Clinical trial NCT05299697: A Study of TG103 Injection in Overweight or Obesity
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Study of TG103 Injection in the Management of Overweight or Obesity
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Overweight or Obesity
Lead sponsor: CSPC Baike (Shandong) Biopharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-03-29
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Relative change from baseline in body weight at week 24
timeFrame: From baseline to week 24
Secondary outcomes:
measure: Relative change from baseline in body weight (%) at week 12 and week 27
timeFrame: From baseline to week 27
measure: Proportion of subjects with weight loss of ≥ 5% and ≥ 10% of baseline body weight at week 12 and week 24
timeFrame: From baseline to week 24
measure: Change from baseline to 12 weeks, 24 weeks and 27 weeks in body weight
timeFrame: From baseline to week 27
measure: Change from baseline to 12 weeks, 24 weeks and 27 weeks in BMI
timeFrame: From baseline to week 27
measure: Change from baseline to 12 weeks, 24 weeks and 27 weeks in waist to hip circumference ratio
timeFrame: From baseline to week 27
measure: Change from baseline to 12 weeks, 24 weeks and 27 weeks in waist circumference
timeFrame: From baseline to week 27
measure: Change from baseline to 12 weeks and 24 weeks in HbA1c
timeFrame: From baseline to week 24
measure: Change from baseline to 12 weeks and 24 weeks in FPG (fasting plasma glucose)
timeFrame: From baseline to week 24
measure: Change from baseline to 12 weeks and 24 weeks in FINS (fasting insulin)
timeFrame: From baseline to week 24
measure: Change from baseline to 12 weeks and 24 weeks in fasting C peptide
timeFrame: From baseline to week 24
measure: Change from baseline to 12 weeks and 24 weeks in HOMA-IR
timeFrame: From baseline to week 24
measure: Change from baseline to 12 weeks and 24 weeks in TC（total cholesterol）
timeFrame: From baseline to week 24
measure: Change from baseline to 12 weeks and 24 weeks in TG（triglyceride）
timeFrame: From baseline to week 24
measure: Change from baseline to 12 weeks and 24 weeks in LDLC（low density lipoprotein cholesterol）
timeFrame: From baseline to week 24
measure: Change from baseline to 12 weeks and 24 weeks in HDLC（high density lipoprotein cholesterol）
timeFrame: From baseline to week 24
measure: Change from baseline to 12 weeks and 24 weeks in systolic blood pressure and diastolic blood pressure
timeFrame: From baseline to week 24
measure: Change from baseline to 12 weeks and 24 weeks in scores of the patient health questionnaire (PHQ-9)
timeFrame: From baseline to week 24
measure: Number of TEAEs and SAEs from baseline to week 27
timeFrame: From baseline to week 27
Other outcomes:
measure: Ctrough (the trough plasma concentration of TG103)
timeFrame: From baseline to week 24
measure: Number of participants with Anti-TG103 antibodies positive
timeFrame: From baseline to week 27
Locations:
city: Baotou
country: China
facility: Baotou City Central Hospital
state: Neimenggu
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Yan Li
role: PRINCIPAL_INVESTIGATOR
References: