T2DM
Conditions
Brief summary
Primary Objectives: •To evaluate the safety and tolerability of a single dose of Exenatide Circular RNA-Lipid Nanoparticle Injection（CR059）in Chinese subjects with T2DM. Secondary Objectives: * To characterize the pharmacokinetic (PK) profile of a single dose of Exenatide Circular RNA-Lipid Nanoparticle Injection（CR059） in Chinese subjects with T2DM; * To characterize the pharmacodynamic (PD) profile of a single dose of Exenatide Circular RNA-Lipid Nanoparticle Injection（ CR059） in Chinese subjects with T2DM; * To evaluate the immunogenicity of a single dose of Exenatide Circular RNA-Lipid Nanoparticle Injection（ CR059） in Chinese subjects with T2DM; Participants : Diagnosed with T2DM for at least 3 months but less than 5 years, according to the Chinese Diabetes Society's diagnostic criteria
Detailed description
This is a single-center, open-label, single ascending dose study designed to evaluate the safety, tolerability, PK, PD, and immunogenicity of Exenatide Circular RNA-Lipid Nanoparticle Injection（ CR059）in Chinese subjects with T2DM. It is planned to enroll 6-9 subjects.The study includes three dose cohorts (low, medium, high: 4 μg/kg, 8 μg/kg, 12 μg/kg). Each cohort plans to enroll 2-3 T2DM subjects. A single dose will be administered, with subjects observed in-hospital for at least 7 days.
Interventions
DRUGExenatide Circular RNA-Lipid Nanoparticle Injection（ CR059））
use one dose per person
Sponsors
The First Affiliated Hospital of Henan University of Science and Technology
PegBio Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Chinese male or female， 18≤age≤-65 years . * Diagnosed with T2DM for at least 3 months but less than 5 years, according to the Chinese Diabetes Society's "Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2024 Edition)" diagnostic criteria. * Patients who have failed treatment with diet and exercise alone, or metformin monotherapy, or a stable regimen for 12 weeks of metformin (dose ≥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%. * 18.5 kg/m²≤Body Mass Index (BMI) ≤40.0 kg/m² at screening and enrollment * 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. * Able to understand and willing to sign the informed consent form, and fully understand the trial content, procedures, and potential adverse reactions. * Able to complete the trial according to the protocol requirements.
Exclusion criteria
* 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). * History of acute diabetic complications, such as ketoacidosis or hyperosmolar coma, within 6 months before screening. * 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. * 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. * Fasting plasma glucose \<3.9 mmol/L at screening or before enrollment, and/or history of ≥2 episodes of severe hypoglycemia or recurrent symptomatic hypoglycemia within 6 months before screening. * History or presence of Cushing's syndrome, polycystic ovary syndrome, or other hereditary endocrine diseases, or obesity secondary to factors such as hormones. * Use of weight-control medications or weight-loss surgery within 3 months before screening, or weight fluctuation exceeding 5% within 3 months. * Clinically significant abnormal TSH, FT3, or FT4 at screening, or previous diagnosis of thyroid dysfunction, deemed unsuitable by the investigator. * 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. * History or presence of malignant tumors (except cured basal cell carcinoma or cervical carcinoma in situ). * 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. * 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. * 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. * History of gout or gout attack within 6 months before screening or before enrollment. * 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. * Heart rate at rest (after at least 10 min) \<50 bpm or \>100 bpm at screening or before enrollment. One re-test is allowed. Exclusion if both readings fail. * 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. * History of clinically significant chronic or acute exacerbating respiratory diseases, including but not limited to asthma, COPD (excluding obstructive sleep apnea). * History of severe gastrointestinal disease (e.g., active ulcer, gastroparesis, pyloric obstruction, inflammatory bowel disease) within 6 months before screening or before enrollment, or gastrointestinal surgery, or long-term use of drugs directly affecting GI motility due to chronic GI disease, deemed unsuitable by the investigator. * Severe renal disease or estimated Glomerular Filtration Rate (eGFR) \<60 mL/min/1.73m² (CKD-EPI formula) at screening or before enrollment. * Serum amylase or lipase \>3x Upper Limit of Normal (ULN) at screening or before enrollment, or history/known chronic pancreatitis, acute pancreatitis, pancreatic injury. * History of cholelithiasis, acute or chronic cholecystitis (except those with no residual biliary stones post-treatment or post-cholecystectomy without sequelae, deemed eligible by the investigator). * Severe dyslipidemia, with LDL-C ≥4.40 mmol/L or triglycerides (TG) ≥5.65 mmol/L at screening or before enrollment. If on lipid-lowering therapy, regimen and dose must be stable for 1 month. * Clear history of psychiatric disorders (e.g., depression, schizophrenia, bipolar disorder) within 2 years before screening. * Major surgery within 1 month before screening, or presence of severe infection or active inflammation. * History of blood donation \>400 mL, transfusion, or blood loss within 90 days before screening or before enrollment. * Any of the following laboratory abnormalities at screening or before enrollment: 1. ALT or AST \>2x ULN; 2. Total Bilirubin \>1.5x ULN; 3. Calcitonin ≥35 pg/mL; 4. Hemoglobin \<110 g/L (female) or \<120 g/L (male); 5. Clinically significant abnormal platelet count; 6. Clinically significant abnormal white blood cell or neutrophil count; * Use of any approved or unapproved weight-affecting drugs or products within 3 months before screening, including but not limited to orlistat, phentermine-topiramate, naltrexone-bupropion, systemic corticosteroids, antidepressants (SSRIs, SNRIs, tricyclics, tetracyclics), antipsychotics/sedatives (e.g., imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid, lithium), etc. * Use of any DPP-4 inhibitor, or GLP-1, GIP, GCG receptor agonists, or FGF-21 within 6 months before screening. * History of bariatric surgery (except liposuction/abdominoplasty \>1 year prior). * Participation in any drug or medical device clinical trial within 3 months before screening or before enrollment (except screen failures). * Positive serology for HBsAg, anti-HCV antibody, anti-TP antibody, or anti-HIV antibody at screening. * History of drug abuse and/or alcoholism (weekly alcohol intake \>14 units) within 6 months before screening * Positive urine drug screen or alcohol breath test at screening. * Pregnant or lactating females, or subjects using oral contraceptives. * Intolerance to venipuncture or history of needle syncope, blood-injury syncope. * Any other physiological, psychological, or situational condition deemed by the investigator as unsuitable for trial participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | From the first dosing (Day 1 ) of study drug until completion of the post treatment follow-up visit(Day 36) | Adverse events (AEs) / Serious adverse events (SAEs) will be collected via: Laboratory tests (including complete blood count, blood biochemistry, glucagon, lipase, amylase, urinalysis, coagulation function, high-sensitivity C-reactive protein, inflammatory factors); Vital signs (blood pressure, pulse rate, body temperature, respiration); Physical examinations (including skin, mucous membranes, lymph nodes, head and neck, chest, abdomen, spine and extremities, and musculoskeletal tissues); 12-lead electrocardiogram (12-lead ECG, including PR interval, QRS duration, QTcF interval); Abnormalities observed by the investigator; Subject-reported complaints. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic | From the first dose (Day 1 ) of study drug until Day 36 | Cmax |
| Anti-Drug Antibodies | Day 1 (first dosing day)、Day 15、Day 29 | ADA positivity rate |
| Pharmacodynamics | From the baseline(Day 2)until completion of the post treatment follow-up visit (Day 36)(Day 1 :first dosing day) | Plasma Glucose |
Countries
China
Contacts
CONTACTHongwei Jiang, PhD Supervisor
Outcome results
None listed