Phase 3 Study of TG103 Injection Combined With Metformin in Treatment of Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06235086
• Other study ID #: SYSA1803-009
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: March 2024
• Est. completion date: November 2026

Study information

• Verified date: January 2024
• Source: CSPC Baike (Shandong) Biopharmaceutical Co., Ltd.
• Contact: Clinical Trials Information Group officer
• Phone: 86-0311-69085587
• Email: ctr-contact[@]cspc.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 618
• Est. completion date: November 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 or maximum tolerated dose (<1500 mg/ day but =1000 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 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, or prior to randomization;
• 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 or acute 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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• TG103
TG103 injection, 7.5mg, 15 mg, SC, once a week
• Dulaglutide
Dulaglutide, SC, once a week

Locations

Country	Name	City	State
China	Peking University People's Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
CSPC Baike (Shandong) Biopharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in glycosylated hemoglobin (HbA1c) from baseline at 28 weeks of treatment		Baseline through Week28
Secondary	Changes in HbA1c from baseline at 52 weeks of treatment		Baseline through Week52
Secondary	The percentage of HbA1c=6.5% and the percentage of HbA1c=7% at week 28 and 52		Week28 and 52
Secondary	Change in fasting plasma glucose (FPG) from baseline at week 28 and 52		Baseline through Week28 and 52
Secondary	Change in weight from baseline at week 28 and 52		Baseline through Week28 and 52
Secondary	Change in 2h-postprandial plasma glucose (2h-PPG) from baseline at week 28 and 52		Baseline through Week28 and 52
Secondary	Mean 7 point blood glucose curve from baseline at week 28 and 52. Change in mean postprandial blood glucose increment from baseline at week 28 and 52.		Baseline through Week28 and 52
Secondary	Change in blood lipids (triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) from baseline at week 28 and 52.		Baseline through Week28 and 52
Secondary	Proportion of subjects receiving remedial therapy at week 28 and 52		Week28 and 52
Secondary	Incidence of adverse events		Week-2 through 52
Secondary	Blood concentrations of TG103		Week 0, 4, 8,16, 28, 36, 44, 52 and 55
Secondary	The occurrence of TG103 anti-drug antibodies (ADA) and neutralizing antibody (NAb).		Week 0, 4, 8,16, 28, 36, 44, 52 and 55