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

Early Phase 1RecruitingNCT07095075

Nanjing Legend Biotech Co.36 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Relapsed/Refractory Autoimmune Diseases

Interventions

LUCAR-DKS1 NK cellsBIOLOGICAL

Prior to the infusion of the LUCAR-DKS1 cells, subjects will receive a conditioning premedication regimen consisting of cyclophosphamide and fludarabine.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

* 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.

Locations (5)

The Third The People's Hospital of BengBu

Bengbu, Anhui, China

NOT_YET_RECRUITING

The First Affiliated Hospital of USTC (Anhui Provincial Hospital)

Hefei, Anhui, China

RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Outcomes

Primary Outcomes

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.

Time frame: 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.