Exploratory Clinical Study on the Safety and Efficacy of Anti- CD19/BCMA CAR-NK Cell Injection for the Treatment of Refractory Pediatric Rheumatic Diseases

NCT07490041 | Recruiting Early Phase 1

• 1 other identifier: 2025-SC-0006-P-02
• 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/BCMA CAR-NK cell injection in patients with refractory pediatric rheumatic diseases.

Conditions

Rheumatic Diseases; Pediatric Rheumatological Condition (i.e., Arthritis, SLE, Kawasaki's Disaese); Systemic Lupus Erythematosus (SLE); Connective Tissue Disease-associated Interstitial Lung Disease

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose-Limiting Toxicity (DLT)

  To characterize the safety of anti-CD19/BCMA CAR NK Cells (KN3601) for patients with Refractory Pediatric Rheumatic Diseases.

  up to 28 days after infusion

Secondary Outcomes (2)

• The proportion of subjects who achieved clinical remission, or clinical inactive status at months 3, 6, 9, and 12.

  up to 52 weeks after infusion

• B cell depletion rate

  up to 52 weeks after infusion

Study Arms (1)

Experimental: KN5601

EXPERIMENTAL

Patients will receive Fludarabine and Cyclophosphamide on day-5, -4, and -3. Multiple doses of anti-CD19/BCMA CAR-NK cells (KN5601) will be administered using dose-escalation strategy.

Biological: KN5601

Interventions

KN5601 BIOLOGICAL

Multiple doses of anti-CD19/BCMA CAR-NK cells (KN5601) will be administered using dose-escalation strategy.

Experimental: KN5601

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Gender unrestricted, age ≥5 years;
• The patient or their legal guardian agrees to participate in this clinical trial and signs the informed consent form, indicating their understanding of the trial's purpose and procedures and willingness to participate;
• Peripheral blood B cells confirmed by flow cytometry to express CD19, with a B cell count \>5 cells/uL;
• If previously treated with B cell-targeted therapy, peripheral blood B cell count at screening has returned to normal or above the pre-treatment level;
• Echocardiography indicates basically normal cardiac structure and left ventricular ejection fraction (LVEF) ≥55%; electrocardiogram shows no significant abnormalities;
• Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0×ULN, total bilirubin (TBIL) ≤2.0×ULN;
• Renal function: estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m²; (If eGFR \<30 mL/min/1.73m² and/or undergoing renal replacement therapy, the subject may be considered for enrollment after the investigator's assessment that the benefit outweighs the risk and with full informed consent from the patient/guardian);
• Pulmonary function: No severe pulmonary lesions, blood oxygen saturation (SpO₂) ≥92%;
• Female subjects of childbearing potential must have a negative urine pregnancy test and agree to use effective contraception during the trial until 1 year after infusion.
• Polyarticular Juvenile Idiopathic Arthritis (pJIA):
• Onset before age 16, disease duration ≥6 weeks, diagnosed as polyarticular JIA according to the 2001 International League of Associations for Rheumatology (ILAR) classification criteria, and positive for rheumatoid factor (RF) and/or anti-citrullinated peptide/protein antibody (ACPA): positive on ≥2 occasions at least 3 months apart during the first 6 months of illness;
• Judged by the investigator to have active disease despite adequate standard-dose treatment prior to screening, meeting the following adequacy of treatment conditions: a. Treatment with conventional disease-modifying antirheumatic drugs (DMARDs) for at least 6 months, with stable doses of 2 DMARDs for ≥12 weeks; b. Treatment with at least 2 biologic agents, with stable doses for ≥12 weeks;
• Juvenile Arthritis Disease Activity Score-27 (JADAS-27) \>8.5;
• Must have at least 5 active joints (defined as the presence of joint swelling; or in the absence of swelling, the presence of limited range of motion accompanied by pain on motion and/or tenderness) as per the American College of Rheumatology (ACR) definition at both screening and baseline;
• No occurrence of macrophage activation syndrome within 1 month prior to screening.

