A Study of TG103 Injection in Overweight or Obesity

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

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.

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.