NK510 Cell Therapy for Refractory Systemic Lupus Erythematosus

Official title

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

Overview

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.

Interventions

• Drug NK510 : allogeneic genetic modified NK
  NK510 is an allogeneic genetic modification of NK cell. NK510 will be administered at a dose of 4x10\^7 NK/kg, 8x10\^7 NK/kg and 1.2x10\^8 NK/kg by a dose-escalation design and administered IV.

Primary outcome measures

• Response rate for SLE response index 4 (SRI4) [Time frame: 3 months, 6 months after the first administration of NK510]
• Incidence of treatment-related adverse events [Time frame: 1 year]
• Dose-limiting toxicity (DLT) rate [Time frame: 28 days after initial study treatment.]

Secondary outcome measures (4)

• Number of subjects who achieved lupus low disease activity state (LLDAS) [Time frame: 3 months, 6 months after the first administration of NK510]
• Number of participants who achieved clinical remission of SLE [Time frame: 3 months, 6 months after the first administration of NK510]
• The change of SLEDAI-2000(Systemic lupus erythematosus disease activity index 2000) scores [Time frame: Day 28, 3 months, 6 months after the first administration of NK510]
• Changes of autoantibody of SLE from baseline [Time frame: Day 14, 3 months, 6 months after the first administration of NK510]

Eligibility criteria

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:

• 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;
• Renal function: serum creatinine ≤ 1.5 times ULN, or creatinine clearance rate ≥ 60 mL/min;
• 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:

• HBsAg positive, and peripheral blood HBV-DNA titer ≥ 1×10³ copies/mL or upper limit of normal;
• Anti-HCV positive.
• Those deemed unsuitable for participation in the study by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07083349 · NK510-14

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