Clinical trial NCT05988216: Universal CAR-T Cells (BRL-301) in Refractory Systemic Lupus Erythematosus
Official title: A Clinical Study on the Safety and Efficacy of BRL-301 (Allogeneic Chimeric Antigen Receptor T Cell Injection Targeting CD19 Gene) in the Treatment of Refractory Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Systemic Lupus Erythematosus (SLE)
Lead sponsor: Bioray Laboratories
Sponsor class: INDUSTRY
Collaborators: name: First Affiliated Hospital of Zhejiang University
First posted: 2023-08-14
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an investigator initiated trial to assess the efficacy and safety of BRL-301 in the refractory systemic lupus erythematosus.

Detailed description: The study had the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation \& Lymphodepleting Chemotherapy), Treatment and Follow-up.

Eligibility criteria: Inclusion Criteria:

1. Age range from 18 to 65 years old (including threshold), regardless of gender;
2. Subjects diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria; ANA ≥ 1:80, or positive for anti dsDNA and/or anti Sm antibodies;
3. The condition becomes active again after conventional treatment is ineffective or the disease relapses. Conventional treatment is defined as the use of two or more drugs, including corticosteroids (more than 1mg/kg/d) and any one or more of the following immunomodulatory drugs for over six months: antimalarial drugs, cyclophosphamide, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, as well as biologics including rituximab, belimumab, etanercept, etc.
4. At least one BILAG2004 Class A or two Class B score, or both;
5. SELENA-SLEDAI score ≥ 8 points;
6. The positive expression and expression rate of CD19 on peripheral blood B cells determined by flow cytometry;
7. The functions of important organs meet the following requirements:

   Bone marrow function needs to meet:
   1. White blood cell count ≥ 3 × 109/L;
   2. Neutrophil count ≥ 1 × 109/L (no Colony-stimulating factor treatment within 2 weeks before examination);
   3. Platelets ≥ 50 × 109/L;d. Hemoglobin ≥ 80g/L

   Liver function:
   1. Alanine Aminotransferase (ALT) ≤ 3 × ULN;
   2. Asparagus cochinchinensis transase (AST) ≤ 3 × ULN;
   3. Total Bilirubin (TBIL) in serum ≤ 1.5 × ULN (excluding Gilbert syndrome, total bilirubin ≤ 3.0 × ULN); Renal function: Creatinine Clearance Rate (CrCl) ≥ 60 ml/minute (Cockcroft/Fault formula) ;

   Coagulation function:
   1. International Normalized Ratio (INR) ≤ 1.5 × ULN,
   2. Prothrombin time (PT) ≤ 1.5 × ULN.

   Cardiac function: good hemodynamic stability, left ventricular Ejection fraction (LVEF) ≥ 55%;
8. Female patients of childbearing potential and male patients whose female sexual partners are of childbearing age should adopt medically recognized contraceptive measures or abstain from sex within at least 6 months after infusion of BRL-301; female patients of childbearing age should have a negative serum HCG test result within 7 days before study enrollment and be not breastfeeding;
9. Willing to participate in this clinical study, sign an ICF, and complete follow-ups, with good compliance.

Exclusion Criteria:

1. Have a serious history of Drug allergy or allergic constitution;
2. Fungi, bacteria, viruses, or other infections that are uncontrollable or require intravenous medication treatment exist or are suspected;
3. Active central nervous system disease caused by SLE or not (including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident, encephalitis, central nervous system Vasculitis);
4. Individuals with relatively serious heart diseases, such as angina pectoris, myocardial infarction, heart failure, and arrhythmia;
5. Subjects with congenital immunoglobulin deficiency;
6. Other malignant tumors (excluding non Melanoma skin cancer, cervical cancer in situ, bladder cancer cancer and breast cancer that have survived for more than 5 years without disease);
7. Subjects with end-stage renal failure;
8. Have received any of the following SLE treatments:

   1. Corticosteroid (defined as prednisone or equivalent\>20 mg/day) of therapeutic dose were used before enrollment or within 72 hours before BRL-301 infusion.
   2. Use any other clinical study drugs for SLE within 4 weeks prior to enrollment. However, if the research treatment period is ineffective or the disease progresses, and at least 3 half-lives have passed before enrollment, enrollment is allowed.
   3. Had received anti CD20 monoclonal antibody (such as Rituximab) within 4 weeks before screening, tetaximab within 6 weeks, or belizumab within 12 weeks.
   4. Previous CAR-T cell or other genetically modified T Cell therapy.
9. Subjects with positive hepatitis B B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and HBV DNA titer in peripheral blood higher than the upper limit of detection; Patients with positive hepatitis C virus (HCV) antibodies and positive peripheral blood HCV RNA; People who are positive for human immunodeficiency virus (HIV) antibodies; Those who have tested positive for syphilis;
10. Having mental illness and severe cognitive impairment;
11. Those who have participated in other clinical trials within the first 3 months of enrollment;
12. Pregnant or intending to conceive women;
13. Patients who are unsuitable for being included into this study as deemed by the investigator due to other reasons.

Primary outcomes:
measure: The safety of BRL-301 in refractory systemic lupus erythematosus
timeFrame: 3 months
Secondary outcomes:
measure: The efficiency of BRL-301 in refractory systemic lupus erythematosus
timeFrame: 3 months
measure: Cellular kinetics
timeFrame: 3 months
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: