Study to Evaluate the Safety and Efficacy of PB-201 in Treatment-naive Patients With Type 2 Diabetes Mellitus

A Multi-center, Randomized, Double-Blinded, Parallel, Vildagliptin and Placebo-Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of PB-201 in Treatment-naive Patients With Type 2 Diabetes Mellitus

This is a multicenter, randomized, double-blind, parallel, Vildagliptin and Placebo-Controlled study to evaluate the efficacy and safety of oral administration of 100 mg of PB-201 in the morning and evening in treatmentnaive patients with type 2 diabetes mellitus.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes Mellitus (T2DM)
• Intervention / Treatment: Drug: PB-201; Drug: Vildagliptin matched placebo; Drug: Vildagliptin; Drug: PB-201 matched placebo

Detailed Description

The study consists of a screening period of up to 2 weeks, a 4-week single-blind run-in period, a 24-week double-blinded treatment period, a 28-week extended treatment period, and a 2-week safety follow-up period.Eligible subjects will be enrolled in a 4-week single-blind run-in period with daily oral administration of 1 tablet of PB-201 matched placebo and 1 Vildagliptin matched placebo in the morning and evening respectively.After the end of the single-blind run-in period, subjects who meet the protocol enrollment requirements will be randomized in the proportion of 2:1:1 to receive double-blinded treatment for 24 weeks in three different treatment groups (test arm, Vildagliptin arm, or placebo arm).

• Study Type: Interventional
• Enrollment (Anticipated): 672
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ying Du, MD,PhD; Phone Number: +86-18911797119; Email: ying.du@pegbio.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Not yet recruiting
      • The Second People's Hospital of Hefei
      • Contact: Wu Dai
    • Lu'an, Anhui, China
      • Not yet recruiting
      • Lu'an People's Hospital
      • Contact: Qi Wang
  • Beijing
    • Beijing, Beijing, China
      • Not yet recruiting
      • Peking University People's Hospital
      • Contact: Linong Ji
    • Beijing, Beijing, China
      • Not yet recruiting
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China
      • Not yet recruiting
      • Beijing Pinggu Hospital
      • Contact: Yufeng Li
    • Beijing, Beijing, China
      • Not yet recruiting
      • Beijing Tsinghua Changgung Hospital
    • Beijing, Beijing, China
      • Not yet recruiting
      • Peking Union Medical College Hospital
      • Contact: Xinhua Xiao
    • Beijing, Beijing, China
      • Not yet recruiting
      • Peking University First Hospital
  • Chongqing
    • Chongqing, Chongqing, China
      • Not yet recruiting
      • Chongqing University Three Gorges Hospital
  • Gansu
    • Lanzhou, Gansu, China
      • Not yet recruiting
      • Lanzhou University Second Hospital
      • Contact: Jiangong Ren
  • Guangdong
    • Huizhou, Guangdong, China
      • Not yet recruiting
      • Huizhou Municipal Central Hospital
      • Contact: Shu Li
  • Hebei
    • Cangzhou, Hebei, China
      • Not yet recruiting
      • Cangzhou People's Hospital
      • Contact: Fang Bian
    • Handan, Hebei, China
      • Not yet recruiting
      • Handan First Hospital
      • Contact: Haifang Wang
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Not yet recruiting
      • The Fourth Hospital of Harbin Medical University
    • Qiqihar, Heilongjiang, China
      • Not yet recruiting
