A Study of LCAR-AIO CAR-T Cells for Treating Relapsed/Refractory Neurological Autoimmune Diseases

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

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.

Study Overview

• Status: Recruiting
• Conditions: Myasthenia Gravis; Multiple Sclerosis (MS); Neuromyelitis Optica Spectrum Disease (NMOSD); Anti-Myelin Oligodendrocyte Glycoprotein-IgG Associated Disorders (MOGAD)
• Intervention / Treatment: Biological: LCAR-AIO T cells

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.

• Study Type: Interventional
• Enrollment (Estimated): 37
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Qiubai li; Phone Number: 18221636229; Email: Tingyu.Zhang@legendbiotech.cn

Study Locations

• China
  • Fuzhou, China
    • Not yet recruiting
    • The Affiliated Hospital of Fujian Medical University
  • Suzhou, China
    • Recruiting
    • the First Affiliated Hospital of Soochow University
  • Wuhan, China
    • Recruiting
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCAR-AIO T Cells; Chimeric antigen receptor T cells (LCAR-AIO) Each subject will be given a single-dose LCAR-AIO cells infusion at each dose level	Biological: LCAR-AIO T cells; Before treatment with LCAR-AIO T cells, subjects will receive a conditioning regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicity (DLT)	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.	30 days after LCAR-AIO infusion (Day 1)
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)	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.	Baseline to 104 Weeks after last subject infusion
Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration	Venous blood samples will be collected for measurement of CAR-T positive cellular concentration.	Baseline to 104 Weeks after last subject infusion
Recommended Phase 2 Dose (RP2D) regimen finding	RP2D established through dose exploratory.	Baseline to 104 Weeks after last subject infusion
Transgene Levels of LCAR-AIO CAR-T Cells	Transgene Levels of LCAR-AIO CAR-T Cells using sensitive assay methods will be assessed	Baseline to 104 Weeks after last subject infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annua Relapse Rate (ARR)	ARR refers to the number of relapses divided by observed year after LCAR-AIO infusion.	Baseline to 104 Weeks after last subject infusion
Change in Expanded Disability Status Scale (EDSS) scores from baseline up to 104 weeks	The EDSS is a method of quantifying disability and monitoring changes in the level of disability over time. EDSS score ranges from 0 (normal neurological exam) to 10 (death from MS). A negative change from baseline indicates improvement.	Baseline to 104 Weeks after last subject infusion
Changes in Visual Acuity from baseline up to 104 weeks	The Visual Acuity is determined by Snellen chart and visual field.	Baseline to 104 Weeks after last subject infusion
Changes in Visual analogue scale (VAS) pain score from baseline up to 104 weeks	VAS pain score is used to evaluate pain. Line from 0 = no pain to10 = worst pain.	Baseline to 104 Weeks after last subject infusion
Changes in MSE proportion from baseline up to 104 weeks	The proportion of patients who achieve Minimal Symptom Expression (MSE, defined as reaching an MG-ADL=0~1 or QMGS=0~2) after LCAR-AIO infusion.	Baseline to 104 Weeks after last subject infusion
Changes in Quantitative Myasthenia Gravis Score (QMGS) from baseline up to 104 weeks	The QMGS is a 13-item scale used to quantify disease severity in MG. The scale measures ocular, bulbar, respiratory, and limb function, grading each finding, and ranges from 0 (no myasthenic findings) to 39 (maximal myasthenic deficits).	Baseline to 104 Weeks after last subject infusion
Changes in Myasthenia Gravis Activities of Daily Living (MG-ADL) score from baseline up to 104 weeks	The MG-ADL is an eight-question survey of symptom severity. The average level of daily activity function in the last 7 days was assessed and the total score was calculated. Each question response graded from 0 (normal) to 3 (most severe). Cumulative MG-ADL scores range from 0 to 24.	Baseline to 104 Weeks after last subject infusion

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Collaborators: Nanjing Legend Biotech Co.

Study record dates

Study Major Dates

• Study Start (Estimated): June 17, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: February 25, 2025
• First Submitted That Met QC Criteria: March 9, 2025
• First Posted (Actual): March 11, 2025

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 6, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• 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)
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Immune System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Multiple Sclerosis; Sclerosis; Myasthenia Gravis; Neuromyelitis Optica; Autoimmune Diseases
• Other Study ID Numbers: LB2305-0003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No