, total bilirubin <3.0 × ULN).

  4. Renal function: Serum creatinine ≤1.5 × ULN or creatinine clearance (CrCl) ≥60 mL/min (Cockcroft Gault formula); if renal involvement, CrCl ≥45 mL/min. |

  5. Cardiac function: New York Heart Association (NYHA) class I or II, left ventricular ejection fraction (LVEF) ≥50% by echocardiography (ECHO), and no clinically significant arrhythmia, pericardial effusion, valvular disease, or ischemic heart disease (IHD) within 8 weeks prior to screening.

  6. Oxygen saturation: ≥92% while breathing room air at rest (by pulse oximetry); no clinically significant pleural effusion.

     Exclusion Criteria:

• Participants meeting **ANY** of the following exclusion criteria cannot be enrolled:

  1. Previous treatment with any cellular immunotherapy, unless there is evidence that engineered immune cells have disappeared and B cells are still present in peripheral blood.

  2. Failure to meet the following treatment washout periods:

     1. Use of therapeutic doses of corticosteroids (prednisone ≥20 mg/day or equivalent) within 72 hours before first dose, though topical or inhaled steroids are allowed.
     2. Use of mycophenolate mofetil or its derivatives, azathioprine, calcineurin inhibitors (e.g., tacrolimus, cyclosporine), mTOR inhibitors (e.g., sirolimus, everolimus), JAK inhibitors (e.g., tofacitinib, ruxolitinib, upadacitinib) within at least 2 weeks before screening.
     3. Use of cytotoxic drugs such as cyclophosphamide, methotrexate within at least 3 weeks before screening.
     4. Use of belimumab, B-cell targeting antibodies (e.g., anti-CD20) within at least 1 month or more; anti-cytokine antibodies within at least 2 months; natalizumab, anti-CD52, anti-CD38, ATG within at least 3 months before screening.
     5. Other monoclonal, bispecific, trispecific antibodies, ADCs, or any B-cell depleting drugs must be washed out for 3 months or 5 half-lives (whichever is shorter) before screening.
     6. Undergone plasmapheresis, plasma separation, hemodialysis, IVIG within 2 weeks before screening.

  3. History of ≥ Grade 2 bleeding within 30 days before screening; or requiring long-term continuous use of anticoagulants (e.g., warfarin, low molecular weight heparin, Factor Xa inhibitors), unless INR ≤1.5 × ULN.

  4. Severe renal disease: Severe lupus nephritis within 8 weeks before screening [defined as urine protein >6g/24h or serum creatinine >2.5 mg/dL or 221 μmol/L or CrCl (Cockcroft Gault) <30 mL/min], or active nephritis requiring treatment with prohibited medications, or requiring prednisone >100 mg/day or equivalent corticosteroid therapy for ≥14 days.

  5. Severe pulmonary disease within 3 months before screening, such as moderate-to-severe pulmonary arterial hypertension (mean pulmonary artery pressure >60 mmHg by ECHO), requiring oxygen therapy via mask or non-invasive/invasive mechanical ventilation at screening.

  6. History of lupus crisis within 3 months before screening, such as active CNS lupus, severe hemolytic anemia, severe thrombocytopenic purpura, severe granulocytopenia, severe myocardial injury, severe lupus pneumonitis or pulmonary hemorrhage, severe lupus hepatitis, severe vasculitis, etc.

  7. History or symptoms of active non-lupus-related CNS disease within 6 months before screening (excluding isolated trigeminal nerve disease), including but not limited to: cerebrovascular disease, encephalitis, brain injury, aneurysm, cerebellar disease, organic brain syndrome, Parkinson's disease, etc., as well as symptoms like epilepsy, convulsions, aphasia, dementia.

  8. Occurrence of any of the following cardiovascular diseases within 6 months before screening (including but not limited to):

     1. Congestive heart failure, myocardial infarction, unstable angina, coronary angioplasty, stent implantation, coronary/peripheral artery bypass grafting.
     2. Severe arrhythmias requiring treatment (e.g., sustained ventricular tachycardia, ventricular fibrillation, Torsade de Pointes); congenital long QT syndrome, left anterior hemiblock (bifascicular block), complete left bundle branch block or high-grade AV block; history of severe non-ischemic cardiomyopathy. Asymptomatic right bundle branch block is allowed.
     3. Uncontrolled hypertension (systolic BP >160 mmHg and/or diastolic BP >100 mmHg), history of hypertensive crisis or hypertensive encephalopathy.
     4. Current evidence of active cardiac involvement, such as pericarditis, pericardial effusion, myocarditis.

  9. Active tuberculosis or latent tuberculosis at screening (defined as positive tuberculin skin test or interferon-gamma release assay, without clinical symptoms or radiological evidence).

  10. Positive for HIV antibodies, or HBV-DNA, HCV-RNA, CMV-DNA exceeding assay upper limit of normal at screening.

  11. Presence of uncontrolled fungal, bacterial, viral, or other infections deemed unsuitable for study participation by the investigator.

  12. Presence of uncontrolled diabetes (HbA1c ≥7.0%); uncontrolled thyroid disease (TSH >10 mIU/L or <0.1 mIU/L, and FT4 outside normal range).

  13. History of major organ transplant (e.g., heart, lung, kidney, liver) or allogeneic hematopoietic stem cell transplant within 12 weeks or autologous stem cell transplant within 6 weeks prior to screening.

  14. Congenital immunoglobulin deficiency.

  15. Thrombotic thrombocytopenic purpura (TTP)/thrombotic microangiopathy (TMA).

  16. History of other autoimmune diseases (including but not limited to eosinophilic granulomatosis with polyangiitis, cryoglobulinemic vasculitis, inclusion body myositis, anti-GBM disease, Behçet's disease, or Takayasu's arteritis) requiring systemic treatment, besides the target indication.

  17. Family history of non-IIM conditions such as drug-induced myopathy, HIV-associated myopathy.

  18. Previous or concurrent other active malignancies, including patients with cancer-associated polymyositis/dermatomyositis. Exceptions: cured cervical carcinoma in situ with no recurrence for at least 2 years, non-invasive basal cell or squamous cell skin cancer, radically treated localized prostate cancer, ductal carcinoma in situ of the breast post-mastectomy, and papillary thyroid cancer.

  19. History of hypersensitivity or life-threatening reaction to the study drug or any of its components or formulation ingredients.

  20. Pregnant or breastfeeding women.

  21. Vaccination with any live attenuated vaccine within 6 weeks before first dose, or planned vaccination within 3 months after treatment.

  22. Participation in other interventional clinical studies, received active investigational drug within 3 months before signing ICF, or intention to participate in another clinical trial or receive autoimmune disease treatment outside the protocol during the entire study.

  23. Psychiatric patients with depression or suicidal tendencies.

  24. Other factors deemed by the investigator to make the participant unsuitable for enrollment or unable to complete the study.