Single-dose exenatide circular RNA in lipid nanoparticles for Chinese adults with type 2 diabetes

A Single-Center, Open-Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Exenatide Circular RNA-Lipid Nanoparticle Injection (CR059) in Chinese Subjects With Type 2 Diabetes Mellitus

This test gives a single injection of CR059 (exenatide circular RNA in a lipid nanoparticle) to see if it is safe and how it behaves in Chinese adults with type 2 diabetes.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: The First Affiliated Hospital of Henan University of Science and Technology (other)
• Locations: 1 site (Luoyang, Henan)
• Trial ID: NCT07347080 on ClinicalTrials.gov

What this trial studies

This is a single-center, open-label, single ascending dose study enrolling 6–9 Chinese adults with type 2 diabetes of 3 months to under 5 years duration. Participants are assigned to one of three dose cohorts (4, 8, or 12 μg/kg) and receive a single intravenous injection of CR059, with in-hospital observation for at least 7 days. Primary outcomes are safety and tolerability, with secondary measurements of pharmacokinetics, pharmacodynamics, and immunogenicity. The study targets patients with HbA1c between 7.5% and 10.0%, BMI 18.5–40 kg/m², and on stable metformin-based regimens or equivalent.

Who should consider this trial

Good fit: Adults 18–65 years old of Chinese ethnicity with type 2 diabetes for 3 months to less than 5 years, HbA1c 7.5–10.0%, BMI 18.5–40 kg/m², and on stable metformin-based therapy are ideal candidates.

Not a fit: People with very long-standing diabetes, HbA1c outside the 7.5–10.0% range, pregnancy, or conditions excluded by the protocol are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this approach could provide a new way to deliver exenatide that prolongs its activity and reduces the need for frequent injections.

How similar studies have performed: Traditional exenatide and other GLP-1 receptor agonists have a strong evidence base for glycemic and weight benefits, but using circular RNA in lipid nanoparticles to deliver exenatide is a novel delivery approach with limited human data.

Eligibility criteria

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.

Where this trial is running

Luoyang, Henan

• The First Affiliated Hospital of Henan University of Science and Technology — Luoyang, Henan, China (RECRUITING)

Study contacts

• Study coordinator: Hongwei Jiang, PhD Supervisor

Conditions: T2DM