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
Overview
- Phase
- Phase 1
- Intervention
- TG103 injection
- Conditions
- Diabetes
- Sponsor
- CSPC Baike (Shandong) Biopharmaceutical Co., Ltd.
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Safety and tolerability assessed by incidence and severity of adverse events
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age between 18 and 75 years (inclusive); no gender limitation;
- •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);
- •Fasting blood glucose 3.9-7.0 mmol/L (exclusive) and the HbA1c \< 6.5%;
- •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;
- •Subjects who fully understand the study, voluntarily participate in the trial and sign the informed consent form。
Exclusion Criteria
- •History of allergy to Glucagon-like peptide-1 (GLP-1) analogues, or history of serious allergy to drugs or food;
- •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);
- •Subjects have confirmed diagnosis of type 1 or type 2 diabetes;
- •History of or current pancreatitis (history of chronic or acute pancreatitis);
- •Previous clinically significant abnormal gastric emptying (e.g., gastric outlet obstruction) and severe chronic gastrointestinal diseases (e.g., active ulcer within 6 months);
- •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;
- •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;
- •History of chronic malabsorption syndrome;
- •Subjects with hematological diseases (e.g., aplastic anemia, myelodysplastic syndrome) or any disease causing hemolysis or erythrocyte instability (e.g., malaria);
- •Severe systemic infectious diseases within 1 month prior to screening;
Arms & Interventions
TG103 injection 15 mg
TG103 injection (15 mg, N=12) and Placebo (N=4) will be administered subcutaneously once weekly in overweight/obese non-diabetic subjects.
Intervention: TG103 injection
TG103 injection 15 mg
TG103 injection (15 mg, N=12) and Placebo (N=4) will be administered subcutaneously once weekly in overweight/obese non-diabetic subjects.
Intervention: Placebo
TG103 injection 22.5 mg
TG103 injection (22.5 mg, N=12) and Placebo (N=4) will be administered subcutaneously once weekly in overweight/obese non-diabetic subjects.
Intervention: TG103 injection
TG103 injection 22.5 mg
TG103 injection (22.5 mg, N=12) and Placebo (N=4) will be administered subcutaneously once weekly in overweight/obese non-diabetic subjects.
Intervention: Placebo
TG103 injection 30 mg
TG103 injection (30 mg, N=12) and Placebo (N=4) will be administered subcutaneously once weekly in overweight/obese non-diabetic subjects.
Intervention: TG103 injection
TG103 injection 30 mg
TG103 injection (30 mg, N=12) and Placebo (N=4) will be administered subcutaneously once weekly in overweight/obese non-diabetic subjects.
Intervention: Placebo
Outcomes
Primary Outcomes
Safety and tolerability assessed by incidence and severity of adverse events
Time Frame: Up to 99 days
Secondary Outcomes
- PK profile- Cmax: Peak Plasma Concentration(Day1, 8, 15, 22, 29, 64, 71, and 78)
- PD profile- Proportion of subjects with a baseline weight loss of more than 5 percent(Day1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85 and 99)
- PD profile- Change of blood fat levels relative to baseline(Day15, 22, 29, 43, 85 and 99)
- PD profile- Change of waist-hip ratio relative to baseline(Day8, 15, 22, 29, 43, 57, 71, 78, 85 and 99)
- PD profile- Change of blood pressure（systolic blood pressure and diastolic blood pressure）relative to baseline(Day15, 22, 29, 43, 85 and 99)
- PD profile- Waistline change relative to baseline(Day8, 15, 22, 29, 43, 57, 71, 78, 85 and 99)
- PK profile-AUC: Area under the plasma concentration versus time curve(Day1, 8, 15, 22, 29, 64, 71, and 78)
- PK profile- Tmax: Time to maximum plasma concentration(Day1, 8, 15, 22, 29, 64, 71, and 78)
- PK profile- t1/2: Half time(Day1, 8, 15, 22, 29, 64, 71, and 78)
- PK profile- CL/F: Apparent clearance(Day1, 8, 15, 22, 29, 64, 71, and 78)
- PD profile- Weight change relative to baseline(Day1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85 and 99)
- The occurrence of TG103 anti-drug antibodies (ADA)(Day1, 15, 29, 57, and 99)