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

Sponsor
Zhejiang University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05846347
Collaborator
Gracell Biotechnology Shanghai Co., Ltd. (Industry)
15
Enrollment
1
Location
1
Arm
23.2
Anticipated Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: GC012F injection
 Phase 1

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 Design

Study Type:
Interventional
Anticipated Enrollment :
15 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I Clinical Study of GC012F Injection in Treatment of Refractory Systemic Lupus Erythematosus
Anticipated Study Start Date :
May 15, 2023
Anticipated Primary Completion Date :
Oct 19, 2023
Anticipated Study Completion Date :
Apr 19, 2025

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. The proportion of subjects with DLT [Within 28 days after GC012F injection infusion]

      DLT definition is dose-limiting toxicity

    2. The proportion of subjects with adverse events [Within 12 weeks after GC012F injection infusion]

      All adverse events were evaluated according to NCI-CTCAE v5.0 criteria

    Secondary Outcome Measures

    1. Proportion of subjects achieving SRI-4 [4, 8, 12 and 24 weeks after GC012F injection infusion]

      SELEAN-SLEDAI，BILAG，PGA

    2. Number of CAR-T cells and CAR gene copies in subjects'blood and bone marrow (if applicable) [After GC012F injection infusion [day 4, 7, 10, 14 and week 4, 8, 12, 24]]

      Test method: flow cytometry and qPCR

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The First Affiliated Hospital,College of Medicine, Zhejiang University Hangzhou Zhejiang China 310003

    Sponsors and Collaborators

    • Zhejiang University
    • Gracell Biotechnology Shanghai Co., Ltd.

    Investigators

    • Principal Investigator: He Huang, Zhejiang University
    • Principal Investigator: Zhihong Liu, Zhejiang university school of medicine
    • Principal Investigator: Jin Lin, Zhejiang University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    He Huang, Professor, Zhejiang University
    ClinicalTrials.gov Identifier:
    NCT05846347
    Other Study ID Numbers:
    • GC012F-614
    First Posted:
    May 6, 2023
    Last Update Posted:
    May 11, 2023
    Last Verified:
    May 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Lupus Erythematosus, Systemic

    Study Results

    No Results Posted as of May 11, 2023