NK510 Cell Therapy for Refractory Systemic Lupus Erythematosus

An Open, Single-Center Exploratory Clinical Study of NK510 Cell Therapy for Refractory Systemic Lupus Erythematosus

This is an investigator-initiated, open-label, single-arm study to determine safety and preliminary efficacy of NK510 for the treatment of patients with refractory systemic lupus erythematosus (SLE) in China.

Inclusion Criteria:

• 18 to 70 years old, male or female.

• A diagnosis of SLE according to the 2019 EULAR (European League Against Rheumatism)/ACR (American College of Rheumatology).

• The subject voluntarily participates in this clinical study and signs the Informed Consent Form (ICF).

• Before screening, the subject must have received glucocorticoid combined with immunosuppressants and/or biological agents for at least 2 months, with a stable dose for more than 2 weeks, but the disease remains active; within 7 days before lymphodepleting conditioning, the blood routine test must meet the following requirements: absolute neutrophil count (ANC) ≥ 1.5×10⁹/L; hemoglobin (Hb) ≥ 80g/L; platelet count (PLT) ≥ 50×10⁹/L.

• SLEDAI-2K score > 8 points at screening.

• Antinuclear antibody (ANA) ≥ 1:80 at screening.

• Having appropriate organ functions:

  1. Liver function: aspartate transaminase (AST) ≤ 3 times the upper limit of normal (ULN); alanine transaminase (ALT) ≤ 3 times ULN; total bilirubin ≤ 1.5 times ULN, unless the subject has a record of Gilbert syndrome; subjects with Gilbert-Meulengracht syndrome with total bilirubin ≤ 3.0 times ULN and direct bilirubin ≤ 1.5 times ULN can be included;
  2. Renal function: serum creatinine ≤ 1.5 times ULN, or creatinine clearance rate ≥ 60 mL/min;
  3. Blood routine: absolute neutrophil count (ANC) ≥ 1.5×10⁹/L; absolute lymphocyte count (ALC) ≥ 0.1×10⁹/L; hemoglobin (Hb) ≥ 80 g/L; platelet count (PLT) ≥ 50×10⁹/L.

• Women of childbearing age must be non-lactating and have a negative serum pregnancy test within 1 week before administration. In addition, all subjects (whether male or female) must agree to use contraception during the period of NK510 treatment starting from enrollment and within 3 months after the end of treatment.

• Able to comply with the study protocol and follow-up procedures.

Exclusion Criteria:

• Patients with active lupus nephritis.

• Those with allergies to the study drug or other medications used in the study protocol.

• Those with any of the following conditions: ① Having received autologous/allogeneic hematopoietic stem cell transplantation within 3 months; ② Having received ultraviolet irradiation therapy within 6 weeks; ③ Having received biologic agent therapy (excluding other medications used in the study protocol) within 4 weeks or 3 half-lives (whichever is longer); ④ Having undergone major surgery or received live vaccines within 4 weeks; ⑤ Having received experimental treatment (except for definite placebo control groups) within 4 weeks.

• Those with other active, known, or suspected autoimmune diseases.

• Presence of uncontrolled active bacterial, viral, fungal, mycobacterial, or other infections requiring treatment with intravenous antibiotics, antiviral drugs, or antifungal drugs within 14 days before lymphodepleting conditioning; however, prophylactic use of these drugs (including intravenous administration) is allowed.

• History of immunodeficiency, including positive HIV test results, or other acquired/congenital immunodeficiency diseases, or history of organ transplantation.

• History of severe cardiovascular and cerebrovascular diseases, including but not limited to: severe cardiac rhythm or conduction abnormalities (e.g., ventricular arrhythmias requiring clinical intervention, third-degree atrioventricular block, etc.); QTc interval > 480 ms on 12-lead electrocardiogram at rest; acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events within 6 months before administration; New York Heart Association (NYHA) cardiac function class ≥ II or left ventricular ejection fraction (LVEF) < 50%.

• Failure to fully recover from major surgery or trauma within 2 weeks before administration.

• History of malignant tumors.

• Screening results of hepatitis B or C virological tests meeting any of the following:

  1. HBsAg positive, and peripheral blood HBV-DNA titer ≥ 1×10³ copies/mL or upper limit of normal;
  2. Anti-HCV positive.

• Those deemed unsuitable for participation in the study by the investigator.