Immune Thrombocytopenia (ITP)
Conditions
Brief summary
Primary Objective: To evaluate the safety and efficacy of CHT105 Injection in subjects with relapsed/refractory autoimmune diseases. Secondary Objective:To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of CHT105 Injection. Indication: Immune Thrombocytopenia (ITP)
Interventions
DRUGCHT105
Single-dose administration and Multiple-dose administration, administered dose：2\*10\^8 CAR-T cells,6\*10\^8 CAR-T cells,1.8\*10\^9 CAR-T cells,3.6\*10\^9 CAR-T cells.
Sponsors
Nanjing Miracle Biotechnology Co., Ltd.
The First Affiliated Hospital of Nanchang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 and ≤65 years (inclusive), no restriction on gender; 2. Positive expression of CD19/CD70 on peripheral blood B-cells as determined by flow cytometry; 3. Key organ functions shall meet the following requirements: 1). Bone marrow function: a. Absolute neutrophil count ≥1×10⁹/L (no colony-stimulating factor therapy within 2 weeks prior to testing, except for neutropenia caused by underlying disease); b. Hemoglobin ≥60 g/L; 2). Liver function: ALT ≤3×ULN (except for ALT elevation due to underlying disease); AST ≤3×ULN (except for AST elevation due to underlying disease); TBIL ≤1.5×ULN (except for TBIL elevation due to underlying disease); 3). Renal function: Creatinine clearance (CrCl) ≥30 mL/min (calculated by the Cockcroft-Gault formula, except for decreased CrCl caused by underlying disease); 4). Coagulation function: International Normalized Ratio (INR) ≤1.5×ULN; Prothrombin Time (PT) ≤1.5×ULN; 5). Cardiac function: Good hemodynamic stability; 4.Female subjects of child-bearing potential and male subjects with partners of child-bearing potential must use medically-accepted contraceptive measures or practice abstinence during study treatment and for at least 6 months after the end of study treatment. Female subjects of child-bearing potential must have a negative serum HCG test result within 7 days prior to study enrollment and shall not be lactating; 5.Voluntarily participate in this clinical study, provide signed informed consent, have good compliance, and be willing to comply with follow-up procedures. 6.Diagnosed with relapsed/refractory immune thrombocytopenia (ITP) according to the 2009 International Working Group (IWG) consensus criteria; 7.latelet count \<50×10⁹/L on at least two consecutive occasions. In addition, peripheral blood smear findings shall support the diagnosis of ITP, with no evidence indicating alternative causes of thrombocytopenia (e.g., pseudothrombocytopenia, myelofibrosis). Physical examination findings shall reveal no diseases other than ITP that may cause thrombocytopenia; 8.Subjects shall have received one or more prior therapies for ITP (including but not limited to glucocorticoids, immunoglobulins, azathioprine, danazol, cyclophosphamide and/or rituximab); 9.Subjects must have either a response to one prior ITP therapy (platelet count \>50×10⁹/L) within the past 3 years, or bone marrow findings consistent with ITP, to rule out myelodysplastic syndrome (MDS) or other alternative causes of thrombocytopenia; 10.Subjects shall have Prothrombin Time (PT) not exceeding ±3 seconds relative to the normal reference range (or the International Normalized Ratio \[INR\] within 80%-120% of the normal range); activated partial thromboplastin time (aPTT) not exceeding ±10 seconds relative to the normal reference range; and no history of hypercoagulable state.
Exclusion criteria
1. Subjects with a severe history of drug allergy or allergic diathesis; 2. Presence or suspicion of uncontrolled or treatable fungal, bacterial, viral or other infections; 3. Subjects with intolerable cardiac function; 4. Subjects with congenital immunoglobulin deficiency; 5. History of malignant neoplasm within the past 5 years; 6. Subjects with end-stage renal failure; 7. Subjects positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA titer above the upper limit of detection; subjects positive for hepatitis C virus (HCV) antibody with detectable peripheral blood HCV RNA; subjects positive for human immunodeficiency virus (HIV) antibody; subjects with positive syphilis test; 8. Presence of psychiatric disorders and severe cognitive impairment; 9. Participation in another clinical trial within 3 months prior to enrollment; 10. Use of disease-modifying immunosuppressive agents within five half-lives prior to enrollment, or use of biological agents (including but not limited to mycophenolate mofetil, methotrexate, leflunomide, belimumab, etc.) within 4 weeks prior to enrollment; 11. Female subjects who are pregnant or planning to become pregnant; 12. Subjects whom the investigator considers ineligible for enrollment for any other reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Types, severity, and frequency of adverse events (AEs) | Throughout the study period, up to 52 weeks. |
| Complete response rate and partial response rate | Week 12，Week 24 |
Secondary
| Measure | Time frame |
|---|---|
| Peripheral blood CAR copy number | Day 1,Day 4,Day 7,Day 10,Day 21 |
| Peripheral blood lymphocyte subsets | Day 1,Day 4,Day 7,Day 10,Week 2,Week 3,Week 4,Week 8,Week 12,Week 24,Week 36,Week 52 |
| Autoantibodies | Day 1,Day 7,Week 2,Week 3,Week 4,Week 8,Week 12,Week 24,Week 36,Week 52 |
Countries
China
Contacts
CONTACTChao Dai
Outcome results
None listed