## Protocol Section
### Identification Module
**NCT ID:** NCT06419166

**Brief Title:** An Exploratory Clinical Study of GC012F Injection for the Treatment of Refractory Generalized Myasthenia Gravis

**Official Title:** An Exploratory Clinical Study of GC012F Injection for the Treatment of Refractory Generalized Myasthenia Gravis

#### Organization Study ID Info
**ID:** TXB2024002
#### Organization
**Class:** OTHER
**Full Name:** Zhejiang University
### Status Module
#### Completion Date
**Date:** 2026-10-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-17

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-13

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2026-06-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-17
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-25
**Study First Submit QC Date:** 2024-05-13
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Gracell Biotechnology Shanghai Co., Ltd.

#### Lead Sponsor

**Class:** OTHER

**Name:** Zhejiang University

#### Responsible Party

**Investigator Affiliation:** Zhejiang University

**Investigator Full Name:** He Huang

**Investigator Title:** Director

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**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.

**Detailed Description:** 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.

The trial consists of several phases: screening period, apheresis day, baseline period, lymphodepletion period, pre-infusion assessment period, GC012F infusion period, safety and efficacy follow-up period, long-term follow-up period, and study discontinuation visit (if applicable).

Qualified subjects will undergo apheresis and receive the infusion after the production of CAR-T products. Subjects will undergo lymphodepletion before CAR-T cell infusion and assessment before infusion. Subjects meeting the cell infusion criteria will receive CAR-T cell infusion according to the dose specified in the protocol. Dose adjustments may occur based on safety and clinical efficacy for subjects in the same group or subsequent trial groups.

### Conditions Module

**Conditions:**

- Refractory Generalized Myasthenia Gravis

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 18

**Type:** ESTIMATED

**Phases:**

- EARLY_PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Refractory Generalized Myasthenia Gravis

