Type 2 Diabetes Mellitus
Conditions
Brief summary
This is a randomized, double-blind, placebo-parallel, multicenter phase 3 clinical trial to evaluate the efficacy of TG103 injection 7.5mg and 15mg once a week monotherapy compared with placebo in subjects with type 2 diabetes with poor glycemic control after diet and exercise.
Interventions
DRUGTG103
TG103 injection, 7.5mg, 15 mg, SC, once a week
DRUGPlacebo
Placebo, SC, once a week
Sponsors
CSPC Baike (Shandong) Biopharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1.Subjects have diagnosed with type 2 diabetes according to the Guidelines for prevention and treatment of type 2 diabetes in China (2020 Edition), and have been diagnosed with T2DM for at least 8 weeks before screening; * 2.Aged 18 to 75 years (inclusive), no gender limitation; * 3\. Body Mass Index (BMI): 18.5≤BMI≤40; * 4\. No hypoglycemic drugs have been used within 8 weeks before screening, and the blood glucose control is poor after diet and exercise therapy alone * 5.The continuous use of insulin ≤14 days (except gestational diabetes), and/or the types of hypoglycemic drugs used in combination \<3 with the continuous use time ≤4 weeks within 1 year (more than 8 weeks) before screening; * 6.HbA1c must meet the following criteria: * Screening: 7.5% ≤ HbA1c ≤ 11.0% (Local laboratory) * Baseline: 7.0% ≤ HbA1c ≤ 10.5% (Central laboratory) * 7.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; * 8\. Willing and able to accurately use home glucose meter for self-glucose monitoring; * 9\. Be able to understand and follow the trial procedure, voluntarily participate in the trial and sign the informed consent form.
Exclusion criteria
* 1\. Type 1 diabetes; * 2\. Body weight change more than 5% within 1 month prior to screening; * 3\. 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 have been used within 8 weeks before screening; * 4\. History of ≥2 episodes of grade 3 hypoglycemia within 6 months prior to screening, or grade 3 hypoglycemia between screening to randomization; * 5\. Acute complications of diabetes, such as diabetic ketoacidosis and hyperglycemic hyperosmolar status, occurred ≥1 time within 6 months prior to screening; * 6\. Severe chronic complications of diabetes (e.g., proliferative diabetic retinopathy, severe diabetic neuropathy, diabetic foot, etc.) within 6 months prior to screening * 7\. History of acute or chronic pancreatitis prior to screening; * 8\. 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; * 9\. 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; 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; * 10\. Hemorrhagic stroke or acute ischemic stroke disease occurred within 6 months prior to screening; * 11\. 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; * 12\. 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); * 13\. Severe or acute infection within 4 weeks prior to screening, or refractory urinary tract or genital infection within 6 months prior to screening; * 14\. 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; * 15\. 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; * 16\. Personal or family history of medullary thyroid cancer (MTC) or type 2 multiple endocrine tumor syndrome at screening; * 17\. 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; * 18\. Known allergy to the test drug, Empagliflozin, or related excipients; * 19\. Subjects who have lost more than 400 mL blood due to blood donation or other reasons within 3 months prior to screening; * 20\. 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); * 21\. Subject participated in any drug or medical device clinical study within 3 months prior to screening (except for screening failure); * 22\. Pregnant or lactating female; * 23\. Not suitable for this study in the investigator's opinion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes in glycosylated hemoglobin (HbA1c) | Baseline through Week28 |
Secondary
| Measure | Time frame |
|---|---|
| Changes in HbA1c | Baseline through Week52 |
| The percentage of HbA1c≤6.5% and the percentage of HbA1c≤7% | Week28 and 52 |
| Change in fasting plasma glucose (FPG) | Baseline through Week 28 and 52 |
| Change in weight | Baseline through Week 28 and 52 |
| Change in 2h-postprandial plasma glucose (2h-PPG) | Baseline through Week 28 and 52 |
| Change in mean 7-point blood glucose curve ， Change in mean postprandial blood glucose increment . | Baseline through Week 28 and 52 |
| Change in blood lipids (triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) | Baseline through Week 28 and 52 |
| Proportion of subjects receiving remedial therapy | Week 28 and 52 |
| Incidence of adverse events | Week-2 through 52 |
| Blood concentrations of TG103 | Week 0, 4, 8,16, 28,36, 44,52 and 55 |
| The occurrence of TG103 anti-drug antibodies (ADA) and neutralizing antibody (NAb) | Week 0, 4, 8,16, 28,36, 44,52 and 55 |
Countries
China
Outcome results
None listed