Clinical trial NCT04855292: A Study of TG103 Injection in Overweight/Obese Subjects Without Diabetes
Official title: A Randomized, Double-blind, Placebo-controlled, Multiple Dose Phase Ib Study in Overweight/Obese Subjects Without Diabetes to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of TG103 Injection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes
Lead sponsor: CSPC Baike (Shandong) Biopharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-04-22
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to assess the safety and tolerability of multiple doses of TG103 injection in overweight/obese subjects without diabetes

Detailed description: This study is a randomized, double-blind, placebo-controlled, multiple-doses, parallel-group study to characterize the safety (including the anti-drug antibodies (ADA)), tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of TG103 injection. The study will consist of 3 periods: an approximately 4-week screening period, followed by a 12-week treatment period, and a 3-week safety follow-up period. Eligible subjects will be enrolled into three paralleled dose groups (15 mg, 22.5 mg and 30 mg) with 16 subjects in each group. Within each group, subjects will be randomized in a 3:1 ratio to receive TG103 injection or placebo subcutaneously (SC) once a week (QW) over a period of 12 weeks. Each group will be started at a low dose of 7.5 mg and gradually up-titrated at weekly intervals until the target dose.

Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 75 years (inclusive); no gender limitation;
2. Body mass index (BMI) ≥ 26.0 kg/m2, BMI = weight(kg)/height2 (m2); body weight ≥ 60 kg; Stable body weight (less than 5% self-reported change within 3 months);
3. Fasting blood glucose 3.9-7.0 mmol/L (exclusive) and the HbA1c \< 6.5%;
4. Subjects of childbearing age must use reliable methods of contraception from the date of signing an informed consent to at least 6 months after the last dose;
5. Subjects who fully understand the study, voluntarily participate in the trial and sign the informed consent form。

Exclusion Criteria:

1. History of allergy to Glucagon-like peptide-1 (GLP-1) analogues, or history of serious allergy to drugs or food;
2. Secondary obesity, such as obesity induced by metabolic disease (e.g., Cushing's syndrome, hypothyroidism etc.) or drug treatment (e.g. with corticosteroids, tricyclic anti-depressants, atypical anti-psychotics);
3. Subjects have confirmed diagnosis of type 1 or type 2 diabetes;
4. History of or current pancreatitis (history of chronic or acute pancreatitis);
5. Previous clinically significant abnormal gastric emptying (e.g., gastric outlet obstruction) and severe chronic gastrointestinal diseases (e.g., active ulcer within 6 months);
6. Individual or family history of medullary thyroid cancer (MTC), type 2 multiple endocrine neoplasia syndrome or other hereditary diseases predisposing to MTC; abnormal and clinically significant thyroid function at screening, requiring pharmacological treatment or not yet clinically stable after treatment;
7. Subjects with history of or current cholestasis or gallbladder stones (previous gallstone removal or lithotripsy) and/or cholecystectomy, who have no further sequelae, can enter into the study at the discretion of the investigator after assessing the risk;
8. History of chronic malabsorption syndrome;
9. Subjects with hematological diseases (e.g., aplastic anemia, myelodysplastic syndrome) or any disease causing hemolysis or erythrocyte instability (e.g., malaria);
10. Severe systemic infectious diseases within 1 month prior to screening;
11. Systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg during screening;
12. Any of the following serious cardiovascular and cerebrovascular events prior to screening: unstable angina pectoris requiring hospitalization, myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention (except for diagnostic angiography), moderate to severe congestive heart failure (NYHA grade III or IV), atrial or ventricular arrhythmia requiring hospitalization (e.g., atrial fibrillation, ventricular tachycardia, tec.), second degree or third degree atrioventricular block without a pacemaker, clinically significant long QT syndrome or prolonged QTc interval, signs of localized ischemic heart disease, pacemaker or defibrillator implantation, stroke or transient ischemic attack or cerebrovascular accident within 6 months, or planned coronary artery bypass grafting or revascularization;
13. The white blood cell count exceeds 10% of the normal range, or hemoglobin\<100 g/L during the screening period;
14. Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) ≥ 2.5 x upper limit of normal (ULN), or fasting triglyceride ≥ 5.64 mmol/L or eGFR \< 60mL/(min\*1.73 m2) during the screening period;
15. History of severe respiratory tract, blood system, central nervous system diseases (e.g., epilepsy, etc.), or history of malignant tumor, mental diseases (e.g., depression, anxiety, etc.), or history of other diseases that may endanger the safety of the subjects and are considered unsuitable for this study in the investigator's opinion;
16. Use of approved weight-lowering pharmacotherapy (e.g., orlistat) within 3 months prior to the first dose;
17. History of surgical treatment for obesity (except for liposuction performed one year ago);
18. Have used incretin analogues or other drugs that might interfere with the trial in the opinion of the investigator within 3 months before the first dose;
19. History of drug abuse or dependence within 5 years prior to screening, with a positive urine drugs of abuse testing at screening;
20. Average alcohol intake is more than 21 units of alcohol (male)/14 units of alcohol (female) per week within the 3 months prior to screening, or positive alcohol breath test before administration;
21. Smoke more than 5 cigarettes per day within 3 months prior to screening;
22. Blood lost ≥ 400 mL due to trauma or major surgery or blood donation ≥ 400 mL within 3 months prior to screening;
23. Have participated in any clinical trial involving an investigational product within 3 months prior to screening;
24. Vaccinated within 28 days before screening or planned to be vaccinated within 1 week after receiving the study drug;
25. Have a positive test result for hepatitis B surface antigen, hepatitis C antibody, anti-human immunodeficiency virus antibody or anti-Treponema pallidum specific antibody;
26. Pregnant (blood pregnancy test positive at screening) and lactating female, or male and female planned to have children during the trial or within 6 months after the last dose;
27. Not suitable for this study in the investigator's opinion.

Primary outcomes:
measure: Safety and tolerability assessed by incidence and severity of adverse events
timeFrame: Up to 99 days
Secondary outcomes:
measure: PK profile-AUC: Area under the plasma concentration versus time curve
timeFrame: Day1, 8, 15, 22, 29, 64, 71, and 78
measure: PK profile- Cmax: Peak Plasma Concentration
timeFrame: Day1, 8, 15, 22, 29, 64, 71, and 78
measure: PK profile- Tmax: Time to maximum plasma concentration
timeFrame: Day1, 8, 15, 22, 29, 64, 71, and 78
measure: PK profile- t1/2: Half time
timeFrame: Day1, 8, 15, 22, 29, 64, 71, and 78
measure: PK profile- CL/F: Apparent clearance
timeFrame: Day1, 8, 15, 22, 29, 64, 71, and 78
measure: PD profile- Weight change relative to baseline
timeFrame: Day1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85 and 99
measure: PD profile- Proportion of subjects with a baseline weight loss of more than 5 percent
timeFrame: Day1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85 and 99
measure: PD profile- Waistline change relative to baseline
timeFrame: Day8, 15, 22, 29, 43, 57, 71, 78, 85 and 99
measure: PD profile- Change of waist-hip ratio relative to baseline
timeFrame: Day8, 15, 22, 29, 43, 57, 71, 78, 85 and 99
measure: PD profile- Change of blood pressure（systolic blood pressure and diastolic blood pressure）relative to baseline
timeFrame: Day15, 22, 29, 43, 85 and 99
measure: PD profile- Change of blood fat levels relative to baseline
timeFrame: Day15, 22, 29, 43, 85 and 99
measure: The occurrence of TG103 anti-drug antibodies (ADA)
timeFrame: Day1, 15, 29, 57, and 99
Other outcomes:
Locations:
city: Beijing
country: China
facility: Gao Huanhuan
state: 河北省
Study officials:
References: