- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT07714798
Universal STAR-T Cell Injection in Generalized Myasthenia Gravis
An Exploratory Clinical Study of Universal STAR-T Cell Injection in Subjects With Generalized Myasthenia Gravis
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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 1
Kontakter og lokationer
Studiekontakt
- Navn: Daishi Tian
- Telefonnummer: 13607178809
- E-mail: tiands@tjh.tjmu.edu.cn
Studiesteder
-
-
Hubei
-
Wuhan, Hubei, Kina, 430030
- Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
-
Kontakt:
- Daishi Tian
- Telefonnummer: 13607178809
- E-mail: tiands@tjh.tjmu.edu.cn
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Beskrivelse
Inclusion Criteria:
Subjects must meet all the following inclusion criteria to be enrolled in this study:
- Age 18-65 years (inclusive), gender (no gender restriction);
- 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;
- Have received MG treatment for at least 3 months and present with any of the following conditions:
- MG-ADL total score increased by ≥2 points, and no single ocular item increased by >1 point;
- QMGS total score increased by ≥3 points, or ≥2 non-ocular items each increased by ≥1 point;
- Increased dose of MG-related drugs, hospitalization, or emergency intervention required due to MG exacerbation; 4. Function of important organs meets the following requirements:
Bone marrow function:
- Absolute neutrophil count ≥1×10⁹/L (no colony-stimulating factor treatment within 2 weeks before testing);
- Hemoglobin ≥80 g/L (excluding neutropenia caused by disease);
- 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);
- Renal function: Serum creatinine (CrCl) ≥45 mL/min (calculated by Cockcroft-Gault formula; acute CrCl decrease due to disease is excluded);
- Coagulation function: International Normalized Ratio (INR) ≤1.5×ULN; Prothrombin Time (PT) ≤1.5×ULN;
- 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 exclusion criteria will be excluded from this study:
- Have used immunomodulatory or immunosuppressive drugs with therapeutic effects on the disease within 5 half-lives before enrollment, or biologics within 4 weeks (except for those who have received rituximab, with the last use of rituximab <3 months prior [B-cell reconstitution is excluded]);
- Have a history of severe drug allergy or allergic constitution;
- Have uncontrolled or requiring treatment for fungal, bacterial, or viral infections;
- Have active tumor lesions at screening;
- Have cardiac insufficiency (New York Heart Association [NYHA] functional class >II), and cannot tolerate platelet and cellular transfusions;
- Have congenital immunodeficiency;
- Have a history of malignant tumor (except for cured cutaneous basal cell carcinoma or cervical carcinoma in situ);
- Have end-stage renal failure;
- Positive for Hepatitis B surface Antigen (HBsAg), or positive for Hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA level or titer above the cutoff value for positive specimens; positive for Hepatitis C virus (HCV) antibody with peripheral blood HCV RNA positive; positive for Human Immunodeficiency Virus (HIV) antibody; positive for syphilis testing;
- Pregnant or planning to become pregnant during the study or within 2 years after the end of study treatment (for both male and female subjects);
- Investigators consider there are other reasons that should not be included in this study.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Universal STAR-T Cell
Subjects will receive infusion of Universal STAR-T Cells at the starting dose of 1.5E6 STAR+T cells/kg.
|
Subjects will receive infusion of Universal STAR-T Cells at the starting dose of 1.5E6 STAR+T cells/kg.
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Type, severity, and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs).
Tidsramme: 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.
|
AEs observation will be follow-up for 24 weeks. The observation period is extended to 104 weeks.
|
|
Incidence of Dose-Limiting Toxicities (DLTs).
Tidsramme: 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.
|
Within 28 days after infusion
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Change in Myasthenia Gravis Quantitative Scale (QMG) or Myasthenia Gravis Activities of Daily Living (MG-ADL) Scores.
Tidsramme: 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.
|
The efficacy endpoint evaluation for 104 weeks.
|
|
Maximum Plasma Concentration of Universal STAR-T Cells (Cmax)
Tidsramme: 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 .
|
Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Universal STAR-T Cells.
Tidsramme: 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.
|
Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.
|
|
Area Under the Plasma Concentration-Time Curve (AUC) of Universal STAR-T Cells.
Tidsramme: 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.
|
Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.
|
|
Change in Serum Cytokine Concentrations (IL-1β, IL-6, etc.) as a PD Biomarker.
Tidsramme: 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.
|
Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.
|
|
PD Biomarker Level Change (B cells Quantification and Phenotypic).
Tidsramme: 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.
|
Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.
|
|
Immunogenicity: Anti-Drug Antibodies (ADA) against universal STAR-T cells.
Tidsramme: 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.
|
Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.
|
|
Change in Replication-Competent Adeno-Associated Virus (RCA) Concentration in Peripheral Blood.
