Safety and Efficacy of Pegylated Exenatine Injection (PB-119) in Drug-naïve T2DM Subjects

Study Overview
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Brief Summary
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A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 24 once-weekly subcutaneous doses of PB-119 in Drug-naïve T2DM Subjects.

Detailed Description
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The study included a maximum 2-week screening period, a 4-week single-blind introduction period, a 24-week double-blind treatment period, a 28-week open extension treatment period, and a 4-week safety follow-up period. At the end of the single-blind entry period, eligible subjects were randomly assigned to two different administration groups in a 1:1 ratio and received a 24-week double-blind treatment. All subjects who completed the double-blind treatment entered the open extension treatment phase.Open extension treatment with subcutaneous injection of 150μg PB-119 once a week for 28 weeks. Safety follow-up was conducted 4 weeks after the end of treatment/completion of early exit visit in the open extension period.

Official Title
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A Phase III, Multicenter, Randomized, Double-blind, Parallel, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Pegylated Exenatine Injection (PB-119) in Drug-naïve T2DM Subjects

Conditions
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Type 2 Diabetes Mellitus (T2DM)

Intervention / Treatment
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* Drug: GLP-1 receptor agonist
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18 75 years old; Confirmed T2DM patients meet the diagnostic criteria for type 2 diabetes published by WHO1999； 18.5 kg/m2 < BMI < 40.0 kg/m2 at screening; 7.5% ≤ HbA1c ≤ 11.0% at screening; 7.0% ≤ HbA1c ≤ 10.5% when the random; 18.5 kg/m2 < BMI < 40.0 kg/m2 during screening and before randomization Exclusion Criteria: T1DM; Continuous use of insulin for more than 14 days within 1 year before screening or before randomization； Treatment with any dipeptidylpeptidase 4 (DPP-4) inhibitor or glucose-dependent insulin-stimulating peptide (GIP) or/and glucagon-like peptide-1 (GLP-1) receptor agonist prior to screening or randomized prior treatment； Screening for any of the following heart diseases within the first 6 months or before randomization； Patients whose hypertension was not effectively controlled during screening or before randomization (after resting ≥5 minutes, systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg)； Serum amylase or lipase >3×ULN or those with previous diagnosis of acute/chronic pancreatitis were screened or randomly screened； Screening for severe trauma or infection that may affect glycemic control within the first month or before randomization； A history or family history of medullary thyroid carcinoma (MTC) or multiple endocrine adenomatosis type 2 (MEN2)； Known to be allergic or intolerant to the study drug or metformin； Female subjects during pregnancy or lactation.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PB-119 once-weekly-subcutaneous injection<br>PB119 (polyethylene glycol exenatide) is a long-acting GLP-1RA for injection, which will be administered 150μg once-weekly subcutaneously to patients in active drug group for 24 weeks. | Drug: GLP-1 receptor agonist<br>* PB-119 is an investigational pegylated human glucagon-like peptide-1 (GLP-1) receptor agonist. The dosing regimen is 150μg once every week as subcutaneous administration. Patients in PB-119 group will be administered the active drugs for 52 weeks (24+28).<br>|
| Placebo Comparator: Placebo once-weekly-subcutaneous injection<br>PB-119 150μg matched placebo which will be used in placebo group for 24 weeks. | Drug: Placebo<br>* PB-119 matched placebo will be used once every week as subcutaneous administration to placebo group for 24 weeks.<br>* Other names: PB-119 Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | Change in HbA1c from baseline(week 1) to week 25 | week 1, week 25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c Below 7.0% | Percentage of participants with HbA1c below 7.0% was evaluated at week 25. | week 1, week 25 | 
| Change in Body Weight (kg) | Change from baseline (week 1) in body weight was evaluated at week 25 | week 1, week 25 | 
| Change in Fasting Plasma Glucose (FPG) | Change from baseline (week 1) in FPG was evaluated at week 25 | week 1, week 25 | 
| Change in Body Mass Index | Change from baseline (week 1) in body mass index (BMI) was evaluated at week 25. | week 1, week 25 |