Clinical trial NCT06863363: PEG-rhGH and Semaglutide Combination Therapy in Non-Diabetic Obese Adults
Official title: A Multicenter, Randomized, Open-label, Parallel-controlled Clinical Trial Comparing the Efficacy and Safety of PEG-rhGH Injection Combined with Semaglutide Injection Versus Semaglutide Injection Monotherapy in Body Composition of Non-Diabetic Obese Adults
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Non-diabetic Obesity
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2025-03-07
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the efficacy and safety of PEG-rhGH Injection combined with Semaglutide Injection versus Semaglutide Injection monotherapy in improving body composition (lean body mass, fat mass, etc.) in non-diabetic obese adults, while also analyzing changes in body weight, blood glucose, and other metabolic parameters.


Eligibility criteria: Inclusion Criteria:

1. Age between 18 years (minimum age) and 50 years (maximum age), inclusive
2. Gender: Male or female, with a ratio of male to female being 2:1;
3. Body Mass Index (BMI) ≥28 kg/m²;
4. No prior use of semaglutide injection or antidiabetic medications;
5. Free Thyroxine (FT4) levels within normal range at screening;
6. Testosterone levels within normal range at screening (males only);
7. No plans for pregnancy from the time of signing the ICF until 2 months after the study ends, willingness to take effective contraceptive measures to prevent pregnancy or causing a partner's pregnancy, and no plans for sperm or egg donation during the study period;
8. Participants must voluntarily agree to and be able to comply with all scheduled visits, treatment plans, laboratory tests, special examinations, neurological assessments, and other trial procedures, and sign a written informed consent form.

Exclusion Criteria:

1. Unable to accept regular follow-up;
2. Those who have difficulty with self-injection;
3. Weight change \>5.0% in the 12 weeks prior to screening (self-reported);
4. History of allergic reactions to the study drug or similar drugs;
5. Evaluated by the investigator as unable to tolerate subcutaneous injection, such as those undergoing anticoagulant therapy, thrombocytopenia, known bleeding disorders, or idiopathic thrombocytopenic purpura;
6. Planning surgery within 1 year; history of gastrointestinal surgery (excluding polypectomy and appendectomy);
7. Positive blood HCG during screening; breastfeeding women; postmenopausal women; women with FSH \>30 IU/L during screening;
8. Any of the following: myocardial infarction, stroke, unstable angina requiring hospitalization, or transient ischemic attack within 180 days before screening, classified as NYHA class III or higher;
9. Clinically significant severe ECG abnormalities (e.g., QT prolongation \[\>450 ms in men, \>470 ms in women\], ventricular Flutter, ventricular fibrillation, torsades de pointes, sick sinus syndrome, third-degree heart block without pacemaker therapy, and other severe abnormalities as assessed by the investigator), uncontrolled blood pressure despite treatment/untreated (systolic BP ≥160 mmHg and/or diastolic BP ≥100 mmHg during screening, systolic BP \<90 mmHg and/or diastolic BP \<50 mmHg), or other cardiovascular diseases deemed unsuitable for the study by the investigator;
10. Triglycerides ≥500 mg/dL (5.65 mmol/L);
11. Current or past history of malignancy, or currently having nodules with malignant potential such as thyroid nodules with TIRADS grade ≥4;
12. Tumor markers during screening: CA125 (for women), CA199, CEA, AFP above upper limit of normal range; PSA above upper limit of normal range (for men);
13. Hemoglobin A1c ≥6.5% during screening;
14. History of diabetes (type 1, type 2, special types, or gestational diabetes) or currently using injectable or oral antidiabetic medications;
15. Current or past history of acromegaly;
16. Proliferative or severe non-proliferative diabetic retinopathy at screening; fundus examination within 90 days before randomization: proliferative retinopathy or macular edema requiring acute treatment;
17. Used growth hormone therapy in the past 6 months;
18. Used any weight loss medications in the past 3 months; previously underwent obesity surgery or planned obesity surgery during the study;
19. Any of the following laboratory tests at screening: AST or ALT \>2.5 ULN; total bilirubin \>1.5 ULN; TSH \<0.4 or \>6 mIU/L; calcitonin \>50 ng/L;
20. IGF-1 SDS \>2.0 (age and gender matched);
21. Serum creatinine \>1.5 ULN, eGFR \<60 mL/min/1.73 m² \[using the modified simplified MDRD equation: eGFR = 175 × (serum creatinine in mg/dL)\^-1.234 × age\^-0.179 × 0.79 for women\], or kidney impairment requiring dialysis;
22. History of pancreatitis, or current acute or chronic pancreatitis;
23. History of cholecystitis, or current gallbladder/biliary disease symptoms, or treatable gallstones or polyps;
24. Family or personal history of multiple endocrine neoplasia type 2 or thyroid cancer (family defined as first-degree relatives);
25. Prior history of pituitary mass;
26. History of seizures;
27. Participated in another clinical trial with approved or investigational drugs/devices within 90 days before screening (excluding those who only signed the consent without receiving any intervention);
28. History of substance abuse and/or alcoholism, or mental disorders; during screening, had impaired consciousness including somnolence, stupor, coma, confusion;
29. Questionnaire PHQ-9 score ≥15; history of suicidal behavior; Columbia-Suicide Severity Rating Scale (C-SSRS) question 1 or 2 indicating suicidal ideation (answering "yes" to question 1 or 2);
30. Other reasons for exclusion as deemed by the investigator, such as any situation endangering participant safety or affecting compliance with the protocol.

Primary outcomes:
measure: The change in lean body weight (kg) from baseline
timeFrame: Week 40
Secondary outcomes:
measure: Change in lean body mass percentage (%)
timeFrame: During 40 weeks
measure: Change in appendicular muscle mass (kg)
timeFrame: During 40 weeks
measure: Change in trunk muscle mass (kg)
timeFrame: During 40 weeks
measure: Change in appendicular fat mass (kg)
timeFrame: During 40 weeks
measure: Change in trunk fat mass (kg)
timeFrame: During 40 weeks
measure: Percentage change in total fat mass (%)
timeFrame: During 40 weeks
measure: Change in total fat mass (kg)
timeFrame: During 40 weeks
measure: Waist circumference change (cm)
timeFrame: During 40 weeks
measure: Body weight change (kg)
timeFrame: During 40 weeks
measure: Glycated hemoglobin change (%)
timeFrame: During 40 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Fudan University
state: Shanghai
Study officials:
References: