Safety and Efficacy of PB-119 in Subjects With Type 2 Diabetes and Not Well-controlled by Metformin Monotherapy

A Multicenter, Randomized, Double-blinded, Placebo-controlled Trial Comparing the Efficacy and Safety of PB-119 in Combination With Metformin in Subjects With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin Alone

This is a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 24 once-weekly subcutaneous doses of PB-119 to subjects with type 2 diabetes mellitus (T2DM) not well-controlled by metformin monotherapy.

Study Overview

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

Detailed Description

This is a phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel dose cohort study to evaluate the efficacy and safety of PB-119 to patients with T2DM not well-controlled by metformin monotherapy. Patients will be assessed for eligibility over a 2 week screening period prior to a 4-week run-in period,a 24-week double-blind treatment period and a 28-week open-label treatment period. The eligible patients will be randomized to PB-119 or placebo cohort at a 1:1 ratio for the first 24-week. Patients in PB-119 group will subsequently be given active drug and patients in placebo group will take placebo, all patients in two groups will remain metformin background therapy. In the 28-week open-label period, all patients will be administered active drugs. After that, there will be a 4-week follow-up period; All randomized patients will be taken blood samples for the pharmacokinetic (PK) analysis.

• Study Type: Interventional
• Enrollment (Actual): 620
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing University People's 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;
• T2DM and treated with Metformin ≥ 1500mg/day or maximum tolerated dose(≥1000mg,<1500mg) constantly for at least 8 consecutive weeks;
• 7.5% ≤ HbA1c ≤ 10.0% at screening;
• 18.5 kg/m2 < BMI < 40.0 kg/m2 at screening;

Exclusion Criteria:

• Any anti-diabetic therapy other than Metformin within 8 weeks before screening；
• T1DM;
• Received insulin therapy more than 14 days within 1 year before screening;
• Female who is pregnant, breast-feeding;
• Any disorder which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol;
• History of acute diabetic complications, such as diabetic ketoacidosis or hyperglycemic hyperosmolar status within 6 months before screening；
• History or presence of pancreatitis (acute or chronic);
• Presence or history of malignant neoplasms within the past 5 years prior to the day of screening

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: HuiMin Zhou, MD，PhD, First Hospital of Hebei Medical University; Principal Investigator: XinLing Wang, Doctor, People's Hospital of Xinjiang Uygur Autonomous Region; Principal Investigator: MingHui Hou, MD，PhD, Affiliated Hospital of Hebei University; Principal Investigator: Linong Ji, MD，PhD, Beijing University People's Hospital; Principal Investigator: Wei Zhang, MD，PhD, Qiqihar First Hospital; Principal Investigator: Hui Liu, MD，PhD, Luoyang Central Hospital; Principal Investigator: Tao Ning, MD，PhD, Baotou Central Hospital; Principal Investigator: Xiaohong Wu, MD，PhD, Zhejiang Province People's Hospital; Principal Investigator: Xueying Wang, MD，PhD, Jingzhou Central Hospital; Principal Investigator: Lan Xu, MD，PhD, Wuxi Central 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): June 23, 2020
• Primary Completion (Actual): September 15, 2022
• Study Completion (Actual): May 26, 2023

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: PB119302

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