Phase 2b Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group Study to Assess the PD Response and Safety of Three Dose Levels of (PB1023) Injection Following 20 Weeks of Weekly SC Dosing in Adults With T2DM

Study Overview
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Brief Summary
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Primary objective: The primary objective of this study is to define the dose response of Glymera as measured as the change from baseline in hemoglobin A1c (HbA1c) following 20 weeks of once-weekly dosing. Secondary objectives: The secondary objectives are to: Describe incidence, severity, and duration of reported gastrointestinal side effects of Glymera compared to active comparator; Compare change from baseline in HbA1c following 20 weeks of dosing compared to placebo and active comparator; Compare change from baseline in fasting plasma glucose (FPG) following 20 weeks of dosing compared to placebo and active comparator; Describe the frequencies of adverse events in the treatment groups; and Describe the above endpoints for the following subgroups of subjects according to baseline type 2 diabetes mellitus (T2DM) therapy: diet and exercise only, metformin only, sulfonylurea only, or metformin and sulfonylurea combination therapy.

Official Title
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Phase 2b Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group Study to Assess the Pharmacodynamic Response and Safety of Three Dose Levels of (PB1023) Injection Following 20 Weeks of Once-Weekly Subcutaneous Dosing in Adult Subjects With Inadequately Treated Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: 50 mg PB1023
* Drug: 70 mg PB1023
* Drug: 100 mg PB1023
* Drug: Placebo (0.9% Sodium Chloride)
* Drug: Victoza®
* Other: Diet and Exercise
* Drug: Metformin
* Drug: Sulfonylurea
* Drug: Metformin and Sulfonylurea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects 18 to 75 years of age, inclusive; Body mass index ≤45 kg/m2; Diagnosed with T2DM with HbA1c of ≥7.0% and ≤11.0% and treated with diet and exercise alone, or with stable doses of metformin alone, sulfonylurea alone or metformin and sulfonylurea. Exclusion Criteria: Currently taking or have taken within the last 6 months non-oral antihyperglycemic agents (eg, insulin, Byetta®, Bydureon®, or Victoza). Short-term use of insulin within this period will not be cause for exclusion if insulin was used during the treatment of an acute intercurrent illness; Known allergy to or serious adverse effect caused by an approved or investigational glucagon-like peptide-1 (GLP-1) receptor analog/agonist; Unstable cardiovascular disease; History of weight loss surgery or other gastrointestinal surgical procedures that could possibly interfere with the mechanism of action of GLP-1 receptor agonists; Based on contraindications/warnings identified with other GLP-1 receptor agonists, subjects will be excluded if they have: History, symptoms, or signs of pancreatitis or severe gastrointestinal disease (ie, gastroparesis) or Personal or family history of medullary thyroid tumors or history of Multiple Endocrine Neoplasia Syndrome Type 2; Clinically significant renal and/or hepatic dysfunction; Pregnant or lactating female subjects.

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: Diet and Exercise<br>Diet and exercise only. | Drug: 50 mg PB1023<br> <br> Drug: 70 mg PB1023<br> <br> Drug: 100 mg PB1023<br> <br> Drug: Placebo (0.9% Sodium Chloride)<br> <br> * Other names: SC Weekly Injection;Drug: Victoza®<br> <br> * Other names: daily SC injection;|
| Experimental: Metformin<br>Metformin only | Drug: 50 mg PB1023<br> <br> Drug: 70 mg PB1023<br> <br> Drug: 100 mg PB1023<br> <br> Drug: Placebo (0.9% Sodium Chloride)<br> <br> * Other names: SC Weekly Injection;Drug: Victoza®<br> <br> * Other names: daily SC injection;|
| Experimental: Sulfonylurea<br>Sulfonylurea only | Drug: 50 mg PB1023<br> <br> Drug: 70 mg PB1023<br> <br> Drug: 100 mg PB1023<br> <br> Drug: Placebo (0.9% Sodium Chloride)<br> <br> * Other names: SC Weekly Injection;Drug: Victoza®<br> <br> * Other names: daily SC injection;|
| Experimental: Metformin and Sulfonylurea<br>Metformin and Sulfonylurea combination therapy | Drug: 50 mg PB1023<br> <br> Drug: 70 mg PB1023<br> <br> Drug: 100 mg PB1023<br> <br> Drug: Placebo (0.9% Sodium Chloride)<br> <br> * Other names: SC Weekly Injection;Drug: Victoza®<br> <br> * Other names: daily SC injection;|
| Experimental: PB1023<br>PB1023 weekly SC injection | Drug: 50 mg PB1023<br> <br> Drug: 70 mg PB1023<br> <br> Drug: 100 mg PB1023<br> <br> Other: Diet and Exercise<br> <br> Drug: Metformin<br> <br> Drug: Sulfonylurea<br> <br> Drug: Metformin and Sulfonylurea<br> <br> |
| Placebo Comparator: Placebo Comparator<br>Placebo (0.9% Sodium Chloride) weekly SC injection | Drug: Placebo (0.9% Sodium Chloride)<br> <br> * Other names: SC Weekly Injection;Other: Diet and Exercise<br> <br> Drug: Metformin<br> <br> Drug: Sulfonylurea<br> <br> Drug: Metformin and Sulfonylurea<br> <br> |
| Active Comparator: Active Comparator<br>Active Comparator (Victoza) daily SC injection | Drug: Victoza®<br> <br> * Other names: daily SC injection;Other: Diet and Exercise<br> <br> Drug: Metformin<br> <br> Drug: Sulfonylurea<br> <br> Drug: Metformin and Sulfonylurea<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of dose response of Glymera as measured as the change from baseline in HbA1c after 20 weeks of dosing with Glymera compared to placebo and active comparator |  | Baseline and 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of the incidence, severity, and duration of reported gastrointestinal side effects of Glymera compared to active comparator |  | Up to 23 weeks | 
| Compare change from baseline in weekly fasting plasma glucose (FPG) following 20 weeks of dosing compared to placebo and active comparator |  | Baseline and 20 weeks | 
| Describe the frequencies of adverse events in the treatment groups |  | Up to 23 weeks | 
| Proportion of subjects reaching HbA1c targets (<7.0%) after 20 weeks of dosing |  | Baseline and 20 weeks |