Type 1 Diabetes
Conditions
Brief summary
This is an open clinical pharmacological translational Research Study, aiming to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of RD13-02 in patients with aT1DM
Interventions
CAR T-cell therapy administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphami
Sponsors
Nanjing Bioheng Biotech Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Patients with type 1 diabetes presenting with any of the following conditions: Impaired hypoglycemia awareness (lack of sufficient autonomic symptoms when plasma glucose is below 54 mg/dL \[3 mmol/L\]) or other clinically diagnosed neuropathy caused by type 1 diabetes, including but not limited to gastrointestinal autonomic neuropathy Metabolic instability: two or more previous severe hypoglycemic events that required assistance from others, or two or more hospitalizations for ketoacidosis in the past year * Age ≤ 60 years * Body weight ≥ 40 kg * At least one positive islet autoantibody, including glutamic acid decarboxylase autoantibody (GADA), protein tyrosine phosphatase autoantibody (IA-2A), insulin autoantibody (IAA) (only applicable within 2 weeks of insulin treatment), zinc transporter 8 antibody (ZnT8), islet cell autoantibody (ICA), etc. * MMTT stimulated C-peptide peak \> 0.1 nmol/L, or fasting C-peptide \> 0.05 nmol/L * Female subjects of childbearing potential must have a negative serum or urine pregnancy test at screening * Both male and female subjects must be willing to use contraception from the time of signing the informed consent form until 12 months after cell infusion * The subject or their legal guardian voluntarily participates in this study and is able to sign the informed consent form
Exclusion criteria
* If any of the following criteria are met, the subject will be excluded from the study. Type 2 diabetes, or diabetes mellitus from pregnancy, single-gene mutation, pancreatic injury, or other secondary causes (e.g., Cushing's syndrome, thyroid dysfunction, or acromegaly) * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 x ULN, or total bilirubin ≥ 1.5 x ULN * Severe heart disease, with any of the following: * Myocardial infarction within 1 year before enrollment * Signs or symptoms of heart failure of NYHA Class ≥ 3 within 1 year before enrollment * Left ventricular ejection fraction (LVEF) \< 50% at screening * QTcF \> 450 msec (males) or \> 470 msec (females), based on the QTcF value from a single ECG or the average of three repeated ECGs taken more than 3 minutes apart (QT interval corrected by Fridericia's formula) * Severe concurrent diabetic nephropathy, with an estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2 * Currently undergoing or expected to require renal replacement therapy during the study * At screening, a subject tests positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B e-antigen (HBeAg); a subject tests positive for hepatitis B e-antibody (HBeAb) with a peripheral blood HBV DNA level above the upper limit of normal; a subject tests positive for hepatitis C virus (HCV) antibody; a subject tests positive for human immunodeficiency virus (HIV) antibody; a subject tests positive for syphilis antibody; a subject tests positive for EBER or has an EBV viral load greater than the upper limit of normal * Participated in another clinical study within 3 months prior to enrollment * Received a live attenuated vaccine within 4 weeks prior to enrollment * The investigator considers the patient to have latent T1DM, including latent autoimmune diabetes in adults (LADA) and latent autoimmune diabetes in the young (LADY) * The investigator believes there are other reasons that make the subject unsuitable for this clinical study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence of dose-limiting toxicity (DLT) of RD13-02 in patients with type 1 diabetes, as well as the incidence of adverse events (AE), serious adverse events (SAE), and adverse events of special interest (AESI) | 1 year |
Countries
China
Outcome results
None listed