A Clinical Study of YTS109 Cell in R/R Systemic Lupus Erythematosus

Phase 1

Recruiting

• Conditions: Lupus Nephritis (LN); Immune Thrombocytopenia (ITP)
• Interventions: Drug: YTS109 cell injection

• Registration Number: NCT06943937
• Lead Sponsor: China Immunotech (Beijing) Biotechnology Co., Ltd.

Brief Summary

This study evaluates the safety and efficacy of YTS109 cells in adults with refractory Lupus Nephritis (LN) and Systemic Lupus Erythematosus-Immune Thrombocytopenia (SLE-ITP). Approximately 36 patients aged 18-65 will receive a single infusion of YTS109 cells (1×10⁶-2×10⁶ cells/kg). The primary endpoint is observations of types, severity, and frequency of dose-limiting toxicities (DLTs) and adverse events (AEs). Secondary endpoints include the complete renal response (CRR) rate at week 12 in LN, and proportion of subjects achieving complete response (CR) or partial response (PR) at week 12 post-treatment in SLE-ITP. This single-arm, open-label trial will enroll patients across Beijing GoBroad Hospital in China.

Detailed Description

Background: Systemic lupus erythematosus (SLE) is characterized by multi-system and multi-organ involvement, recurrent flares and remissions, and the presence of numerous autoantibodies. LN and SLE-ITP are the most common and severe clinical manifestations of SLE. Recently, the therapeutic advancements have been made in the management of SLE. However, the patients with refractory SLE, particularly those complicated by LN and SLE-ITP, continue to face significant unmet clinical needs. CAR-T cell therapy has emerged as one of the innovative therapeutic modalities for autoimmune diseases, characterized by its controllable safety profile and durable therapeutic efficacy, warranting further clinical exploration and investigation in the future. YTS109 cell is a universal allogeneic STAR-T cell therapy targeting CD19, designed to efficiently eliminate B cells in patients with SLE and mitigate autoimmune responses. Design: This is a single-center, single-arm, prospective exploratory clinical trial designed to evaluate the safety profile, preliminary therapeutic efficacy, and pharmacokinetic/pharmacodynamic (PK/PD) characteristics of YTS109 cell therapy in patients with refractory SLE. Approximately 36 patients aged 18-65 will receive a single infusion of YTS109 cells (1×10⁶-2×10⁶ cells/kg). The primary endpoint is observations of types, severity, and frequency of dose-limiting toxicities (DLTs) and adverse events (AEs). This study was approved by the IRB of Beijing GoBroad Hospital (Approval Number: RP2025-013-002), All participants provided written informed consent.

Study Timeline

• Status Verified: 2025-04
• Study Start: 2025-04-16
• Study First Submitted: 2025-04-16
• Study First Submitted QC: 2025-04-17
• Study First Posted: 2025-04-25
• Last Update Submitted: 2025-05-08
• Last Update Posted: 2025-05-13
• Primary Completion: 2026-04-25
• Study Completion: 2027-04-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment in this study:

1. Age ranges from 18 to 65 years old (including threshold), regardless of gender.
2. Meet the EULAR/ACR 2019 SLE Classification Criteri:

Cohort 1: Refractory Lupus Nephritis: Defined as failure to achieve remission after treatment with corticosteroids and ≥2 immunosuppressants (e.g., CTX, tacrolimus, MMF, cyclosporine) and/or biologics, with urine protein/creatinine ratio (UPCR ≥1.0 g/g) , and renal pathology requirement scriteria: ISN/RPS 2003 Class III/IV proliferative lupus nephritis (or combined with type V features) , with ≤50% glomerulosclerosis.

Cohort 2: Refractory Immune Thrombocytopenia: Requires treatment failure with: Failed treatment with at least 1 course of MP shock (1g for 3 days) or high- dose glucocorticosteroids (1mg/kg/d equivalent dose of glucocorticosteroids) in combination with 1 or more immunosuppressive agents. At least 2 consecutive routine blood tests for platelets less than 50×10^9/L and >30×10^9/L were performed prior to enrolment. other non-SLE causes of thrombocytopenia, such as infections, myelosuppression and hypersplenism, were excluded.

3. Essential Organ Function Criteria:

4. Bone marrow: Neutrophils ≥1×10^9/L (within 2 weeks, excluding granulocyte colony-stimulating factor use).

   Hemoglobin ≥60 g/L.

5. Liver: ALT/AST ≤3×ULN (disease-related elevations permitted). TBIL

   ≤1.5×ULN (disease-related elevations permitted).

6. Renal: CrCl≥30mL/min (Cockcroft-Gault formula, excluding acute declines).

7. Coagulation: INR/PT ≤1.5×ULN.

8. Cardiovascular: Hemodynamic stability. 4. Fertile females or males with partners of childbearing age must use medically approved contraception or abstain during and ≥12 months post- treatment. Negative serum HCG test (within 7 days pre-enrollment) for fertile females; non-lactating.

9. Voluntary participation with signed informed consent and compliance.

Exclusions Criteria:

Subjects who meet any of the following exclusion criteria will not be admitted to the study:

1. Severe drug allergies or hypersensitivity.
2. Uncontrolled/untreated infections (fungal, bacterial, viral, etc.).
3. CNS disorders (exceptions: epilepsy, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis, CNS vasculitis).
4. Heart failure intolerance.
5. Congenital immunoglobulin deficiency.
6. Malignancy within 5 years (exceptions: localized cancers with negligible metastasis risk).
7. End-stage renal failure.
8. Subjects positive for: HBsAg / HBcAb with HBV DNA > detection limit; HCV Ab + HCV RNA; HIV Ab; Syphilis test.
9. Deep vein thrombosis/pulmonary embolism within 6 months pre- screening.
10. Severe mental illness/cognitive impairment.
11. Participation in other clinical trials within 3 months pre-screening.
12. Use of immunosuppressants (within 5 half-lives) or biologics (within 4 weeks) pre-screening.
13. Pregnancy/breastfeeding or planned conception.
14. Other researcher-determined ineligibility.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
YTS109 cell	YTS109 cell injection	Subjects will receive YTS109 cell (1E6 STAR+T cell/kg or 2E6 STAR+T cell/kg) once in this study.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events	28 days for DLT during the treatment assessment period, and observation AEs will be conducted up to 52 weeks post-treatment.	1. Dose-limiting toxicity (DLT); 2. Types, severity, and frequency of adverse events (AEs).

Secondary Outcome Measures

Name	Time	Method
Time to Peak (Tmax) of YTS109	These detections will be conducted up to 52 weeks post-treatment.	To evaluate the metabolic characteristics of YTS109
Peak Plasma Concentration (Cmax) of YTS109	These detections will be conducted up to 52 weeks post-treatment.	To evaluate the metabolic characteristics of YTS109
Efficacy Evaluation in LN	The complete renal response (CRR) rate at week 12 in LN, and observation will be conducted up to 52 weeks post-treatment.	The proportion of subjects who achieved complete renal response (CRR) at 12 weeks
Efficacy Evaluation in SLE-ITP	The proportion of subjects achieving complete response (CR) or partial response (PR) at week 12 post-treatment in SLE-ITP, and observation will be conducted up to 52 weeks post-treatment.	The proportion of subjects achieving complete response (CR) or partial response (PR) at 12 weeks
PD parameters	These detections will be conducted up to 52 weeks post-treatment.	Changes in B cells quantification and phenotypic in peripheral blood
Area under the plasma concentration versus time curve (AUC) of YTS109	These detections will be conducted up to 52 weeks post-treatment.	To evaluate the metabolic characteristics of YTS109

Trial Locations

Locations (1)

Beijing GoBroad Hospital; 🇨🇳 Beijing, Beijing, China