An Early Exploratory Clinical Study of GC012F Injection in the Treatment of Refractory Generalized Myasthenia Gravis

NCT06759948 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: KY2024-853
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label and early exploratory clinical study, with the purpose to study the safety, tolerability and initial clinical efficacy of GC012F Injection in the treatment of refractory GMG and to evaluate the PK, PD characteristics and immunogenicity in subjects with refractory GMG infused with GC012F Injection.

Conditions

Generalized Myasthenia Gravis (gMG)

Outcome Measures

Primary Outcomes (2)

• Primary endpoints

  1、DLT incidence; DLT is defined as any of the following conditions associated with GC012F Injection occurring within 28 days post cell infusion: 1. Neurotoxicity: Grade 3 and 4, which cannot recover to Grade 2 or lower within 7 days after therapeutic intervention; 2. CRS: Grade 4, which cannot recover to Grade 2 or lower within 3 days after therapeutic intervention; 3. Non-hematological toxicity: Grade 3 and Grade 4, involving heart, lung and kidney, which cannot recover to Grade 2 or lower within 28 days after therapeutic intervention; Grade 5; 4. Hematological toxicity: Grade 4, which cannot recover to Grade 2 or lower within 3 days after therapeutic intervention. The predictable complication for chemotherapeutics is not included as a DLT in this study.

  Since signing the ICF until 24-week post-infusion or premature withdrawal from the study, whichever comes first.

• Primary endpoints

  Abnormal results of physical examination, vital signs, laboratory tests, electrocardiography and echocardiography, and the frequency and severity of AEs. The grading criteria for adverse event severity were based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0

  Since signing the ICF until 24-week post-infusion or premature withdrawal from the study, whichever comes first.

Secondary Outcomes (3)

• Secondary endpoints

  Since signing the ICF until 24-week post-infusion or premature withdrawal from the study, whichever comes first.

• Secondary endpoints

  Since signing the ICF until Long-term follow-up period or withdraw

• Secondary endpoints

  Since signing the ICF until 24-week post-infusion or premature withdrawal from the study, whichever comes first.

Other Outcomes (3)

• Exploratory endpoints

  Baseline to 24 weeks post GC012F infusion;

• Exploratory endpoints

  baseline to 24 weeks post GC012F infusion

• Exploratory endpoints

  on D-1 ,M1/3/6/12/18/24

Study Arms (1)

There're 3 dose groups in this study.Dose will be escalated based on "3+3" rule.

EXPERIMENTAL

There're 3 dose groups in this study for CAR-T cell infusion: 1×10\^5/kg, 2×10\^5/kg, 3×10\^5/kg. Dose will be escalated based on "3+3" rule. 3\~6 subjects will be enrolled into each dose group, approximately 9\~18 subjects in total will be enrolled. Subjects of each dose group will be observed for DLT within 28 days (Dose-limiting toxicities (DLT) observation period) after GC012F injection infusion.

Drug: GC012F injection

Interventions

GC012F injection DRUG

Subjects will be infused with GC012F Injection within 48-72 hours after lymphodepletion pretreatment, the infusion dose (CAR-T cells) and groups are as follows: 1. Dose group 1: 1 × 10\^5/kg; 2. Dose group 2: 2 × 10\^5/kg; 3. Dose group 3: 3 × 10\^5/kg; Note: For subjects weighing ≤70 kg: number of infused CAR-T cells = (1, 2 or 3) (±20%) × 10\^5 × body weight(kg); for subjects weighing \>70 kg: number of infused CAR-T cells (fixed doses of GC012F Injection) = (1, 2 or 3) (±20%) × 10\^5 × 70 kg.

There're 3 dose groups in this study.Dose will be escalated based on "3+3" rule.

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 who meet all the following criteria can be included in this study:
• Subjects or their legal representative voluntary signing the ICF, and willing and able to follow the procedure in this study.
• Aged between 18 and 75 years old (including 75), no gender limitation;
• Patients with confirmed refractory GMG, and the clinical classification according to MGFA is IIa-IVb (including IIa, IIb, IIIa, IIIb, IVa and IVb) at screening;
• At screening, the MG-ADL score must be ≥6, with ocular symptoms accounting for less than 50% of the total score, and QMG must be ≥11;
• Ineffectiveness of conventional treatment and/or lack of effective therapeutic options, referring to relapse or exacerbation after standard treatments with hormones, immunosuppressants (e.g., azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine A, cyclophosphamide, methotrexate, etc.), or biological agents (e.g., rituximab);
• If the subject is currently using corticosteroids, the dose of prednisone must not exceed 30 mg/day (or the equivalent dose of other corticosteroids) and must remain stable for at least 4 weeks prior to infusion;
• Only subjects with positive MG-specific autoantibodies: the titer/level of anti-acetylcholine receptor (anti-AChR) antibodies or muscle-specific kinase (anti-MuSK) antibodies must be above the reference laboratory's upper normal limit (UNL);
• 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 childbearing potential (WCBP) should:

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from the study:
• Subjects have a history of severe hypersensitivity or allergy;
• Any contraindication for fludarabine, cyclophosphamide and any component of the investigational product;
• Administration of intravenous immunoglobulin or plasmapheresis or immunoadsorption treatment within 4 weeks prior to infusion;
• Use of B-cell targeting drugs, including but not limited to rituximab, Belimumab, and Telitacicept, within 6 months prior to apheresis;
• Used tacrolimus, cyclosporine, azathioprine, mycophenolate, mycophenolate, methotrexate, etc., within 3 weeks prior to apheresis;
• Treatment with neonatal Fc receptor (FcRn) antagonists (such as Efgartigimod, etc.) within 3 weeks prior to apheresis
• Use of complement inhibition therapy (such as eculizumab, etc.) within 3 weeks prior to apheresis;
• Subjects with any of the following heart diseases:
• Congestive heart failure (New York Heart Association (NYHA) Class III or IV);
• Experienced unstable angina, 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.
• Serious cardiovascular abnormalities (such as abnormal brain natriuretic peptide BNP/ troponin and other indicators) and the investigators estimate that the patients should not be enrolled;
• Accompanied by other uncontrolled malignant tumors. Subjects with the following conditions will be eligible: early-stage tumors that have received curative treatment (carcinoma in situ or stage I 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 curative treatment;

Sponsors & Collaborators

• Chongbo Zhao: lead
• Gracell Biotechnologies (Shanghai) Co., Ltd.: collaborator

Study Sites (1)

Huashan Hospital, affiliated to Fudan University, Shanghai,

Shanghai, Shanghai Municipality, 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

Central Study Contacts

Jie Song, Subi

CONTACT

18317086762; sdsj1990@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician of Neurology

Study Record Dates

• First Submitted: December 19, 2024
• First Posted: January 6, 2025
• Study Start: February 15, 2025
• Primary Completion (Estimated): February 13, 2027
• Study Completion (Estimated): September 10, 2027
• Last Updated: January 6, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)