NCT06469190RecruitingEarly Phase 1
An Exploratory Clinical Study of the Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor NK Cell Injections (KN5501) in the Treatment of Relapsed/Refractory Immune Nephropathy
Conditions
Interventions
Trial Snapshot
- Phase
- Early Phase 1
- Status
- Recruiting
- Sponsor
- Changhai Hospital
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Incidence of Dose-Limiting Toxicity (DLT)
Study Overview
Brief Summary
A single arm, open-label pilot study is designed to determine the safety and effectiveness of anti-CD19 CAR NK cell injection (KN5501) in patients with immune nephropathy. 36 patients are planned to be enrolled in the dose-escalation trial. The primary endpoints are DLT and TEAEs. The secondary endpoints are the overall response rates (ORR) and disease control rate (DCR)
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Common Inclusion Criteria:
- •Age: ≥ 18 years old and ≤ 70 years old, male or female;
- •Positive CD19 expression in peripheral blood B cells as determined by flow cytometry;
- •The functions of important organs meet the following requirements:
- •Bone marrow hematopoietic function: a. White blood cell count ≥ 3 x 10^9/L b. Neutrophil count ≥ 1 x 10^9/L (no colony-stimulating factor treatment within 2 weeks before examination); c. Hemoglobin ≥60g/L.
- •Liver function: ALT ≤ 3 x ULN,AST≤3 x ULN, TBIL≤1.5 x ULN(excluding Gilbert syndrome, total bilirubin ≤ 3.0 x ULN)
- •Coagulation function: International standardized ratio (INR) ≤ 1.5 x ULN, prothrombin time (PT) ≤1.5 x ULN.
- •Cardiac function: good hemodynamic stability, left ventricular ejection fraction (LVEF) ≥55%.
- •Female subjects of childbearing potential and male subjects whose partner is a female of childbearing potential are required to use medically approved contraception or abstain from sex for at least 6 months during and at least 6 months after the end of the study treatment period; female subjects of childbearing potential have had a negative serum HCG test within 7 days prior to study enrollment and are not lactating;
- •Voluntarily participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.
- •Criteria for Recurrent/refractory primary membranous nephropathy
- •Primary membranous nephropathy diagnosed pathologically by renal biopsy;
- •Screening period 24-hour urine protein quantification ≥3.5 g;
- •Individuals who have not achieved partial remission (PR) after more than 6 months of treatment with hormonal and/or cytotoxic drugs, immunosuppressive therapy, and/or biologics (including but not limited to anti-CD20 monoclonal antibody); or individuals who have relapsed again after achieving complete remission/partial remission (CR/PR) with treatment (24h urine protein quantification ≥3.5g);
- •Glomerular filtration rate (eGFR, CKD-EPI formula) ≥45 ml/min/1.73m2 during the screening period.
- •Criteria for Relapsed/refractory IgA nephropathy
- •Primary IgA nephropathy pathologically confirmed by renal biopsy;
- •Treated (ACEI/ARB analogs) for at least 3 months;
- •Treatment with hormonal and/or cytotoxic drugs, immunosuppressive therapy, and/or biologics (including, but not limited to anti-CD20 monoclonal antibody) for more than 6 months, 24-hour urine protein quantification ≥ 1.0 g; or rapid progression of renal function (≥ 50% decrease in eGFR within 3 months); or relapse after treatment to achieve complete remission/partial remission (CR/PR) (24-hour urine protein quantification ≥ 1.0 g);
- •Glomerular filtration rate (eGFR, CKD-EPI formula) ≥30 ml/min/1.73m2 during the screening period.
