Obesity
Conditions
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.
Interventions
DRUGXW003
XW003 (from 0.2 mg to 1.2 mg, 1.8 mg, and 2.4 mg once weekly), should take place during the first 14 weeks after randomization as described: Dose Escalation Schedule of Investigational Product (XW003). All eligible participants assigned to the XW003 study groups should aim to reach the respective final target dose of XW003 at 1.2 mg, 1.8 mg, or 2.4 mg once weekly.
DRUGSaxenda
If a participant does not tolerate the recommended target dose of Saxenda group (e.g., 3.0 mg once daily), the participant may stay at the preceding highest tolerable dose (e.g., 2.4 mg once daily).
Sponsors
Hangzhou Sciwind Biosciences Co., Ltd.
Sciwind Biosciences APAC CO Pty. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change in participants body weight (%) from the Baseline | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportions of participants with body weight loss ≥5%, ≥10% and ≥15% of the Baseline | Week 26 | It is anticipated that XW003 can achieve considerable body weight loss and improve obesity-related markers in participants with obesity. |
| Absolute change in body weight (kg) of participants | Week 26 | Body weight should be measured at all site visits without shoes, on an empty bladder and only wearing light clothing. |
| Changes in waist circumference and hip circumference (cm) in participants | Week 26 | The waist circumference will be measured at the specified visits and is defined as the abdominal circumference located the midpoint between the lower rib margin and the iliac crest. The hip circumference is defined as the widest circumference around the buttocks. |
| Change in BMI in participants | Week 26 | Calculated by dividing the participant's body weight in kilograms by the participant's height in meters squared (kg/m2) |
| Change in fasting plasma glucose (FPG) | Week 26 | Calculated based on XW003 measured in blood. |
| Change in fasting serum insulin | Week 26 | Calculated based on XW003 measured in blood. |
| Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | Week 26 | Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) |
| Changes in fasting lipids (triglyceride, low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) | Week 26 | Lipids: triglyceride, low-density lipoprotein \[LDL\], and high-density lipoprotein \[HDL\]. |
| Number and severity of treatment-emergent adverse events (TEAEs) | Week 26 | The most common treatment-emergent adverse events (TEAEs) were nausea, dyspepsia, constipation, vomiting, and loss of appetite, all of which deemed possibly related to XW003 injection and only occurred in the highest dose groups (0.6 mg and 1.0 mg). The severity of these TEAEs was mild or moderate. |
| Physical examinations | Week 26 | It should include general appearance, thyroid gland, respiratory system, cardiovascular system, gastrointestinal system including mouth, musculoskeletal system, central and peripheral nervous system, skin, lymph node palpation, and head, ears, eyes, nose, throat and neck. |
| 36-Item Short Form Survey (SF-36) | Week 26 | Physical and mental component summary scores and scores on the individual sub-domains, i.e., physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health |
| Number and severity of new and ongoing gastrointestinal (GI) disorder (nausea, vomiting, diarrhea, and constipation) events by week | Week 26 | Analysis of the safety profile and tolerability of XW003 showed that the most common adverse events (AEs) of XW003 was gastrointestinal (GI) disorder, including nausea, bloating, loss of appetite, and weight loss. |
| Vital signs - participants' blood pressure change | Week 26 | After resting in a supine position for at least 5 minutes, the participant's systolic and diastolic blood pressure change. |
| Vital signs - participants' pulse rate change | Week 26 | After resting in a supine position for at least 5 minutes, the participant's pulse rate, and body temperature. |
| Vital signs - participants' ody temperature change | Week 26 | After resting in a supine position for at least 5 minutes, the participant's body temperature change. |
| Electrocardiograms (ECGs) | Week 26 | There was no XW003 injection related clinically significant effect 12-lead electrocardiography (ECG). |
| Haematology, biochemistry, coagulation, and calcitonin | Week 26 | Parameters to be tested are: * Haemoglobin (HGB) * Haematocrit (HCT) * Erythrocytes (RBC) * Platelets (PLAT) * Leucocytes (WBC) with differential * Urea * Creatinine (CREAT) * Total Bilirubin (BILI) and direct bilirubin (BILIDIR) * Urate * Albumin (ALB) * Alkaline phosphatase (ALP) * Creatine kinase (CK) * Alanine aminotransferase (ALT) * Aspartate aminotransferase (AST) * Gamma-glutamyl transferase (GGT) * Sodium (NA) * Potassium (K) * Calcium (CA) * Chloride (CL) * Phosphate (PHOS) * Bicarbonate (BICARB) * Amylase * Lipase * International Normalised Ratio (INR) * Activated partial thromboplastin time (APTT) |
| Injection site reactions (ISRs) | Week 26 | There were no hypoglycaemic episodes reported during the trial. Injection site reaction (ISRs) were reported in 1 participant in Cohort A2 (0.2/0.25 mg) and 2 participants in Cohort A6 (0.6 mg). The ISRs were mild in severity and recovered within 3 hours of dosing. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentrations of XW003 on treatment | Week 26 | Calculated based on XW003 measured in blood. |
| Anti-XW003 antibodies on treatment | Week 26 | Calculated based on XW003 measured in blood. |
Countries
Australia
Outcome results
None listed