Relapsed/Refractory Autoimmune Diseases
Conditions
Keywords
Relapsed/Refractory Systemic lupus erythematosus (r/r SLE), Relapsed/Refractory Systemic Sclerosis (SSc), ), Relapsed/Refractory Anti-neutrophil cytoplastic antibodies (ANCA)-associated vasculitis (AAV), Idiopathic Relapsed/Refractory Inflammatory Myopathies (IIM)
Brief summary
This is a prospective, single-arm, open-label, dose-exploration and expansion clinical study of LCAR-AIO in adult subjects with relapsed/refractory autoimmune diseases.
Detailed description
This is a prospective, single-arm, open-label exploratory clinical study to evaluate the safety, tolerability, pharmacokinetics and efficacy profiles of LCAR-AIO, a chimeric antigen receptor (CAR) -T cell therapy in subjects with relapsed/refractory autoimmune diseases. Patients who meet the eligibility criteria will receive LCAR-AIO infusion. The study will include the following sequential stages: screening, apheresis, pre-treatment (cell product preparation: lymphodepleting chemotherapy), treatment (LCAR AIO infusion) and follow-up.
Interventions
BIOLOGICALLCAR-AIO T cells
Before treatment with LCAR-AIO T cells, subjects will receive a conditioning regimen.
Sponsors
Nanjing Legend Biotech Co.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects voluntarily participate in clinical research. 2. Age 18-65 years. 3. Adequate organ function at screening. 4. Clinical laboratory values meet criteria at screening. SLE: * Have been diagnosed of SLE at least 6 months before screening. * At screening, antinuclear antibody, and/or anti-dsDNA antibody, and/or anti-Smith antibody should be positive. * Fulfill relapsed/refractory SLE conditions. AAV: * Have been diagnosed of AAV before screening. * Positive test for anti-PR3 or anti-MPO antibodies at screening. * Fulfill relapsed/refractory AAV conditions. SSc: * Have been diagnosed of SSc before screening. * At screening, mRSS is higher than 10. * Fulfill relapsed/refractory SSc conditions. IIM: * Have been diagnosed of IIM before screening. * Positive test for myositis-associated antibodies or myositis-specific antibodies at screening. * Fulfill relapsed/refractory IIM 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, or planning to become pregnant while participating in this study or within 1 year of receiving LCAR-AIO treatment. 5. Participated in other clinical trials within 4 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes from baseline in immunological markers and Immunogenicity (anti-drug antibody) from baseline up to 104 weeks | Minimum 104 Weeks after LCAR-AIO infusion (Day 1) | • Detection of Immunoglobulins, autoantibodies (anti-dsDNA antibody, anti-Smith antibody, etc.) and anti-drug antibody. |
| Change in Birmingham vasculitis activity score (BVAS) from baseline up to 104 weeks | Minimum 104 Weeks after LCAR-AIO infusion (Day 1) | • The BVAS is a cumulative and weighted index used to assess disease activity across 9 organ systems 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. |
| Change in modified Rodnan skin score (mRSS) from baseline up to 104 weeks | Minimum 104 Weeks after LCAR-AIO infusion (Day 1) | • The mRSS is a scale used to assess skin thickness and scope of SSc patients by physically evaluating 17 positions. A total score can fall between 0 and 51, with a higher score representing a more significant degree of skin involvement. |
| Change in manual muscle testing (MMT-8) score from baseline up to 104 weeks | Minimum 104 Weeks after LCAR-AIO infusion (Day 1) | • This validated tool assesses muscle strength through muscle testing an abbreviated group of 8 proximal, distal, and axial muscles in IIM patients. A total score can fall between 0 and 150, with a lower score representing a more significant degree of muscle involvement. |
| Change in Physician global assessment (PGA) scores from baseline up to 104 weeks | Minimum 104 Weeks after LCAR-AIO infusion (Day 1) | • The physician will evaluating the global activity of AID patients by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary represents no activity, and the right-hand boundary represents the most severe activity. |
| Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores from baseline up to 104 weeks | Minimum 104 Weeks after LCAR-AIO infusion (Day 1) | • The SLEDAI-2K scale is a cumulative and weighted index used to assess disease activity across 24 different disease descriptors in patients with SLE. A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicity (DLT) | 30 days after LCAR-AIO infusion (Day 1) | • DLTs are severe adverse events 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. |
| Pharmacokinetics in peripheral blood | Minimum 104 Weeks after LCAR-AIO infusion (Day 1) | • CAR positive T cells levels in peripheral blood after LCAR-AIO infusion. |
| Recommended Dose regimen finding | Maximum 104 Weeks after LCAR-AIO infusion (Day 1) | Recommended Dose regimen established through dose exploratory. |
| Incidence, severity, and type of treatment-emergent adverse events (TEAEs) | Minimum 104 Weeks after LCAR-AIO infusion (Day 1) | • An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment. |
Countries
China
Outcome results
None listed