An Exploratory Clinical Study of CD19 CAR NK Cell Injection for the Treatment of Relapsed/Refractory Autoimmune Diseases

NCT06464679 | Recruiting Phase 1 DMC

• 1 other identifier: CHEC2024-181
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

A single arm, open-label pilot study is designed to determine the safety and effectiveness of CD19 CAR NK cells in patients with autoimmune diseases. 36-72 patients are planned to be enrolled in the dose-escalation trial. The primary objective of the study was to evaluate the safety and feasibility of CD19 CAR-NK cells for the treatment of patients with autoimmune diseases. The secondary objective is to evaluate the efficacy of CD19 CAR-NK cells in patients with autoimmune diseases.

Conditions

Autoimmune Diseases

Outcome Measures

Primary Outcomes (2)

• Incidence of Dose-Limiting Toxicity (DLT)

  To characterize the safety of CD19 CAR NK Cells (KN5501) for Relapsed/Refractory autoimmune diseases

  up to 48 weeks after infusion

• Incidence of Treatment Emergent Adverse Events (TEAEs)

  To characterize the safety of CD19 CAR NK Cells (KN5501) for Relapsed/Refractory autoimmune diseases

  up to 48 weeks after infusion

Secondary Outcomes (2)

• The overall response rate (ORR)

  Time Frame: 1, 3, 6, 12 and 12 months after infusion

• Disease control rate (DCR)

  Time Frame: 1, 3, 6, 12 and 12 months after infusion

Study Arms (1)

CD19 CAR NK cells

EXPERIMENTAL

Biological: anti-CD19 CAR NK cells

Interventions

anti-CD19 CAR NK cells BIOLOGICAL

Patients will receive Fludarabine (25 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) on day -5, -4, and -3. Multiple doses of CD19 CAR NK cells will infused using the dose-escalation strategy.

CD19 CAR NK cells

Eligibility Criteria

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

You may qualify if:

• Age: ≥ 18 years old and ≤ 65 years old, male or female;
• The functions of important organs meet the following requirements:
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• Bone marrow hematopoietic function needs to meet: 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) (No requirements for conditions caused by the disease itself);
• Renal function: creatinine clearance rate (CrCl) ≥ 60 ml/minute(Cockcroft/Fault formula);
• Coagulation function: International standardized ratio (INR) \< 1.5 x ULN,prothrombin time(PT) \< 1.5 x ULN;
• Cardiac function: Good hemodynamic stability. 3. 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; 4. Voluntarily participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.
• Meets 2002 AECG criteria or 2016 ACR/EULAR classification criteria for primary dry syndrome (pSS);
• Definition of disease activity: investigator-assessed disease ESSDAI score of 5 or higher;
• Definition of relapsed and refractory disease: ineffective conventional treatment or relapse of disease activity after remission. Definition of routine treatment: Use of glucocorticoids (above 1mg/Kg/d) and cyclophosphamide, as well as any of the following immunomodulatory drugs for more than 6 months: antimalarials, methotrexate, leflunomide, cyclophosphamide, azathioprine, mertiomate, tacrolimus, cyclosporine, and biologics, including rituximab, belimumab and tetracycline;
• Meets 2013 ACR classification criteria for systemic sclerosis;
• If combined with interstitial pneumonia, interstitial changes suggestive of ground-glass exudates on chest HRCT and FVC or DLCO \<70% predictive value on pulmonary function tests;
• IDefinition of relapsed and refractory disease: ineffective conventional treatment or relapse of disease activity after remission. Definition of routine treatment: use of glucocorticoids and one or more immunomodulatory drugs for more than 6 months, including antimalarials, methotrexate, leflunomide, cyclophosphamide, azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, and tetanuscept;
• Definition of progressiveness; 1) Definition of cutaneous progression: increase in mRSS \>10%; 2) Definition of lung disease progression: 10% decrease in FVC or 5% decrease in FVC with 15% decrease in DLCO (OMERACT progression).

You may not qualify if:

• \. Subjects 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; 2. Subjects with active or suspected fungal, bacterial, viral, or other infections that are uncontrolled or require treatment; 3. Subjects with central nervous system disorders due to autoimmune diseases or non-autoimmune diseases(including epilepsy, psychosis, organic encephalopathy syndromes, cerebrovascular accidents, encephalitis, central nervous system vasculitis); 4. Subjects with relatively serious heart diseases, such as angina pectoris, myocardial infarction, heart failure, and arrhythmia; 5. Subjects with congenital immunodeficiency diseases; 6. 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); 7. Subjects with end-stage renal failure; 8. SSubjects 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; subjects with positive hepatitis C virus (HCV) antibodies and positive peripheral blood HCV RNA; subjects with positive human immunodeficiency virus (HIV) antibodies; subjects with positive for syphili; 9. Subjects with mental illness and severe cognitive impairment; 10. Subjects who have received other clinical trial treatment within 3 months; 11. Pregnant or intending to conceive women; 12. In the opinion of the investigator, there are other reasons why subjects cannot be included in this study.
• Combined cirrhosis of the liver;
• Combination of aplastic anemia (AA), myelodysplastic syndrome (MDS), or other myeloproliferative disease (MPD).
• Drug-induced myositis;
• Tumor-associated myositis (myositis occurring within 2 years of tumor diagnosis).
• Functional status of rheumatoid arthritis graded at level 4 according to ACR.

Sponsors & Collaborators

• Changhai Hospital: lead
• Rui Therapeutics: collaborator

Study Sites (1)

Changhai Hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Autoimmune Diseases

Condition Hierarchy (Ancestors)

Immune System Diseases

Central Study Contacts

Dongbao Zhao, Dr

CONTACT

+86-15921061314; dongbaozhao@163.com

Study Design

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

Study Record Dates

• First Submitted: June 13, 2024
• First Posted: June 18, 2024
• Study Start: June 27, 2024
• Primary Completion: December 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: August 29, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)