Anti-CD19 IL-10 CAR-NK Cells in Refractory/Relapsed Autoimmune Diseases

Not Applicable

Recruiting

• Conditions: Systemic Sclerosis (SSc); ANCA Associated Vasculitis (AAV); Idiopathic Inflammatory Myopathy (IIM); Sjogren's Syndrome; Antiphospholipid Syndrome
• Interventions: Drug: anti-CD19 CAR-NK cells

• Registration Number: NCT06614270
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary

This study is a single-center, open-label, single-arm, dose-escalation trial. The aim of this study is to investigate the safety and efficacy of anti-CD19 IL-10 CAR-NK cells in patients with refractory/relapsed autoimmune diseases, including systemic sclerosis, idiopathic inflammatory myositis, ANCA associated vasculitis, sjogren syndrome, and antiphospholipid syndrome.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-09-24
• Study First Submitted QC: 2024-09-24
• Study First Posted: 2024-09-26
• Study Start: 2025-01-06
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-11
• Primary Completion: 2026-01-06
• Study Completion: 2027-01-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

1. Combined with other connective tissue diseases;
2. Involvement of important organs: heart (individuals with more severe heart disease, such as angina, myocardial infarction, heart failure, and arrhythmias), kidney (eGFR < 15 ml/min/1.73m2), liver (ALT>3×ULN, AST>3×ULN, TBIL >1.5×ULN), lung (FVC<50% predicted or hemoglobin-corrected DLCO<40% predicted), hematologic (leukocyte < 2.5×109/L, neutrophil count <1.0×109/L, HGB<60g/L), etc.;
3. Abnormal hepatitis B or hepatitis C test indicating active infection or chronic infection, including positive HBsAg or HBcAb test and positive hepatitis C antibody;
4. Have active tuberculosis or latent tuberculosis;
5. Human immunodeficiency virus (HIV) serology positivity or known history of HIV infection;
6. Presence of any known serious active infection (including bacterial, viral, fungal, etc.), including those requiring hospitalization or intravenous antibiotic therapy within 4 weeks prior to screening and oral antibiotic therapy within 2 weeks prior to screening; Those who have various chronic infections and are currently receiving corresponding treatment, such as pneumocystosis, cytomegalovirus, herpes zoster, atypical mycobacteria, etc.;
7. Patients with primary or secondary immunodeficiency;
8. IgA deficiency (<10 mg/dL) or IgG deficiency (<400 mg/dL);
9. Receiving other investigational drug treatment or participating in any other drug trial within 3 months before screening;
10. History of documented and confirmed malignancy within 5 years prior to screening, with the exception of basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been appropriately treated or resected;
11. Patients who are pregnant, breastfeeding, or planning a recent pregnancy, or who are unwilling to use a reliable contraceptive method of contraception for the duration of the study;
12. Those who have been allergic to human or murine proteins and monoclonal antibodies in the past;
13. Received live vaccine or live attenuated vaccine within 4 weeks prior to randomization;
14. Patients who are not expected to comply with the requirements of the protocol or are not expected to complete the trial as planned (such as those with psychiatric disorders, history of alcoholism, drug or other substance abuse);
15. Other conditions that the investigator considers the patient not suitable to enter the trial.

Systemic Sclerosis Exclusion Criteria:

1. Localized cutaneous SSc;
2. the duration of the disease is greater than 5 years (defined as the onset of the first non-RP symptom);
3. SSc-like syndrome related to environmental factors, such as vinyl chloride, bleomycin, etc.;
4. Any history of scleroderma renal crisis;
5. intermediate- and high-risk pulmonary hypertension;
6. Active antral vasodilation.

Idiopathic Inflammatory myopathy exclusion criteria:

1. drug-induced myopathy;
2. inclusion body myositis;
3. Tumor-associated myositis (myositis occurring within 2 years of diagnosis of tumor).

ANCA-associated vasculitis exclusion criteria:

1. alveolar hemorrhage, requiring invasive lung ventilation, which is expected to last longer than the screening time;
2. Need for dialysis or plasmapheresis during screening;
3. Have undergone a kidney transplant.

Sjögren's syndrome exclusion criteria:

1. Combined with liver cirrhosis;
2. Combined with aplastic anemia (AA), myelodysplastic syndrome (MDS) or other myeloproliferative disorders (MPD);
3. drug-induced thrombocytopenia;
4. Thrombotic thrombocytopenic purpura (TTP)/microthrombotic vascular disease (TMA).

Antiphospholipid syndrome exclusion criteria:

1. Obstetric APS;
2. APS incorporates other CTDs;
3. APS involves the nervous system.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Participant Group	anti-CD19 CAR-NK cells	anti-CD19 CAR-NK cells

Primary Outcome Measures

Name	Time	Method
The proportion of subjects with DLT	Within 28 days after anti-CD19 CAR-NK cells infusion	DLT definition is dose-limiting toxicity.
The proportion of subjects with adverse events	12 months	Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs as assessed by CTCAE v5.0.

Secondary Outcome Measures

Name	Time	Method
changes of mRSS score for systemic sclerosis	48 weeks
definition of improvement by IMACS for IIM	48 weeks
STAR score for sjogren's syndrome	48 weeks
BVAS for AAV	48 weeks
Thrombosis/death for APS	48 weeks

Trial Locations

Locations (1)

the second affiliated hospital Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China