An Exploratory Clinical Study of GC012F Injection for Refractory gMG

NCT06419166 | Withdrawn Early Phase 1

• 1 other identifier: TXB2024002
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-arm, open-label early exploratory clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of GC012F injection in subjects with refractory GMG. Additionally, the study aims to assess the pharmacokinetic (PK), pharmacodynamic (PD) characteristics, and immunogenicity of GC012F injection in subjects.

Conditions

Refractory Generalized Myasthenia Gravis

Outcome Measures

Primary Outcomes (8)

• Incidence of DLT

  DLT

  Within 28 days after GC012F injection infusion

• Frequency and severity of abnormal findings in electrocardiograms

  The electrocardiography shall be measured after 5 minutes of rest, and assessments included as follows: Heart rate, RR interval, PR interval, QT interval, QRS wave, QT interval and other indexes.

  Within 96 weeks after GC012F injection infusion

• Frequency and severity of abnormal findings of adverse events.

  Any untoward medical event that occurs after a subject has administered an investigational product, which may be manifested as a symptom, sign, disease or laboratory abnormality but does not necessarily have a causal relationship with the investigational product.

  Within 96 weeks after GC012F injection infusion

• Frequency and severity of abnormal findings in physical examinations

  The full physical examination at least includes assessments of skin, mucosa, lymph nodes, head, neck, chest, abdomen, spine/limbs, and nervous system. A full physical examination needs to be completed only during the screening period, and the physical examination can be performed in subsequent visit as per changes in signs and symptoms.

  Within 96 weeks after GC012F injection infusion

• Frequency and severity of abnormal findings in laboratory tests

  Laboratory tests include blood test，Coagulation function ，Infectious disease detection and tests recommended by the Investigator

  Within 96 weeks after GC012F injection infusion

• Frequency and severity of abnormal findings in vital signs

  Vital signs shall be measured after 5 minutes of rest, and assessments included as follows: Temperature, oxygen saturation, heart rate, respiratory rate, resting systolic and diastolic blood pressure.

  Within 96 weeks after GC012F injection infusion

• RP1D

  Recommended phase I dose

  2 years after GC012F injection infusion

• MTD

  maximum tolerated dose

  2 years after GC012F injection infusion

Secondary Outcomes (9)

• PK parameters of CAR-T cells in peripheral blood after GC012F infusion (Cmax);

  Within 96 weeks after GC012F injection infusion

• PK parameters of CAR-T cells in peripheral blood after GC012F infusion (Tmax);

  Within 96 weeks after GC012F injection infusion

• PK parameters of CAR-T cells in peripheral blood after GC012F infusion ( AUC);

  Within 96 weeks after GC012F injection infusion

• Levels of cytokines [IL-6、IL-10、IFN-γ、TNF-α、MCP-1(as applicable)], lymphocyte subsets, and soluble BCMA in peripheral blood after GC012F infusion;

  Within 28 days after GC012F injection infusion

• Disease activity indices:MG-ADL

  Within 96 weeks after GC012F injection infusion

Other Outcomes (3)

• • Detection rate of CAR-T cell antibodies in peripheral blood within 24 weeks post-GC012F infusion;

  within 24 weeks post-GC012F infusion;

• • Changes in serum immunoglobulin levels (including IgG, IgM, IgA, and IgE) in patients within 24 weeks post-GC012F infusion;

  within 24 weeks post-GC012F infusion

• • Detection rate of replication-competent lentivirus (RCL).

