Universal CAR-T Cells (BRL-301) in Relapse or Refractory Autoimmune Diseases

NCT05859997 | Enrolling By Invitation DMC

• 1 other identifier: 2022-BRL-301A-ADS-IIT
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator initiated trial to assess the efficacy and safety of BRL-301 in the relapse or refractory autoimmune diseases of China.

Conditions

Systemic Lupus Erythematosus (SLE); Sjogren's Syndrome; Systemic Sclerosis; Inflammatory Myopathy; ANCA Associated Systemic Vasculitis; Antiphospholipid Syndrome

Outcome Measures

Primary Outcomes (1)

• Safety and efficacy outcomes

  Safety assessments are conducted using the NCI-CTCAE version 5.0 standards；Efficacy assessments: Relapsed refractory systemic lupus erythematosus-SLE Response Index 4 (SRI-4) response;Sjögren's Syndrome with relapsed refractory thrombocytopenia-assessment of treatment response for thrombocytopenia(CR, PR, NR);Relapsed refractory/progressive systemic sclerosis-Composite Response Index in Systemic Sclerosis(CRISS);Relapsed refractory/progressive inflammatory myopathy-Total Improvement Score (TIS);Relapsed refractory ANCA-associated vasculitis-BVAS score;Recurrent Refractory/Catastrophic Antiphospholipid Syndrome-new thrombosis

  First 30 days for DLT, 3 months for safety and efficacy measurements during the treatment assessment period, and then follow-up every 3 months for up to a year after the treatment.

Secondary Outcomes (2)

• PK parameters

  3 months

• PD parameters

  3 months

Study Arms (1)

BRL-301

EXPERIMENTAL

Allogeneic CD19-targeted Chimeric Antigen Receptor (CAR) T Cells

Biological: BRL-301

Interventions

BRL-301 BIOLOGICAL

Single dose of Allogeneic Anti-CD19 CAR T cells will be infused

Also known as: Allogeneic Anti-CD19 CAR T cells

BRL-301

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ranges from 18 to 65 years old (including threshold), regardless of gender.
• Positive expression of CD19 on peripheral blood B cells determined by flow cytometry.
• The functions of important organs meet the following requirements:
• Bone marrow hematopoietic function needs to meet: a. White blood cell count ≥ 3 x 10\^9/L b. Neutrophil count ≥ 1 x 10\^9/L (no colony-stimulating factor treatment within 2 weeks before examination); c. Hemoglobin ≥60g/L.
• Liver function:ALT ≤ 3 x ULN,AST≤3 x ULN, TBIL≤1.5 x ULN(excluding Gilbert syndrome, total bilirubin ≤ 3.0 x ULN) (No requirements for conditions caused by the disease itself).
• Renal function: creatinine clearance rate (CrCl) ≥ 60 ml/minute(Cockcroft/Fault formula).
• Coagulation function: International standardized ratio (INR) \< 1.5 x ULN,prothrombin time(PT) \< 1.5 x ULN.
• Cardiac function: Good hemodynamic stability.
• Female subjects with fertility and male subjects whose partners are women of childbearing age are required to use medically approved contraception or abstinence during the study treatment period and at least 6 months after the end ofthe study treatment period; Female subjects of childbearing age tested negative for serum HCG within 7 days before enrollment in the study and were not in lactation.
• Voluntarily participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.
• Criteria for SLE:
• Complies with the classification standards of the 2019 European Union Against Rheumatology/American Society of Rheumatology (EULAR/ACR) SLE.
• In the moderate to severe active phase of the disease, with SLEDAI-2000 score\>6.
• And at least one British Isle Lupus Rating Group Index (BILAG-2004) Class A (severe manifestation) or two Class B (moderate manifestation) organ scores, or both.
• Ineffective conventional treatment or relapse of disease activity after remission. Definition of routine treatment: Use of glucocorticoids (above 1mg/Kg/d) and cyclophosphamide, as well as any of the following immunomodulatory drugs for more than 6 months: antimalarial drugs, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, as well as biological agents such as rituximab, belimumab and telitacicept.

You may not qualify if:

• Individuals with a history of severe drug allergies or allergic constitution.
• Existence or suspicion of uncontrollable or treatable fungal, bacterial, viral or other infections.
• Individuals with relatively serious heart diseases, such as angina pectoris, myocardial infarction, heart failure, and arrhythmia.
• Subjects with congenital immunoglobulin deficiency.
• Other malignant tumors (excluding non-melanoma skin cancer, cervical cancer in situ, bladder cancer and breast cancer that have survived for more than 5 years without disease).
• Subjects with end-stage renal failure.
• Subjects with positive hepatitis 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.
• Having mental illness and severe cognitive impairment.
• Those who have participated in other clinical trials within the first 3 months of enrollment.
• Pregnant or intending to conceive women.
• The researchers believe that there are other reasons why subjects cannot be included in this study.

Sponsors & Collaborators

• Bioray Laboratories: lead
• Shanghai Changzheng Hospital: collaborator

Study Sites (1)

Shanghai ChangZheng hospital

Shanghai, Shanghai Municipality, 200433, China

Location

Related Publications (2)

• Wang D, Wang X, Tan B, Wen X, Ye S, Wu Y, Cao X, Zhang X, Wang C, Geng L, Zhang H, Feng X, Zheng B, He Y, Liu M, Wu X, Du B, Sun L, Xu H. Allogeneic CD19-targeted CAR-T therapy in refractory systemic lupus erythematosus achieved durable remission. Med. 2025 Oct 10;6(10):100749. doi: 10.1016/j.medj.2025.100749. Epub 2025 May 29.

  PMID: 40446794 DERIVED

• Wang X, Wu X, Tan B, Zhu L, Zhang Y, Lin L, Xiao Y, Sun A, Wan X, Liu S, Liu Y, Ta N, Zhang H, Song J, Li T, Zhou L, Yin J, Ye L, Lu H, Hong J, Cheng H, Wang P, Li W, Chen J, Zhang J, Luo J, Huang M, Guo L, Pan X, Jin Y, Ye W, Dai L, Zhu J, Sun L, Zheng B, Li D, He Y, Liu M, Wu H, Du B, Xu H. Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis. Cell. 2024 Sep 5;187(18):4890-4904.e9. doi: 10.1016/j.cell.2024.06.027. Epub 2024 Jul 15.

  PMID: 39013470 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Sjogren's Syndrome; Scleroderma, Systemic; Myositis; Antiphospholipid Syndrome

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Skin Diseases; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2023
• First Posted: May 16, 2023
• Study Start: May 17, 2023
• Primary Completion: May 27, 2024
• Study Completion: May 27, 2025
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)