An Exploratory Clinical Study of SCAR02 Targeting BCMA and CD19 for the Treatment of Refractory Autoimmune Diseases (SCAR02)

An Exploratory Clinical Study of a Fourth-generation Autologous CAR-T Cell Injection (SCAR02) Targeting BCMA and CD19 for the Treatment of Refractory Autoimmune Diseases

This is an open label, single-site, dose-escalation study in up to 18 participants with refractory autoimmune diseases. This study aims to evaluate the safety and efficacy of the treatment with Anti-BCMA and CD19 CART

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Diseases
• Intervention / Treatment: Drug: Anti-BCMA and CD19 CART cells will be injected intravenously on a one-time basis.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: zhu chen, M.D; Phone Number: 860551-62283843; Email: doczchen@gmail.com
• Study Contact Backup: Name: xiaojuan zhao, master; Phone Number: +86 15955139303; Email: zhaoxiaojuan198694@163.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410119
      • Recruiting
      • Hunan Siweikang Therapeutic Co.Ltd
      • Contact: Zhu chen, M.D.; Phone Number: 800-555-5555; Email: doczchen@ustc.edu.cn
      • Contact: Zhu Chen Professor
      • Contact: Xingbing Wang Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Sign the informed consent form.
2. At the time of signing the informed consent form, the age of 18 years old or above, both male and female.
3. Bone marrow hematopoietic function is satisfied: white blood cell count ≥3×10^9/L; neutrophil count ≥1×10^9/L (not receiving colony-stimulating factor within 2 weeks prior to screening); hemoglobin ≥60g/L.
4. Liver function fulfillment: ALT≤3×ULN; AST≤3×ULN; TBIL≤3×ULN.
5. Renal function fulfillment: creatinine clearance CrCl ≥ 60mL/min.
6. Coagulation function meets: international standard ratio INR <1.5 times ULN, prothrombin time PT <1.5 times ULN.

Patients with rheumatoid arthritis must also meet the following enrollment criteria:

1. Diagnosis of rheumatoid arthritis according to the 2010 ACR / EULAR diagnostic criteria.
2. Fulfillment of one of the following conditions: DAS28-ESR >3.2 or CDAI >10 at 3 months after use of a standard treatment regimen prior to screening; inability to taper hormones (prednisone) to less than 7.5 mg/day; and number of swollen joints and/or number of joints with tenderness ≥3. Standard treatment regimen is defined as the stable use of any of the following (alone or in combination): corticosteroids, nonsteroidal anti-inflammatory drugs ( NSAIDs) and csDMARDs, including methotrexate, leflunomide, hydroxychloroquine, salazosulfapyridine, elamodex, tretinoin, and paeonia lactiflora total, as well as biological agents (including TNF inhibitors, non-TNF inhibitors, and JAK inhibitors).
3. Stable treatment with 1 or 2 cs DMARD(s) prior to enrollment as follows: at least 12 weeks of methotrexate and at least 4 weeks of administration at a dose of 7.5-25 mg/week; at least 4 weeks of stable hydroxychloroquine doses of ≤400 mg/d; at least 4 weeks of stable oral salicylazosulfapyridine 1 to 3 g/d; at least 4 weeks of stable oral leflunomide 10-20 mg /d.

Patients with SLE will also be required to meet the following enrollment criteria:

1. Diagnosis of SLE according to the 2019 EULAR/ACR classification criteria for SLE.
2. A history of SLE for at least 6 months prior to screening, with the disease remaining active 2 months after the use of a standard treatment regimen prior to screening. Standard treatment regimen is defined as stable use of any of the following (alone or in combination): corticosteroids, antimalarials, nonsteroidal anti-inflammatory drugs (NSAIDs), and other immunosuppressive or biologic agents, including azathioprine, mertiomaxolide, cyclophosphamide, methotrexate, leflunomide, tacrolimus, cyclosporine, belimumab, rituximab, and tetracycline.
3. BILAG-2004 assessment of the presence of at least 1 grade A or 2 grade B organ scores.
4. Positive for at least one of the following antibodies: anti-nuclear antibody, anti-ds-DNA antibody, anti-Sm antibody.
5. SLEDAI-2000 score ≥ 8 during the screening period.

Patients with dry syndrome were also required to meet the following enrollment criteria:

1. Diagnosis of dry syndrome according to the 2002 International Classification Criteria for Primary Dry Syndrome or the 2016 ACR/EULAR classification criteria.
2. Diagnosis of pSS-TP with platelet count <30 x 10^9/L.
3. History of dry syndrome for at least 6 months prior to screening and disease still active 2 months after use of conventional treatment regimen prior to screening. Definition of conventional therapy:Use of glucocorticoids (above 1 mg/Kg/d) and cyclophosphamide, and any of the following immunomodulatory drugs for more than 6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, and cyclosporine, as well as biologics, such as rituximab, belimumab, and tetraciprazole.

Patients with systemic sclerosis were also required to meet the following enrollment criteria:

1. Diagnosis of systemic sclerosis according to the 2013 ACR classification criteria for systemic sclerosis.
2. Positive antinuclear antibodies at screening.
3. Presence of clear evidence of HRCT progression.
4. History of systemic sclerosis for at least 6 months prior to screening, and active disease 2 months after use of a conventional treatment regimen prior to screening. Definition of conventional therapy:Use of glucocorticoids (above 0.5 mg/Kg/d) and cyclophosphamide for more than 6 months, as well as any of the following immunomodulatory medications: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, and cyclosporine, as well as biologics, such as rituximab and belimumab.

Exclusion Criteria:

1. pre-screening presence of clinically significant CNS disease or pathological changes not caused by the disease itself, including, but not limited to: stroke, apoplexy, aneurysm, epilepsy, convulsions, aphasia, severe craniocerebral injury, dementia, Parkinson's disease, cerebellar disorders, organic brain syndromes, or insanity.
2. Those suffering from relatively serious heart diseases such as angina pectoris, myocardial infarction, heart failure and arrhythmia.
3. History of major organ transplantation or hematopoietic stem cell/bone marrow transplantation.
4. vaccination, B-cell targeted therapy within 4 weeks prior to screening.
5. History of any malignant disease.
6. Patients with end-stage renal failure.
7. Presence or suspected presence of uncontrolled fungal, bacterial, viral or other infections.
8. History of severe allergy to drugs used in clinical studies or raw materials of test drugs, such as cyclophosphamide, fludarabine, DMSO.
9. The patient is positive for HBV surface antigen, or HBV core antibody and positive for DNA by RT-PCR; positive for HCV antibody or positive for HIV antibody or positive for syphilis or positive for CMV DNA or positive for EBV DNA.
10. Females who are pregnant or breastfeeding or who plan to have a pregnancy within 2 years of return infusion of the test drug; partners of male patients who plan to become pregnant within 2 years of treatment with the test drug.
11. Evidence of active tuberculosis infection.
12. other circumstances assessed by the investigator as unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anti-BCMA and CD19 CART; Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CART infusion. A dose of Anti-BCMA and CD19 CART will be infused on day 0.	Drug: Anti-BCMA and CD19 CART cells will be injected intravenously on a one-time basis.; A single intravenous infusion of anti-BCMA and CD19 CART cells (dose-escalating infusion of 0.5-3 x10^6 CART cells/kg）.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Total number, incidence and severity of adverse events (AEs) in patients of SCAR02 infusion. The AEs will be assessed according to the 2019 Consensus on Cytokine Release Syndrome and Immune-cell-associated Neurotoxicity published by the American Society of Transplantation and Cell Therapy (ASTCT), the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and EBMT 2019 consensus.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The persistence, accumulation, and migration of Anti-BCMA and CD19 CART cells	Assessing the trafficking of Anti-BCMA and CD19 CART cells in the peripheral blood at the time of each infusion as well as at each time of follow-up by Quantitative Real-time Polymerase Chain Reaction or flow cytometry. Peripheral blood will be collected prior to the initial infusion and will be set as baseline.	up to 2 years
Erythrocyte Sedimentation Rate	To evaluate disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
American College of Rheumatology (ACR) criteria 20, 50, 70 response rate	To evaluate RA disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Swollen and tender joint count	To evaluate RA disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Visual Analogue Scale	To evaluate RA disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Changes in the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) from baseline	Range [0, 105]，higher score represents worse disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Changes in the Physician Global Assessment (PGA) score from baseline	Range [0, 3]，higher score represents worse disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Changes in the BILAG-2004 score from baseline	Range [0, 72]，higher score represents worse disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Changes in immunological indexes from baseline	Serum IgA, IgG and IgM will be evaluated	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Changes in level of anti-nuclear antibody (ANA) in peripheral blood from baseline	To evaluate disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Changes in level of anti-double stranded DNA (dsDNA) antibody in peripheral blood from baseline	To evaluate disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Changes in levels of complement in peripheral blood from baseline	To evaluate SLE disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24	To evaluate SLE disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Changes in levels of anti-Ro/SSA antibodies in peripheral blood from baseline	To evaluate disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Changes in levels of Changes in levels of anti-Ro/SSA antibodies in peripheral blood from baseline in peripheral blood from baseline	To evaluate disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Changes in levels of Changes in levels of RF in peripheral blood from baseline in peripheral blood from baseline	To evaluate disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Changes in levels of Changes in levels of anti-topoisomerase I antibody in peripheral blood from baseline in peripheral blood from baseline	To evaluate disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Change in Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline	Change in Health Assessment Questionnaire Disability Index (HAQ-DI) describes the patient's self-assessed degree of disability. HAQ-DI comprises 8 categories of questions rated from 0 to 3, where 3 indicates the worst degree of disability.	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24
Changes in levels of Changes in levels of anti-RNA polymerase III antibody in peripheral blood from baseline in peripheral blood from baseline	To evaluate disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of University of Science and Technology of China
• Investigators: Principal Investigator: zhu chen, M.D, The First Affiliated Hospital of University of Science and Technology of China; Principal Investigator: xingbing wang, M.D, The First Affiliated Hospital of University of Science and Technology of China

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2024
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: July 7, 2024
• First Submitted That Met QC Criteria: July 14, 2024
• First Posted (Actual): July 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; systemic lupus erythematosus; systemic sclerosis; dry syndrome
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases
• Other Study ID Numbers: SWKCART24031101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No