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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
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.
RTX dose of 1 g administered IV over 60 minutes at the first day of the treatment phase.
Guangdong Provincial People's Hospital
Guangzhou, Guangdomg, China
RECRUITINGResponse rate for SLE response index 4 (SRI4)
SRI4 response defined as a reduction of ≥4 points on SLEDAI-2000, no new domain A scores and no more than 1 new domain B score on BILAG 2004, and no deterioration in PGA (\<0.3 point increase).
Time frame: Day 14, day 28, 2 months, 3 months, 6 months, 9 months, 12 months after the first administration of NK010 or NK042 infusion
Number of participants who achieved renal response
For subjects with LN: evaluate the number of participants achieved complete renal response (CRR) and partial renal response (PRR) according to European Alliance of Associations for Rheumatology (EULAR)/European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA) criteria.
Time frame: Day 14, day 28, 2 months, 3 months, 6 months, 9 months, 12 months after the first administration of NK010 or NK042 infusion
Number of subjects who achieved lupus low disease activity state (LLDAS)
Low lupus disease activity was defined as (i) SLEDAI-2K total score ≤ 4, no active lesions in major organ systems (including kidney, central nervous system, cardiopulmonary, vasculitis, and fever) and no hemolytic anemia or gastrointestinal lesions; (ii) no new indications of lupus disease activity compared with previous evaluations (according to SLEDAI-2K); (iii) Physician's Global Assessment (PGA) ≤ 1; and (iv) prednisone ≤ 7.5 mg d for use of malaria and biologic agents. Assessment (PGA) ≤ 1 point; ④ Prednisone ≤ 7.5 mg/d, maintenance of standard therapy. biologics.
Time frame: Day 14, day 28, 2 months, 3 months, 6 months, 9 months, 12 months after the first administration of NK010 or NK042 infusion
Number of participants who achieved clinical remission of SLE
Clinical remission of SLE was defined by 2021 DORIS SLE remission criteria.
Time frame: Day 14, day 28, 2 months, 3 months, 6 months, 9 months, 12 months after the first administration of NK010 or NK042 infusion
The change of Physician Global Assessment (PGA) score
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The change of PGA score will be compared to baseline.
Time frame: Day 14, day 28, 2 months, 3 months, 6 months, 9 months, 12 months after the first administration of NK010 or NK042 infusion
The change of SLEDAI-2000 scores
The change of SLEDAI-2000 score will be compared to baseline.
Time frame: Day 14, day 28, 2 months, 3 months, 6 months, 9 months, 12 months after the first administration of NK010 or NK042 infusion
Changes of autoantibody of SLE from baseline
Autoantibody include anti-dsDNA, anti-nuclear antibody, ANA, anti-Sm antibody, and complement C3, C4.
Time frame: Day 14, day 28, 2 months, 3 months, 6 months, 9 months, 12 months after the first administration of NK010 or NK042 infusion
Dose-limiting toxicity (DLT) rate
This is to measure the dose-limiting toxicity of NK 010 or NK 042.
Time frame: 28 days after initial study treatment.
Incidence of treatment-related adverse events
This is to measure safety and tolerability of NK 010 or NK 042.
Time frame: 1 year