Clinical trial NCT05111912: Effects of XW003 Versus Liraglutide on Body Weight of Adult Participants With Obesity
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity
Lead sponsor: Sciwind Biosciences APAC CO Pty. Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Hangzhou Sciwind Biosciences Co., Ltd.
First posted: 2021-11-08
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

To be eligible for this study, a participant has to meet all of the following inclusion criteria:

1. Male or female, aged 18 to 70 years (inclusive at the time of informed consent);
2. Participants must have a BMI ≥ 30.0 kg/m2 and ≤40.0 kg/m2 at Screening;
3. Participants must have a stable body weight for at least 3 months prior to Screening (\<5% change, self-reported);
4. Participants must have glycated haemoglobin (HbA1c) level \<6.5% at Screening;
5. 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.
6. Participants must have the ability and willingness to attend the necessary visits to the clinical research unit (CRU);
7. 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.

Exclusion Criteria:

A participant who meets any of the following exclusion criteria must be excluded from the study:

1. Diagnosis of type 2 (HbA1c ≥6.5%) or other types of diabetes mellitus;
2. Obesity induced by endocrine disorders (e.g., Cushing syndrome);
3. Calcitonin ≥50 ng/L (pg/mL) at Screening;
4. History of severe allergic or hypersensitivity to any of the investigational products or its excipients or to drugs of similar chemical classes;
5. History of cerebral stroke (including but not limited to cerebral infarction/haemorrhage) within 6 months prior to Screening;
6. 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;
7. 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:

1. Male or female, aged 18 to 70 years (inclusive at the time of informed consent);
2. Participants must have a BMI ≥ 30.0 kg/m2 and ≤40.0 kg/m2 at Screening;
3. Participants must have stable body weight for at least 3 months prior to Screening (\<5% change, self-reported);
4. Participants must have glycated hemoglobin (HbA1c) level \<6.5% at Screening;
5. 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.
6. Participants must have the ability and willingness to attend the necessary visits to the clinical research unit (CRU);
7. 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:

1. Diagnosis of type 2 (HbA1c ≥6.5%) or other types of diabetes mellitus;
2. Obesity induced by endocrine disorders (e.g., Cushing syndrome);
3. Calcitonin ≥50 ng/L (pg/mL) at Screening;
4. History of severe allergic or hypersensitivity to any of the investigational products or its excipients or to drugs of similar chemical classes;
5. History of cerebral stroke (including but not limited to cerebral infarction/haemorrhage) within 6 months prior to Screening;
6. 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;
7. Impaired liver function defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>5 times upper limit of normal (ULN) at Screening;
8. Estimated glomerular filtration rate (eGFR), calculated using the modified diet in renal disease (MDRD) formula \< 60 mL/min/1.73m2;
9. History of acute or chronic pancreatitis or defined as amylase \>ULN at Screening;
10. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2);
11. Positive infection with human immunodeficient virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV);
12. History of primary or recurrent malignancy, except for non-melanoma skin cancer excised more than 2 years prior to Screening;
13. History of clinically significant endocrine condition(s);
14. History of major depressive disorder within 2 years before randomisation;
15. History of surgical treatment for obesity;
16. Having been exposed to any GLP-1 analogues within 6 months before Screening;
17. 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;
18. Use of any other investigational products or medical devices within 3 months prior to Screening;
19. 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);
20. Known or suspected abuse of alcohol or recreational drugs;
21. 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;
22. 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.

Primary outcomes:
measure: Percentage change in participants body weight (%) from the Baseline
timeFrame: Week 26
Secondary outcomes:
measure: Proportions of participants with body weight loss ≥5%, ≥10% and ≥15% of the Baseline
timeFrame: Week 26
measure: Absolute change in body weight (kg) of participants
timeFrame: Week 26
measure: Changes in waist circumference and hip circumference (cm) in participants
timeFrame: Week 26
measure: Change in BMI in participants
timeFrame: Week 26
measure: Change in fasting plasma glucose (FPG)
timeFrame: Week 26
measure: Change in fasting serum insulin
timeFrame: Week 26
measure: Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
timeFrame: Week 26
measure: Changes in fasting lipids (triglyceride, low-density lipoprotein [LDL], and high-density lipoprotein [HDL])
timeFrame: Week 26
measure: Number and severity of treatment-emergent adverse events (TEAEs)
timeFrame: Week 26
measure: Number and severity of new and ongoing gastrointestinal (GI) disorder (nausea, vomiting, diarrhea, and constipation) events by week
timeFrame: Week 26
measure: Vital signs - participants' blood pressure change
timeFrame: Week 26
measure: Vital signs - participants' pulse rate change
timeFrame: Week 26
measure: Vital signs - participants' ody temperature change
timeFrame: Week 26
measure: Electrocardiograms (ECGs)
timeFrame: Week 26
measure: Haematology, biochemistry, coagulation, and calcitonin
timeFrame: Week 26
measure: Injection site reactions (ISRs)
timeFrame: Week 26
measure: Physical examinations
timeFrame: Week 26
measure: 36-Item Short Form Survey (SF-36)
timeFrame: Week 26
Other outcomes:
measure: Plasma concentrations of XW003 on treatment
timeFrame: Week 26
measure: Anti-XW003 antibodies on treatment
timeFrame: Week 26
Locations:
city: Brisbane
country: Australia
facility: Paratus Clinical Research Brisbane
state: Queensland
Study officials:
affiliation: Paratus Clinical
name: Sheetal Bull
role: PRINCIPAL_INVESTIGATOR
References: