Safety and Efficacy of Pegylated Exenatine Injection (PB-119) in Drug-naïve T2DM Subjects (PB119)

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus (T2DM)
• Intervention / Treatment: Drug: GLP-1 receptor agonist; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 273
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China
      • Central South University The Second Xiangya Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PB-119 once-weekly-subcutaneous injection; 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; 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).
Placebo Comparator: Placebo once-weekly-subcutaneous injection; PB-119 150μg matched placebo which will be used in placebo group for 24 weeks.	Drug: Placebo; PB-119 matched placebo will be used once every week as subcutaneous administration to placebo group for 24 weeks.; Other Names: PB-119 Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: PegBio Co., Ltd.
• Investigators: Principal Investigator: Zhiguang Zhou, MD,PhD, Central South University The Second Xiangya Hospital; Principal Investigator: Jiarui Li, MD,PhD, Cangzhou Central Hospital; Principal Investigator: Guixia Wang, MD,PhD, The First Hospital of Jilin University; Principal Investigator: Zhinong Zhang, MD,PhD, Qiqihar First Hospital; Principal Investigator: WeiHong Song, MD，PhD, First People's Hospital of Chenzhou; Principal Investigator: YanJun Wang, MD，PhD, Second Hospital of Jilin University; Principal Investigator: Jing Yang, MD，PhD, The First Affiliated Hospital of Shanxi Medical University; Principal Investigator: Bin Gao, MD，PhD, Tang-Du Hospital; Principal Investigator: Lin Liao, MD，PhD, Qianfoshan Hospital; Principal Investigator: Minxiu Yao, MD，PhD, Qingdao Central Hospital; Principal Investigator: Huige Shao, MD，PhD, Changsha Central Hospital; Principal Investigator: Jingna Lin, MD，PhD, Tianjin People's Hospital; Principal Investigator: Xiaohong Lin, MD，PhD, ZhuZhou Central Hospital; Principal Investigator: Jianhua Ma, MD，PhD, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2020
• Primary Completion (Actual): March 30, 2022
• Study Completion (Actual): November 28, 2022

Study Registration Dates

• First Submitted: August 5, 2020
• First Submitted That Met QC Criteria: August 5, 2020
• First Posted (Actual): August 7, 2020

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: PB119301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No