A Study of TG103 Injection in 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 II study to evaluate efficacy, safety, pharmacokinetics characteristics and immunogenicity of two dose levels of TG103 injection, a GLP-1 receptor agonist, in the management of overweight or obesity, to support dose selection for further development.

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

Conditions
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Overweight or Obesity

Intervention / Treatment
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* Drug: TG103 15 mg
* 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. <5 kg self-reported change) within 12 weeks before screening as well as body weight ≥ 60 kg at screening. Weight loss less than 5% or weight increase after simple diet and exercise efforts for at least 3 months. 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: Screening HbA1c ≥ 6.5%, or screening FPG ≥ 7.0mmol/L or<2.8mmol/L, or history of diabetes mellitus or hypoglycemia. Overweight or obesity due to single gene mutation, disease or drug, or weight increase due to non-fat mass increase. Treatment with any medication or product which in the investigator's opinion will cause change in weight to influence trial evaluations within 12 weeks before screening or during this study. Subjects who underwent bariatric surgery within 12 months before screening, or are not yet recovered from any surgery or injury at screening. Subjects who participated in any clinical trial and received the treatment within 12 weeks before screening, or who participated in the clinical trial and received treatment with TG103 injection. History of allergy or suspected allergy to GLP-1 receptor agonists or antibody agents, or other severe allergy history based on which the subjects may be allergic to the study drugs in investigator's opinion. Personal history or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN-2), or screening calcitonin ≥ 50 ng/L. Previous history or screening ultrasound includes one of the following: chronic pancreatitis, acute pancreatitis, gallstone with at least one of less than 5mm, choledocholithiasis, except that there was no cholelithiasis after treatment or cholecystectomy. No recovery from gastrointestinal disease or symptom at screening, or previous withdrawl of GLP-1 receptor agonist, GLP-1/GIP receptor agonist, GLP-1/GCG receptor agonist or metformin by gastrointestinal adverse drug reaction, or previous history of gastrointestinal surgery that influences the gastrointestinal motility in the investigators' opinions. Acute infection at screening. History of easily relapsed skin disease (e.g. urticaria), or present skin injury in any administration site at screening. History of acute coronary syndrome, stroke, severe asthma, epilepsy, systemic lupus erythematosus, hemolytic anemia, cirrhosis and the other severe disease, or history of malignant tumor. One of the followings at screening: systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg, or NYHA ≥ grade III, or QTc interval prolongation (i.e. QTcF>450ms in males or >470ms in females) or severe arrhythmia (e.g. atrioventricular block equal to or more than II degree, ventricular tachycardia). History of abnormal thyroid function with requirement of medication treatment at screening, or TSH beyond the normal reference range at screening. One of the followings at screening: 1) ALT or AST>3 × UNL (upper normal limit), or total bilirubin>1.5 × UNL, 2) blood amylase or lipase>1.5 × UNL, 3) TG>5.6mmol/L, 4) eGFR<60ml/min/1.73m^2 (calculated by CKD-EPI formula), 5) HBsAg, HCV-antibody, HIV-antibody or anti-TP antibody positive, 6) WBC< 3×10^9/L, or Hb <100g/L, 7) 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 male or female cannot use an effective contraceptive method during the trial and for 3 months after the end of treatment. Other situations that are not suitable for the 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TG103 15 mg<br>Administered subcutaneously (s.c., under the skin) once every week for 24 weeks. Doses gradually increased to 15 mg. | Drug: TG103 15 mg<br>* Administered subcutaneously (s.c., under the skin) as well as calorie restrict diet and increased physical activity for 24 weeks. Doses gradually increased from 7.5 mg to 15 mg.<br>|
| Experimental: TG103 22.5 mg<br>Administered subcutaneously (s.c., under the skin) once every week for 24 weeks. Doses gradually increased to 22.5 mg. | Drug: TG103 22.5 mg<br>* Administered subcutaneously (s.c., under the skin) as well as calorie restrict diet and increased physical activity for 24 weeks. Doses gradually increased from 7.5 mg, 15 mg to 22.5 mg.<br>|
| Placebo Comparator: Placebo<br>Administered subcutaneously (s.c., under the skin) once every week for 24 weeks. | Drug: Placebo<br>* Administered subcutaneously (s.c., under the skin) as well as calorie restrict diet and increased physical activity for 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change from baseline in body weight at week 24 | percent change in body weight | From baseline to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change from baseline in body weight (%) at week 12 and week 27 | percent change in body weight | From baseline to week 27 | 
| Proportion of subjects with weight loss of ≥ 5% and ≥ 10% of baseline body weight at week 12 and week 24 |  | From baseline to week 24 | 
| Change from baseline to 12 weeks, 24 weeks and 27 weeks in body weight | weight in kg | From baseline to week 27 | 
| Change from baseline to 12 weeks, 24 weeks and 27 weeks in BMI | BMI in kg/m^2 | From baseline to week 27 | 
| Change from baseline to 12 weeks, 24 weeks and 27 weeks in waist to hip circumference ratio | waist circumference and hip circumference will be combined to report waist to hip circumference ratio | From baseline to week 27 | 
| Change from baseline to 12 weeks, 24 weeks and 27 weeks in waist circumference | waist circumference in cm | From baseline to week 27 | 
| Change from baseline to 12 weeks and 24 weeks in HbA1c | HbA1c in % | From baseline to week 24 | 
| Change from baseline to 12 weeks and 24 weeks in FPG (fasting plasma glucose) | FPG (fasting plasma glucose) in mmol/L | From baseline to week 24 | 
| Change from baseline to 12 weeks and 24 weeks in FINS (fasting insulin) | FINS (fasting insulin) in mU/L | From baseline to week 24 | 
| Change from baseline to 12 weeks and 24 weeks in fasting C peptide | fasting C peptide in nmol/L | From baseline to week 24 | 
| Change from baseline to 12 weeks and 24 weeks in HOMA-IR | FPG and FINS will be combined to report HOMA-IR in mmol/mU | From baseline to week 24 | 
| Change from baseline to 12 weeks and 24 weeks in TC（total cholesterol） | TC in mmol/L | From baseline to week 24 | 
| Change from baseline to 12 weeks and 24 weeks in TG（triglyceride） | TG in mmol/L | From baseline to week 24 | 
| Change from baseline to 12 weeks and 24 weeks in LDLC（low density lipoprotein cholesterol） | LDLC in mmol/L | From baseline to week 24 | 
| Change from baseline to 12 weeks and 24 weeks in HDLC（high density lipoprotein cholesterol） | HDLC in mmol/L | From baseline to week 24 | 
| Change from baseline to 12 weeks and 24 weeks in systolic blood pressure and diastolic blood pressure | systolic blood pressure, diastolic blood pressure in mmHg, respectively | From baseline to week 24 | 
| Change from baseline to 12 weeks and 24 weeks in scores of the patient health questionnaire (PHQ-9) | There are 9 items in PHQ-9 and the score ranges from 0-3 for each item. The total score will be the sum of the scores of all items. | From baseline to week 24 | 
| Number of TEAEs and SAEs from baseline to week 27 |  | From baseline to week 27 |