A Phase 2, Open-label, Randomised, Dose-Finding Study of XW003, Once-Weekly Human Glucagon-Like Peptide 1 Analogue, Compared With Once-Daily Liraglutide 3 mg in Adult Participants With Obesity
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 206
- 试验地点
- 1
- 主要终点
- Percentage change in participants body weight (%) from the Baseline
研究概览
简要总结
XW003 is an acylated human glucagon-like peptide 1 (GLP-1) analogue and is being developed for type 2 diabetes mellitus (T2DM) and obesity management.
详细描述
The study treatment period for 4 groups in the study will be divided into the four Titration Treatment periods and one Core Treatment period. The overall duration of the study treatment for each group will be 26 weeks. The duration of Titration Treatment will be up to 14 weeks for the three groups of XW003 treatment but 4 weeks for Saxenda group.
Approximately 250 participants who are adults with obesity, in the absence of type 2 or any other type of diabetes, are planned to be screened. Based on a 20% screening failure rate, a total of 200 participants are expected to be enrolled for the four groups.
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
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible for this study, a participant has to meet all of the following inclusion criteria:
- •Male or female, aged 18 to 70 years (inclusive at the time of informed consent);
- •Participants must have a BMI ≥ 30.0 kg/m2 and ≤40.0 kg/m2 at Screening;
- •Participants must have a stable body weight for at least 3 months prior to Screening (<5% change, self-reported);
- •Participants must have glycated haemoglobin (HbA1c) level <6.5% at Screening;
- •Women of childbearing potential (WOCBP) must be non-pregnant and must use an acceptable, highly effective contraception from Screening until the study completion, including the follow-up period.
- •Participants must have the ability and willingness to attend the necessary visits to the clinical research unit (CRU);
- •Participants must be willing and able to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.
排除标准
- •A participant who meets any of the following exclusion criteria must be excluded from the study:
- •Diagnosis of type 2 (HbA1c ≥6.5%) or other types of diabetes mellitus;
- •Obesity induced by endocrine disorders (e.g., Cushing syndrome);
- •Calcitonin ≥50 ng/L (pg/mL) at Screening;
- •History of severe allergic or hypersensitivity to any of the investigational products or its excipients or to drugs of similar chemical classes;
- •History of cerebral stroke (including but not limited to cerebral infarction/haemorrhage) within 6 months prior to Screening;
- •History of acute coronary syndrome (angina pectoris and/or myocardial infarction) and any other major cardiac conditions (including but not limited to myocarditis, cardiac insufficiency/failure, and any clinically significant arrythmia[s]) within 6 months prior to Screening;
- •Impaired liver function defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times upper limit of normal (ULN) at Screening;
- •Main Inclusion Criteria:
- •To be eligible for this study, a participant has to meet all of the following inclusion criteria:
- •Male or female, aged 18 to 70 years (inclusive at the time of informed consent);
- •Participants must have a BMI ≥ 30.0 kg/m2 and ≤40.0 kg/m2 at Screening;
- •Participants must have stable body weight for at least 3 months prior to Screening (<5% change, self-reported);
- •Participants must have glycated hemoglobin (HbA1c) level <6.5% at Screening;
- •Women of childbearing potential (WOCBP) must be non-pregnant and must use an acceptable, highly effective contraception from Screening until the study completion, including the follow-up period.
- •Participants must have the ability and willingness to attend the necessary visits to the clinical research unit (CRU);
- •Participants must be willing and able to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.
