Phase I Clinical Study of GC012F Injection in Treatment of Refractory Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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This is a phase I, single arm, non-randomized, open label, treatment study trial to determine the recommended phase II dose of GC012F injection (CD19-BCMA CAR-T cells) in patients with refractory systemic lupus erythematosus.

Detailed Description
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Systemic lupus erythematosus (SLE) is a kind of autoimmune diseases mediated by autoantibody-forming immune complexes, which involving multiple systems and organs. Autoreactive B cells can self-activate and differentiate into plasma cells releasing large amounts of autoantibodies, while they can also present their own antigens to autoimmune T cells, thus activating T cells and promoting the release of inflammatory factors. Traditional SLE treatment aims at long-term remission, while, CD19- BCMA CAR-T cells can theoretically completely deplete abnormal antibody-producing B cells, allowing immune rebuilding and restoring the patient's normal immune function, achieving drug-free survival, which fully reflects the application prospects of CAR-T therapy in SLE.

Official Title
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Phase I Clinical Study of GC012F Injection in Treatment of Refractory Systemic Lupus Erythematosus

Conditions
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CAR-T

Intervention / Treatment
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* Drug: GC012F injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-70 years old; Total score ≥ 10 on the EULAR/ACR 2019 SLE classification criteria; SELENA-SLEDAI≥8; Patients with CD19+ B-cell; Active organ involvement; Hemoglobin≥85 g/L; WBC≥2.5×10^9/L NEUT≥1×10^9/L; PLT≥50×10^9/L; AST/ALT below 2 times the upper limit of normal; Creatinine clearance ≥30 mL/min; blood bilirubin ≤2.0 mg/dl; echocardiography indicates that the ejection fraction is ≥50%; Adequate venous access for apheresis, and no other contraindications for leukapheresis; Women of childbearing age should have a negative serum or urine pregnancy test at screening and baseline. Subjects agree to take effective contraceptive measures during the trial until at least 1 year after CAR-T cells infusion. Agree to attend follow-up visits as required; Voluntary participation and informed consent signed by the patient or his/her legal/authorized representative; Exclusion Criteria: Renal disease: severe lupus nephritis (serum creatinine > 2.5 mg/dL or 221 μmol/L) within 8 weeks prior to leukapheresis, or subjects who need prohibited drugs to treat active nephritis or subjects who need hemodialysis; CNS disease: including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident [CVA], encephalitis or CNS vasculitis, psychiatric patients with depression or suicidal thoughts; Patients with serious lesions and history of present illness of vital organs such as heart, liver, kidney and blood and endocrine system; Patients with immunodeficiency, uncontrolled active infections and active or recurrent peptic ulcers; Received immunosuppressive therapy within 1 week prior to leukapheresis; Patients with HIV infection; Active infection of hepatitis B virus or hepatitis C virus; Patients with syphilis infection; The presence or suspicion of an active fungal, bacterial, viral or other infection that cannot be controlled during screening; Received live vaccine treatment within 4 weeks prior to screening; Severe allergies or hypersensitivity; Contraindication to cyclophosphamide in combination with fludarabine; Subjects who have undergone major surgery within 2 weeks prior to signing the informed consent form, or who are scheduled to have surgery (other than local anesthetic surgery) during the trial or within 2 weeks of the infusion; cannula or drainage tubes other than central venous catheters; Pregnant or lactating women, or subjects who plan to have children within 1 year of treatment; Subjects with prior CD19 or BCMA-targeted therapy Participated in any clinical study within 3 months prior to enrollment Any situations that the investigator believes the patients are not suitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GC012F injection (CD19-BCMA CAR-T cells)<br>Dose level： DL1：1±20%×10^5/kg, DL2：2±20%×10^5/kg DL3：3±20%×10^5/kg | Drug: GC012F injection<br>* Each subject will receive GC012F injection (CD19-BCMA CAR-T cells) once by intravenous infusion on Day 0.<br>* Other names: CD19-BCMA CAR-T cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects with DLT | DLT definition is dose-limiting toxicity | Within 28 days after GC012F injection infusion | 
| The proportion of subjects with adverse events | All adverse events were evaluated according to NCI-CTCAE v5.0 criteria | Within 12 weeks after GC012F injection infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving SRI-4 | SELEAN-SLEDAI，BILAG，PGA | 4, 8, 12 and 24 weeks after GC012F injection infusion | 
| Number of CAR-T cells and CAR gene copies in subjects'blood and bone marrow (if applicable) | Test method: flow cytometry and qPCR | After GC012F injection infusion [day 4, 7, 10, 14 and week 4, 8, 12, 24] |