Type 2 Diabetes Mellitus (T2DM)
Conditions
Interventions
Trial group:Subcutaneous injection of Exenatide circular RNA lipid nanoparticle injection (CR059). The study plans to enroll 6-9 subjects, divided into 3 dose groups (4µg/kg, 8µg/kg, 12µg/kg), with 2-
Sponsors
The First Affiliated Hospital of Henan University of Science and Technology
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Chinese male or female, 18=1500 mg/day or maximum tolerated dose >=1000 mg/day) combined with one of the following oral antidiabetic drugs (or their fixed-dose combinations): sulfonylureas, glinides, alpha-glucosidase inhibitors, SGLT2 inhibitors, or thiazolidinediones (at >=1/2 the maximum approved dose, or the recommended minimum maintenance dose for SGLT2 inhibitors e.g., empagliflozin 10mg, canagliflozin 100mg). Fasting Plasma Glucose (FPG) must be <13.0 mmol/L, and 7.5%<=HbA1c <=10.0%. 4. 18.5 kg/m^2<=Body Mass Index (BMI) <=40.0 kg/m^2 at screening and enrollment. 5. Subjects have no pregnancy plan from screening until 3 months after the last dose and are willing to use at least one effective method of contraception during the entire trial period until 3 months after the last dose. 6. Able to understand and willing to sign the informed consent form, and fully understand the trial content, procedures, and potential adverse reactions. 7. Able to complete the trial according to the protocol requirements.
Exclusion criteria
Exclusion criteria: 1.Diagnosis of type 1 diabetes, diabetes due to pancreatic injury, or specific types of diabetes due to other diseases (e.g., acromegaly or Cushing's syndrome). 2.History of acute diabetic complications, such as ketoacidosis or hyperosmolar coma, within 6 months before screening. 3.Presence of severe chronic diabetic complications (e.g., proliferative diabetic retinopathy, severe diabetic neuropathy, diabetic foot, etc.) within 6 months before screening, deemed by the investigator as unsuitable for participation. 4.Allergic constitution (allergy to >=2 types of drugs or foods) or keloid tendency, or clear history of drug allergy, or investigator suspects potential allergy to the investigational product or its components or similar drugs. 5.Fasting plasma glucose =2 episodes of severe hypoglycemia or recurrent symptomatic hypoglycemia within 6 months before screening. 6.History or presence of Cushing's syndrome, polycystic ovary syndrome, or other hereditary endocrine diseases, or obesity secondary to factors such as hormones. 7.Use of weight-control medications or weight-loss surgery within 3 months before screening, or weight fluctuation exceeding 5% within 3 months. 8.Clinically significant abnormal TSH, FT3, or FT4 at screening, or previous diagnosis of thyroid dysfunction, deemed unsuitable by the investigator. 9.Personal or family history of multiple endocrine neoplasia type 2; personal or family history of medullary thyroid carcinoma; or thyroid nodules classified as C-TIRADS category 4 or higher on ultrasound. 10.History or presence of malignant tumors (except cured basal cell carcinoma or cervical carcinoma in situ). 11.History of thrombotic diseases (e.g., deep vein thrombosis, pulmonary embolism, stroke), known bleeding diathesis or coagulation dysfunction, major thrombotic event within 6 months, or any coagulation parameter >=1.5x ULN, or clinically significant abnormal coagulation function deemed unsuitable by the investigator. 12.Long-term use (over 1 month) or current use of anticoagulants (e.g., warfarin,rivaroxaban, dabigatran) or antiplatelet drugs (e.g., aspirin, clopidogrel) before screening. 13.Diagnosis of significant cardiovascular or cerebrovascular disease within 6 months before screening, including but not limited to acute stroke, transient ischemic attack (TIA), acute coronary syndrome, coronary heart disease, heart failure, arrhythmia requiring treatment, etc. 14.History of gout or gout attack within 6 months before screening or before enrollment. 15.Untreated or poorly controlled hypertension (systolic BP >160 mmHg and/or diastolic BP >100 mmHg) at screening or before enrollment. Patients on antihypertensive therapy must have a stable regimen and dose for 1 month. If BP criteria are not met at screening/enrollment, one re-test is allowed. Exclusion if both readings fail. 16.Heart rate at rest (after at least 10 min) 100 bpm at screening or before enrollment. One re-test is allowed. Exclusion if both readings fail. 17.PR interval >210 ms and/or QRS complex duration >120 ms, and/or QTcF >450 ms at rest at screening or before enrollment. If criteria not met, repeat ECG twice on the same day; use the average of 3 measurements for judgment. 18.History of clinically significant chronic or acute exacerbating respiratory diseases, including but not limited to asthma, COPD (excluding obstructive sleep apnea). 19.History of severe gastrointes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and Tolerability Endpoints: Include AE/SAE, laboratory tests (including hematology, blood biochemistry, lipase, amylase, urinalysis, fasting plasma glucose, etc.), 12-lead ECG (including PR interval, QRS duration, QTcF interval, etc.), physical examination (including skin, mucous membranes, lymph nodes, head and neck, chest, abdomen, and other areas), and vital signs (blood pressure, pulse rate, body temperature, respiration).; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic data, including Cmax, Tmax, and AUC0-last; if data permit, AUC0-inf, CL/F, t1/2, and Vz/F will also be calculated.;PD Endpoints Assessment;Immunogenicity Analysis;Other endpoints include changes from baseline in HbA1c, FPG, body weight (absolute value and percentage reduction), BMI, waist-to-hip ratio, waist circumference, hip circumference, lipid profile, blood pressure, insulin resistance index (HOMA-IR), and body composition components measured by body fat analyzer (including visceral fat, peripheral fat, and muscle mass) after treatment.; | — |
Countries
China
Contacts
Public ContactJiang Hongwei
The First Affiliated Hospital of Henan University of Science and Technology
Outcome results
None listed