Clinical trial NCT06866080: A Study of LCAR-AIO in Subjects With Relapsed/Refractory Autoimmune Diseases
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Relapsed/Refractory Autoimmune Diseases
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)
Lead sponsor: Nanjing Legend Biotech Co.
Sponsor class: INDUSTRY
First posted: 2025-03-10
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
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 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 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 18-65 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.

Primary outcomes:
measure: Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores from baseline up to 104 weeks
timeFrame: Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
measure: Change in Birmingham vasculitis activity score (BVAS) from baseline up to 104 weeks
timeFrame: Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
measure: Change in modified Rodnan skin score (mRSS) from baseline up to 104 weeks
timeFrame: Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
measure: Change in manual muscle testing (MMT-8) score from baseline up to 104 weeks
timeFrame: Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
measure: Change in Physician global assessment (PGA) scores from baseline up to 104 weeks
timeFrame: Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
measure: Changes from baseline in immunological markers and Immunogenicity (anti-drug antibody) from baseline up to 104 weeks
timeFrame: Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
Secondary outcomes:
measure: Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
timeFrame: Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
measure: Incidence of dose-limiting toxicity (DLT)
timeFrame: 30 days after LCAR-AIO infusion (Day 1)
measure: Pharmacokinetics in peripheral blood
timeFrame: Minimum 104 Weeks after LCAR-AIO infusion (Day 1)
measure: Recommended Dose regimen finding
timeFrame: Maximum 104 Weeks after LCAR-AIO infusion (Day 1)
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of USTC (anhui provincial hospital)
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Wenzhou
country: China
facility: The 1st Affiliated Hospital of WHU
city: Xuzhou
country: China
facility: The Affiliated Hospital of XUZHOU Medical University
Study officials:
References: