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

Официальное название

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

Обзор

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

Вмешательства

• Препарат 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）.

Первичные конечные точки

• Adverse events [Срок оценки: up to 2 years]

Вторичные конечные точки (12)

• The persistence, accumulation, and migration of Anti-BCMA and CD19 CART cells [Срок оценки: up to 2 years]
• Erythrocyte Sedimentation Rate [Срок оценки: Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24]
• American College of Rheumatology (ACR) criteria 20, 50, 70 response rate [Срок оценки: Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24]
• Swollen and tender joint count [Срок оценки: Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24]
• Visual Analogue Scale [Срок оценки: 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 [Срок оценки: Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24]
• Changes in the Physician Global Assessment (PGA) score from baseline [Срок оценки: Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24]
• Changes in the BILAG-2004 score from baseline [Срок оценки: Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24]
• Changes in immunological indexes from baseline [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24]
• Changes in levels of complement in peripheral blood from baseline [Срок оценки: Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24]

Критерии участия

Критерии включения

• Sign the informed consent form.
• At the time of signing the informed consent form, the age of 18 years old or above, both male and female.
• 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.
• Liver function fulfillment: ALT≤3×ULN; AST≤3×ULN; TBIL≤3×ULN.
• Renal function fulfillment: creatinine clearance CrCl ≥ 60mL/min.
• 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:

• Diagnosis of rheumatoid arthritis according to the 2010 ACR / EULAR diagnostic criteria.
• 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).
• 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:

• Diagnosis of SLE according to the 2019 EULAR/ACR classification criteria for SLE.
• 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.
• BILAG-2004 assessment of the presence of at least 1 grade A or 2 grade B organ scores.
• Positive for at least one of the following antibodies: anti-nuclear antibody, anti-ds-DNA antibody, anti-Sm antibody.
• SLEDAI-2000 score ≥ 8 during the screening period.

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

• Diagnosis of dry syndrome according to the 2002 International Classification Criteria for Primary Dry Syndrome or the 2016 ACR/EULAR classification criteria.
• Diagnosis of pSS-TP with platelet count <30 x 10\^9/L.
• 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:

• Diagnosis of systemic sclerosis according to the 2013 ACR classification criteria for systemic sclerosis.
• Positive antinuclear antibodies at screening.
• Presence of clear evidence of HRCT progression.
• 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.

Критерии исключения

• 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.
• Those suffering from relatively serious heart diseases such as angina pectoris, myocardial infarction, heart failure and arrhythmia.
• History of major organ transplantation or hematopoietic stem cell/bone marrow transplantation.
• vaccination, B-cell targeted therapy within 4 weeks prior to screening.
• History of any malignant disease.
• Patients with end-stage renal failure.
• Presence or suspected presence of uncontrolled fungal, bacterial, viral or other infections.
• History of severe allergy to drugs used in clinical studies or raw materials of test drugs, such as cyclophosphamide, fludarabine, DMSO.
• 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.
• 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.
• Evidence of active tuberculosis infection.
• other circumstances assessed by the investigator as unsuitable for enrollment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Hunan Siweikang Therapeutic Co.Ltd — Чанша

Идентификаторы

NCT: NCT06503224 · SWKCART24031101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