Dose-finding of PB-119 Administered Subcutaneously Once-weekly Versus Placebo in Drug-naïve T2DM Subjects

Study Overview
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Brief Summary
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This is a multicenter, randomized, double-blind, placebo-controlled, parallel dose cohort, multiple dose study to evaluate the efficacy, safety, and tolerability of different doses of PB-119 in drug-naïve subjects with T2DM.

Detailed Description
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Subjects will be assessed for eligibility over a 2-week screening period prior to a 2-week run-in period and a 12-week double-blind treatment period,4-week follow up period. The eligible patients will be randomized to 1 of 3 dose cohorts (A, B, or C). Each patient will subsequently be randomized within the designated cohort to active drug or placebo at a 3:1 active drug:placebo ratio.

Official Title
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A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Dose Cohort Study to Evaluate the Efficacy and Safety of Twelve Once-weekly Subcutaneous Doses of PB-119 in Drug-naïve Subjects With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: PB-119 75ug
* Drug: PB-119 150ug
* Drug: PB-119 200ug
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and/or females between the ages of ≥18 and ≤70 years at Screening Patients in whom T2DM has been diagnosed according to 1999 WHOT2DM diagnostic criteria HbA1c ≥7.5% and ≤11% at Screening and at Week -1 Body mass index (BMI) ≥18.5 and ≤35.0 kg/m2 at Screening Exclusion Criteria: Female who is pregnant, intends to become pregnant or breast-feeding or is of child-bearing potential and not using adequate contraception methods throughout the trial Treatment with any glucose lowing agent(s) within 3 months prior to screening.An exception is short-term treatment (no longer than 7 days in total) with insulin in connection with inter-current illness Calcitonin ≥50 ng/L at screening Patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia, type 2 Fasting triglyceride ≥500 mg/dL at Screening, or patients with a history of lipid disorders taking unstable treatment dosage (eg, statins) within 3 months prior to screening Any acute or chronic condition that, in the opinion of the Investigator, would limit the patient's ability to complete and/or participate in this trial Blood amylase or lipase >3x ULN, history of acute or chronic pancreatitis, or history of symptomatic gallbladder disease at Screening Serum creatinine ≥1.5 mg/dL (male patients) or ≥1.4 mg/dL (female patients), or estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 at Screening Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2x upper limit of normal (ULN) at Screening and pre-randomization Severe cardiovascular diseases occurring within 6 months prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PB-119 75ug<br>PB-119 injection 75ug subcutaneously injected once-weekly for 12 weeks | Drug: PB-119 75ug<br>* 60 eligible patients will be included in this group<br>|
| Experimental: PB-119 150ug<br>PB-119 injection 150ug subcutaneously injected once-weekly for 12 weeks | Drug: PB-119 150ug<br>* 60 eligible patients will be included in this group<br>|
| Experimental: PB-119 200ug<br>PB-119 injection 200ug subcutaneously injected once-weekly for 12 weeks | Drug: PB-119 200ug<br>* 60 eligible patients will be included in this group<br>|
| Placebo Comparator: placebo<br>placebo injection subcutaneously injected once-weekly for 12 weeks | Drug: placebo<br>* 60 eligible patients will be included in this group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of glycosylated hemoglobin(HbA1c) | Change of HbA1c from baseline value to end of treatment | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients achieving HbA1c <7% | Percentage of patients achieving HbA1c <7% at Week 12 | 12 weeks | 
| Percentage of patients achieving HbA1c ≤6.5% | Percentage of patients achieving HbA1c ≤6.5% at Week 12 | 12 weeks | 
| HbA1c | Changes of HbA1c from baseline value at Weeks 2, 4, and 8 | 2, 4, and 8 weeks | 
| Fasting plasma glucose(FPG) | Changes of fasting plasma glucose(FPG) from baseline value at Weeks 2, 4, 8, and 12. | 2, 4, 8, and 12 weeks | 
| 2-hour postprandial glucose(2-h PPG) | Changes of 2-hour postprandial glucose(2-h PPG) from baseline value at Weeks 4, 8, and 12. | 4, 8, and 12 weeks | 
| Insulin | Changes of insulin from baseline value at Weeks 4, 8, and 12 | 4, 8, and 12 weeks | 
| C-peptide | Changes of C-peptide from baseline value at Weeks 4, 8, and 12 | 4, 8, and 12 weeks | 
| Self-monitoring of blood glucose (SMBG) | Changes of mean profile and mean increments from baseline value of the 7-point SMBG | 4, 8, and 12 weeks |