NCT07715136招募中1 期
A Single-arm, Open-label Phase I Clinical Study to Evaluate ICG318 CAR-T in Adults With Refractory Inflammatory Myopathy
iCell Gene Therapeutics1 个研究点 分布在 1 个国家目标入组 10 人开始时间: 2025年3月20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
- 10
- 试验地点
- 1
- 主要终点
- Number of Adverse Events (AEs) after ICG318 CAR-T infusion.
研究概览
简要总结
This single-arm, open-label, phase I trial evaluates the safety and tolerability of ICG318 CAR-T (BCMA-CD19-IL-15/IL15sushi cCAR T cells) in patients with refractory Idiopathic inflammatory myopathy (IIM).
详细描述
Idiopathic inflammatory myopathy (IIM) is a group of chronic autoimmune diseases with the most common types in adults being dermatomyositis, immune-mediated necrotizing myopathy, polymyositis, and antisynthetase syndrome. IIM is driven by humoral immune cell dysfunction including B cells, plasma cells and long-lived plasma cells.
ICG318 CAR-T, the investigational agent in this clinical trial, is an armored, compound chimeric antigen receptor (cCAR) composed of two independently functioning CARs that target the CD19 and BCMA surface antigens on B cells and plasma/long-lived plasma cells, respectively.
This study is being conducted to evaluate the safety and tolerability of ICG318 CAR-T in patients with refractory IIM. A single dose of ICG318 CAR-T will be evaluated after cyclophosphamide lymphodepletion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-60 (age ≥18 years at first symptom onset), gender not limited;
- •The diagnosis meets the criteria for IIM according to the 2017 EULAR/ACR criteria and is confirmed to be of the following subtype:
- •a. Dermatomyositis: i. Presence of Gottron's rash or sunspot rash; ii. At least one serological result is positive: anti-transcriptional mediator (TIF1-gamma/P155) antibody, anti-matrix protein 2 (NXP2/P140) antibody, anti-Mi2 antibody, anti-melanoma differentiation-associated gene 5 (MDA5) antibody, anti-small ubiquitin-like modifier-1 activator (SAE1) antibody and/or SAE2 antibody, anti-histyl-tRNA synthetase (Jo-1) antibody, anti-alanyl-tRNA synthetase (PL-12) antibody, anti-threonyl-tRNA synthetase (PL-7) antibody, anti-glycyl-tRNA synthetase (EJ) antibody, anti-leucyl-tRNA synthetase (0J) antibody; b. Immune-mediated necrotizing myopathy: i. No characteristic skin manifestations of dermatomyositis were observed (i.e. Gottron's rash or sun-facing rash); ii. Muscle weakness characterized by IIM (e.g., symmetrical proximal muscle weakness of the upper/lower limbs; or more pronounced weakness of the neck flexors than the neck extensors; or more pronounced proximal muscle weakness of the lower limbs than distal muscle weakness).
- •iii. At least one serological result must be positive: anti-human signal recognition particle (SRP) antibody, or trihydroxytrimethylcoenzyme A reductase (HMGCR) antibody; c. Antisynthetic enzyme syndrome: i. At least one of the following clinical manifestations must be present: Raynaud's phenomenon, arthritis, interstitial lung disease, fever (with no other cause of fever found), or technician's hand (thickened and cracked skin on the hands, especially the fingertips).
- •ii. At least one serological result is positive: anti-histyl-tRNA synthetase (Jo-1) antibody, anti-threonyl-tRNA synthetase (PL-7) antibody, anti-alanyl-tRNA synthetase (PL-12) antibody, anti-glycyl-tRNA synthetase (EJ) antibody, anti-leucyl-tRNA synthetase (OJ) antibody, anti-aspartyl-tRNA synthetase (KS) antibody, anti-phenylalanyl-tRNA synthetase (Zo) antibody, anti-glutamyl-tRNA synthetase (JS) antibody, anti-lysyl-tRNA synthetase (SC) antibody, anti-tyrosyl-tRNA synthetase (YRS) antibody;
- •Refractory IIM: At least one round of high-dose corticosteroid therapy and/or intravenous immunoglobulin, and at least two immunosuppressants (including but not limited to cyclophosphamide, mycophenolate mofetil, tacrolimus, cyclosporine, and azathioprine) have been used in adequate doses for more than 6 months;
- •At the time of enrollment, participants must be receiving background medication at a stable dose, defined as: receiving background therapy with one oral glucocorticoid and/or one immunosuppressant at a stable dose for ≥ 12 weeks;
- •Severity of enrollment met the following criteria:
- •MMT-8 score ≤141 (out of 150);
- •Students must meet at least one of the following CSM numerical scale criteria based on abnormal visual analog scale (VAS) scores: Overall activity assessed by study participants ≥2; overall disease activity assessed by physicians ≥2; extra-muscular activity (MDAAT) ≥2; HAQ-DI ≥0.25;
- •At least one muscle enzyme level >1.5 times ULN;
- •Through examinations such as tumor markers, lung and abdominal CT scans, thyroid ultrasound, breast ultrasound, and gastroscopy and colonoscopy, possible potential tumors have been ruled out.
排除标准
- •During the screening period, individuals with active viral, bacterial, or other infections requiring systemic treatment are excluded.
- •The presence of a serious, poorly controlled comorbidity that the investigator considers clinically significant, such as (but not limited to) neurological, cardiovascular, renal, hepatic, endocrine, or gastrointestinal disorders;
- •Patients with severe organ dysfunction:
- •The estimated glomerular filtration rate (eGFR) using the MDRD formula is <40 ml/min/1.73m² ; [eGFR = 186 × (age) - 0.203 × SCr - 1.154 (mg/dl), for women, the result is multiplied by 0.742].
- •Study participants with total bilirubin >1.5 times the upper limit of normal (no specific restrictions are made for liver enzymes because inflammatory myopathy can cause elevated ALT/AST).
- •Cardiovascular: Assessed by echocardiography (ECHO) or cardiac radionuclide angiography (MUGA), with a left ventricular ejection fraction (LVEF) <50% and oxygen saturation <94%. Alternatively, patients may have poorly controlled hypertension or other conditions, or have NYHA class III or IV heart failure, myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, any ventricular arrhythmias, or other clinically significant heart disease.
- •Bone marrow function: Absolute neutrophil count (ANC) <1×10⁹/L; Absolute lymphocyte count (ALC) <0.1×10⁹/L; Platelet count <50×10⁹/L; Hemoglobin <8.0 g/dL;
- •Research participants who have a history of or current malignancy;
- •Infectious diseases: Research participants with active hepatitis B (defined as positive hepatitis B surface antigen or positive hepatitis B core antibody, with hepatitis B virus DNA detection value >1000 copies/mL) or hepatitis C (HCV RNA positive); research participants with positive HIV antibody or positive treponema pallidum antibody and positive non-treponemal syphilis antibody test; active tuberculosis (negative interferon release; if positive, chest X-ray or CT scan is required to rule out active infection);
- •Central nervous system diseases, including cerebrovascular diseases, epilepsy, etc.;
- •Allergies to components of treatment or pre-conditioning.
- •Those with elective surgery planned during the study period;
- •Those who do not wish to take necessary contraceptive measures during the research period;
- •Any other situation that researchers deem unsuitable for participation in the study including poor compliance and being involved in another clinical study.
结局指标
主要结局
Number of Adverse Events (AEs) after ICG318 CAR-T infusion.
时间窗: Starting day 0 and up to 2 years after ICG318 CAR-T infusion.
Number of participants with AEs, Serious Adverse Events (SAEs), Treatment Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESI), and Dose Limiting Toxicities (DLTs).
次要结局
- C-reactive protein(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
- Determine the recommended phase 2 dose (RP2D) regimen.(Starting day 0 and assessed 2 years after ICG318 CAR-T infusion.)
- The proportion of subjects who achieved drug-free remission.(At 6 months (M), 12M, 24M after ICG318 CAR-T infusion.)
- Basic Metabolic Panel(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
- Coagulation studies(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
- Cytokine testing(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
- Manual Muscle Testing 8 (MMT8) score(Days 14, 28; Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
- Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
- Procalcitonin levels(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
- Myositis Disease Activity Assessment Tool (MDAAT) score(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
- 36-item short form survey (SF-36) score. 0 (worst health) and 100 (best health)(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
- Creatinine kinase levels(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
- Lactate dehydrogenase levels(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
- Hydroxybutyrate dehydrogenase levels(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
- Transaminase levels(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
- Ferritin levels(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
- Tmax(Months 3, 6, 12, 24 after ICG318 CAR-T administration)
- Cmax(Months 3, 6, 12, 24 after ICG318 CAR-T administration)
- AUC 0-28d(Months 3, 6, 12, 24 after ICG318 CAR-T administration)
- AUC 0-∞(Months 3, 6, 12, 24 after ICG318 CAR-T administration)
- Peripheral blood lymphocyte subsets (T, B, NK, CD4/CD8(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6 post-ICG318 CAR-T)
- Anti-myositis antibody levels(Days 14, 28 ; Months 2, 3, 6, 9, 12, 18, 24 post-ICG318.)
- Immunoglobulins(Days 1-7, 10, 14, 21, and 28, Months 2, 3, 6, 9, 12, 18, 24 post-ICG318 CAR-T)
研究者
研究点 (1)
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