A Randomized, Double-blind, Placebo-controlled Phase Ib Study to Evaluate the Safety,Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of Efsubaglutide Alfa in Chinese Adolescents With Obesity
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 36
- 试验地点
- 10
- 主要终点
- Safety and tolerability: incidence of TEAEs, SAEs, and AESI
研究概览
简要总结
This is a Phase Ib, randomized, double-blind, placebo-controlled clinical study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of Efsubaglutide Alfa Injection following multiple-dose administration in Chinese adolescent participants with obesity.
详细描述
The prevalence of obesity in adolescents is rising and threatening physiological and psychological health. Different from adults with obesity, there is still no approved drug to manage the obesity in adolescents, In order to provide the therapeutical option earlier, the weight-reduction study in obese adolescents is planned. The primary objective of this Phase Ib study is to evaluate the safety, tolerability, and pharmacokinetic (PK) characteristics of multiple doses of Efsubaglutide Alfa at different dose levels in Chinese adolescent participants with obesity. The secondary objectives include the evaluations of the pharmacodynamic (PD) effects, PK-PD relationship , and immunogenicity of multiple doses of Efsubaglutide Alfa at different dose levels. This randomized, double-blind, placebo-controlled, parallel-group study will enroll a total of 36 adolescent participants aged 12 to 17 years with obesity . 36 participants will be randomized in a 3:1 ratio to receive Efsubaglutide Alfa or placebo administered subcutaneously once weekly (QW) for up to 12 weeks. Safety will be monitored throughout the study by assessment of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESI), laboratory parameters, vital signs, and 12-lead electrocardiograms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Informed consent must be obtained from the participant's parent or legally authorized representative and assent from the adolescent participant before any study-related procedures.
- •2. Adolescent participants aged ≥12 years and <18 years (at the time of informed consent).
- •3. At screening, meet the obesity criteria defined in "WS/T586-2018 Screening for Overweight and Obesity among School-age Children and Adolescents".
- •4. Before screening, have been on dietary and exercise control alone for at least 3 months with <5.0% reduction in body mass index (based on self-report or report by parent or legally authorized representative).
- •5.Must be willing to follow the diet and exercise guidance and able to maintain such stable diet and exercise lifestyle during the study period.
- •6. Female participants of childbearing potential must have a negative serum pregnancy test at screening.
- •7. Able to understand all study procedures, willing to strictly comply with the study protocol, complete the study visits as scheduled, and finish the study.
排除标准
- •1. Pre-pubertal participants (Tanner Stage I).
- •2. History of severe allergic reactions or suspected allergy to study drug or its ingredients.
- •3. Pregnant or lactating women; men or women of childbearing potential planning pregnancy or unwilling to use highly effective contraception throughout the study.
- •4. Use of weight-affecting medications before screening.
- •5. Known monogenic obesity, obesity caused by other diseases or medications,
- •6. Previously diagnosed Type 1 diabetes, Type 2 diabetes, or special types of diabetes;
- •7. history of severe hypoglycemia or recurrent symptomatic hypoglycemia (≥2 times within half a year).
- •8. Clinically significant gastric emptying abnormalities, severe chronic gastrointestinal diseases, long-term use of medications directly affecting gastrointestinal motility, or gastrointestinal surgery within 6 months prior to screening, deemed unsuitable for the study by the investigator.
- •9. History of malignancy within 5 years prior to screening, excluding clinically cured cervical intraepithelial neoplasia, squamous cell carcinoma, or basal cell carcinoma within 5 years.
- •10. Major surgery within 6 months prior to screening, or planned surgery during the study that may affect study completion or compliance;
- •11. history of bariatric surgery or planned bariatric surgery during the study (e.g., gastric bypass, gastric banding).
- •12. History of acute or chronic pancreatitis, symptomatic gallbladder disease at screening, history of pancreatic injury, or other high-risk factors for pancreatitis; or amylase or lipase >2.0×ULN at screening.
- •13. Known or suspected drug/substance abuse at screening; positive HBsAg;
- •14. Positive HCV antibody with HCV RNA above the lower limit of detection; positive HIV antibody; positive Tp-Ab.
- •15. Currently receiving or received chronic (>14 days) systemic glucocorticoid therapy within 3 months prior to screening, or evidence of severe active autoimmune disease that may require systemic glucocorticoid therapy within the next 12 months as judged by the investigator.
