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

NCT ID: NCT05846347

Last Updated: 2023-05-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-15
• Study Completion Date: 2025-04-19

Brief 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.

Detailed 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.

Conditions

CAR-T

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GC012F injection (CD19-BCMA CAR-T cells)

Dose level： DL1：1±20%×10\^5/kg, DL2：2±20%×10\^5/kg DL3：3±20%×10\^5/kg

Group Type: EXPERIMENTAL

GC012F injection

Intervention Type: DRUG

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

Interventions

GC012F injection

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

Intervention Type: DRUG

Other Intervention Names

CD19-BCMA CAR-T cells

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gracell Biotechnologies (Shanghai) Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

He Huang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

He Huang

Role: PRINCIPAL_INVESTIGATOR

Zhejiang University

Zhihong Liu

Role: PRINCIPAL_INVESTIGATOR

Zhejiang university school of medicine

Jin Lin

Role: PRINCIPAL_INVESTIGATOR

Zhejiang University

Locations

The First Affiliated Hospital,College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

He Huang, PhD

Role: CONTACT

hehuangyu@126.com

86-13605714822

Yongxian Hu, MD

Role: CONTACT

huyongxian2000@aliyun.com

+8615957162012

Facility Contacts

He Huang, PhD

Role: primary

hehuangyu@126.com

86-13605714822

Yongxian Hu, PhD

Role: backup

huyongxian2000@aliyun.com

86-15957162012

Other Identifiers

GC012F-614

Identifier Type: -

Identifier Source: org_study_id