Exploratory Clinical Study of Second-generation CD19/BCMA Chimeric Antigen Receptor NK Cell Injection in Treating Paediatric B Cell-related Autoimmune Diseases

NCT07283315 | Recruiting Early Phase 1

• 1 other identifier: 2025-SC-0007-P-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluating the efficacy and safety of anti-CD19/BCMA CAR-NK Cells in Paediatric B cell-related autoimmune diseases

Conditions

Autoimmune Diseases; Paediatric B Cell-related Autoimmune Diseases; CAR

Outcome Measures

Primary Outcomes (3)

• Incidence and severity of dose-limiting toxicity (DLT) and treatment-emergent adverse events (TEAEs)

  The safety of CAR-NK cell therapy in patients with B cell mediated autoimmune disease

  1 month

• response rate

  The Efficacy of CAR-NK cell therapy in patients with SLE, MDR-SRNS, IgA nephropathy, or ANCA-AAV

  3 month

• CRISS score

  The Efficacy of CAR-NK cell therapy in patients with Systemic Sclerosis

  3 month

Secondary Outcomes (1)

• Complete response or partial response rate

  6 month

Study Arms (1)

anti-CD19/BCMA CAR NK cells

EXPERIMENTAL

Biological: anti-CD19/BCMA CAR NK cells (KN5601-K)

Interventions

anti-CD19/BCMA CAR NK cells (KN5601-K) BIOLOGICAL

The study adopted a dose-escalation and expansion study design. All subjects will receive fludarabine/ cyclophosphamide lymphodepletion followed by anti-CD19/BCMA CAR NK cells infusion.

anti-CD19/BCMA CAR NK cells

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent: The participant (and guardian if the participant is a minor) must provide written informed consent, indicating understanding of the study purpose and procedures and willingness to participate.
• Cardiac Function: Echocardiography shows no significant structural abnormalities and left ventricular ejection fraction (LVEF) ≥ 55%.
• Hepatic Function: ALT ≤ 3 × ULN (except when elevation is attributable to inflammatory myopathy); AST ≤ 3 × ULN (except when elevation is attributable to inflammatory myopathy); Total bilirubin ≤ 2.0 × ULN (≤ 3.0 × ULN allowed for Gilbert syndrome).
• Renal Function: eGFR ≥ 30 mL/min/1.73 m².(Participants with eGFR \< 30 mL/min/1.73 m² and/or those receiving renal replacement therapy may be considered eligible if, in the investigator's judgment, the potential benefit outweighs the risk and the participant or guardian provides fully informed consent.)
• Pulmonary Function: No severe pulmonary disease, and SpO₂ ≥ 92%.
• Women of childbearing potential must use medically acceptable contraception or practice abstinence during the study treatment period and for at least 12 months after the end of study treatment.
• SLE:
• Age ≥ 5 years.
• Meets the 2012 SLICC or 2019 EULAR/ACR classification criteria for SLE.
• Must meet at least one of the following adequate treatment conditions:
• Treated with glucocorticoids (≥1 mg/kg/day prednisone or equivalent) plus one or more immunomodulatory agents (including cyclophosphamide, MMF, azathioprine, methotrexate, cyclosporine, tacrolimus, sirolimus, leflunomide, thalidomide, belimumab, or rituximab) for at least 3 months.
• Patients unable to tolerate conventional therapy may be eligible if, in the investigator's judgment, the potential benefit outweighs the risk and the participant (or guardian if minor) provides fully informed consent.
• Patients who cannot taper glucocorticoids to ≤5 mg/day after 6 months of conventional therapy.
• SLE disease activity: SLEDAI-2K score ≥ 6.
• No occurrence of macrophage activation syndrome within 1 month prior to screening.

You may not qualify if:

• Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, tocilizumab), or subjects with a history of severe allergic reactions.
• Uncontrollable infection, or active infection that requires systemic treatment at screening.
• Subjects with grade III or IV heart failure (NYHA classification).
• Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs.
• Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; Or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilis test positive; Or cytomegalovirus (CMV) DNA test positive.
• History of severe herpes infection prior to screening, such as herpetic encephalitis, ocular herpes, or disseminated herpes; Signs of herpes or varicella-zoster virus infection (especially chickenpox, shingles) within 12 weeks prior to screening.
• Patients with active central nervous system disease.
• Patients with malignant diseases such as tumors before screening.
• Secondary or congenital immunodeficiency.
• History of any cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal disease or other major medical condition that would prevent the administration of KN5601-K, except for lupus.
• Received solid organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening; Acute graft-versus host disease (GVHD) of grade 2 or above was present within 2 weeks prior to screening.
• Received live vaccine within 4 weeks before screening.
• Tested positive in Blood pregnancy test.
• Patients who had participated in other clinical trials and received any intervention within 3 months before enrollment.
• Any situation judged by the investigators that may increase the risk of the subjects or interfere with the clinical trial outcome

Sponsors & Collaborators

• The Children's Hospital of Zhejiang University School of Medicine: lead
• Rui Therapeutics: collaborator

Study Sites (1)

Children's Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310052, China

RECRUITING

MeSH Terms

Conditions

Autoimmune Diseases

Condition Hierarchy (Ancestors)

Immune System Diseases

Central Study Contacts

Jianhua Mao, Ph.D

CONTACT

13516819071; maojh88@zju.edu.cn

Qiuyu Li, Ph.D

CONTACT

17794588355; liqiuyu1992@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 1, 2025
• First Posted: December 15, 2025
• Study Start: December 3, 2025
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2029
• Last Updated: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)