      • The First Hospital of Qiqihar
      • Contact: Xuhong Wang
  • Henan
    • Kai Feng, Henan, China
      • Not yet recruiting
      • Huaihe Hospital of Henan University
    • Luoyang, Henan, China
      • Not yet recruiting
      • The first affiliated hospital of Henan University of science and technology
      • Contact: Yujin Ma
  • Hubei
    • Shiyan, Hubei, China
      • Not yet recruiting
      • Shiyan Renmin Hospital
      • Contact: Hongcheng Ding
  • Hunan
    • Changsha, Hunan, China
      • Not yet recruiting
      • The Third Hospital of Changsha
      • Contact: Debin Huang
    • Chenzhou, Hunan, China
      • Not yet recruiting
      • Chenzhou No.1 People's Hospital
  • Inner Mongolia
    • Baotou, Inner Mongolia, China
      • Not yet recruiting
      • Inner Mongolia Baogang Hospital
      • Contact: Ziling Li
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • Nanjing First Hospital
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • Nanjing Jiangning Hospital
      • Contact: Kun Wang
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • Sir Run Run Hospital Nanjing Medical Universtiy
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • The Second Affiliated Hospital of Nanjing Medical University
    • Nantong, Jiangsu, China
      • Not yet recruiting
      • Affiliated Hospital of Nantong University
      • Contact: Yunjuan Gu
    • Nantong, Jiangsu, China
      • Not yet recruiting
      • Nantong First People's Hospital
      • Contact: Xueqin Wang
  • Jiangxi
    • Pingxiang, Jiangxi, China
      • Not yet recruiting
      • Jiangxi Pingxiang People's Hospital
      • Contact: Yawei Zhang
  • Jilin
    • Changchun, Jilin, China
      • Not yet recruiting
      • The Second Hospital of Jilin University
  • Liaoning
    • Panjin, Liaoning, China
      • Not yet recruiting
      • Panjin LiaoHe Oil Field Gem Flower Hospital
  • Shaanxi
    • Xi'an, Shaanxi, China
      • Not yet recruiting
      • Tangdu Hospital, Air Force Medical University
      • Contact: Bin Gao
  • Shandong
    • Jinan, Shandong, China
      • Not yet recruiting
      • Jinan Central Hospital
    • Qingdao, Shandong, China
      • Not yet recruiting
      • Qingdao Central Hospital
      • Contact: Minxiu Yao
  • Shanxi
    • Changzhi, Shanxi, China
      • Not yet recruiting
      • Peace Hospital Affiliated to Changzhi Medical College
      • Contact: Huwei Shen
    • Datong, Shanxi, China
      • Not yet recruiting
      • The Third People's Hospital of Datong
      • Contact: Yan Liu
    • Ya'an, Shanxi, China
      • Not yet recruiting
      • Yan'an University Affiliated Hospital
      • Contact: Sheli Li
  • Sichuan
    • Chengdu, Sichuan, China
      • Not yet recruiting
      • Chengdu Fifth People's Hospital
      • Contact: Hongyi Cao
  • Zhejiang
    • Huzhou, Zhejiang, China
      • Not yet recruiting
      • Huzhou Central Hospital
      • Contact: Xiaohui Zhou
    • Jiaxing, Zhejiang, China
      • Recruiting
      • Jiaxing Second Hospital
      • Contact: Pengfei Du
• Hong Kong
  • Hong Kong, Hong Kong
    • Not yet recruiting
    • The Chinese University of Hong Kong, Prince of Wales Hospital
    • Contact: Elaine Chow
  • Hong Kong, Hong Kong
    • Not yet recruiting
    • The University of Hong Kong, Queen Mary Hospital
    • Contact: Wing Sun Chow
• Taiwan
  • Taipei, Taiwan
    • Not yet recruiting
    • National Taiwan University Hospital
    • Contact: Kuo-Chin Huang

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients must meet all of the following inclusion criteria to be eligible for this study:
• Males or females aged ≥18 years and ≤ 75 years at screening;
• Diagnosed T2DM patients who meet the diagnostic criteria for type 2 diabetes mellitus issued by WHO in 1999 (see Appendix 2 for diagnostic criteria of type 2 diabetes mellitus);
• Receive diet and exercise interventions for at least eight weeks before screening and do not receive any anti-diabetes medications within eight weeks before screening;

• The Glycosylated hemoglobin (HbA1c) must meet the following criteria:

  1. HbA1c ≥ 7.5% and ≤ 11.0% at screening (local laboratory);
  2. HbA1c ≥ 7.0% and ≤ 10.5% (central laboratory) prior to randomization (V3);
• Body mass index (BMI) ≥ 18.5 kg/m2 and ≤ 40.0 kg/m2 at screening or prior to randomization (V3);
• Able to understand and willing to sign the written informed consent form (ICF) and follow the protocol.

Exclusion Criteria:

• Patients cannot be randomized if they meet any of the following criteria:
• Patients diagnosed with type 1 diabetes mellitus, diabetes due to pancreatic injury, or special type of diabetes due to other diseases (e.g., acromegaly or Cushing's syndrome);
• Patients who receive other glucokinase activators prior to screening or randomization;
• Patients who have acute diabetic complications such as diabetic ketoacidosis, lactic acidosis or hyperglycemia and hyperglycemic hyperosmolar status within six months before screening or prior to randomization;
• Patients who have severe chronic diabetic complications (such as proliferative diabetic retinopathy, severe diabetic neuropathy, diabetic foot, etc.) within six months before screening.
• Patients who have two or more episodes of severe hypoglycemia within six months before screening, or who have had severe hypoglycemia prior to randomization since screening ;
• Patients who have hemorrhagic stroke or acute ischemic stroke within six months before screening or prior to randomization;
• Patients who have a history of acute or chronic pancreatitis at screening or prior to randomization;
• Patients who suffer from any serious gastrointestinal diseases (such as gastroparesis, inflammatory bowel disease, intestinal obstruction) that affect drug absorption within six months before screening or prior to randomization, or have underwent gastrointestinal operations that affect drug absorption (such as gastrectomy, gastroenterostomy or enterectomy, etc.);
• Patients who have severe trauma or serious infection that may affect glycaemic control within one month before screening or prior to randomization, such as bone fracture, pneumonia, etc.;
• Patients with any type of treated or untreated malignancy (whether cured or not) within five years before screening or prior to randomization. However, patients with cured basal cell carcinoma of the skin do not need to be excluded;
• Patients with thyroid dysfunction not controlled by stable drug dosage at screening or abnormalities of thyroid function test with clinically significant at screening and requiring medical treatment;

• Patients who have any of the following laboratory abnormalities at screening:

  1. Human immunodeficiency virus antibody or Treponema pallidum specific antibody positive;
  2. Hepatitis C antibody positive;
  3. Hepatitis B surface antigen is positive, and the result of hepatitis B virus DNA quantitative test is higher than the lower limit of the test reference range (Note: If the local laboratory cannot carry out quantitative detection of hepatitis B virus, the sample will be sent to the central laboratory.);
• Patients who have any disease at screening or prior to randomization that may cause hemolysis or red blood cell instability affecting HbA1c testing, such as hemolytic anemia;
• Subject who has participated in any drug or medical device clinical study within three months before screening or prior to randomization (except those who fail in screening or do not receive any trial drug);
• Patients who have a prior history of clearly diagnosed psychiatric disorders, unwilling or unable to fully understand and cooperate, or assessed by the investigator as unsuitable for participation in this clinical study;
• Patients who have a prior history of drinking [(>2 units of alcohol per day and >14 units of alcohol per week (one unit of alcohol corresponds to 150mL of grape wine or 350mL of beer or 50 mL of spirits)] or history of drug abuse;
• Patients who are known to be allergic or intolerant to the test drug or Vildagliptin or their excipients, or who have contraindications;
• Patients who have refractory urinary or genital infections within six months before screening, or are known to be allergic to Empagliflozin or its excipients;
• Female in pregnancy or lactation period;
• Partners of male subjects or female subjects who plan to become pregnant or who are unable or unwilling to use contraceptive methods required by the protocol from the signing of the informed consent form to 30 days after the last dose of the drug;
• The investigator judges that the subject is unable to comply with the protocol requirements, such as unable to adhere to diet and exercise treatment during the study, unable to take drugs and meals on time according to the protocol requirements, and unable to conduct self-monitoring of blood glucose (SMBG) in time and record;
• Other circumstances that, in the opinion of the investigator, are not appropriate for participation in this clinical study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test arm; PB-201: 100 mg each time, orally in the morning and evening respectively; Vildagliptin matched placebo: One tablet each time, orally in the morning and evening respectively;	Drug: PB-201; PB-201: 100 mg each time, orally in the morning and evening respectively; Drug: Vildagliptin matched placebo; One tablet each time, orally in the morning and evening respectively;
Active Comparator: Vildagliptin arm; Vildagliptin: 50 mg each time, orally in the morning and evening respectively; PB-201 matched placebo: One tablet each time, orally in the morning and evening respectively;	Drug: Vildagliptin; Vildagliptin: 50 mg each time, orally in the morning and evening respectively; Drug: PB-201 matched placebo; PB-201 matched placebo: One tablet each time, orally in the morning and evening respectively;
Placebo Comparator: Placebo arm; PB-201 matched placebo: One tablet each time, orally in the morning and evening respectively; Vildagliptin matched placebo: One tablet each time, orally in the morning and evening respectively;	Drug: Vildagliptin matched placebo; One tablet each time, orally in the morning and evening respectively; Drug: PB-201 matched placebo; PB-201 matched placebo: One tablet each time, orally in the morning and evening respectively;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c	Change from baseline in HbA1c after 24 weeks of treatment	Week 1,Week 25

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2021
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: October 20, 2021
• First Submitted That Met QC Criteria: October 20, 2021
• First Posted (Actual): November 1, 2021

Study Record Updates

• Last Update Posted (Actual): February 8, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: February 1, 2022

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; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Vildagliptin
• Other Study ID Numbers: PB201303

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