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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: PB-119 75ug; Drug: PB-119 150ug; Drug: PB-119 200ug; Drug: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 251
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Peking, China, 100000
    • Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and/or females between the ages of ≥18 and ≤70 years at Screening
2. Patients in whom T2DM has been diagnosed according to 1999 WHOT2DM diagnostic criteria
3. HbA1c ≥7.5% and ≤11% at Screening and at Week -1
4. Body mass index (BMI) ≥18.5 and ≤35.0 kg/m2 at Screening

Exclusion Criteria:

1. 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
2. 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
3. Calcitonin ≥50 ng/L at screening
4. Patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia, type 2
5. 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
6. 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
7. Blood amylase or lipase >3x ULN, history of acute or chronic pancreatitis, or history of symptomatic gallbladder disease at Screening
8. 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
9. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2x upper limit of normal (ULN) at Screening and pre-randomization
10. Severe cardiovascular diseases occurring within 6 months prior to screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body mass index(BMI)	Changes of BMI from baseline value at Weeks 2, 4, 8, and 12.	2, 4, 8, and 12 weeks
Waist and hip circumferences and waist-to-hip ratio	Change of waist and hip circumferences and waist-to-hip ratio from baseline value at end of treatment(waist and hip circumferences will be used to calculate waist-to-hip ratio	12 weeks
Blood pressure(both systolic and diastolic)	Changes of blood pressure from baseline value at Weeks 2, 4, 8, and 12.	2, 4, 8, and 12 weeks
Blood lipid	Changes of blood lipid from baseline value at Weeks 2, 4, 8, and 12	2, 4, 8, and 12 weeks

Collaborators and Investigators

• Sponsor: PegBio Co., Ltd.
• Collaborators: Tigermed Consulting Co., Ltd
• Investigators: Principal Investigator: Linong Ji, MD,PhD, Peking University People's Hospital

Publications and helpful links

General Publications

• Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.
• Ji L, Du Y, Xu M, Zhou X, Mo Z, Ma J, Li J, Li Y, Lin J, Wang Y, Yang J, Song W, Jin H, Pang S, Liu H, Li P, Liu J, Yao M, Li W, Jiang X, Shen F, Geng H, Zhou H, Ran J, Lei M, Du Y, Ye S, Guan Q, Lv W, Tan H, Chen T, Yang J, Qin G, Li S, Chen L. Efficacy and safety of PEGylated exenatide injection (PB-119) in treatment-naive type 2 diabetes mellitus patients: a Phase II randomised, double-blind, parallel, placebo-controlled study. Diabetologia. 2021 May;64(5):1066-1078. doi: 10.1007/s00125-021-05392-9. Epub 2021 Mar 9. Erratum In: Diabetologia. 2021 Aug;64(8):1900-1901.

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2018
• Primary Completion (Actual): July 29, 2019
• Study Completion (Actual): July 29, 2019

Study Registration Dates

• First Submitted: April 18, 2018
• First Submitted That Met QC Criteria: April 27, 2018
• First Posted (Actual): May 11, 2018

Study Record Updates

• Last Update Posted (Actual): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 21, 2020
• Last Verified: January 1, 2020

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: PB119201

Drug and device information, study documents

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