NCT06546436尚未招募早期 1 期
An Open, Dose-escalation Clinical Study to Evaluation of the Safety and Efficiency of a Single Dose of CARC-101C in Patients With Autoimmune Type 1 Diabetes Mellitus
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School1 个研究点 分布在 1 个国家目标入组 12 人开始时间: 2024年8月15日最近更新:
适应症
干预措施
试验速览
- 阶段
- 早期 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Incidence and severity of adverse events within 3 weeks after administration (NCI CTCAE V5.0).
研究概览
简要总结
This study investigated the safety, efficiency, pharmacokinetics and pharmacokinetics of CARC-101C in patients with autoimmune type 1 diabetes. A single dose, dose escalation, open study design was used.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients are eligible to be included in this study only if all of the following criteria apply:
- •Males and females aged between ≥18 and ≤40 years old at the time of screening.
- •Diagnosed with Autoimmune type 1 diabetes(T1D) within 3 to 6 months before screening, based on the 2021 version of the Chinese Guidelines for Diagnosis and Treatment of Type 1 Diabetes, with positive pancreatic autoantibodies:
- •Must be tested Insulin a(utoantibody)IAA-positive at the time of diagnosis.
- •Must not have undergone any form of insulin therapy before diagnosis.
- •Currently undergoing insulin therapy and possesses HbA1c levels between ≥7.0% and ≤12%.
- •Possess a body mass index (BMI) between at the time of screening ≥18.0 kg/m2 and ≤ 35.0 kg/m
- •Fasting C-peptide ≥0.10 nmol/L (0.30 ng/ml) or post-MMTT peak C-peptide ≥0.2 pmol/mL (0.6 ng/mL).
- •Males and females of childbearing potential must agree to use highly effective contraception, from providing informed consent till withdrawal or 3 months post-medication (whichever occurs later).
- •Must be capable of providing written, signed, and dated informed consent and willing to comply with research requirements in the study.
排除标准
- •Inclusion Criteria
- •Patients are eligible to be included in this study only if all of the following criteria apply:
- •Males and females aged between ≥18 and ≤40 years old at the time of screening.
- •Diagnosed with T1D within 3 to 6 months before screening, based on the 2021 version of the Chinese Guidelines for Diagnosis and Treatment of Type 1 Diabetes, with positive pancreatic autoantibodies:
- •Must be tested IAA-positive at the time of diagnosis.
- •Must not have undergone any form of insulin therapy before diagnosis.
- •Currently undergoing insulin therapy and possesses HbA1c levels between ≥7.0% and ≤12%.
- •Possess a body mass index (BMI) between at the time of screening ≥18.0 kg/m2 and ≤ 35.0 kg/m
- •Fasting C-peptide ≥0.10 nmol/L (0.30 ng/ml) or post-MMTT peak C-peptide ≥0.2 pmol/mL (0.6 ng/mL).
- •Males and females of childbearing potential must agree to use highly effective contraception, from providing informed consent till withdrawal or 3 months post-medication (whichever occurs later).
- •Must be capable of providing written, signed, and dated informed consent and willing to comply with research requirements in the study.
- •Exclusion Criteria
- •Patients are not eligible to be included in this study if any of the following criteria apply:
- •Average daily total insulin use was >1.0IU/kg(international unit) per day or <15IU per day 7 days before screening.
- •Any of the following abnormalities were detected in the laboratory during screening:
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 of ULN
- •Total bilirubin >1.5 of ULN
- •Hemoglobin <120g/L or > 165g/L (male), or < 110g/L or > 160g/L (female).
- •Serum creatinine >1.5 of ULN(Upper limits of normal).
- •HIV-Ab or HBsAg or HCV-Ab(Hepatitis C virus) or treponema pallidum positive at screening
- •Have a serious/uncontrolled autoimmune disease in addition to T1D at the time of screening.
- •Have diabetic retinopathy stage 3 or above in addition requiring laser or surgical procedures 3 months prior to screening.
- •Possess pre-existing diseases affecting erythrocyte production and stability, including glucose-6-phosphate dehydrogenase (G6PD) deficiency, autoimmune hemolytic anemia, paroxysmal sleep hemoglobinuria, hereditary spherocytosis, hemoglobinopathy, pyruvate kinase deficiency etc.
- •History of acute or chronic pancreatitis.
- •History of hereditary bleeding tendency or coagulation dysfunction, or have a history of thrombosis, hemolysis or bleeding.
- •Diagnosed with DKA(Diabetic Ketoacidosis) or hyperosmotic hyperglycemia syndrome 1 month before screening.
