NCT06414135招募中1 期
A Dose Ranging Study to Evaluate the Safety, Tolerance, Pharmacokinetics and Pharmacodynamics of Relmacabtagene Autoleucel (Relma-cel) in Patients With Refractory/Progressive Systemic Sclerosis
Liangjing Lu1 个研究点 分布在 1 个国家目标入组 6 人开始时间: 2024年6月12日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Occurrence of AEs and SAEs
研究概览
简要总结
Relma-cel is a product containing CD19-CAR-transduced T cells. The purpose of this study is to evaluate the safety of Relma-cel at different dose levels in patients with early diffuse systemic sclerosis. Efficacy will be explored too. If enrolled, participants will undergo leukapheresis, lymphodepleting chemotherapy and administration of Relma-cel.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •voluntary to sign the ICF
- •aged between 18-65 years old (inclusive)
- •diagnosed with diffuse systemic sclerosis according to 2013 ACR Systemic Sclerosis Classification Criterion
- •meet the definitions of refractory/progressive as below:
- •refractory: non-respondent to or disease recurrence after remission with conventional therapies. Conventional therapies are defined as treated for more than 6 months with low dose steroids (≤ 15 mg prednisone equivalent), cyclophosphamide, antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporin or biologics such as rituximab, belimumab, telitacicept, tocilizumab;
- •progressive: having below manifestations within 6 months
- •mRSS increases by >= 3
- •FVC decreases by > 10% or FVC decreases by > 5% and DLCO decreases by > 15%
- •without systemic active infections within 2 weeks of leukapheresis, e.g., infectious pneumonia, tuberculosis
- •available vascular access for leukapheresis
- •major organ functions:
- •Renal function: CrCl ≥50 ml/min (Cockcroft/Gault equation)
- •Bone marrow function: ANC ≥ 1000/uL, absolute lymphocyte count ≥100/uL, Hb ≥90 g/L, Platelet count ≥75 x 10^9/L. Blood transfusion and infusion of growth factors within 7 days of eligibility assessment are not allowed.
- •Liver function: ALT ≤ 3 x ULN, AST ≤ 3 x ULN, total bilirubin ≤ 2 x ULN (in case of Gilbert syndrome, total bilirubin ≤ 3 x ULN)
- •Coagulation: INR ≤ 1.5 x ULN, PT ≤1.5 x ULN
- •Cardiac function: LVEF ≥ 55%
- •negative result of serum β-hCG measurement for women of childbearing potential at screening and within 48 hours of the first dose of lymphodepletion
- •Female subjects with childbearing potential or male subjects with partners of childbearing potential should adopt medically effective contraception or abstinence from enrollment to 2 years after the end of the study; female subjects with childbearing potential should have a negative serum hCG test within 7 days of enrollment and not in lactation
排除标准
- •NYHA class IV
- •FVC predicted < 45% or DLCO predicted < 40%
- •abnormalities on HRCT not attributable to systemic sclerosis
- •history of autologous stem cell transplantation
- •with manifestations of renal crisis
- •with other autoimmune comorbidities that need systemic treatment
- •with a history of severe drug allergy
- •with congenital immunoglobulin deficiency
- •with malignant tumors, except for nonmelanoma skin cancer, in situ cervical cancer, bladder cancer, breast cancer which has been disease free for more than 2 years
- •with psychiatric diseases or severe cognition dysfunctions
- •within 5 half-life cycles of the last administration of an investigational product
- •pregnant, lactation or plan to be pregnant within one year
- •a history of CAR-T therapy or other gene-modified T cell targeted therapies
- •other conditions that are not suitable for enrollment of the study in the judgement of the investigator
- •the use of any live vaccines against infections within one month of the screening
- •with any manifestations of active tuberculosis at screening
结局指标
主要结局
Occurrence of AEs and SAEs
时间窗: 3 months
frequency and severity of AEs and SAEs
DLT rate
时间窗: 28 days
the incidence of dose-limiting toxicity
次要结局
- the change from baseline in Composite Response Index in Systemic Sclerosis (CRISS)(baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration)
- the change from baseline in modified Rodnan Skin Score (mRSS)(baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration)
- the change from baseline in skin stiffness (measuring the thickness of epiderm and dermis) by skin ultrasound(12 months)
- the change from baseline in IgG, IgM, IgE, IgA(baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration)
- Relma-cel cell numbers and transgene copy numbers and duration in blood(baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration)
- the changes of CD19+ cells and other B cell subsets(baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration)
- systemic sclerosis specific antibodies, e.g., anti-scl-70 antibodies, anti-RNA polymerase III antibodies, anti-centrosome antibodies, antinuclear antibody (ANA)(baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration)
- the change from baseline in Sclerodema Clinical Trial Consortium-Damage Index (SCTC-DI)(baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration)
- the change from baseline in cardiac function (left ventricular ejection fraction, LVEF)(baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration)
- the change from baseline in disease activity score -28 (DAS-28) if any joint involvement(baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration)
- the change from baseline in the levels of inflammation biomarkers including C-reactive protein (CRP), erythropoietin sedimentation rate (ESR) and ferritin(baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration)
- the change from baseline in pulmonary function (forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO))(baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration)
- the change from baseline in high resolution computed tomography (HRCT)(baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration)
- the change from baseline in skin biopsy pathology, e.g., the number of lymphocytes, the thickness of epiderm(baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration)
- the change from baseline in nailfold capillaroscopy examination, e.g., the capillary density, the diameter of capillaries(12 months)
- the change from baseline in health assessment questionnaire -damage index (HAQ-DI)(12 months)
研究者
Liangjing Lu
Professor
RenJi Hospital
研究点 (1)
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