Overweight or Obesity
Conditions
Brief summary
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.
Interventions
DRUGTG103 15 mg
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.
DRUGTG103 22.5 mg
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.
DRUGPlacebo
Administered subcutaneously (s.c., under the skin) as well as calorie restrict diet and increased physical activity for 24 weeks.
Sponsors
CSPC Baike (Shandong) Biopharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative change from baseline in body weight at week 24 | From baseline to week 24 | percent change in body weight |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative change from baseline in body weight (%) at week 12 and week 27 | From baseline to week 27 | percent change in body weight |
| 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 | From baseline to week 27 | weight in kg |
| Change from baseline to 12 weeks, 24 weeks and 27 weeks in BMI | From baseline to week 27 | BMI in kg/m\^2 |
| Change from baseline to 12 weeks, 24 weeks and 27 weeks in waist to hip circumference ratio | From baseline to week 27 | waist circumference and hip circumference will be combined to report waist to hip circumference ratio |
| Change from baseline to 12 weeks, 24 weeks and 27 weeks in waist circumference | From baseline to week 27 | waist circumference in cm |
| Change from baseline to 12 weeks and 24 weeks in HbA1c | From baseline to week 24 | HbA1c in % |
| Change from baseline to 12 weeks and 24 weeks in FPG (fasting plasma glucose) | From baseline to week 24 | FPG (fasting plasma glucose) in mmol/L |
| Change from baseline to 12 weeks and 24 weeks in FINS (fasting insulin) | From baseline to week 24 | FINS (fasting insulin) in mU/L |
| Change from baseline to 12 weeks and 24 weeks in scores of the patient health questionnaire (PHQ-9) | From baseline to week 24 | 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. |
| Number of TEAEs and SAEs from baseline to week 27 | From baseline to week 27 | — |
| Change from baseline to 12 weeks and 24 weeks in fasting C peptide | From baseline to week 24 | fasting C peptide in nmol/L |
| Change from baseline to 12 weeks and 24 weeks in HOMA-IR | From baseline to week 24 | FPG and FINS will be combined to report HOMA-IR in mmol/mU |
| Change from baseline to 12 weeks and 24 weeks in TC（total cholesterol） | From baseline to week 24 | TC in mmol/L |
| Change from baseline to 12 weeks and 24 weeks in TG（triglyceride） | From baseline to week 24 | TG in mmol/L |
| Change from baseline to 12 weeks and 24 weeks in LDLC（low density lipoprotein cholesterol） | From baseline to week 24 | LDLC in mmol/L |
| Change from baseline to 12 weeks and 24 weeks in HDLC（high density lipoprotein cholesterol） | From baseline to week 24 | HDLC in mmol/L |
| Change from baseline to 12 weeks and 24 weeks in systolic blood pressure and diastolic blood pressure | From baseline to week 24 | systolic blood pressure, diastolic blood pressure in mmHg, respectively |
Other
| Measure | Time frame | Description |
|---|---|---|
| Ctrough (the trough plasma concentration of TG103) | From baseline to week 24 | Ctrough will be measured once every 4 week until week 24. |
| Number of participants with Anti-TG103 antibodies positive | From baseline to week 27 | Anti-TG103 antibodies will be measured once every 4 week until week 27. |
Countries
China
Contacts
Primary ContactYan Li
Backup ContactTianhao Zhang
Outcome results
None listed