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

An Exploratory Clinical Study of the Safety and Efficacy of CD19 Chimeric Antigen Receptor NK Cell Injection for the Treatment of Relapsed/Refractory Autoimmune Diseases

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.

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Diseases
• Intervention / Treatment: Biological: anti-CD19 CAR NK cells

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Dongbao Zhao, Dr; Phone Number: +86-15921061314; Email: dongbaozhao@163.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Changhai Hospital
    • Contact: Dongbao Zhao, Dr; Phone Number: +86-15921061314; Email: dongbaozhao@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Common inclusion criteria:

1. Age: ≥ 18 years old and ≤ 65 years old, male or female;
2. The functions of important organs meet the following requirements:

1. 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;
2. 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);
3. Renal function: creatinine clearance rate (CrCl) ≥ 60 ml/minute(Cockcroft/Fault formula);
4. Coagulation function: International standardized ratio (INR) < 1.5 x ULN,prothrombin time(PT) < 1.5 x ULN;
5. 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.

Inclusion Criteria for Relapsing refractory dry syndrome:

1. Meets 2002 AECG criteria or 2016 ACR/EULAR classification criteria for primary dry syndrome (pSS);
2. Definition of disease activity: investigator-assessed disease ESSDAI score of 5 or higher;
3. 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;

Inclusion criteria for Systemic Sclerosis:

1. Meets 2013 ACR classification criteria for systemic sclerosis;
2. 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;
3. 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;
4. 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).

Inclusion criteria for Recurrent refractory idiopathic inflammatory myopathy:

1. Classification criteria for inflammatory myopathy in accordance with 2017 EULAR/ACR (including DM, PM, ASS, and NM);
2. For those with muscle involvement, the MMT-8 score is lower than 142 and at least two abnormalities are found in the following five core measurements (PhGA, PtGA, or extramuscular disease activity score ≥ 2 points; total HAQ score ≥ 0.25; muscle enzyme levels are 1.5 times the upper limit of the normal range);
3. Positive myositis antibodies;
4. 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.

Inclusion criteria for relapsing refractory rheumatoid arthritis:

1. Meets the diagnostic criteria of the 2010 ACR/EULAR classification. Diagnosis of moderately or severely active rheumatoid arthritis with a previous diagnosis of rheumatoid arthritis ≥ 6 months;
2. A swollen joint count of ≥ 6 (based on 66 joint counts) and a tender joint count of ≥ 6 (based on 68 joint counts) during the Screening Period;
3. C-reactive protein (CRP) ≥ 10 mg/L or erythrocyte sedimentation rate (ESR) ≥ 28 mm/h during the Screening Period;
4. EULAR definition of refractory rheumatoid arthritis:

1. Failure of treatment according to EULAR recommended guidelines and failure of treatment with ≥2 b/tsDMARDs despite failure of treatment with csDMARDs. (i) unless treatment with bDMARDs/tsDMARDs is limited due to socioeconomic factors; and (ii) if treatment with csDMARDs is contraindicated, then failure of treatment with ≥2 b/tsDMARDs of different mechanisms also fulfills the condition);
2. Symptom management of RA is considered problematic by both the patient and the physician;

3. Signs suggestive of active or progressive disease if at least 1 of the following 5 items is met

   1. At least moderate disease activity (DAS28-ESR >3.2 or CDAI >10);
   2. Signs and/or symptoms suggestive of active disease;
   3. Inability to reduce glucocorticoids to less than 7.5 mg/day prednisone or equivalent;
   4. Rapid imaging progression (1-year increase of ≥5 points in van der Heijde modified Sharp score);
   5. Decreased quality of life due to RA, although RA is well controlled;
   6. Refractory rheumatoid arthritis is diagnosed if three of the above criteria are met.

Common exclusion criteria:

1. 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.

Exclusion criteria for relapsing refractory dry syndrome:

1. Combined cirrhosis of the liver;
2. Combination of aplastic anemia (AA), myelodysplastic syndrome (MDS), or other myeloproliferative disease (MPD).

Exclusion criteria for recurrent refractory idiopathic inflammatory myopathies:

1. Drug-induced myositis;
2. Inclusion body myositis;
3. Tumor-associated myositis (myositis occurring within 2 years of tumor diagnosis).

Exclusion criteria for relapsed refractory rheumatoid arthritis:

Functional status of rheumatoid arthritis graded at level 4 according to ACR.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CD19 CAR NK cells	Biological: anti-CD19 CAR NK cells; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
The overall response rate (ORR)	To characterize the efficacy of CD19 CAR NK Cell (KN5501) for Relapsed/Refractory autoimmune diseases	Time Frame: 1, 3, 6, 12 and 12 months after infusion
Disease control rate (DCR)	To characterize the efficacy of CD19 CAR NK Cell (KN5501) for Relapsed/Refractory autoimmune diseases	Time Frame: 1, 3, 6, 12 and 12 months after infusion

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Collaborators: Rui Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2024
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: June 13, 2024
• First Submitted That Met QC Criteria: June 13, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases
• Other Study ID Numbers: CHEC2024-181

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No