Generalized Myasthenia Gravis
Conditions
Keywords
Generalized Myasthenia Gravis
Brief summary
This is a Phase I, single-arm, open-label, dose-escalation and dose-expansion study. This is an exploratory clinical study of universal STAR-T cell injection in patients with refractory generalized myasthenia gravis (GMG). Approximately 10-24 participants aged 18-65 years (inclusive) with the condition are planned to be enrolled. The primary objective is to evaluate the safety, tolerability, preliminary efficacy, pharmacokinetic/pharmacodynamic (PK/PD) profile, and immunogenicity of universal STAR-T cell injection. The starting dose is 1.5E6 STAR+ T cells/kg, administered as a single intravenous infusion.Based on safety, PK results, and preliminary efficacy data obtained from the initial dose cohorts, a recommended dose will be selected for subsequent dose-expansion studies to further systematically evaluate the safety and efficacy of universal STAR-T cell injection. 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). The study is being conducted at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
Interventions
Subjects will receive infusion of Universal STAR-T Cells at the starting dose of 1.5E6 STAR+T cells/kg.
Sponsors
Daishi Tian
China Immunotech (Beijing) Biotechnology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must meet all the following inclusion criteria to be enrolled in this study: 1. Age 18-65 years (inclusive), gender (no gender restriction); 2. Previously diagnosed with Generalized Myasthenia Gravis (GMG), meeting the 2020 MGFA diagnostic criteria, with MG-ADL total score ≥6 and ocular-related subscore \<50% of the total score, positive relevant antibodies, MGFA classification Grade II-IV, and having received at least 2 kinds of immunosuppressants or biological agents for standardized treatment; 3. Have received MG treatment for at least 3 months and present with any of the following conditions: <!-- --> 1. MG-ADL total score increased by ≥2 points, and no single ocular item increased by \>1 point; 2. QMGS total score increased by ≥3 points, or ≥2 non-ocular items each increased by ≥1 point; 3. Increased dose of MG-related drugs, hospitalization, or emergency intervention required due to MG exacerbation; 4. Function of important organs meets the following requirements: <!-- --> 1. Bone marrow function: 1. Absolute neutrophil count ≥1×10⁹/L (no colony-stimulating factor treatment within 2 weeks before testing); 2. Hemoglobin ≥80 g/L (excluding neutropenia caused by disease); 2. Liver function: ALT ≤3×ULN (elevated ALT due to disease is excluded); AST ≤3×ULN (elevated AST due to disease is excluded); TBIL ≤1.5×ULN (elevated TBIL due to disease is excluded); 3. Renal function: Serum creatinine (CrCl) ≥45 mL/min (calculated by Cockcroft-Gault formula; acute CrCl decrease due to disease is excluded); 4. Coagulation function: International Normalized Ratio (INR) ≤1.5×ULN; Prothrombin Time (PT) ≤1.5×ULN; 5. Cardiac function: Systolic blood pressure \>90 mmHg, no need for vasoactive drug maintenance; 5. Female subjects of childbearing potential and their male partners (of childbearing age) must use medically recognized contraceptive measures or abstain from sex during the study treatment period and for at least 12 months after the end of study treatment; female subjects of childbearing age must have a negative serum HCG test within 7 days before enrollment and not be in lactation; 6. Voluntarily participate in this clinical study, sign the informed consent form, be compliant, and cooperate with follow-up.
Exclusion criteria
* Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Type, severity, and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs). | AEs observation will be follow-up for 24 weeks. The observation period is extended to 104 weeks. | Characterization of treatment-emergent adverse events (TEAEs) graded by NCI-CTCAE v6.0, including laboratory abnormalities, vital sign changes, and infusion-related reactions. |
| Incidence of Dose-Limiting Toxicities (DLTs). | Within 28 days after infusion | To assess the safety and tolerability of \[Drug Name\] and determine the Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D). DLTs are defined according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v6.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Myasthenia Gravis Quantitative Scale (QMG) or Myasthenia Gravis Activities of Daily Living (MG-ADL) Scores. | The efficacy endpoint evaluation for 104 weeks. | Evaluation of preliminary efficacy based on the Myasthenia Gravis Quantitative Scale (QMG) and Myasthenia Gravis Activities of Daily Living (MG-ADL) scale. Response is defined as a ≥5-point reduction from baseline in either the QMG score or the MG-ADL score. Both scales are standardized patient-reported outcome measures. |
| Maximum Plasma Concentration of Universal STAR-T Cells (Cmax) | Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks. | To evaluate the maximum observed plasma concentration of Universal STAR-T Cells . |
| Time to Reach Maximum Plasma Concentration (Tmax) of Universal STAR-T Cells. | Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks. | To evaluate the time to reach the maximum observed plasma concentration of Universal STAR-T Cells. |
| Area Under the Plasma Concentration-Time Curve (AUC) of Universal STAR-T Cells. | Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks. | To evaluate the total systemic exposure to Universal STAR-T Cells over time. |
| Change in Serum Cytokine Concentrations (IL-1β, IL-6, etc.) as a PD Biomarker. | Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks. | Evaluation of pharmacodynamic (PD) effects via serial measurement of serum cytokine concentrations, including IL-1β, IL-2R, IL-6, IL-8, TNF-α, and IFN-γ, using validated ELISA kits. |
| PD Biomarker Level Change (B cells Quantification and Phenotypic). | Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks. | Evaluation of Pharmacodynamic (PD) effects of Universal STAR-T Cells via serial quantification of CD19-positive B cells in peripheral blood, expressed as cells per microliter (cells/μL). Measurement will be performed using flow cytometry according to standardized laboratory protocols. |
| Immunogenicity: Anti-Drug Antibodies (ADA) against universal STAR-T cells. | Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks. | To evaluate the development of anti-drug antibodies (ADA) against allogeneic universal STAR-T cells in peripheral blood. |
| Change in Replication-Competent Adeno-Associated Virus (RCA) Concentration in Peripheral Blood. | Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks. | To quantitatively detect replication-competent adeno-associated virus (RCA) in peripheral blood using droplet digital PCR (ddPCR). Results will be reported as copies/mL. RCA detection serves as a safety biomarker to assess potential vector shedding or replication in vivo. |
Countries
China
Contacts
CONTACTDaishi Tian
STUDY_DIRECTORDaishi Tian
Tongji Hospital
Outcome results
None listed