- •Criteria for Relapsed/refractory ANCA-associated vasculitis
- •Meets 2022 ACR/EULAR diagnostic criteria for ANCA vasculitis, including microscopic polyangiitis, granulomatous polyangiitis, eosinophilic granulomatous polyangiitis;
- •Positive ANCA related antibodies (MPO-ANCA or PR3-ANCA positive);
- •Renal biopsy pathology consistent with renal damage in ANCA-associated vasculitis;
- •The Birmingham Vasculitis Activity Scale (BVAS) is ≥ 15 points (a total score of 63 points), indicating the activity of the vasculitis condition;
- •BVAS score includes at least 2 abnormalities in the renal program;
- •Definition of relapse/refractory : ineffective conventional treatment or relapse of disease activity after remission. Definition of routine treatment: use of glucocorticoids (more than 1 mg/kg/d) and cyclophosphamide for ≥3 months, and any of the following immunomodulatory drugs: antimalarial drugs, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, as well as biological agents such as rituximab and belimumab;
- •Glomerular filtration rate (eGFR, CKD-EPI formula) ≥15 ml/min/1.73m2 during the screening period.
Exclusion Criteria
- •Individuals with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, tozumabs), or subjects with a history of severe allergic reactions;
- •Existence or suspicion of uncontrollable or treatable fungal, bacterial, viral or other infections;
- •Individuals with central nervous system disorders caused by ADs or not caused by ADs (including epilepsy, psychiatric disorders, organic encephalopathy syndromes, cerebrovascular accidents, encephalitis, central nervous system vasculitis);
- •Individuals with relatively serious heart diseases, such as angina pectoris, myocardial infarction, heart failure, and arrhythmia;
- •Subjects with congenital immunoglobulin deficiency;
- •Subjects with malignant tumors (except for non-melanoma skin cancer and in situ cervical, bladder, and breast cancers that have been disease-free for more than 5 years);
- •Subjects with end-stage renal failure;
- •Subjects with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and HBV DNA titer in peripheral blood higher than the upper limit of detection; Patients with positive hepatitis C virus (HCV) antibodies and positive peripheral blood HCV RNA; People who are positive for human immunodeficiency virus (HIV) antibodies; Those who have tested positive for syphilis;
- •Subjects with mental illness and severe cognitive impairment;
- •Subjects who have received other clinical trial treatment within 3 months;
- •Pregnant or intending to conceive women;
- •In the opinion of the investigator, there are other reasons why subjects cannot be included in this study.
- •Exclusion Criteria for Recurrent/refractory primary membranous nephropathy
- •Secondary membranous nephropathy (e.g., hepatitis B, systemic lupus erythematosus, drug-associated, malignancy-associated, etc.), or in combination with other renal diseases confirmed by renal biopsy;
- •Type 1 or type 2 diabetes.
- •Exclusion Criteria for Relapsed/refractory IgA nephropathy
- •Exclude secondary IgA nephropathy, including but not limited to: anaphylactic purpura, ankylosing spondylitis, systemic lupus erythematosus, desiccation syndrome, viral hepatitis, cirrhosis of the liver, rheumatoid arthritis, and mixed connective tissue disease; or in combination with other renal diseases confirmed by renal biopsy;
- •Crescentic nephritis (pathologic diagnosis of >50% crescentic bodies), micrognathic nephropathy with IgA deposition, and other specific types of pathologic or clinical renal disease.
- •Exclusion Criteria for Relapsed/refractory ANCA-associated vasculitis
- •Estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2;
- •If the patient has alveolar hemorrhage invasive lung ventilation is required, estimated to last longer than the screening period.
Arms & Interventions
KN5501
Experimental
Intervention: anti-CD19 CAR NK cells (Biological)
Outcomes
Primary Outcomes
Incidence of Dose-Limiting Toxicity (DLT)
Time Frame: up to 48 weeks after infusion
To characterize the safety of anti-CD19 CAR NK Cells (KN5501) for Relapsed/Refractory Immune Nephropathy
Incidence of Treatment Emergent Adverse Events (TEAEs)
Time Frame: up to 48 weeks after infusion
To characterize the safety of anti-CD19 CAR NK Cells (KN5501) for Relapsed/Refractory Immune Nephropathy
Secondary Outcomes
- The overall response rate (ORR)(1, 3, 6, 12 and 12 months after infusion)
- Disease control rate (DCR)(1, 3, 6, 12 and 12 months after infusion)
- B cell depletion rate(1, 3, 6, 12 and 12 months after infusion)
- B cell reconstitution(1, 3, 6, 12 and 12 months after infusion)
Investigators
Study Sites (1)
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