**Intervention Names:**

- Drug: GC012F injection

**Label:** Refractory gMG subjects

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Refractory gMG subjects

**Description:** 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

**Name:** GC012F injection

**Type:** DRUG

### Outcomes Module

#### Other Outcomes

**Description:** Safety of GC012F

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

**Time Frame:** within 24 weeks post-GC012F infusion;

**Description:** Safety of GC012F

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

**Time Frame:** within 24 weeks post-GC012F infusion

**Description:** Safety of GC012F

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

**Time Frame:** Within 15 years after GC012F injection infusion

#### Primary Outcomes

**Description:** DLT

**Measure:** Incidence of DLT

**Time Frame:** Within 28 days after GC012F injection infusion

**Description:** 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.

**Measure:** Frequency and severity of abnormal findings in electrocardiograms

**Time Frame:** Within 96 weeks after GC012F injection infusion

**Description:** 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.

**Measure:** Frequency and severity of abnormal findings of adverse events.

**Time Frame:** Within 96 weeks after GC012F injection infusion

**Description:** 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.

**Measure:** Frequency and severity of abnormal findings in physical examinations

**Time Frame:** Within 96 weeks after GC012F injection infusion

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

**Measure:** Frequency and severity of abnormal findings in laboratory tests

**Time Frame:** Within 96 weeks after GC012F injection infusion

**Description:** 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.

**Measure:** Frequency and severity of abnormal findings in vital signs

**Time Frame:** Within 96 weeks after GC012F injection infusion

**Description:** Recommended phase I dose

**Measure:** RP1D

**Time Frame:** 2 years after GC012F injection infusion

**Description:** maximum tolerated dose

**Measure:** MTD

**Time Frame:** 2 years after GC012F injection infusion

#### Secondary Outcomes

**Description:** PK results of GC012F

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

**Time Frame:** Within 96 weeks after GC012F injection infusion

**Description:** PK results of GC012F

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

**Time Frame:** Within 96 weeks after GC012F injection infusion

**Description:** PK results of GC012F

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

**Time Frame:** Within 96 weeks after GC012F injection infusion

**Description:** PK results of GC012F

**Measure:** 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;

**Time Frame:** Within 28 days after GC012F injection infusion

**Description:** Efficacy results of GC012F

**Measure:** Disease activity indices:MG-ADL

**Time Frame:** Within 96 weeks after GC012F injection infusion

**Description:** Efficacy results of GC012F

**Measure:** Disease activity indices:MGC

**Time Frame:** Within 96 weeks after GC012F injection infusion

**Description:** Efficacy results of GC012F

**Measure:** Disease activity indices:QMG

**Time Frame:** Within 96 weeks after GC012F injection infusion

**Description:** Efficacy results of GC012F

**Measure:** Disease activity indices: MG-QoL 15r

**Time Frame:** Within 96 weeks after GC012F injection infusion

**Description:** Efficacy results of GC012F

**Measure:** Disease activity indices: post-intervention status according to the Myasthenia Gravis Foundation of America (MGFA) classification

**Time Frame:** Within 96 weeks after GC012F injection infusion

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Subjects or his/her legal proxy/guardian voluntary signing the ICF, and willing and able to follow the procedure in this study.
2. Aged ≥18 years old, no gender limitation;
3. Patients with confirmed refractory GMG, and the clinical classification is IIa-IVb (including IIa, IIb, IIIa, IIIb, IVa and IVb) in screening;
4. Patients whose MG-ADL score is 5 or more, and the proportion of ocular symptoms is less than 50% in the total score;
5. 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;
6. 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;
7. 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;
8. Life expectancy ≥3 months;
9. The results of laboratory test during screening period shall meet all following criteria:

   1. Neu ≥1.0 × 109/L; Hb ≥8.0 g/dL; PLT ≥50 × 109/L;
   2. ALT ≤3 × ULN; AST ≤3 × ULN; TBIL \<2 × ULN (DBIL ≤1.5 × ULN for subjects with Gilbert's syndrome)
   3. Creatinine clearance (19.3 Appendix 3) ≥30 mL/min;
   4. APTT ≤1.5 × ULN, PT ≤1.5 × ULN;
   5. LVEF ≥50% based on echocardiography, no findings of pericardial effusion.
10. Women of child-bearing age should:

    1. Have a negative serum β human chorionic gonadotropin (β-hCG) pregnancy test confirmed by investigators during the screening period;
    2. Agree to avoid breastfeeding during the study period until at least 1 year after the infusion of GC012F Injection or until two consecutive flow cytometry tests show the absence of CAR-T cells (whichever occurs later).
11. Any male subjects who have sexual partners and female subjects with childbearing potential shall agree to take effective contraceptive methods (e.g. oral contraceptive pills, intrauterine device or condoms) from the screening starting until at least 1 year post GC012F Injection infusion or until two consecutive flow cytometry tests show the absence of CAR-T cells (whichever occurs later. Male subjects must agree to use condoms during sexual contact with pregnant females or females with fertility for at least 1 year after the infusion of GC012F Injection, even if a successful vasectomy has been performed;
12. Venous access available for blood collection, and no contraindications for leukapheresis.

exclusion criteria:

1. Subjects have a history of severe hypersensitivity or allergy;
2. Any contraindication for fludarabine, cyclophosphamide and any component of the investigational product;
3. Subjects with any of the following heart diseases:

   1. Congestive heart failure (New York Heart Association (NYHA) Class III or IV);
   2. Experienced myocardial infarction or underwent coronary artery bypass grafting (CABG) within 6 months prior to screening period;
   3. 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;
   4. History of severe non-ischemic cardiomyopathy.
4. 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;
5. Severe underlying medical conditions, such as:

   1. Fungal, bacterial, viral or other infections or suspected fungal, bacterial, viral or other infections that cannot be controlled or require general intravenous administration;
   2. Significant clinical evidence of dementia or mental status changes;
   3. 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).
6. Positive results in any of the following tests:

   1. HIV antibody positive;
   2. HBsAg positive; or HBcAb positive and HBV-DNA above the lower limit of detection of the analytical method;
   3. HCV antibody positive with HCV RNA above the lower limit of detection of the analysis method; or known history of hepatitis C without completion of antiviral therapy for ≥24 weeks;
   4. Syphilis antibody positive.
7. Received therapy of non-hormonal immunosuppressants within 3 weeks prior to apheresis;
8. Major surgery within 2 weeks prior to leukapheresis or surgery plan during the study (except for local anesthesia surgery, but not performed within 2 weeks after infusion);
9. Receipt of a live-attenuated vaccine within 4 weeks prior to leukapheresis;
10. Intravenous injection of immunoglobulins or therapy of plasma exchange (PE);
11. Receipt of other biologics for MG within 3 weeks prior to apheresis or within 8 weeks prior to infusion;
12. Participation in any other clinical trial within 4 weeks prior to signing ICF, or the date of signing the ICF still within 5 half-lives of the drug from the last dose in the last clinical trial (whichever is longer);
13. Thymectomy within 12 months prior to ICF signing;
14. Pregnant women or lactating women who do not agree to abstain from breastfeeding, men and women who have a fertility plan during participation in this study or within 1 year after receiving study treatment;
15. Any situation that may hinder subjects' participation in the entire trial or confuse the results, or any situation in which investigators believe that participation in this study is not in the subject's best interests.

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** hehuangyu@126.com

**Name:** He Huang, PhD

**Phone:** 86-13605714822

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Hanzhou

**Contacts:**

***Contact 1:***

- **Email:** hehuangyu@126.com

- **Name:** He Huang, PhD

- **Phone:** 86-13605714822

- **Role:** CONTACT

***Contact 2:***

- **Email:** huyongxian2000@aliyun.com

- **Name:** Yongxian Hu, PhD

- **Phone:** 86-15957162012

- **Role:** CONTACT

**Country:** China

**Facility:** The First Affiliated Hospital,College of Medicine, Zhejiang University

**State:** Zhejiang

**Status:** RECRUITING

**Zip:** 310003

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009135

- Term: Muscular Diseases

- ID: D000009140

- Term: Musculoskeletal Diseases

- ID: D000020879

- Term: Neuromuscular Manifestations

- ID: D000009461

- Term: Neurologic Manifestations

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000010335

- Term: Pathologic Processes

- ID: D000020361

- Term: Paraneoplastic Syndromes, Nervous System

- ID: D000009423

- Term: Nervous System Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000010257

- Term: Paraneoplastic Syndromes

- ID: D000020274

- Term: Autoimmune Diseases of the Nervous System

- ID: D000019636

- Term: Neurodegenerative Diseases

- ID: D000020511

- Term: Neuromuscular Junction Diseases

- ID: D000009468

- Term: Neuromuscular Diseases

- ID: D000001327

- Term: Autoimmune Diseases

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M12112

- Name: Myasthenia Gravis

- Relevance: HIGH

- As Found: Myasthenia Gravis

- ID: M20944

- Name: Muscle Weakness

- Relevance: HIGH

- As Found: Myasthenia

- ID: M13204

- Name: Paresis

- Relevance: LOW

- As Found: Unknown

- ID: M4554

- Name: Asthenia

- Relevance: LOW

- As Found: Unknown

- ID: M12092

- Name: Muscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12097

- Name: Musculoskeletal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22619

- Name: Neuromuscular Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M12404

- Name: Neurologic Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M13170

- Name: Paraneoplastic Syndromes

- Relevance: LOW

- As Found: Unknown

- ID: M22160

- Name: Paraneoplastic Syndromes, Nervous System

- Relevance: LOW

- As Found: Unknown

- ID: M12367

- Name: Nervous System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M4629

- Name: Autoimmune Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22094

- Name: Autoimmune Diseases of the Nervous System

- Relevance: LOW

- As Found: Unknown

- ID: M21558

- Name: Neurodegenerative Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22297

- Name: Neuromuscular Junction Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12411

- Name: Neuromuscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3973

- Name: Myasthenia Gravis

- Relevance: HIGH

- As Found: Myasthenia Gravis

### Condition Browse Module - Meshes

- ID: D000009157

- Term: Myasthenia Gravis

- ID: D000018908

- Term: Muscle Weakness

### Misc Info Module

- Version Holder: 2024-05-31
