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

CAR-T Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05846347
• Other study ID #: GC012F-614
• Status: Recruiting
• Phase: Phase 1
• Start date: May 15, 2023
• Est. completion date: April 19, 2025

Study information

• Verified date: May 2023
• Source: Zhejiang University
• Contact: He Huang, PhD
• Phone: 86-13605714822
• Email: hehuangyu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: April 19, 2025
• Est. primary completion date: October 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. 18-70 years old;

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

3. SELENA-SLEDAI=8;

4. Patients with CD19+ B-cell;

5. Active organ involvement;

6. Hemoglobin=85 g/L;

7. WBC=2.5×10^9/L

8. NEUT=1×10^9/L;

9. PLT=50×10^9/L;

10. 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%;

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

12. 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.

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

14. 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.

Related Conditions & MeSH terms

• CAR-T
• Lupus Erythematosus, Systemic

Intervention

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

Locations

Country	Name	City	State
China	The First Affiliated Hospital,College of Medicine, Zhejiang University	Hangzhou	Zhejiang

Sponsors (2)

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of subjects with DLT	DLT definition is dose-limiting toxicity	Within 28 days after GC012F injection infusion
Primary	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	Proportion of subjects achieving SRI-4	SELEAN-SLEDAI,BILAG,PGA	4, 8, 12 and 24 weeks after GC012F injection infusion
Secondary	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]