A Phase 3 Study to Evaluate the Efficacy of XW003 Compared With Dulaglutide in Participants With T2DM

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to compare the efficacy and safety of two XW003 doses versus dulaglutide as add-on therapy to metformin in participants with type 2 diabetes mellitus (T2DM)

Detailed Description
-----------------
In this Phase 3 study, eligible participants will be randomized in a 1:1:1 ratio to receive once-weekly subcutaneous XW003 (high or dose) or active comparator dulaglutide as add-on to metformin treatment for 52 weeks, including a dose-escalation period.

Official Title
-----------------
A Phase 3, Multi-center, Open-label, Randomized Study to Evaluate the Efficacy and Safety of XW003 Versus Dulaglutide in Patients With T2DM Inadequately Controlled by Metformin

Conditions
-----------------
T2DM, Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: Ecnoglutide high dosage
* Drug: Ecnoglutide low dosage
* Drug: Dulaglutide
* Drug: Metformin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ability and willingness to participate in the study, give written informed consent, and comply with the study specific requirements and all protocol procedures Sex: male or female; Age: 18 to 75 years, inclusive BMI: 20.0 kg/m^2 to 35.0 kg/m^2, inclusive Have been diagnosed with T2DM for at least 3 months and treated with a stable dose of metformin (≥1500 mg/day) in addition to diet and exercise during the 8 weeks prior to screening. HbA1c ranging from 7.5% to 11.0% at screening, inclusive FPG ≤13.9 mmol/L at screening Exclusion Criteria: History of type 1 or other types of diabetes mellitus Use of insulin during the 6 months preceding screening History of proliferative diabetic retinopathy, diabetic maculopathy, diabetic neuropathy, or diabetic foot during the 6 months prior to screening. History of acute or chronic pancreatitis or high-risk factors for pancreatitis Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. History of stomach surgeries or disorders associated with slowed emptying of the stomach during the past 6 months. History of heart attack, stroke or congestive heart failure of Grade 3 or 4 in the past 6 months.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: B1: XW003+MET<br>High dosage of XW003 once weekly | Drug: Ecnoglutide high dosage<br>* Administered subcutaneously<br>* Other names: XW003;Drug: Metformin<br>* Administered orally<br>|
| Experimental: B2: XW003+MET<br>Low dosage of XW003 once weekly | Drug: Ecnoglutide low dosage<br>* Administered subcutaneously<br>* Other names: XW003;Drug: Metformin<br>* Administered orally<br>|
| Active Comparator: B3: Dulaglutide+MET<br>1.5mg Dulaglutide once weekly | Drug: Dulaglutide<br>* Administered subcutaneously<br>Drug: Metformin<br>* Administered orally<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HbA1c |  | Baseline, week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HbA1c |  | Baseline, Week 5, Week 9, Week 13, Week 17, Week 25, Week 43 and Week 52 | 
| Change from baseline in fasting plasma glucose (FPG) |  | Baseline, Week 32 and Week 52 | 
| Change from baseline in lipid panel |  | Baseline, Week 32 and Week 52 | 
| Change from baseline in body weight |  | Baseline, Week 32 and Week 52 | 
| Pharmacokinetics: plasma trough level of XW003 |  | Baseline, Day 29, Day 57, Day 85, Day 224, Day 364 and Day 399 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
T2DM, Glucagon-like peptide-1, GLP-1, Ecnoglutide, XW003