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

• Status: Recruiting
• Trial end date: 2025-04-19
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Zhejiang University
• Collaborator: Gracell Biotechnology Shanghai Co., Ltd.

Criteria

Inclusion Criteria:

1. 18-70 years old;

2. Total score ≥ 10 on the EULAR/ACR 2019 SLE classification criteria;

3. Subject who has used at least two immunosuppressive agents and at least one approved biological agent for more than 6 months without achieving LLDAS remission criteria; Conventional treatment is not effective and (or) no effective treatment;

4. SELENA-SLEDAI≥8;

5. Patients with CD19+ B-cell;

6. Active organ involvement;

7. Hemoglobin≥85 g/L;

8. WBC≥2.5×10^9/L

9. NEUT≥1×10^9/L;

10. PLT≥50×10^9/L;

11. 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%;

12. Adequate venous access for apheresis, and no other contraindications for leukapheresis;

13. 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.

14. Agree to attend follow-up visits as required;

15. Voluntary participation and informed consent signed by the patient or his/her legal/authorized representative;

Exclusion Criteria:

1. 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;

2. CNS disease: including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident [CVA], encephalitis or CNS vasculitis, psychiatric patients with depression or suicidal thoughts;

3. Patients with serious lesions and history of present illness of vital organs such as heart, liver, kidney and blood and endocrine system;

4. Patients with immunodeficiency, uncontrolled active infections and active or recurrent peptic ulcers;

5. Received immunosuppressive therapy within 1 week prior to leukapheresis;

6. Patients with HIV infection; Active infection of hepatitis B virus or hepatitis C virus; Patients with syphilis infection;

7. The presence or suspicion of an active fungal, bacterial, viral or other infection that cannot be controlled during screening;

8. Received live vaccine treatment within 4 weeks prior to screening;

9. Severe allergies or hypersensitivity;

10. Contraindication to cyclophosphamide in combination with fludarabine;

11. 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;

12. cannula or drainage tubes other than central venous catheters;

13. Pregnant or lactating women, or subjects who plan to have children within 1 year of treatment;

14. Subjects with prior CD19 or BCMA-targeted therapy

15. Participated in any clinical study within 3 months prior to enrollment

16. Any situations that the investigator believes the patients are not suitable for the study.