Clinical trial NCT06869278: A Study of LCAR-AIO CAR-T Cells for Treating Relapsed/Refractory Neurological Autoimmune Diseases
Official title: An Open Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LCAR-AIO CAR-T Cells for Treating Relapsed/Refractory Neurological Autoimmune Diseases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple Sclerosis (MS)
Neuromyelitis Optica Spectrum Disease (NMOSD)
Anti-Myelin Oligodendrocyte Glycoprotein-IgG Associated Disorders (MOGAD)
Myasthenia Gravis
Keywords: Relapsed/Refractory Multiple Sclerosis (r/r MS)
Relapsed/Refractory Neuromyelitis Optica Spectrum Disease (r/r NMOSD)
Relapsed/Refractory Anti-Myelin Oligodendrocyte Glycoprotein-IgG Associated Disorders (r/r MOGAD)
Relapsed/Refractory Myasthenia Gravis (r/r MG)
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
Collaborators: name: Nanjing Legend Biotech Co.
First posted: 2025-03-11
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 neurological 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 neurological 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.

Eligibility criteria: Inclusion Criteria:

1. Subjects voluntarily participate in clinical research.
2. Age 18-70 years.
3. Adequate organ function at screening.
4. Clinical laboratory values meet criteria at screening visit.
5. Indications include:

MS;

1. Have been diagnosed of MS at least 6 months before screening.
2. Fulfill relapsed/refractory MS conditions.

NMOSD/MOGAD:

1. Have been diagnosed of NMOSD/MOGAD at least 6 months before screening.
2. AQP-4 IgG (NMOSD), or MOG-IgG (MOGAD) should be positive by CBA (Cell based transfection immunofluorescence assay).
3. Fulfill relapsed/refractory NMOSD/MOGAD conditions.

MG:

1. Have been diagnosed of MG at least 6 months before screening.
2. AChR-IgG or MuSK-IgG should be positive.
3. Fulfill relapsed/refractory NMOSD/MOGAD conditions.

Exclusion Criteria:

1. Active infections such as hepatitis and tuberculosis.
2. Other autoimmune diseases.
3. Serious underlying diseases such as tumor, uncontrolled diabetes and clinically significant cardiovascular disease.
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.

Primary outcomes:
measure: Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
timeFrame: Baseline to 104 Weeks after last subject infusion
measure: Incidence of dose-limiting toxicity (DLT)
timeFrame: 30 days after LCAR-AIO infusion (Day 1)
measure: Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration
timeFrame: Baseline to 104 Weeks after last subject infusion
measure: Recommended Phase 2 Dose (RP2D) regimen finding
timeFrame: Baseline to 104 Weeks after last subject infusion
measure: Transgene Levels of LCAR-AIO CAR-T Cells
timeFrame: Baseline to 104 Weeks after last subject infusion
Secondary outcomes:
measure: Annua Relapse Rate (ARR)
timeFrame: Baseline to 104 Weeks after last subject infusion
measure: Change in Expanded Disability Status Scale (EDSS) scores from baseline up to 104 weeks
timeFrame: Baseline to 104 Weeks after last subject infusion
measure: Changes in Visual Acuity from baseline up to 104 weeks
timeFrame: Baseline to 104 Weeks after last subject infusion
measure: Changes in Visual analogue scale (VAS) pain score from baseline up to 104 weeks
timeFrame: Baseline to 104 Weeks after last subject infusion
measure: Changes in MSE proportion from baseline up to 104 weeks
timeFrame: Baseline to 104 Weeks after last subject infusion
measure: Changes in Quantitative Myasthenia Gravis Score (QMGS) from baseline up to 104 weeks
timeFrame: Baseline to 104 Weeks after last subject infusion
measure: Changes in Myasthenia Gravis Activities of Daily Living (MG-ADL) score from baseline up to 104 weeks
timeFrame: Baseline to 104 Weeks after last subject infusion
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: The Affiliated Hospital of Fujian Medical University
city: Suzhou
country: China
facility: The First Affiliated Hospital of SOOCHOW University
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College HUAZHONG University of Science and Technology
Study officials:
References: