A Study on the Safety and Tolerability of Universal STAR-T Cell Therapy for Multiple Sclerosis.

A Clinical Study on the Safety and Tolerability of Universal STAR-T Cell Injection in Patients With Multiple Sclerosis.

This is a Phase I, single-arm, open-label, dose-escalation and dose-expansion study.

The main objective is to explore the safety and tolerability of the universal STAR-T cell injection in patients with progressive or relapsing-remitting multiple sclerosis (MS).The secondary objectives are to evaluate the efficacy of the universal STAR-T cell injection in treating patients with progressive or relapsing-remitting MS; and to assess the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the universal STAR-T cell injection.

The primary endpoint of this study is the incidence rate of dose-limiting toxicity (DLT), as well as the types, severity and frequency of adverse events (AE).The secondary research endpoints of this study are the efficacy endpoints as well as the expansion and persistence of the universal STAR-T cells in the body.

This study is an exploratory clinical trial of the universal STAR-T cell injection for the treatment of progressive or relapsed-remitting MS. The study will be conducted in two phases: dose escalation and dose expansion. The dose escalation group 1 (1.5E6 STAR-T cells) begins, followed by dose escalation group 2 (3E6 STAR-T cells), and dose escalation group 3 (4.5E6 STAR-T cells).

Expansion study phase: After the dose escalation stage is completed, based on the safety, PK results and preliminary efficacy data of each dose group during the escalation stage, the recommended dose will be determined for the dose expansion study. It is planned to include 3 to 6 subjects to further systematically evaluate the safety and efficacy of the universal STAR-T cell.

This study includes the screening period (from D-28 to D-6), the pre-clearance treatment and rest observation period (from D-5 to D-1), the cell infusion and main study endpoint observation period (from D0 to W12 after infusion), and the follow-up period (from W12 after infusion to W104).

Inclusion Criteria:

• 1. Aged from 18 to 65 years (inclusive), with no gender restriction.

• 2. Patients with MS who have been diagnosed according to the specified diagnostic criteria in the past and currently have no effective treatment options need to meet the following requirements, including:

  1. According to the revised 2024 McDonald diagnostic criteria, they are clinically diagnosed with progressive MS (including primary progressive PPMS or secondary progressive SPMS) or relapsing-remitting MS (RRMS), and their disability status at the time of screening meets an EDSS score of 2-7 (inclusive).
  2. For RRMS patients, they need to meet any of the following conditions: a) They have failed treatment with ≥1 effective DMT (fenogomide, cinemodide, ozamod, and anti-CD20 monoclonal antibody therapy, etc.); b) They have had at least 2 clinical relapses in the past 2 years, or they have had 1 clinical relapse in the past 2 years and MRI shows ≥1 new Gd-enhanced lesion, or they have had ≥1 new Gd-enhanced lesion on MRI within the past 6 months; c) There are ≥2 active Gd-enhanced lesions on T1-weighted brain MRI at the time of screening.

• 3. The functions of important organs should meet the following requirements:

  1. Bone marrow function should satisfy: a. Neutrophil count ≥ 1×109/L (no colony-stimulating factor treatment within 2 weeks before the examination, and neutrophil reduction caused by the disease is excluded); b. Hemoglobin ≥ 60g/L;
  2. Liver function: ALT ≤ 3×ULN (ALT elevation caused by the disease can be excluded); AST ≤ 3×ULN (AST elevation caused by the disease can be excluded); TBIL ≤ 1.5×ULN (TBIL elevation caused by the disease can be excluded);
  3. Kidney function: Creatinine clearance rate (CrCl) ≥ 30 ml/minute (Cockcroft/Gault formula, acute CrCl decline caused by the disease is excluded);
  4. Coagulation function: International normalized ratio (INR) ≤ 1.5×ULN, prothrombin time (PT) ≤ 1.5×ULN;
  5. Cardiac function: Good hemodynamic stability;

• 4. For female subjects with reproductive capacity and their male partners, as well as male subjects whose female partners are of childbearing age, they are required to adopt medically approved contraceptive measures or abstain from sexual activity during the study treatment period and for at least 12 months after the end of the study treatment; female subjects of childbearing age must have a negative serum HCG test result within 7 days before study enrollment and must not be in the lactation period.

• 5. Voluntarily participated in this clinical study, signed the informed consent form, had good compliance, and cooperated with the follow-up.

Exclusion Criteria:

If the subjects meet any of the following exclusion criteria, they will not be included in this study:

• 1. The period of using immunosuppressants with therapeutic effects on the disease before enrollment is within five half-lives or the biological agents have been used for 4 weeks. For subjects who have received rituximab treatment, the time since the last use of rituximab is less than 3 months (except for those with B-cell reconstitution);
• 2. Have a severe history of drug allergy or are allergic constitution;
• 3. Have uncontrollable or require treatment infections such as fungi, bacteria, viruses, etc.;
• 4. Have active tuberculosis at the time of screening;
• 5. Have heart dysfunction (NYHA cardiac function classification > grade II) and cannot tolerate the study's lymphocyte purification and cell reinfusion.
• 6.Subjects with congenital immunoglobulin deficiencies;
• 7. Subjects with a history of unremitting malignant tumors within the past five years;
• 8. Subjects with end-stage renal failure;
• 9. Subjects with positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and peripheral blood HBV DNA titer higher than the detection limit; subjects with positive hepatitis C virus (HCV) antibody and positive HCV RNA in peripheral blood; subjects with positive human immunodeficiency virus (HIV) antibody; subjects with positive syphilis test results;
• 10. Male and female subjects who are pregnant or have a fertility plan during the participation in this study or within 2 years after receiving study treatment;
• 11. Subjects that the researchers consider have other reasons that prevent them from being included in this study.