Clinical trial NCT05846347: Phase I Clinical Study of GC012F Injection in Treatment of Refractory Systemic Lupus Erythematosus
Official title: Phase I Clinical Study of GC012F Injection in Treatment of Refractory Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: CAR-T
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Gracell Biotechnologies (Shanghai) Co., Ltd.
First posted: 2023-05-06
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The proportion of subjects with DLT
timeFrame: Within 28 days after GC012F injection infusion
measure: The proportion of subjects with adverse events
timeFrame: Within 12 weeks after GC012F injection infusion
Secondary outcomes:
measure: Proportion of subjects achieving SRI-4
timeFrame: 4, 8, 12 and 24 weeks after GC012F injection infusion
measure: Number of CAR-T cells and CAR gene copies in subjects'blood and bone marrow (if applicable)
timeFrame: After GC012F injection infusion [day 4, 7, 10, 14 and week 4, 8, 12, 24]
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital,College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: He Huang
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhejiang university school of medicine
name: Zhihong Liu
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhejiang University
name: Jin Lin
role: PRINCIPAL_INVESTIGATOR
References: