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This is a prospective, single-arm, open-label and dose-escalation Investigator Initialed study to evaluate LUCAR-DKS1 in adult subjects with relapsed/refractory autoimmune diseases.
This is a prospective, single-arm, open-label clinical study to evaluate the safety, tolerability, pharmacokinetics and efficacy profiles of LUCAR-DKS1, a chimeric antigen receptor (CAR) -NK cell therapy in subjects with relapsed/refractory autoimmune diseases. Patients who meet the eligibility criteria will receive LUCAR-DKS1 infusion. The study will include the following sequential stages: screening, pre-treatment (lymphodepleting chemotherapy), treatment LUCAR-DKS1 infusion) and follow-up.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chimeric antigen receptor NK cells (LUCAR-DKS1), single-dose for each subject. | Experimental | Experimental: chimeric antigen receptor NK cells (LUCAR-DKS1). Dose level1：25 millions /kg Dose level2：50 millions /kg Dose level3：100 millions /kg Dose level4：200 millions /kg Dose level5：400 millions /kg Totally 5 dose groups, each subject will be given a single-dose LUCAR-DKS1 cells infusion at a certain level, subject will be administered at day 1. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LUCAR-DKS1 NK cells | Biological | Prior to the infusion of the LUCAR-DKS1 cells, subjects will receive a conditioning premedication regimen consisting of cyclophosphamide and fludarabine. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence, severity, and type of treatment-emergent adverse events (TEAEs) . | ≥Grade 1 clinical symptoms, laboratory test abnormalities, and clinical events that are possibly, likely, or definitely related to study treatment. Accessed by CTCAE5.0. | About 2 years after LUCAR-DKS1infusion (Day 1) |
| Incidence of dose-limiting toxicity (DLT) | DLTs are severe adverse events that refers to any untoward medical occurred in a subject participated in a clinical investigation, which have a causal relationship with the treatment and will limit the dose escalation. | About 2 years after LUCAR-DKS1 infusion (Day 1) |
| Cmax | CAR positive NK cells in peripheral blood after LUCAR-DKS1 infusion, maximum concentration (Cmax). | About 2 years after LUCAR-DKS1 infusion (Day 1) |
| Tmax | CAR positive NK cells levels in peripheral blood after LUCAR-DKS1 infusion, time to Cmax (Tmax). | About 2 years after LUCAR-DKS1 infusion (Day 1) |
| AUC | CAR positive NK cells levels in peripheral blood after LUCAR-DKS1 infusion， area under the concentration-time curve (AUC) . | About 2 years after LUCAR-DKS1 infusion (Day 1) |
| Recommended phase 2 dose regimen finding | Recommended phase 2 dose regimen established through dose exploratoration finding. | About 2 years after LUCAR-DKS1 infusion (Day 1) |
| Measure | Description | Time Frame |
|---|---|---|
| SLE disease activity: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) | Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores from baseline up to 2 years, a total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity. | About 2 years after LUCAR-DKS1infusion (Day 1) |
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Inclusion Criteria:
SLE:
AAV:
SSc:
IIM:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Wenbo Hu | Contact | 13581888439 | wenbo.hu@legendbiotech.cn | |
| Liyuan Yu | Contact | 18618406418 | liyuan.yu@legendbiotech.cn |
| Name | Affiliation | Role |
|---|---|---|
| Wenfeng Tan Principal Investigator | The First Affiliated Hospital with Nanjing Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Third The People's Hospital of BengBu | Not yet recruiting | Bengbu | Anhui | 233000 | China |
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| ID | Term |
|---|---|
| D001327 | Autoimmune Diseases |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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This study is a dose exploration study that employs an accelerated titration design combined with BF-BOIN, planned to investigate 5 dose groups. Dose Level1 （25×10^6 cells/kg) and Level 2(50×10^6 cells/kg)belong to the accelerated titration method for dose assessment, three dosage levels of 100×10^6 cells/kg, 200×10^6 cells/kg, and 400×10^6 cells/kg are assessed using the BOIN dose escalation and de-escalation rules.
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| SSc disease activity :Modified rodnan skin score(mRSS) | Change in modified Rodnan skin score (mRSS) from baseline up to 2 years in SSc patients. The mRSS is used to assess skin thickness and scope of SSc patients ,with a total score can fall between 0 and 51, with a higher score representing a more significant degree of skin involvement. | About 2 years after LUCAR-DKS1 infusion (Day 1) |
| AAV disease activity： Birmingham vasculitis activity score (BVAS) | Change in Birmingham vasculitis activity score (BVAS) from baseline up to 2 years in patients with AAV. A total score can fall between 0 and 64, with a higher score representing a more significant degree of disease activity. | About 2 years after LUCAR-DKS1 infusion (Day 1) |
| IIM disease activity ：Manual muscle test-8 | Change in manual muscle testing (MMT-8) score from baseline up to 2 years in IIM patients. This tool assesses muscle strength by testing 8 proximal, distal, and axial muscles ,assess unilateral(score range 0-80 points)handedness side, with a lower score representing a more significant degree of muscle involvement. | About 2 years after LUCAR-DKS1 infusion (Day 1) |
| SjS disease activity: Sjögren's Tool for Assessing(STAR) | Proportion and duration of Sjögren's syndrome(r/r SjS) subjects achieving Sjögren's Tool for Assessing Response(STAR) response from baseline up to 2 years. STAR can be used to assess the treatment response of all SjS patients. It is generally believed that a STAR score of ≥ 5 is an effective response to treatment. | About 2 years after LUCAR-DKS1 infusion (Day 1) |
| The First Affiliated Hospital of USTC (Anhui Provincial Hospital) | Recruiting | Hefei | Anhui | 230036 | China |
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| Jiangsu Province Hospital | Recruiting | Nanjing | Jiangsu | 210029 | China |
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| The First Affiliated Hospital of Soochow University | Recruiting | Suzhou | Jiangsu | 215006 | China |
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| The First Affiliated Hospital of Wenzhou Medical University | Not yet recruiting | Wenzhou | Zhejiang | 325015 | China |
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