- •16. History of hyperthyroidism or hypothyroidism, or TSH <1.0×LLN, or TSH >1.5×ULN, or history of medullary thyroid carcinoma.
- •17. Serum calcitonin ≥50 ng/L (pg/mL) at screening; ALT >3.0×ULN, or AST >3.0×ULN, or total bilirubin >2.0×ULN; eGFR <60 mL/min/1.73 m² at screening; fasting triglycerides ≥5.64 mmol/L (500 mg/dL).
- •18. Blood donation and/or blood loss ≥400 mL or bone marrow donation within 3 months prior to screening, or presence of hemoglobinopathy, hemolytic anemia, sickle cell anemia, or hemoglobin <118 g/L (ages 12-<13 years), <129 g/L (males ≥13 years), or <114 g/L (females ≥13 years).
- •19. Participation in vaccine or medical device clinical trials within 3 months prior to screening, or any drug clinical trial within less than 3 months or 5 half-lives (whichever is longer).
- •20. History of moderate to severe depression, anxiety disorder, or severe psychiatric illness.
- •21. Any other condition that, in the opinion of the investigator, may affect the participant's safety or compliance with the study protocol.
研究组 & 干预措施
Efsubaglutide Alfa 5 mg QW
Efsubaglutide Alfa, 5 mg once weekly，12 weeks Solution for injection in pre-filled auto-injector pen
干预措施: Efsubaglutide Alfa 5 mg QW (Drug)
Efsubaglutide Alfa 10 mg QW
Efsubaglutide Alfa, 10 mg once weekly，12 weeks Solution for injection in pre-filled auto-injector pen
干预措施: Efsubaglutide Alfa 10 mg QW (Drug)
Efsubaglutide Alfa 20 mg QW
Efsubaglutide Alfa, 20 mg once weekly，12 weeks Solution for injection in pre-filled auto-injector pen
干预措施: Efsubaglutide Alfa 20 mg QW (Drug)
Efsubaglutide Alfa placebo
Efsubaglutide Alfa placebo, once weekly，12 weeks Solution for injection in pre-filled auto-injector pen
干预措施: Efsubaglutide Alfa placebo (Drug)
结局指标
主要结局
Safety and tolerability: incidence of TEAEs, SAEs, and AESI
时间窗: Throughout the study (up to Week 18)
Safety and tolerability assessed by monitoring treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESI) throughout the study
Pharmacokinetic (PK) characteristics at steady state following multiple doses
时间窗: Throughout the study (up to Week 18)
PK parameters including plasma drug concentrations at steady state following multiple-dose administration of Efsubaglutide Alfa
次要结局
- Change in fasting insulin from baseline(Week 12)
- Change in blood uric acid from baseline(Week 12)
- The correlation between Efsubaglutide Alfa Cmax, ss and BMI(Throughout the study (up to Week 18))
- The correlation between Efsubaglutide Alfa AUC0-168h, ss and BMI(Throughout the study (up to Week 18))
- Incidence, titer, and persistence of anti-drug antibodies (ADA)(Throughout the study (up to Week 18))
- Incidence, titer, and persistence of neutralizing antibodies(Throughout the study (up to Week 18))
- Change in waist circumference from baseline(Week 12)
- Change in fasting blood glucose from baseline(Week 12)
- Change in body mass index (BMI) from baseline (absolute and percentage)(Week 12)
- Change in BMI from baseline over time (absolute and percentage)(Weeks 4, 8, and 12)
- Change in fasting body weight from baseline (absolute and percentage)(Week 12)
- Change in fasting body weight from baseline over time (absolute and percentage)(Weeks 4, 8, and 12)
- Change in HbA1c from baseline(Week 12)
- Change in hip circumference from baseline(Week 12)
- Change in waist-to-hip ratio (WHR) from baseline(Week 12)
- Change in waist-to-height ratio from baseline(Week 12)
- Proportion of participants achieving ≥5%, ≥10%, and ≥15% reduction in BMI and/or fasting body weight from baseline(Week 12)
- Change in systolic blood pressure and diastolic blood pressure from baseline(Week 12)
- Change in lipid levels(TC、HDL-C、LDL-C、TG) from baseline(Week 12)