A Study of LCAR-AIO in Subjects With Relapsed/Refractory Systemic Lupus Erythematosus

An Open-label Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LCAR-AIO for the Treatment of Relapsed/Refractory Systemic Lupus Erythematosus (r/r SLE)

This is a prospective, single-arm, open-label, dose-exploration and expansion clinical study of LCAR-AIO in adult subjects with relapsed/refractory systemic lupus erythematosus.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus (SLE)
• 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 systemic lupus erythematosus. 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): 34
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Qiubai Li, professor; Phone Number: 027 85726808; Email: qiubaili@hust.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Wuhan Union Hospital

Participation Criteria

Eligibility Criteria

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

Description

1. Subjects voluntarily participate in clinical research.
2. Age 18-65 years.
3. Have been diagnosed of SLE at least 6 months before screening.
4. At screening, antinuclear antibody, and/or anti-dsDNA antibody, and/or anti-Sm antibody should be positive.
5. Fulfill relapsed/refractory SLE conditions.
6. Adequate organ function at screening.
7. Clinical laboratory values meet criteria at screening.

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

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; 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
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 Phase 2 Dose (RP2D) regimen finding	RP2D established through dose exploratory.	Minimum 104 Weeks after LCAR-AIO infusion (Day 1)

Secondary 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 SELENA-2K scale is a cumulative and weighted index used to assess disease activity across 24 different disease descriptors in patients with lupus. A patient's SELENA-2K total score is the sum of all marked lupus related descriptors (seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, cerebrovascular accident, vasculitis, arthritis, myositis, urinary casts, hematuria, proteinuria, pyuria, new rash, alopecia, mucosal ulcers, pleurisy, pericarditis, low complement, increased DNA binding, fever, thrombocytopenia, leukopenia). 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 Physician global assessment (PGA) scores from baseline up to 104 weeks	The physician will place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (Score 0) represents "no activity", and the right-hand boundary (score 3) represents "the most severe activity".	Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
Lupus Low Disease Activity State (LLDAS) response rates at multiple visits post-infusion	Percentage of participants achieving the LLDAS. The LLDAS is a composite measure designed to identify patients achieving a state of low disease activity. The LLDAS response criteria were: (1) SLEDAI-2K <=4, with no activity in major organ systems (Central nervous system, vascular, renal, cardiorespiratory and constitutional); where "no activity" is defined as all items of SLEDAI-2K within these major organ systems equal to 0. (2) no new features of lupus disease activity compared to previous occurred visit, where the "new feature" is defined as any of the SLEDAI-2K 24 items changed from 0 to greater than 0; (3) Physician global assessment (PGA) (score 0-3), <=1; (4) current prednisolone (or equivalent) dose <=7.5 mg dailyultiple visits.	Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
24h urinary protein/urine protein-to-creatinine ratio (UPCR) changes from baseline up to 104 weeks	Proteinuria will be assessed in lupus nephritis patients basing on 24h urinary protein/UPCR at multiple visits.	Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
Changes from baseline in immunological markers and Immunogenicity (anti-drug antibody)	Detection of Immunoglobulins, anti-drug antibodies (anti-dsDNA antibody, anti-Sm antibody, etc.) and anti-drug antibody.	Time Frame: Minimum 104 Weeks after LCAR-AIO infusion (Day 1)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2029

Study Registration Dates

• First Submitted: October 11, 2024
• First Submitted That Met QC Criteria: October 20, 2024
• First Posted (Actual): October 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 8, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Refractory pulmonary Hypertension (PAH); Recurrent/refractory autoimmune hemolytic anemia (r/r AIHA); Recurrent/refractory lupus nephritis (r/r LN)
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: LB2305-0001

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