Clinical trial NCT06056921: Safety and Efficacy of CD19 Targeted CAR-T Therapy for Refractory Autoimmune Disease
Official title: Clinical Study of CD19 Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of Refractory Autoimmune Diseases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: SLE (Systemic Lupus)
Sjogren's Syndrome
Systemic Scleroderma
Dermatomyositis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Keywords: CAR-T
CD19
Lead sponsor: Chongqing Precision Biotech Co., Ltd
Sponsor class: INDUSTRY
First posted: 2023-09-28
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single arm study to evaluate the efficacy and safety of CD19 targeted CAR-T cells therapy for patients with Refractory Autoimmune Disease

Detailed description: the CD19 targeted CAR-T cell therapies have gained significant results in patients with relapsed and refractory B-cell Leukemia and Lymphoma. Otherwise, some studies have shown that the use of CD19-targeted CAR-T therapy in refractory SLE can improve the autoimmune symptoms of patients, and at the same time, immunosuppressants and hormones can be stopped to maintain long-term autoimmune indicators normal.To verify the safety and efficacy, the investigators launch such a clinical trial using CD19 targeted CAR-T cells for patients with Refractory Autoimmune Disease.

Eligibility criteria: Inclusion Criteria:

1. ≥18 years old, male or female;
2. diagnosed with one of the following diseases:

   * Systemic Lupus Erythematosus (SLE), EULAR/ACR 2019 standard;
   * Sjogren's Syndrome (SS), 2016 ACR/EULAR standard;
   * Systemic Scleroderma (SSc), 2013 ACR/EULAR Standards;
   * Dermatomyositis (DM), 2017 EULAR/ACR classification standard + one positive myositis specific antibody (Jo-1, Zo, EJ, PL-7, KS, OJ, PL-12, YRS, Anti-NXP-2, Anti-TIF1g, Anti-Mi-2, Anti-SAE, Anti-MDA-5, Anti-SRP, Anti-HMGCR);
   * Anti-neutrophil cytoplasmic antibody associated vasculitis (ANCA-AAV), including granulomatosis with polyangiitis (GPA), or microscopic vasculitis (MPA), or eosinophilic granulomatosis with polyangiitis (EGPA), 2022 ACR/EULAR standard.
3. Disease activity meets the following requirements:

   * SLEDAI score ≥8 for SLE patients;
   * For SS patients, ESSDAI≥14 points;
   * For patients with SSc, mRSS score in the range of 10-35 (including the boundary value) with interstitial pneumonia (ILD);
   * Patients with DM who have been diagnosed for at least 1 year and meet the following conditions:

     1. Skin rash VAS score (based on MDAAT) ≥3cm with at least 3 abnormalities in CSM;

     2, muscle biopsy pathology or muscle nuclear magnetic evidence of active inflammation;

     3. Bilateral manual muscle strength test (MMT-8) is less than 125/150, and at least 2 additional Core set measures (CSM) meet the following criteria: Patient score, 10 cm visual analogue scale (VAS) no less than 2.0 cm; b. Physician score, no less than 2.0 cm on the 10 cm VAS scale; c. Health Assessment Questionnaire (HAQ) disability index (Appendix 10) of not less than 0.25; d. Elevation of at least one muscular enzyme (including creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), with a minimum level of 1.3× the upper limit of normal; e. Disease activity score of extramuscular organs, no less than 1.0 cm on the 10 cm VAS scale (this VAS is the physician's comprehensive assessment of myositis disease Activity Assessment Tool (MDAAT) based on the general condition, skin, bone, gastrointestinal, lung, and heart scale activity score);
   * For ANCA-AAV patients, the BVAS score was ≥15.
4. ECOG 0\~1 score;
5. The functions of important organs are basically normal:

