A Study of TG103 Injection in Non-diabetic Overweight or Obesity

Study Overview
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Brief Summary
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This study is a multicenter, randomized, double-blind, placebo-controlled, parallel phase 3 study to evaluate efficacy, safety, pharmacokinetics characteristics and immunogenicity of TG103 injection, a GLP-1 receptor agonist, for weight management in non-diabetic patients with BMI greater than or equal to 28 kg/m2 or greater than 24 kg/m2 in the presence of comorbidities, in addition to lifestyle intervention (calorie restrict diet and increased physical activity).

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 3 Study of TG103 Injection in the Management of Non-diabetic Overweight or Obesity

Conditions
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Overweight or Obesity

Intervention / Treatment
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* Drug: TG103 22.5 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 years ≤ age ≤ 75 years. Body Mass Index (BMI) ≥ 28 kg/m^2, or 24 kg/m^2 < BMI ≤ 28 kg/m^2 with at least one of obesity-related complications. Regular diet and exercise and stable body weight (i.e., self-reported body weight change < 5%) within 12 weeks before screening as well as body weight ≥ 60 kg at screening. Weight loss less than 5% or no weight loss after diet and exercise intervention for at least 12 weeks. Be able to understand the trial and complete the procedures, and be voluntary to participate in this study and sign the informed consent. Exclusion Criteria: History of type 2 diabetes, type 1 diabetes or hypoglycemia. Overweight or obesity due to disease or drug; or weight increase due to non-fat mass increase; or monogenic obesity. Medications or products which are judged by investigators to cause change in weight and influence trial evaluations have been used within 12 weeks before screening or will be used during study. Weight loss less than 5% by monotherapy or combination with GLP-1 receptor agonists for at least 12 weeks before screening. Bariatric surgery within 12 months before screening; or no full recovery from any surgery or injury at screening; or gastrointestinal motility dysfunction due to gastrointestinal surgery. Participation in any clinical trial to receive treatment within 12 weeks before screening, or participation in clinical trial to receive TG103 before screening. History of allergy or suspected allergy to GLP-1 receptor agonists or antibody agents, or suspected allergy to TG103 judged by investigator due to other severe allergy history. Personal history or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN-2). History or screening ultrasound reports of chronic pancreatitis, acute pancreatitis, etc. History of severe gastrointestinal disease; or gastrointestinal symptom at screening; or discontinuation of GLP-1 receptor agonist, GLP-1/GIP receptor agonist, GLP-1/GCG receptor agonist or metformin due to gastrointestinal adverse reaction. Severe infection at screening. Skin disorder that influences safety evaluation at screening. History of severe disease or malignant tumor. Systolic blood pressure ≥ 160 mmHg, diastolic blood pressure ≥ 100 mmHg, NYHA Grade Ⅲ-Ⅳ, QTc interval prolongation or severe arrhythmia at screening. History of abnormal thyroid function with requirement of medication treatment at screening, or screening TSH beyond the normal reference range. One of the followings at screening: 1) HbA1c ≥ 6.5%, or screening FPG ≥ 7.0mmol/L or<2.8mmol/L; 2) calcitonin ≥ 50 ng/L; 3) ALT or AST>3 × UNL (upper normal limit), or total bilirubin>1.5 × UNL; 4) blood amylase or lipase>1.5 × UNL, 5) TG>5.6mmol/L, 6) eGFR<60ml/min/1.73m2 , 7) positive of HBsAg, HCV-antibody, HIV-antibody or anti-TP antibody, 8) WBC< 3×10^9/L, or Hb <100g/L, 9) INR>1.2. History of drug abuse, drug dependence or alcoholism. History of moderate to severe depression, or screening Patient Health Questionaire-9 (PHQ-9) score ≥ 15. The fertile female who is pregnant, breast-feeding or with blood HCG positive at screening; or the fertile participants and their partner cannot use an effective contraceptive method during the trial and within 3 months after the end of treatment. Other situations unsuitable for this study in the investigator's opinion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TG103 22.5 mg<br>Administered subcutaneously once every week for 52 weeks. Doses gradually increased to 22.5 mg. | Drug: TG103 22.5 mg<br>* Subcutaneous injections with calorie restrict diet and increased physical activity for 52 weeks. Doses gradually increased from 7.5 mg to 22.5 mg.<br>|
| Placebo Comparator: Placebo<br>Administered subcutaneously once every week for 52 weeks. | Drug: Placebo<br>* Subcutaneous injections with calorie restrict diet and increased physical activity for 52 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with weight loss of ≥ 5% at week 40 | Weight loss is percentage change at week 40 compared with baseline. | From baseline to week 40 | 
| Relative percentage change from baseline in body weight at week 40 | Weight loss is percentage change at week 40 compared with baseline. | From baseline to week 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with weight loss of ≥ 5% at week 52 | Weight loss is percentage change at week 52 compared with baseline. | From baseline to week 52 | 
| Relative percentage change from baseline in body weight at week 52 | Weight loss is percentage change at week 52 compared with baseline. | From baseline to week 52 | 
| Proportion of participants with weight loss of ≥ 10% | Weight loss is percentage change at week 40 and week 52 compared with baseline. | From baseline to week 40, 52 | 
| Change from baseline in body weight (kg) |  | From baseline to week 40, 52 | 
| Change from baseline in waist circumference (cm) |  | From baseline to week 40, 52 | 
| Change from baseline in HbA1c (%) |  | From baseline to week 40, 52 | 
| Change from baseline in fasting plasma glucose (mmol/L) |  | From baseline to week 40, 52 | 
| Change from baseline in fasting insulin (mU/L) |  | From baseline to week 40, 52 | 
| Change from baseline in total cholesterol (mmol/L) |  | From baseline to week 40, 52 | 
| Change from baseline in triglyceride (mmol/L) |  | From baseline to week 40, 52 | 
| Change from baseline in low density lipoprotein cholesterol (mmol/L) |  | From baseline to week 40, 52 | 
| Change from baseline in high density lipoprotein cholesterol (mmol/L) |  | From baseline to week 40, 52 | 
| Change from baseline in systolic blood pressure (mmHg) |  | From baseline to week 40, 52 | 
| Change from baseline in diastolic blood pressure (mmHg) |  | From baseline to week 40, 52 |