NK010 or NK042 in Combination With Rituximab for Refractory Systemic Lupus Erythematosus/Lupus Nephritis

NCT ID: NCT06676631

Last Updated: 2025-05-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-19
• Study Completion Date: 2027-12-31

Brief Summary

This is an investigator-initiated, open-label, single-arm study to determine safety and preliminary efficacy of NK010 or NK042 in combination with rituximab (RTX) for the treatment of patients with refractory systemic lupus erythematosus (SLE) or lupus nephritis (LN) in China.

Detailed Description

The study will consist of 3 study periods for each study subject inclusive of screening, treatment and follow-up. During the treatment phase, the subjects will receive 1000 mg of rituximab treatment on day 1, followed by NK010 or NK042 treatment on days 4, 6, and 8, respectively. The subject will be followed at the day 14, day 28, Month 2, Month 3, and every 3 months for 1 year.

Conditions

Refractory Systemic Lupus Erythematosus; Refractory Lupus Nephritis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NK 010 or NK 042 infusion

Subjects with refractory SLE or LN will receive rituximab followed by NK010 or NK042.

Group Type: EXPERIMENTAL

NK 010 or NK042

Intervention Type: BIOLOGICAL

NK010 is an allogeneic non-genetically modified NK cell infusion. NKX010 will be administered at a dose of 2.5 × 109 NK cells, 5.0 × 109 NK cells and 7.5 × 109 NK cells by a dose-escalation design and administered IV. N042 is an allogeneic genetic modification of NK cell. NKX042 will be administered at a dose of 6 × 108 NKR positive NK cells, 1.2 × 109 NKR positive NK cells and 2.4 × 109 NKR positive NK cells by a dose-escalation design and administered IV.

Rituximab

Intervention Type: DRUG

RTX dose of 1 g administered IV over 60 minutes at the first day of the treatment phase.

Interventions

NK 010 or NK042

NK010 is an allogeneic non-genetically modified NK cell infusion. NKX010 will be administered at a dose of 2.5 × 109 NK cells, 5.0 × 109 NK cells and 7.5 × 109 NK cells by a dose-escalation design and administered IV. N042 is an allogeneic genetic modification of NK cell. NKX042 will be administered at a dose of 6 × 108 NKR positive NK cells, 1.2 × 109 NKR positive NK cells and 2.4 × 109 NKR positive NK cells by a dose-escalation design and administered IV.

Intervention Type: BIOLOGICAL

Rituximab

RTX dose of 1 g administered IV over 60 minutes at the first day of the treatment phase.

Intervention Type: DRUG

Other Intervention Names

NK010 or NK042 infusion; RTX

Eligibility Criteria

Inclusion Criteria

• 18 to 65 years old, male or female.
• A diagnosis of SLE according to the 2019 EULAR (European League Against Rheumatism)/ACR (American College of Rheumatology).
• One of the following at screening: positive antinuclear antibody (ANA) OR positive anti-dsDNA OR positive anti-Smith antibody.
• SLEDAI-2000 score ≥ 8.
• Prior to screening, having received glucocorticoids combined with immunosuppressants and/or biologics for at least 3 months with stable doses for >2 weeks, but disease still active (i.e., received glucocorticoids + immunosuppressants or glucocorticoids + immunosuppressants + biologics; monotherapy with any of the above drugs is not eligible).
• Hematologic, hepatic, renal, pulmonary, and cardiac function criteria at screening were as follows: ① leukocytes ≥ 2 ×109/L and lymphocyte count ≥ 0.5 ×109 /L; ② serum ALT and AST ≤ 3 times the upper limit of normal; ③ total bilirubin ≤ 1.5 times the upper limit of normal, with the exception of patients with Gilbert's syndrome, for whom total bilirubin was ≤ 3.0 times the upper limit of normal; ④ eGFR (based on the creatinine based on the CKD-EPI formula) ≥ 30 ml/min/1.73m2; ⑤ oxygen saturation ≥ 92% in non-oxygenated state under indoor ventilation; no clinically significant pleural effusion; ⑥ left ventricular ejection fraction ≥ 45%, and no clinically significant abnormal findings on ECG.
• For participants not receiving therapeutic anticoagulation: International standardized ratio (INR) ≤ 1.5 times the upper limit of normal, or prothrombin time (PT) ≤ 1.5 times the upper limit of normal.
• Participants receiving hematopoietic growth factor support therapy, including erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage-colony-stimulating factor (GM-CSF), and platelet agonists (TPO), must have a 2-week interval between the last growth factor support therapy and the screening period assessment; those receiving blood product transfusion that require at least 1 week between the screening period platelet assessment and the last platelet transfusion, and at least 2 weeks between the screening period hemoglobin assessment and the last red blood cell transfusion.
• Female participants of childbearing potential must have a negative serum pregnancy test at screening (women who are surgically sterilized or have been menopausal for at least 2 years are not considered to be of childbearing potential). Female subjects of childbearing potential and male subjects must use highly effective methods of contraception throughout the clinical study and for 1 year after the last study treatment; they should also commit not to donate eggs (oocytes, oocytes)/sperm for assisted reproduction for 1 year after the last study treatment.
• Participants are willing to participate in this study and sign a paper version of the informed consent form.