   * Hematology: hemoglobin ≥60g/L, platelet count ≥30×109/L;
   * Cardiac function: Left ventricular ejection fraction (LVEF) ≥55%, no obvious abnormality in electrocardiogram;
   * Renal function: eGFR≥30ML/min/1.73m2;
   * Liver function: AST and ALT≤3.0 ULN, total bilirubin ≤2.0 ULN;
   * Lung function: DLCO≥40% predicted value; FVC≥50% expected value;
   * Have criteria for simple or intravenous blood collection, and no other contraindications for cell collection;
6. 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;
7. The patient or his/her guardian agrees to participate in the clinical trial and signs the 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. Had previously received CAR T cell therapy;
2. patients with serious heart, liver, lung, blood system, endocrine system diseases, and the risk of participating in the trial is higher than the benefit judged by the researcher;
3. There is an active or uncontrollable infection that requires systemic treatment within 1 week prior to screening;
4. have previously received hematopoietic stem cell transplantation or solid organ transplantation (except corneal and hair transplantation), or have grade 2 or higher acute graft-versus-host disease (GVHD) within 2 weeks prior to screening;
5. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; Or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilis test positive; Or cytomegalovirus (CMV) DNA test positive;
6. Had received live vaccine within 4 weeks before screening;
7. pregnancy test positive;
8. Patients with malignant diseases such as malignant tumors before screening, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and ductal carcinoma in situ after radical surgery;
9. Patients who had participated in other clinical trials within 3 months prior to screening;
10. Situations in which other investigators consider it inappropriate to participate in the study.

Primary outcomes:
measure: Incidence of Adverse events after CD19 CAR-T cells infusion [Safety and Tolerability]
timeFrame: 1 month
measure: Obtain the maximum tolerated dose of CD19 CAR-T cells[Safety and Tolerability]
timeFrame: 1month
measure: Efficacy of CAR-T cell preparations in Refractory systemic lupus erythematosus [Effectiveness]
timeFrame: 3 months
measure: Efficacy of CAR-T cell preparations in Refractory Systemic scleroderma [Effectiveness]
timeFrame: 3 months
measure: Efficacy of CAR-T cell preparations in Refractory Sjogren's syndrome [Effectiveness]
timeFrame: 3 months
measure: Efficacy of CAR-T cell preparations in Refractory dermatomyositis [Effectiveness]
timeFrame: 3 months
measure: Efficacy of CAR-T cell preparations in Refractory The antineutrophil cytoplasmic antibody-associated vasculitides [Effectiveness]
timeFrame: 3 months
Secondary outcomes:
measure: AUCS of CD19 CAR-T cells [Cell dynamics]
timeFrame: 3 months
measure: CMAX of CD19 CAR-T cells [Cell dynamics]
timeFrame: 3 months
measure: TMAX of CD19 CAR-T cells[Cell dynamics]
timeFrame: 3 months
measure: Pharmacodynamics of CD19 CAR-T cells[Cell dynamics]
timeFrame: 3 months
measure: Immunogenicity after infusion of CD19 CAR-T
timeFrame: 2 years
measure: Immunological reconstitution of CAR-T after infusion of CD19 CAR-T
timeFrame: 2 years
Other outcomes:
measure: Refractory systemic lupus erythematosus -specific secondary study endpoint [Effectiveness]
timeFrame: 2 years
measure: Refractory Systemic scleroderma-specific secondary study endpoint [Effectiveness]
timeFrame: 2 years
measure: Refractory Sjogren's syndrome-specific secondary study endpoint [Effectiveness]
timeFrame: 2 years
measure: Refractory dermatomyositis-specific secondary study endpoint [Effectiveness]
timeFrame: 2 years
measure: Refractory The antineutrophil cytoplasmic antibody-associated vasculitides -specific secondary study endpoint [Effectiveness]
timeFrame: 2 years
Locations:
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
Study officials:
affiliation: Shanxi Bethune Hospital
name: Liyun Zhang, M.D
role: PRINCIPAL_INVESTIGATOR
References: