A Study of LCAR-AIO in Subjects With Relapsed/Refractory Autoimmune Diseases

An Open-label Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LCAR-AIO for the Treatment of Relapsed/Refractory Autoimmune Diseases (r/r AID)

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.

Study Overview

• Status: Withdrawn
• Conditions: Relapsed/Refractory Autoimmune Diseases
• 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 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
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Hefei, China
    • The First Affiliated Hospital of USTC (Anhui Provincial Hospital)
  • Nanjing, China
    • Jiangsu Province Hospital
  • Wenzhou, China
    • The 1st Affiliated Hospital of WHU
  • Xuzhou, China
    • The Affiliated Hospital of Xuzhou Medical University

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 18-65 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.

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: 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
Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores from baseline up to 104 weeks	• 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.	Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
Change in Birmingham vasculitis activity score (BVAS) from baseline up to 104 weeks	• 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.	Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
Change in modified Rodnan skin score (mRSS) from baseline up to 104 weeks	• 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.	Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
Change in manual muscle testing (MMT-8) score from baseline up to 104 weeks	• 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.	Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
Change in Physician global assessment (PGA) scores from baseline up to 104 weeks	• 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".	Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
Changes from baseline in immunological markers and Immunogenicity (anti-drug antibody) from baseline up to 104 weeks	• Detection of Immunoglobulins, autoantibodies (anti-dsDNA antibody, anti-Smith antibody, etc.) and anti-drug antibody.	Minimum 104 Weeks after LCAR-AIO infusion (Day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
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)
Pharmacokinetics in peripheral blood	• CAR positive T cells levels in peripheral blood after LCAR-AIO infusion.	Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
Recommended Dose regimen finding	Recommended Dose regimen established through dose exploratory.	Maximum 104 Weeks after LCAR-AIO infusion (Day 1)

Collaborators and Investigators

• Sponsor: Nanjing Legend Biotech Co.

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2025
• Primary Completion (Actual): June 17, 2025
• Study Completion (Actual): June 17, 2025

Study Registration Dates

• First Submitted: March 4, 2025
• First Submitted That Met QC Criteria: March 4, 2025
• First Posted (Actual): March 10, 2025

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• 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)
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases
• Other Study ID Numbers: LB2305-0002

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
• product manufactured in and exported from the U.S.: No