CD19 CAR NK cell injection for treating 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

This study is testing if CD19 CAR NK cell injections can safely help people with tough autoimmune diseases feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Changhai Hospital (Academic / other)
• Drugs / interventions: rituximab, belimumab, methotrexate, cyclophosphamide, fludarabine, prednisone
• Locations: 1 site (Shanghai)
• Trial ID: NCT06464679 on ClinicalTrials.gov

What this trial studies

This pilot study aims to evaluate the safety and effectiveness of CD19 CAR NK cell injections in patients suffering from relapsed or refractory autoimmune diseases. It is a single-arm, open-label trial that plans to enroll between 36 to 72 participants in a dose-escalation format. The primary focus is on assessing the safety and feasibility of this innovative treatment, while the secondary objective is to measure its efficacy in managing autoimmune conditions.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 65 with relapsed or refractory autoimmune diseases who meet specific organ function criteria.

Not a fit: Patients with severe organ dysfunction or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel therapeutic option for patients with difficult-to-treat autoimmune diseases.

How similar studies have performed: While the use of CAR NK cells is a relatively novel approach, similar studies have shown promising results in other conditions, suggesting potential for success in this context.

Eligibility criteria

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:

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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:

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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.

Where this trial is running

Shanghai

• Changhai Hospital — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Dongbao Zhao, Dr

Conditions Autoimmune Diseases