Exclusion Criteria

• Requires dialysis treatment (hemodialysis or peritoneal dialysis) at the time of screening or is expected to require dialysis treatment during study treatment.
• Have received a solid organ or hematopoietic cell transplant or plan to do so during study period.
• Have a congenital or acquired immunodeficiency that results in a serious infection, or are receiving chronic immunoglobulin replacement therapy.
• Presence of active mixed connective tissue or systemic sclerosis, an overlapping syndrome, in the 12 months prior to or during screening, and the adverse condition or other treatment may affect study efficacy or safety assessment or outcomes. Overlapping syndromes in which the anticipated condition or treatment does not affect the assessment or outcome are not excluded.
• Receipt of any B-cell depletion therapy (e.g., anti-CD20, anti-CD19 monoclonal antibody), including but not limited to zolmitriptan in rituximab, obinutuzumab, bortezomib, within 6 months prior to screening; or treatment with any biologic, such as, but not limited to, belimumab, anifrolumab, or tetracycline, within 1 month prior to screening.
• Participants with known anaphylaxis, hypersensitivity, intolerance, or contraindication to NK010 Cell Injection, NK042 Cell Injection, RTX, or any of the components of the drugs that may be used in the study, or subjects who have had a previous severe allergic reaction.
• Clinically significant central nervous system disease or pathological changes not due to lupus within 3 months prior to the first dose, including, but not limited to, cerebrovascular accident (ischemia/hemorrhage), aneurysm, epilepsy, convulsions/convulsions, aphasia, severe brain injury, dementia, parkinson's disease, cerebellar disorders, organic brain syndromes, or psychiatric disorders.
• Unstable cardiovascular function: ① Uncontrollable angina pectoris or life-threatening unstable arrhythmia; ② Myocardial infarction or unstable angina pectoris within 3 months prior to the screening; ③ Previous coronary artery or graft revascularization; ④ Uncontrolled, clinically significant arrhythmia (e.g., sustained ventricular tachycardia, ventricular fibrillation, tip-twisting); ⑤ Mobitz type II Mobitz type II or III atrioventricular block; (6) congestive heart failure or severe cardiac insufficiency with New York Heart Association classification ≥ grade 3; (7) prolongation of the QT interval (QTc) corrected for heart rate (Fridericia) by > 480 milliseconds; (8) uncontrolled hypertension (systolic blood pressure >160 mm Hg and/or diastolic blood pressure > 100 mm Hg), or associated with hypertensive crisis or hypertensive encephalopathy.
• Active bleeding.
• Any active infection, excluding fungal infections of the nail beds; history of severe recurrent or chronic infections.
• Presence of active infection treated with intravenous antibiotics within 14 days prior to screening, except for antibiotic prophylaxis (including intravenous administration).
• Positive serum HIV viral antibodies or history of active HIV infection and positive syphilis antibodies at screening.
• Positive Hepatitis B Surface Antigen (HBsAg). Participants who are HBsAg negative and Hepatitis B Core Antibody (HBcAb) positive, but Hepatitis B Virus (HBV) DNA negative are eligible for enrollment, but will require monitoring of HBV DNA at each follow-up visit.
• Positive Hepatitis C Serology. Participants with hepatitis C antibodies positive but do not have detectable hepatitis C virus (HCV) RNA for at least 6 months after completion of antiviral therapy are eligible for enrollment, but require monitoring of HCV RNA at each follow-up visit.
• Risk of active tuberculosis at screening, with or without completion of adequate treatment, including the presence of signs or symptoms of active tuberculosis (e.g., fever, cough, night sweats, and weight loss) as judged by the investigator at screening; documented active tuberculosis on chest imaging (e.g., chest x-ray, chest CT scan) performed at screening or at any time during the 6 months prior to screening; latent tuberculosis at screening evidence of infection such as a positive gamma-interferon release test.
• Participants with a malignant tumor, including tumor-associated polymyositis/dermatomyositis, within 5 years prior to screening. Except for surgically resected and cured non-melanoma skin cancer, cervical carcinoma in situ, localized prostate cancer, low-stage bladder cancer, ductal carcinoma in situ of the breast, or cured participants with no evidence of recurrence within the last 2 years and no need for treatment.
• Previous received cell therapy such as CAR-T, CAR-NK, ect.
• Pregnant or lactating women, or (if of childbearing potential) subjects who are not using adequate contraception or planning to donate oocytes and sperm.
• The presence of any life-threatening disease, medical condition, or organ system dysfunction that, in the opinion of the Investigator, may affect the safety of the subject or compliance with the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangdong Provincial People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xueqing Yu

Role: PRINCIPAL_INVESTIGATOR

Guangdong Provincial People's Hospital

Locations

Guangdong Provincial People's Hospital

Guangzhou, Guangdomg, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xueqing Yu, Ph.D

Role: CONTACT

yuxueqing@gdph.org.cn

8620-83827897

Li Fan

Role: CONTACT

fanli@gdph.org.cn

8615913106705

Facility Contacts

Xueqing Yu

Role: primary

yuxueqing@gdph.org.cn

Other Identifiers

NK010-NK042-I-SLE-01

Identifier Type: -

Identifier Source: org_study_id