NK510 Cell Therapy for Refractory Systemic Lupus Erythematosus

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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.

Первичные конечные точки

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

Вторичные конечные точки (4)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07083349 · NK510-14

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