  Within 15 years after GC012F injection infusion

Study Arms (1)

Refractory gMG subjects

EXPERIMENTAL

Refractory Generalized Myasthenia Gravis

Drug: GC012F injection

Interventions

GC012F injection DRUG

Each subject will receive GC012F injection (CD19-BCMA CAR-T cells) once by intravenous infusion on Day 0. Other Name: CD19-BCMA CAR-T cells

Refractory gMG subjects

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects or his/her legal proxy/guardian voluntary signing the ICF, and willing and able to follow the procedure in this study.
• Aged ≥18 years old, no gender limitation;
• Patients with confirmed refractory GMG, and the clinical classification is IIa-IVb (including IIa, IIb, IIIa, IIIb, IVa and IVb) in screening;
• Patients whose MG-ADL score is 5 or more, and the proportion of ocular symptoms is less than 50% in the total score;
• Patients with poor efficacy of conventional treatment and/or no effective treatment means relapse or exacerbation despite conventional hormone, immunosuppressant (e.g., azathioprine, mycophenolate mofetil, tacrolimus, cyclosporin A, cyclophosphamide, etc.), or rituximab treatment;
• Patients who are on corticosteroids, the dose of prednisone should not exceed 20 mg/d (or no more than an equivalent dose of another corticosteroid) during the 3 weeks prior to apheresis, and the dose isn't escalated during 3weeksk prior to apheresis, the dose isn't changed within 4 weeks prior to infusion;
• Patients with positive MG-specific autoantibodies in the screening period: acetylcholine receptor autoantibody (anti-AChR) titer or muscle-specific tyrosine kinase autoantibody (anti-MuSK) or low-density lipoprotein receptor-associated protein 4 autoantibody (anti-LRP4) or anti-acetylcholine receptor cluster antibody must be higher than the upper limit of the laboratory reference normal value;
• Life expectancy ≥3 months;
• The results of laboratory test during screening period shall meet all following criteria:
• Neu ≥1.0 × 109/L; Hb ≥8.0 g/dL; PLT ≥50 × 109/L;
• ALT ≤3 × ULN; AST ≤3 × ULN; TBIL \<2 × ULN (DBIL ≤1.5 × ULN for subjects with Gilbert's syndrome)
• Creatinine clearance (19.3 Appendix 3) ≥30 mL/min;
• APTT ≤1.5 × ULN, PT ≤1.5 × ULN;
• LVEF ≥50% based on echocardiography, no findings of pericardial effusion.
• Women of child-bearing age should:

You may not qualify if:

• Subjects have a history of severe hypersensitivity or allergy;
• Any contraindication for fludarabine, cyclophosphamide and any component of the investigational product;
• Subjects with any of the following heart diseases:
• Congestive heart failure (New York Heart Association (NYHA) Class III or IV);
• Experienced myocardial infarction or underwent coronary artery bypass grafting (CABG) within 6 months prior to screening period;
• Clinically significant ventricular arrhythmias or a history of unexplained syncope not due to vasovagal reaction or dehydration; or a QTc interval \>480 ms during screening;
• History of severe non-ischemic cardiomyopathy.
• Accompanied by other uncontrolled malignancies. Subjects with the following conditions should be excluded: early-stage tumors that have received radical treatment (carcinoma in situ or grade 1 tumors, or non-ulcerated primary melanoma with a depth \<1 mm and no involvement of lymph nodes), basal cell skin cancer, skin squamous cell carcinoma, cervical carcinoma in situ, or breast cancer in situ that has received potential radical treatment;
• Severe underlying medical conditions, such as:
• Fungal, bacterial, viral or other infections or suspected fungal, bacterial, viral or other infections that cannot be controlled or require general intravenous administration;
• Significant clinical evidence of dementia or mental status changes;
• History of any central nervous system (CNS) or neurodegenerative diseases, (e.g., epilepsy, seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, psychiatric disorders).
• Positive results in any of the following tests:
• HIV antibody positive;
• HBsAg positive; or HBcAb positive and HBV-DNA above the lower limit of detection of the analytical method;

Sponsors & Collaborators

• Zhejiang University: lead
• Gracell Biotechnologies (Shanghai) Co., Ltd.: collaborator

Study Sites (1)

The First Affiliated Hospital,College of Medicine, Zhejiang University

Hanzhou, Zhejiang, 310003, China

Location

MeSH Terms

Conditions

Myasthenia Gravis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: May 17, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: June 27, 2025

Record last verified: 2025-06

Locations

CN (1)