A Study of LUCAR-DKS1 in Subjects With Relapsed/Refractory Autoimmune Diseases

Not Applicable

Not yet recruiting

• Conditions: Relapsed/Refractory Autoimmune Diseases
• Interventions: Biological: LUCAR-DKS1 NK cells

• Registration Number: NCT07095075
• Lead Sponsor: Nanjing Legend Biotech Co.

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2025-06-23
• Status Verified: 2025-07
• Study First Submitted QC: 2025-07-23
• Last Update Submitted: 2025-07-23
• Study First Posted: 2025-07-31
• Last Update Posted: 2025-07-31
• Study Start: 2025-08-22
• Primary Completion: 2029-12-31
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1. Subjects voluntary agreement to provide written informed consent.
2. Aged 18 to 70 years, either sex.
3. Clinical laboratory values meet screening criteria.
4. Positive test for CD19 and/ or BCMA

SLE:

• Meets at least 1 classification criteria≥6 months for SLE.
• At screening, antinuclear antibody, and/or anti-dsDNA antibody, and/or anti-Smith antibody should be positive.
• Fulfill relapsed/refractory SLE conditions.

AAV:

• Meets the 2022 ACR/EULAR classification criteria for AAV.
• Positive test for anti-MPO or p-ANCA or anti-PR3 or anti-MPO antibodies at screening.
• Fulfill relapsed/refractory AAV conditions.

SSc:

• Meets the 2013 ACR/EULAR classification criteria for SSc.
• At screening, mRSS is higher than 10.
• Fulfill relapsed/refractory SSc conditions.

IIM:

• Meets 2017 EULAR/ACR classification criteria for IIM.
• Positive test for myositis-associated antibodies or myositis-specific antibodies at screening.
• Fulfill relapsed/refractory IIM conditions. SjS：
• Meets the 2016 ACR/EULAR diagnostic criteria for SjS.
• Positive test for anti-SSA and/or anti-SSB antibodies at screening.
• Fulfill relapsed/refractory SjS conditions.

Exclusion Criteria

1. Active infections such as hepatitis and tuberculosis.
2. Other autoimmune diseases.
3. Serious underlying diseases such as tumor, uncontrolled diabetes.
4. Female subjects who were pregnant, breastfeeding.
5. Those with a history of major organ transplantation.
6. Have received autologous cell therapy of any target before.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Chimeric antigen receptor NK cells (LUCAR-DKS1), single-dose for each subject.	LUCAR-DKS1 NK cells	Experimental: chimeric antigen receptor NK cells (LUCAR-DKS1). Dose level1：50 millions /kg Dose level2：150 millions /kg Dose level3：300 millions /kg Dose level4：600 millions /kg Totally 4 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.

Primary Outcome Measures

Name	Time	Method
Tmax	About 2 years after LUCAR-DKS1 infusion (Day 1)	CAR positive NK cells levels in peripheral blood after LUCAR-DKS1 infusion, time to Cmax (Tmax).
Incidence, severity, and type of treatment-emergent adverse events (TEAEs) .	About 2 years after LUCAR-DKS1infusion (Day 1)	≥Grade 1 clinical symptoms, laboratory test abnormalities, and clinical events that are possibly, likely, or definitely related to study treatment. Accessed by CTCAE5.0.
Incidence of dose-limiting toxicity (DLT)	About 2 years after LUCAR-DKS1 infusion (Day 1)	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.
Cmax	About 2 years after LUCAR-DKS1 infusion (Day 1)	CAR positive NK cells in peripheral blood after LUCAR-DKS1 infusion, maximum concentration (Cmax).
AUC	About 2 years after LUCAR-DKS1 infusion (Day 1)	CAR positive NK cells levels in peripheral blood after LUCAR-DKS1 infusion， area under the concentration-time curve (AUC) .
Recommended phase 2 dose regimen finding	About 2 years after LUCAR-DKS1 infusion (Day 1)	Recommended phase 2 dose regimen established through dose exploratoration finding.

Secondary Outcome Measures

Name	Time	Method
SLE disease activity: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)	About 2 years after LUCAR-DKS1infusion (Day 1)	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.
SSc disease activity :Modified rodnan skin score(mRSS)	About 2 years after LUCAR-DKS1 infusion (Day 1)	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.
AAV disease activity： Birmingham vasculitis activity score (BVAS)	About 2 years after LUCAR-DKS1 infusion (Day 1)	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.
IIM disease activity ：Manual muscle test-8	About 2 years after LUCAR-DKS1 infusion (Day 1)	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.
SjS disease activity: Sjögren's Tool for Assessing(STAR)	About 2 years after LUCAR-DKS1 infusion (Day 1)	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.

Trial Locations

Locations (5)

The Third The People's Hospital of BengBu; 🇨🇳 Bengbu, Anhui, China

The First Affiliated Hospital of USTC (Anhui Provincial Hospital); 🇨🇳 Hefei, Anhui, China

Jiangsu Province Hospital; 🇨🇳 NanJing, Jiangsu, China

The First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China

The First Affiliated Hospital of Wenzhou Medical University; 🇨🇳 Wenzhou, Zhejiang, China