You may not qualify if:

• History of malignancy (except for basal cell or squamous cell skin cancer or carcinoma in situof the cervix that has been excised and cured for at least 5 years), or current malignancy.
• Known allergy, hypersensitivity, intolerance, or contraindication to CD19/BCMA CAR-NK cells or any component of the drugs that may be used in the study (including fludarabine, cyclophosphamide, and tocilizumab), or subjects who have experienced a severe allergic reaction in the past.
• Evidence of severe active viral or bacterial infection, or uncontrolled systemic fungal infection at screening or baseline visits, or subjects with active or uncontrolled infection requiring parenteral antimicrobial therapy.
• Subjects with cardiac insufficiency classified as Class III or IV according to the New York Heart Association (NYHA) functional classification (see Appendix).
• Subjects with congenital heart disease, or history of acute myocardial infarction within 6 months prior to screening, or severe arrhythmia (including multifrequent ventricular premature beats, supraventricular tachycardia, ventricular tachycardia, etc.); or combined with moderate to large pericardial effusion, severe myocarditis, etc.; or unstable vital signs requiring vasopressors to maintain blood pressure.
• Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with detectable hepatitis B virus (HBV) DNA levels above the normal reference range in peripheral blood at screening; OR positive hepatitis C virus (HCV) antibody with detectable HCV RNA levels above the normal reference range; OR positive human immunodeficiency virus (HIV) antibody; OR positive syphilis test; OR positive cytomegalovirus (CMV) DNA test.
• History of severe herpes infection, such as herpes encephalitis, ocular herpes, or disseminated herpes; signs of herpes or varicella-zoster virus infection (particularly varicella, herpes zoster) within 12 weeks prior to screening.
• Current active tuberculosis or history of active tuberculosis, or subjects whose interferon-gamma release assay for tuberculosis infection cannot yield a negative result during the screening period.
• Subjects with interstitial lung disease (ILD), meeting any of the following conditions are excluded: Forced vital capacity (FVC) \<50% of predicted value at screening, OR diffusing capacity of the lungs for carbon monoxide (DLCO) \<40% of predicted value; Requiring long-term oxygen therapy or non-invasive ventilation; Acute exacerbation of interstitial pneumonia/acute respiratory failure within the past 6 months, or hospitalization due to ILD requiring intravenous pulse corticosteroid therapy; Rapidly progressive ILD as judged by the investigator.
• Subjects with pulmonary arterial hypertension (PAH), meeting any of the following conditions are excluded: Results from right heart catheterization or echocardiography (non-invasive estimation) meeting any of the following: a. Estimated systolic pulmonary artery pressure (sPAP) \>50 mmHg (assessed in conjunction with tricuspid regurgitation velocity); b. Diagnosis of WHO functional class III or IV PAH.
• Hospitalization within the past 6 months due to acute exacerbation of PAH or right heart failure; Requiring intravenous prostacyclin analog therapy during the screening period; Presence of signs of right ventricular dysfunction, including but not limited to ascites, hepatic congestion, peripheral edema, accompanied by significantly elevated BNP/NT-proBNP levels and clinically unstable symptoms.
• History of epilepsy or other active central nervous system diseases.
• Subjects with acquired or congenital immunodeficiency diseases.
• History of any clinically significant cardiac, endocrine, hematological, hepatic, immunological, metabolic, urological, pulmonary, neurological, dermatological, psychiatric, renal disease, or other major condition that, in the investigator's judgment, precludes the administration of KN5601.
• Solid organ or hematopoietic stem cell transplantation within 3 months prior to screening; OR acute graft-versus-host disease (GVHD) of grade 2 or higher within 2 weeks prior to screening.

Sponsors & Collaborators

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

Study Sites (1)

The Children's Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Rheumatic Diseases; Arthritis; Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Joint Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Meiping Lu

  The Children's Hospital of Zhejiang University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meiping Lu, Prof.

CONTACT

+86-13685773988; 12218532@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: SPONSOR

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: March 24, 2026
• Study Start: March 19, 2026
• Primary Completion (Estimated): December 19, 2026
• Study Completion (Estimated): December 19, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-03

Locations

CN (1)