An Exploratory Clinical Study of Anti-CD19 CAR NK Cell (KN5501) in the Treatment of Relapsed/Refractory Immune Nephropathy

NCT06469190 | Recruiting Early Phase 1

• 1 other identifier: CHEC2024-188
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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)

Conditions

Nephropathy

Outcome Measures

Primary Outcomes (2)

• Incidence of Dose-Limiting Toxicity (DLT)

  To characterize the safety of anti-CD19 CAR NK Cells (KN5501) for Relapsed/Refractory Immune Nephropathy

  up to 48 weeks after infusion

• Incidence of Treatment Emergent Adverse Events (TEAEs)

  To characterize the safety of anti-CD19 CAR NK Cells (KN5501) for Relapsed/Refractory Immune Nephropathy

  up to 48 weeks after infusion

Secondary Outcomes (4)

• 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

Study Arms (1)

KN5501

EXPERIMENTAL

Biological: anti-CD19 CAR NK cells

Interventions

anti-CD19 CAR NK cells BIOLOGICAL

Patients will receive Fludarabine (30 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) on day -5, -4, and -3. Multiple doses of anti-CD19 CAR NK cells (KN5501) will infused in each group using the "3 + 3" dose-escalation strategy.

KN5501

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.
• 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;

Sponsors & Collaborators

• Changhai Hospital: lead
• Rui Therapeutics Co., Ltd: collaborator

Study Sites (1)

Shanghai Changhai hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Kidney Diseases

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Central Study Contacts

Qi Bian, M.D.

CONTACT

+862131161418; angelbq@126.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2024
• First Posted: June 21, 2024
• Study Start: June 21, 2024
• Primary Completion: June 20, 2025
• Study Completion (Estimated): June 20, 2026
• Last Updated: April 30, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)