- •Used immunosuppressants 3 months prior to screening.
- •Used systemic glucocorticoid therapy 2 weeks prior to screening or during the study period (except for inhaled and topical glucocorticoid therapies).
- •Participated in any drug or medical device clinical research within 3 months before screening.
- •Previously received cell therapy.
- •Previously reported malignant tumors (whether cured or not).
- •Systemic infection, severe trauma or other states of stress confirmed by laboratory tests or clinical manifestations at the time of screening.
- •Pregnant or lactating women.
- •Have other conditions that the investigator considers inappropriate to participate in this clinical study.
研究组 & 干预措施
Low-dose group
Active Comparator
Subjects enrolled in this group will received a one-dose injection of CARC-101C, 3×1010 eRBC(engineered Red Blood Cells) in one dose.
干预措施: CARC-101C (Drug)
High-dose group
Active Comparator
Subjects enrolled in this group will received a one-dose injection of CARC-101C, 3×1011 eRBC in one dose.
干预措施: CARC-101C (Drug)
结局指标
主要结局
Incidence and severity of adverse events within 3 weeks after administration (NCI CTCAE V5.0).
时间窗: 21 days
次要结局
- Diachronic change of HbA1c from baseline at 12, 24, 36, 52 and 76 weeks.(12, 24, 36, 52 and 76 weeks)
- Homeostatic model assessment of β-cell function (HOMA-β) from baseline at 4, 12, 24, 36, 52 and 76 weeks.(4, 12, 24, 36, 52 and 76 weeks)
- Percentage of subjects with HbA1c < 7% at 12, 24, 36, 52 and 76 weeks.(12, 24, 36, 52 and 76 weeks)
- Changes of AUC(Area Under Curve) compared with baseline fasting and MMTT-stimulated C-peptide at 4, 12, 24, 36, 52 and 76 weeks.(4, 12, 24, 36, 52 and 76 weeks)
- Changes of C-peptide compared with baseline in fasting and 2h after MMTT(Mixed-meal tolerance test)-stimulated at 4, 12, 24, 36, 52 and 76 weeks.(4, 12, 24, 36, 52 and 76 weeks)
- Time in Range (TIR, time of glucose readings at 3.9 to 10.0 mmol/L) changes from baseline in indicators associated with continuous glucose monitoring at 12, 24, 36, 52 and 76 weeks.(12, 24, 36, 52 and 76 weeks)
- Percentage of subjects whose weekly mean insulin requirement decreased by 50% or more at 4, 12, 24, 36, 52 and 76 weeks.(4, 12, 24, 36, 52 and 76 weeks)
- Diachronic change in weekly mean insulin requirement from baseline at 4, 12, 24, 36, 52 and 76 weeks.(4, 12, 24, 36, 52 and 76 weeks)
- Percentage of subjects with TIR >70% from baseline by continuous glucose monitors compared with baseline at 12, 24, 36, 52 and 76 weeks;(12, 24, 36, 52 and 76 weeks)
- Maximum concentration observed (Cmax) of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12;(Day1，Day2，Day5，Day7，Day21，Week4，Week12)
- Time at which the maximum concentration (Tmax ) of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12;(Day1，Day2，Day5，Day7，Day21，Week4，Week12)
- AUC up to the last measurable concentratio（AUC (0-t)）: of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12;(Day1，Day2，Day5，Day7，Day21，Week4，Week12)
- AUC curve to infinite time（AUC (0--∞)） of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12;(Day1，Day2，Day5，Day7，Day21，Week4，Week12)
- Terminal phase rate constant(λz) of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12;(Day1，Day2，Day5，Day7，Day21，Week4，Week12)
- Terminal phase half-life (t1/2) of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12;(Day1，Day2，Day5，Day7，Day21，Week4，Week12)
- Changes of the T cell subpopulation compared with baseline at 3, 4, 12, 24, 36, 52 and 76 weeks;(3, 4, 12, 24, 36, 52 and 76 weeks)
- Changes of the presence of pathogenicity related T cells compared with baseline at 3, 4, 12, 24, 36, 52 and 76 weeks;(3, 4, 12, 24, 36, 52 and 76 weeks)
- Incidence and severity of adverse events within 76 weeks after administration according to version 5.0 of NCI CTCAE.(76 weeks)
- Changes of Insulin Autoimmune Antibodies(IAA）compared with baseline at 4, 12, 24, 36, 52 and 76 weeks;(4, 12, 24, 36, 52 and 76 weeks)
- Changes in cytokine levels.(76 weeks)
研究者
研究点 (1)
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