Phase 3 Study of TG103 Injection Monotherapy in Treatment of Type 2 Diabetes Mellitus

Phase 3

Not yet recruiting

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: TG103; Drug: Placebo

• Registration Number: NCT06258148
• Lead Sponsor: CSPC Baike (Shandong) Biopharmaceutical Co., Ltd.

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-01
• Study First Submitted: 2024-02-06
• Study First Submitted QC: 2024-02-06
• Last Update Submitted: 2024-02-06
• Study First Posted: 2024-02-14
• Last Update Posted: 2024-02-14
• Study Start: 2024-03
• Primary Completion: 2026-03
• Study Completion: 2026-11

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 300

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:

  4. Prior discontinuation of DPP-4 inhibitors or GLP-1 receptor agonists for efficacy, tolerability, and safety reasons;

  5. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TG103, 7.5 mg	TG103	TG103 (7.5 mg) will be administered via subcutaneous injection once a week in subjects with type 2 diabetes.
TG103, 7.5 mg placebo	Placebo	Placebo will be administered via subcutaneous injection once a week in subjects with type 2 diabetes.
TG103, 15 mg placebo	Placebo	Placebo will be administered via subcutaneous injection once a week in subjects with type 2 diabetes.
TG103, 15 mg	TG103	TG103 (15 mg) will be administered via subcutaneous injection once a week in subjects with type 2 diabetes.

Primary Outcome Measures

Name	Time	Method
Changes in glycosylated hemoglobin (HbA1c) from baseline at 24 weeks of treatment	Baseline through Week24

Secondary Outcome Measures

Name	Time	Method
Change in weight from baseline at week 24 and 52	Baseline through Week24 and 52
Changes in HbA1c from baseline at 52 weeks of treatment	Baseline through Week52
Incidence of adverse events	Week-2 through 52
The percentage of HbA1c≤6.5% and the percentage of HbA1c≤7% at week 24 and 52	Week24 and 52
Change in fasting plasma glucose (FPG) from baseline at week 24 and 52	Baseline through Week24 and 52
Change in 2h-postprandial plasma glucose (2h-PPG) from baseline at week 24 and 52	Baseline through Week24 and 52
Proportion of subjects receiving remedial therapy at week 24 and 52	Week24 and 52
Blood concentrations of TG103	Week 0, 4, 8,16, 24,36, 44,52 and 55
Change in mean 7-point blood glucose curve from baseline at week 24 and 52. Change in mean postprandial blood glucose increment from baseline at week 24 and 52.	Baseline through Week24 and 52
Change in blood lipids (triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) from baseline at week 24 and 52	Baseline through Week24 and 52
The occurrence of TG103 anti-drug antibodies (ADA) and neutralizing antibody (NAb)	Week 0, 4, 8,16, 24,36, 44,52 and 55