A Study of YTS109 Cell in Subjects With Relapsed/Refractory Autoimmune Hemolytic Anemia

Not Applicable

Recruiting

• Conditions: Autoimmune Hemolytic Anemia
• Interventions: Drug: YTS109 cell

• Registration Number: NCT07075484
• Lead Sponsor: China Immunotech (Beijing) Biotechnology Co., Ltd.

Brief Summary

This is a Phase I, single-arm, open-label, dose-escalation and dose-expansion study. The primary objective is to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of YTS109 STAR-T cell therapy in patients with autoimmune hemolytic anemia who have failed ≥3 lines of therapy. The objective is to evaluate the safety, preliminary efficacy, pharmacokinetics/pharmacodynamics (PK/PD), and immune cell reconstitution characteristics of YTS109 cell therapy in Multi-rAIHA subjects who have failed third-line or higher-line treatments.

This study will also conduct an exploratory investigation into the impact of non-lymphodepleting conditioning prior to the infusion of STAR-T cells. For the non-lymphodepleting exploratory cell infusion, it can be administered as a single infusion or divided into 1 to 3 infusions (with the fractionated infusions to be completed within 7 days (and in any case no later than 15 days)). Dose escalation will commence at 5E6 cells/kg or the starting dose may be adjusted based on accumulated data.

Detailed Description

Not provided

Study Timeline

• Status Verified: 2025-01
• Study Start: 2025-01-15
• Study First Submitted: 2025-07-11
• Study First Submitted QC: 2025-07-11
• Study First Posted: 2025-07-20
• Last Update Submitted: 2025-07-24
• Last Update Posted: 2025-07-29
• Primary Completion: 2025-12-30
• Study Completion: 2026-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

• Age ≥12 years, regardless of gender.
• Diagnosis of AIHA or Evans syndrome [including warm antibody, mixed AIHA and cold antibody AIHA (Cold agglutinin disease)].
• Failure or intolerance to at least 3 lines of therapy: glucocorticoids and/or rituximab, and any one of the following treatments (splenectomy, cyclosporine, cyclophosphamide, azathioprine, mycophenolate mofetil, bendamustine, fludarabine, bortezomib, etc.Biologics, including anti-CD38 monoclonal antibody, BTK inhibitor, Syk inhibitor and complement inhibitor) (HGB < 100g/L).
• Adequate organ function: a. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN. b. Creatinine clearance (CrCl) (Cockcroft-Gault formula) ≥60ml/min. c.Blood oxygen saturation (SpO2) ≥92%.
• ECOG performance status≤2
• Subjects of childbearing potential will be required to follow contraception requirements from the time of enrollment until the end of the 12-month safety follow-up period.
• The subjects voluntarily participate in the study, sign the informed consent, demonstrate good compliance, and cooperate with follow-up.

Exclusion Criteria

• Diagnosis of lymphoproliferative tumor
• Other hereditary or acquired hemolytic diseases (Secondary AIHA caused by drugs or infection)
• The platelet count in peripheral blood<30×10^9/L
• Pregnant or breast-feeding subjects
• Receive any of the following treatments within the specified time before cell infusion: a.anti-CD20 monoclonal antibodies <12 weeks, b.sutimlimab or other marketed biologics <5 half-lives,c.plasma exchange <4 weeks, d.post-splenectomy <12 weeks, e. BTK inhibitors, anti-CD38 monoclonal antibody, Syk inhibitors, BAFF inhibitors < 5 half-lives.
• Previously received organ or stem cell transplantation
• History of new thrombosis or organ infarction in the past 6 months
• Diagnosis of the active stage of the connective tissue disease.
• Have active infections, such as sepsis, bacteremia, fungemia, uncontrolled pulmonary infection and active tuberculosis, etc.
• Positive hepatitis B surface antigen (HBsAg) or hepatitis B e antigen (HBeAg); positive hepatitis B e antibody (HBe-Ab) or hepatitis B core antibody (HBc-Ab), and the HBV-DNA copy number is above the lower limit of the measurable capacity; positive hepatitis C (HCV) antibody; positive human immunodeficiency virus (HIV) antibody; positive syphilis test.
• Underwent major surgery within 4 weeks before screening, as determined by the investigator to be unsuitable for enrollment.
• Have malignant tumors within 5 years before enrollment, except tumors with negligible risk of metastasis or death and curable tumors, such as adequately treated cervical carcinoma in situ, cutaneous basal cell carcinoma, etc.
• Have any of the following cardiovascular diseases: a.Left ventricular ejection fraction (LVEF) ≤45%, b. presence of active heart disease or congestive heart failure (New York Heart Association [NYHA] Class III or IV)), c.severe arrhythmias requiring treatment, d.have myocardial infarction, bypass surgery, or stent placement within the 6 months before the study, e.other heart diseases judged by the researcher to be unsuitable for enrollment.
• Have a history of live attenuated vaccines within 6 weeks before enrollment.
• Have a history of epilepsy or other active central nervous system diseases.
• Have an allergy to the ingredients of the medicine used in this study.
• Previously received CAR-T cell therapy.
• Patients considered to be ineligible for the study by the investigator for reasons other than the above.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
YTS109 cell	YTS109 cell	Subjects will receive YTS109 cell, and dose escalation will commence at 5E6 cells/kg or the starting dose may be adjusted based on accumulated data.

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicity	Within 28 days after infusion
The incidence and frequency of treatment-emergent adverse events	Within 12 months after infusion	Safety assessments are conducted using the NCI-CTCAE version 5.0 standards.

Secondary Outcome Measures

Name	Time	Method
Best overall response rate (BOR) of each dose group	Within 12 weeks after infusion	BOR is determined as the most favorable response observed after cell infusion, until either disease relapse or the completion of a specified observation period.
Time to response (TTR)	Within 6 months after infusion	TTR is defined as the duration from cell infusion to the achievement of a hematological response.
Area under the plasma concentration versus time curve (AUC) of YTS109	Within 12 months after infusion	To evaluate the metabolic characteristics of YTS109
The reconstitution of B cell in peripheral blood	Within 12 months after infusion	Changes in B cells quantification and phenotypic in peripheral blood
Objective response rate (ORR) of each dose group	Within 4 weeks after infusion
Peak Plasma Concentration (Cmax) of YTS109	Within 12 months after infusion	To evaluate the metabolic characteristics of YTS109
Time to Peak (Tmax) of YTS109	Within 12 months after infusion	To evaluate the metabolic characteristics of YTS109

Trial Locations

Locations (1)

Institute of Hematology & Blood Diseases Hospital, China; 🇨🇳 Tianjin, Tianjin, China