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

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.

Study Overview

• Status: Recruiting
• Conditions: CAR-T
• Intervention / Treatment: Drug: GC012F injection

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.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yongxian Hu, MD; Phone Number: +8615957162012; Email: huyongxian2000@aliyun.com
• Study Contact Backup: Name: He Huang, PhD; Phone Number: 86-13605714822; Email: hehuangyu@126.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital，College of Medicine, Zhejiang University
      • Contact: He Huang, PhD; Phone Number: 86-13605714822; Email: hehuangyu@126.com
      • Contact: Yongxian Hu, PhD; Phone Number: 86-15957162012; Email: huyongxian2000@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: GC012F injection; Each subject will receive GC012F injection (CD19-BCMA CAR-T cells) once by intravenous infusion on Day 0.; Other Names: CD19-BCMA CAR-T cells

What is the study measuring?

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]

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Gracell Biotechnology Shanghai Co., Ltd.
• Investigators: Principal Investigator: He Huang, Zhejiang University; Principal Investigator: Jin Lin, Zhejiang University; Principal Investigator: Zhihong Liu, Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): May 15, 2023
• Primary Completion (Anticipated): October 19, 2023
• Study Completion (Anticipated): April 19, 2025

Study Registration Dates

• First Submitted: April 26, 2023
• First Submitted That Met QC Criteria: April 26, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: GC012F-614

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No