Clinical trial NCT05997576: A Study of TG103 Injection in Non-diabetic Overweight or Obesity
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 3 Study of TG103 Injection in the Management of Non-diabetic Overweight or Obesity
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Overweight or Obesity
Lead sponsor: CSPC Baike (Shandong) Biopharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-08-18
Enrollment: 675
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 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).


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., 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.

Primary outcomes:
measure: Proportion of participants with weight loss of ≥ 5% at week 40
timeFrame: From baseline to week 40
measure: Relative percentage change from baseline in body weight at week 40
timeFrame: From baseline to week 40
Secondary outcomes:
measure: Proportion of participants with weight loss of ≥ 5% at week 52
timeFrame: From baseline to week 52
measure: Relative percentage change from baseline in body weight at week 52
timeFrame: From baseline to week 52
measure: Proportion of participants with weight loss of ≥ 10%
timeFrame: From baseline to week 40, 52
measure: Change from baseline in body weight (kg)
timeFrame: From baseline to week 40, 52
measure: Change from baseline in waist circumference (cm)
timeFrame: From baseline to week 40, 52
measure: Change from baseline in HbA1c (%)
timeFrame: From baseline to week 40, 52
measure: Change from baseline in fasting plasma glucose (mmol/L)
timeFrame: From baseline to week 40, 52
measure: Change from baseline in fasting insulin (mU/L)
timeFrame: From baseline to week 40, 52
measure: Change from baseline in total cholesterol (mmol/L)
timeFrame: From baseline to week 40, 52
measure: Change from baseline in triglyceride (mmol/L)
timeFrame: From baseline to week 40, 52
measure: Change from baseline in low density lipoprotein cholesterol (mmol/L)
timeFrame: From baseline to week 40, 52
measure: Change from baseline in high density lipoprotein cholesterol (mmol/L)
timeFrame: From baseline to week 40, 52
measure: Change from baseline in systolic blood pressure (mmHg)
timeFrame: From baseline to week 40, 52
measure: Change from baseline in diastolic blood pressure (mmHg)
timeFrame: From baseline to week 40, 52
Other outcomes:
measure: Number of TEAEs and SAEs assessed by CTCAE V5.0
timeFrame: From baseline to week 55
measure: Proportion of participants categorized by patient health questionnaire-9 (PHQ-9) score
timeFrame: From baseline to week 52
measure: Concentration of TG103 (Ctrough)
timeFrame: From baseline to week 55
measure: Proportion of anti-TG103-antibody-positive participants
timeFrame: From baseline to week 55
Locations:
city: Shijiazhuang
country: China
facility: Clinical Trials Information Group
state: Hebei
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Li Yan
role: PRINCIPAL_INVESTIGATOR
References: