Clinical Study of CD19 CAR-T in the Treatment of Refractory Systemic Sclerosis

Launched by THE CHILDREN'S HOSPITAL OF ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE · Jan 20, 2025

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment option for people with systemic sclerosis (SSc), a serious autoimmune disease that can cause skin and internal organ problems. Specifically, the study is testing a type of therapy called anti-CD19 CAR-T cell therapy, which uses modified immune cells to target and attack disease-causing cells. The trial is currently recruiting participants, and is open to both children aged 5 and older, as well as adults up to 74 years old, regardless of gender.

To be eligible for the trial, participants must have been diagnosed with systemic sclerosis and have specific antibodies in their blood. They should also have experienced limited success with other treatments for at least three months. Participants will undergo evaluations to ensure their major organ functions are stable before joining the study. Those who enroll can expect to receive the CAR-T therapy and will be closely monitored for safety and effectiveness throughout the trial. It’s important for potential participants and their families to understand the purpose of the study and provide informed consent before taking part.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Gender unlimited, age ≥5 years;
• • 2. Meet the classification criteria for Systemic sclerosis (SSc) as defined by the 2013ACR/EULAR standards;
• • 3. any one of the anti-nuclear antibodies or systemic sclerosis specific antibodies positive;
• • 4. Improved Rodnan skin score (mRSS) ≥15 points (total 51 points);
• • 5. Meet the definition of intractable disease: Glucocorticoids (≥0.5mg/kg/d) and cyclophosphamide, as well as one or more of the following immunomodulators (including antimalarial drugs, azathioprine,motecophanate, methotrexate, leflunomide, tachlimus, cyclosporine, and biologics including rituximab, Beliumab, and titacept, etc.), did not show significant remission of the disease for more than 3 months; Or meet the criteria for rapid disease progression , clinical routine treatment is ineffective, and the benefits outweigh the risks as determined by the investigator and the patient's or guardian's full and informed consent can be considered for inclusion.
• • 6. Major organ functions were basically normal: left ventricular ejection fraction (LVEF) ≥55%, no obvious abnormality in electrocardiogram; eGFR≥30ML/min/1.73m2；AST and ALT≤3.0ULN, total bilirubin ≤2.0×ULN; SpO2≥92%, DLCO≥ 40% of predicted value, FVC≥ 50% of predicted value;
• • 7. The subject of childbearing age has a negative urine pregnancy test result and agrees to take effective contraceptive measures during the test period until 1 year after the infusion;
• • 8. The patient or his/her guardian agrees to participate in the clinical trial and signs an informed consent indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study
• Exclusion Criteria:
• • （1） Severe pulmonary hypertension (PHA) (mean pulmonary pressure \> 45mmHg) or other severe major organ involvement; (2) have previously received CAR T cell therapy (except those whose safety risks have been ruled out by the investigators); (3) patients with active central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, etc.; (4) Congenital heart disease or history of acute myocardial infarction within 6 months before screening, or severe arrhythmias (including multi-source frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with a large number of pericardial effusion, serious myocarditis, etc.; Or patients with unstable vital signs who require vasoactive drugs to maintain blood pressure; (5) Active tuberculosis at the time of screening; (6) There are active infections or uncontrollable infections that require systemic treatment at the time of screening; (7) Received solid organ transplantation or hematopoietic stem cell transplantation within 3 months before screening; Acute graft-versus-host disease (GVHD) of grade 2 or above was present within 2 weeks prior to screening; (8) Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA detection greater than the normal range; Hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Positive for human immunodeficiency virus (HIV) antibodies; Treponema pallidum antibody positive; (9) Had received live vaccine within 4 weeks before screening; (10) Positive blood pregnancy test; (11) Patients with known malignant diseases such as tumors before screening; (12) Patients who had participated in other interventional clinical trials within 3 months before enrollment; (13) Situations in which other investigators consider it inappropriate to participate in the study