Tidsramme: 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.
|
Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.
|
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Studieleder: Daishi Tian, Tongji Hospital
Datoer for undersøgelser
Studer store datoer
Studiestart (Anslået)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Sygdomme i nervesystemet
- Neoplasmer efter sted
- Neoplasmer
- Neuromuskulære sygdomme
- Autoimmune sygdomme
- Sygdomme i immunsystemet
- Autoimmune sygdomme i nervesystemet
- Neurodegenerative sygdomme
- Paraneoplastiske syndromer, nervesystemet
- Neoplasmer i nervesystemet
- Paraneoplastiske syndromer
- Neuromuskulære Junction-sygdomme
- Myasthenia gravis
Andre undersøgelses-id-numre
- YTS209-002
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
Kliniske forsøg med Generaliseret myasthenia gravis
-
Myasthenia Gravis Foundation of AmericaAlira HealthRekrutteringMyasthenia gravis | Myasthenia Gravis, generaliseret | Myasthenia Gravis krise | Myasthaenia Gravis | Myasthenia Gravis, okulær | Myasthenia Gravis, Thymectomy | Myasthenia Gravis, voksen form | Myasthenia Gravis generaliseret | Myasthenia Gravis, MuSK | Myasthenia gravis eksacerbationer | Myasteni | Myasthenia... og andre forholdForenede Stater
-
argenxIkke rekrutterer endnugMG | MG - Myasthenia Gravis | AChR-Ab-seropositiv generaliseret myasthenia gravis | Myasthenia Gravis (MG)
-
Assiut UniversityRekrutteringSygdomme i nervesystemet | Autoimmune sygdomme i nervesystemet | Thymom | Myasthenia gravis | Neuromuskulære Junction-sygdomme | Myasthenia Gravis, generaliseret | Myasthenia Gravis krise | Myasthenia Gravis, okulær | Myasthenia Gravis, juvenil form | Thymus hyperplasi | Myasthenia gravis med eksacerbation (lidelse) og andre forholdEgypten
-
argenxRekrutteringGeneraliseret myasthenia gravis | Myasthenia gravis | gMG | Generaliseret myasthenia gravis (gMG) | MG | AChR-Ab-seropositiv generaliseret myasthenia gravisForenede Stater, Polen, Italien, Belgien, Spanien
-
argenxRekrutteringGeneraliseret myasthenia gravis | Myasthenia gravis | gMG | Generaliseret myasthenia gravis (gMG) | MG | AChR-Ab-seropositiv generaliseret myasthenia gravisForenede Stater, Spanien, Belgien, Polen, Italien
-
Shanghai Zhongshan HospitalHuashan Hospital; West China Hospital; Tang-Du Hospital; Second Affiliated... og andre samarbejdspartnereIkke rekrutterer endnuMyasthenia Gravis forbundet med Thymoma | Efgartigimod | Intravenøs immunoglobulinKina
-
University of Colorado, DenverargenxRekrutteringMyasthenia Gravis krise | Myasthenia gravis eksacerbationer | AChR Myasthenia GravisForenede Stater
-
argenxAfsluttetGeneraliseret myasthenia gravis | gMG | MG - Myasthenia GravisGeorgien, Forenede Stater, Østrig, Belgien, Canada, Frankrig, Tyskland, Italien, Holland, Polen, Spanien
-
argenxAktiv, ikke rekrutterendeGeneraliseret myasthenia gravis | Myasthenia gravis | Myasthenia Gravis, generaliseret | gMGForenede Stater, Belgien, Danmark, Tyskland, Kina, Holland, Norge, Spanien, Saudi Arabien, Det Forenede Kongerige, Tjekkiet, Serbien, Polen, Grækenland, Georgien, Rumænien, Finland, Ungarn, Frankrig, Canada, Portugal, Cypern
-
IRCCS San RaffaeleIkke rekrutterer endnuThymom | Myasthenia Gravis forbundet med Thymoma | Myasthenia Gravis (MG)Italien
Kliniske forsøg med Universal STAR-T Cell
-
Daishi TianChina Immunotech (Beijing) Biotechnology Co., Ltd.Ikke rekrutterer endnuMultipel sklerose (MS)Kina
-
Xuanwu Hospital, BeijingBioray LaboratoriesIkke rekrutterer endnuMultipel sclerose | Neuromyelitis Optica Spectrum Disorders | Kronisk inflammatorisk demyeliniserende polyradiculoneuropati | Myasthenia Gravis, generaliseretKina
-
Peking UniversityIkke rekrutterer endnu
-
The Children's Hospital of Zhejiang University...RekrutteringSystemisk lupus erythematosusKina
-
The Affiliated Nanjing Drum Tower Hospital of Nanjing...RekrutteringSystemisk lupus erythematosus (SLE)Kina
-
Wuhan Union Hospital, ChinaGuangzhou Bio-gene Technology Co., LtdRekrutteringSystemisk lupus erythematosusKina
-
CARsgen Therapeutics Co., Ltd.Aktiv, ikke rekrutterendeMyelomatoseForenede Stater, Canada
-
920th Hospital of Joint Logistics Support Force...Gracell Biotechnology Shanghai Co., Ltd.; Kunming Hope of Health HospitalRekrutteringRecidiverende eller refraktær B-celle akut lymfoblastisk leukæmi | Recidiverende eller refraktær B-celle non-hodgkin lymfomKina
-
Changzhou No.2 People's HospitalIkke rekrutterer endnuSystemisk lupus erythematosus | Systemisk sklerose | Myasthenia gravis | Autoimmun hæmolytisk anæmi | ANCA-associeret vaskulitis | Inflammatorisk myopati | IgG4-RDKina
-
First Affiliated Hospital of Zhejiang UniversityST Phi Therapeutics Co., LtdRekruttering