- •Main Exclusion Criteria:
- •A participant who meets any of the following exclusion criteria must be excluded from the study:
- •Diagnosis of type 2 (HbA1c ≥6.5%) or other types of diabetes mellitus;
- •Obesity induced by endocrine disorders (e.g., Cushing syndrome);
- •Calcitonin ≥50 ng/L (pg/mL) at Screening;
- •History of severe allergic or hypersensitivity to any of the investigational products or its excipients or to drugs of similar chemical classes;
- •History of cerebral stroke (including but not limited to cerebral infarction/haemorrhage) within 6 months prior to Screening;
- •History of acute coronary syndrome (angina pectoris and/or myocardial infarction) and any other major cardiac conditions (including but not limited to myocarditis, cardiac insufficiency/failure, and any clinically significant arrythmia[s]) within 6 months prior to Screening;
- •Impaired liver function defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times upper limit of normal (ULN) at Screening;
- •Estimated glomerular filtration rate (eGFR), calculated using the modified diet in renal disease (MDRD) formula < 60 mL/min/1.73m2;
- •History of acute or chronic pancreatitis or defined as amylase >ULN at Screening;
- •Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2);
- •Positive infection with human immunodeficient virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV);
- •History of primary or recurrent malignancy, except for non-melanoma skin cancer excised more than 2 years prior to Screening;
- •History of clinically significant endocrine condition(s);
- •History of major depressive disorder within 2 years before randomisation;
- •History of surgical treatment for obesity;
- •Having been exposed to any GLP-1 analogues within 6 months before Screening;
- •Treatment with orlistat, zonisamide, topiramate, phentermine, lorcaserin, bupropion and naltrexone alone or in combination or any other medications that could promote weight loss within 90 days prior to Screening;
- •Use of any other investigational products or medical devices within 3 months prior to Screening;
- •Participation in any medical (e.g., assisted by a clinical dietician or nutritionist) or non-medical (e.g., by a gym coach) diet and/or exercise program within 3 months prior to Screening and for the duration of the study (including the follow-up period);
- •Known or suspected abuse of alcohol or recreational drugs;
- •Being pregnant or lactating at Screening or planning to become pregnant (self or female partner) at any time during the study and for at least 3 months after the last dose of study drug;
- •Presence of any underlying physical and/or psychological medical condition that, in the opinion of the investigator, would make it unlikely that the participant will comply with the protocol or complete the study per protocol.
研究组 & 干预措施
Cohort A
Participants will follow a fixed up-titration scheme. For XW003 groups, the dose will be up-titrated to 1.2, 1.8, or 2.4 mg once weekly starting with 0.2 mg in dose increments of 0.2, 0.4, 0.6, or 0.8 mg. In order to mitigate the dose-related side effects, liraglutide is up-titrated over 4 weeks to the maintenance dose, 3.0 mg once daily.
干预措施: XW003 (Drug)
Cohort B
Participants will follow a fixed up-titration scheme. For XW003 groups, the dose will be up-titrated to 1.2, 1.8, or 2.4 mg once weekly starting with 0.2 mg in dose increments of 0.2, 0.4, 0.6, or 0.8 mg. In order to mitigate the dose-related side effects, liraglutide is up-titrated over 4 weeks to the maintenance dose, 3.0 mg once daily.
干预措施: XW003 (Drug)
Cohort C
Participants will follow a fixed up-titration scheme. For XW003 groups, the dose will be up-titrated to 1.2, 1.8, or 2.4 mg once weekly starting with 0.2 mg in dose increments of 0.2, 0.4, 0.6, or 0.8 mg. In order to mitigate the dose-related side effects, liraglutide is up-titrated over 4 weeks to the maintenance dose, 3.0 mg once daily.
干预措施: XW003 (Drug)
Cohort D
Dose titration Saxenda (from 0.6 mg to 3.0 mg liraglutide once daily), should take place during the first 4 weeks after randomisation as described: Dose Escalation Schedule of Reference Product (Saxenda). All participants assigned to the open-labeled control group should aim to reach the final target dose of 3.0 mg liraglutide once daily.
干预措施: Saxenda (Drug)
结局指标
主要结局
Percentage change in participants body weight (%) from the Baseline
时间窗: Week 26
Analysis of covariance (ANCOVA), with treatment, baseline body weight, and stratification factor as covariate, will be used to determine the difference between one of the XW003 groups and Saxenda group.
次要结局
- Absolute change in body weight (kg) of participants(Week 26)
- Change in fasting plasma glucose (FPG)(Week 26)
- Proportions of participants with body weight loss ≥5%, ≥10% and ≥15% of the Baseline(Week 26)
- Changes in waist circumference and hip circumference (cm) in participants(Week 26)
- Change in BMI in participants(Week 26)
- Change in fasting serum insulin(Week 26)
- Changes in fasting lipids (triglyceride, low-density lipoprotein [LDL], and high-density lipoprotein [HDL])(Week 26)
- Number and severity of new and ongoing gastrointestinal (GI) disorder (nausea, vomiting, diarrhea, and constipation) events by week(Week 26)
- Vital signs - participants' blood pressure change(Week 26)
- Haematology, biochemistry, coagulation, and calcitonin(Week 26)
- Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)(Week 26)
- Vital signs - participants' ody temperature change(Week 26)
- Injection site reactions (ISRs)(Week 26)
- Number and severity of treatment-emergent adverse events (TEAEs)(Week 26)
- Vital signs - participants' pulse rate change(Week 26)
- Electrocardiograms (ECGs)(Week 26)
- Physical examinations(Week 26)
- 36-Item Short Form Survey (SF-36)(Week 26)