NK010 or NK042 in Combination With Rituximab for Refractory Systemic Lupus Erythematosus/Lupus Nephritis
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-65
SponsorGuangdong Provincial People's Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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).
Inclusion criteria applicable to the LN subgroup: active type III or IV lupus nephritis (with or without type V) confirmed by renal biopsy according to the 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria. An activity index ≥2 and a chronicity index no more than moderate according to the 2018 RPS Task Force for LN pathologic types and the National Institutes of Health (NIH) Lupus Nephritis Activity and Chronicity Index Score criteria. Urine protein/creatinine ratio (UPCR) ≥ 1.0 g/g or 24-hour urine protein quantification ≥ 1.0 g/day.
One of the following at screening: positive antinuclear antibody (ANA) OR positive anti-dsDNA OR positive anti-Smith antibody.
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
NK 010 or NK042
Biological/VaccineNK010 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
DrugRTX dose of 1 g administered IV over 60 minutes at the first day of the treatment phase.
Treatment groups
18 Participants
are divided into 1 treatment groupGroup A: NK 010 or NK 042 infusionExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Response 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 infusion2
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 infusion3
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 infusion4
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 infusionSponsors and contacts
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Source ClinicalTrials.gov