A Study of TG103 Injection Combined With Metformin in Treatment of Type 2 Diabetes Mellitus

A Multicenter, Randomized, Open-label, Controlled Phase 3 Trial of TG103 Injection in Combination With Metformin in Subjects With Type 2 Diabetes Mellitus

This is a randomized, open-label, dulaglutide-controlled, multicenter Phase 3 trial to evaluate the efficacy, safety, and immunogenicity of different doses of TG103 injection in combination with metformin in subjects with type 2 diabetes with poor glycemic control treated with metformin monotherapy.

Inclusion Criteria:

• Subjects have diagnosed with type 2 diabetes according to the Guidelines for prevention and treatment of type 2 diabetes in China (2020 Edition), T2DM was diagnosed at least 8 weeks before screening;

• Aged 18 to 75 years (inclusive), no gender limitation;

• Body Mass Index (BMI): 18.5≤BMI≤40;

• Received stable dose of metformin hydrochloride monotherapy for ≥8 weeks before screening and metformin dose ≥1500 mg/ day ;

• HbA1c must meet the following criteria:

  • Screening: 7.5% ≤ HbA1c ≤ 11.0% (Local laboratory)
  • Baseline: 7.0% ≤ HbA1c ≤ 10.5% (Central laboratory)

• Subjects of childbearing potential must use reliable methods of contraception throughout the study period and at least 3 months after the last dose to avoid pregnancy in female subjects or pregnancy in the male subject's partner;

• Willing and able to accurately use home glucose meter for self-glucose monitoring;

• Be able to understand and follow the trial procedure, voluntarily participate in the trial and sign the informed consent form.

Exclusion Criteria:

• Type 1 diabetes;

• Body weight change more than 5% within 1 month prior to screening;

• Received any of the following medications:

  1. Prior discontinuation of DPP-4 inhibitors or GLP-1 receptor agonists for efficacy, tolerability, and safety reasons;
  2. Systemic glucocorticoid and growth hormone,or other drugs affecting glucose metabolism have been used within 8 weeks before screening;

• History of ≥2 episodes of grade 3 hypoglycemia within 6 months prior to screening, or grade 3 hypoglycemia between screening to randomization;

• Acute complications of diabetes, such as diabetic ketoacidosis and hyperglycemic hyperosmolar status, occurred ≥1 time within 6 months prior to screening;

• Severe chronic complications of diabetes (e.g., proliferative diabetic retinopathy, severe diabetic neuropathy, diabetic foot, etc.) within 6 months prior to screening

• History of acute or chronic pancreatitis prior to screening;

• Subjects with clinically significant gastric emptying abnormalities (e.g., gastric outlet obstruction), severe chronic gastrointestinal diseases (e.g., gastroparesis, inflammatory bowel disease, or intestinal obstruction) within 6 months prior to screening, or who have undergone gastrointestinal surgery that affects gastric emptying;

• Any of the following cardiovascular events within 6 months prior to screening: decompensated cardiac insufficiency (NYHA class III or IV); history of unstable angina pectoris, myocardial infarction, coronary artery bypass grafting, or coronary stent implantation; or long QT syndrome or prolonged QTcF interval (QTcF: male >450 ms, female >470 ms) on 12-lead ECG; severe arrhythmias that are evaluated by the investigator to be inappropriate for participation in this clinical trial;

• Hemorrhagic stroke or acute ischemic stroke disease occurred within 6 months prior to screening;

• History of psychiatric diseases (such as depression, anxiety, etc.) during screening; or symptomatic gallbladder disease; or history of other diseases that may endanger the safety of the subject and that the investigator deems inappropriate for enrollment;

• Any type of malignant tumor treated or untreated within 5 years prior to screening (except for clinically cured basal cell carcinoma or carcinoma in situ);

• Severe infection within 4 weeks prior to screening, or refractory urinary tract or genital infection within 6 months prior to screening;

• Having a significant blood system disease (e.g., aplastic anemia, myelodysplastic syndrome) or any disease causing hemolysis or red blood cell instability (e.g., malaria) at screening;

• Subjects with thyroid dysfunction that cannot be controlled by a stable drug dose at screening, or with clinically significant abnormalities in thyroid function examination results requiring drug treatment at screening;

• Personal or family history of medullary thyroid cancer (MTC) or type 2 multiple endocrine tumor syndrome at screening;

• Any of the indicators meet the following criteria:

  • i. Systolic blood pressure ≥ 160mmHg or diastolic blood pressure ≥ 100mmHg at screening or before randomization;

  • ii. Laboratory tests show any of the following abnormalities:

    1. FPG≥13.9 mmol/L;
    2. ALT or AST≥2.5×ULN;
    3. Total bilirubin (TBiL) ≥2.0×ULN;
    4. Triglyceride >5.7 mmol/L;
    5. eGFR<45 mL/(min*1.73 m^2);
    6. Serum amylase and/or lipase ≥3×ULN;
    7. Hemoglobin <100 g/L;
    8. Calcitonin≥50 ng/L(pg/mL);

  • iii. Serological examination:

    1. Human immunodeficiency virus antibody or treponema pallidum antibody is positive;
    2. Hepatitis C antibody is positive, and HCV RNA was higher than the lower limit of the detection reference range;
    3. Hepatitis B surface antigen is positive, and the quantitative detection result of HBV DNA was higher than the lower limit of the detection reference range;

• Known allergy to the test drug, Dulaglutide, Empagliflozin, or related excipients;

• Subjects who have lost more than 400 mL blood due to blood donation or other reasons within 3 months prior to screening;

• Average alcohol intake more than 21 units of alcohol (male)/14 units of alcohol (female) per week within the 3 months prior to screening (1 unit ≈360 mL beer, or 45 mL spirits with 40% alcohol content, or 150 mL wine);

• Subject participated in any drug or medical device clinical study within 3 months prior to screening (except for screening failure);

• Pregnant or lactating female;

• Not suitable for this study in the investigator's opinion.