Relapsed/Refractory Autoimmune Diseases
Conditions
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.
Interventions
BIOLOGICALLUCAR-DKS1 NK cells
Prior to the infusion of the LUCAR-DKS1 cells, subjects will receive a conditioning premedication regimen consisting of cyclophosphamide and fludarabine.
Sponsors
Nanjing Legend Biotech Co.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). |
| 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). |
| 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) . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
China
Contacts
Primary ContactWenbo Hu
Backup ContactLiyuan Yu
Outcome results
None listed