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

Early Phase 1WithdrawnNCT06866080

Nanjing Legend Biotech Co.

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Conditions

Relapsed/Refractory Autoimmune Diseases

Interventions

LCAR-AIO T cellsBIOLOGICAL

Before treatment with LCAR-AIO T cells, subjects will receive a conditioning regimen.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (4)

The First Affiliated Hospital of USTC (anhui provincial hospital)

Hefei, China

Jiangsu Province Hospital

Nanjing, China

The 1st Affiliated Hospital of WHU

Wenzhou, China

The Affiliated Hospital of XUZHOU Medical University

Xuzhou, China

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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".

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: 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.

Time frame: 30 days after LCAR-AIO infusion (Day 1)

Pharmacokinetics in peripheral blood

• CAR positive T cells levels in peripheral blood after LCAR-AIO infusion.

Time frame: Minimum 104 Weeks after LCAR-AIO infusion (Day 1)

Recommended Dose regimen finding

Recommended Dose regimen established through dose exploratory.

Time frame: Maximum 104 Weeks after LCAR-AIO infusion (Day 1)