A Phase 3 Study to Evaluate the Efficacy of JY09 Compared With Placebo in T2DM Patients

A Phase 3, Multi-center, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of JY09 in Patients With T2DM Inadequately Controlled by Diet and Exercise Alone

The main purpose of this study is to investigate the efficacy and safety of JY09 versus placebo in patients with type 2 diabetes mellitus (T2DM) inadequately controlled by diet and exercise alone

Study Overview

• Status: Not yet recruiting
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Exendin-4 Fc fusion protein injection; Drug: Exendin-4 Fc fusion protein injection; Drug: Placebo

Detailed Description

This study was designed as a multicenter, randomized, double-blind, placebo-parallel controlled Phase III clinical study to evaluate the efficacy and safety of Exendin-4Fc fusion protein (JY09) injection in adult subjects with type 2 diabetes mellitus (T2DM) who have poor glycemic control after dietary exercise intervention only.

The proposed plan is to enroll 270 subjects with T2DM, using stratified block group randomization, with the stratification factor being baseline HbA1c (≤8.5% or >8.5%), and randomly assign them to the 1.2 mg JY09 injection group (n=90 subjects), the 2.4 mg JY09 injection group (n=90 subjects), and the placebo group (n=90 subjects) in a 1:1:1 ratio.

The trial was divided into 4 phases, i.e., a screening period of 2 weeks, a single-blind introduction period of 4 weeks, a treatment period of 54 weeks (26 weeks for the core treatment period and 28 weeks for the extended treatment period), and a safety follow-up period of 4 weeks. Total 64 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 270
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xuefeng Li, Master; Phone Number: 13683259746; Email: lixuefeng@east-bt.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
      • Contact: Linong Ji, Doctor; Phone Number: 010-88324105; Email: jiln@bjmu.edu.cn
      • Sub-Investigator: Leili Gao, Doctor
      • Principal Investigator: Linong Ji, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female subjects ≥18 years of age and ≤75 years of age at the time of signing the informed consent form.
2. Those who met the diagnostic criteria for type 2 diabetes mellitus promulgated by World Health Organization(WHO) in 1999 and who had been diagnosed with T2DM for ≥12 weeks.
3. Those who received dietary and exercise interventions for ≥8 weeks prior to screening and who had not received any antidiabetic medications in the 8 weeks prior to screening.
4. HbA1c ≥7.5% and ≤11.0% at screening (local laboratory) and HbA1c ≥7.0% and ≤10.5% before randomization (V3) (central laboratory).
5. FPG 13.9 mmol/L at screening (local laboratory) and FPG 13.9 mmol/L before randomization (V3) (central laboratory).
6. Body mass index (BMI) ≥18.5 kg/m2 and ≤35.0 kg/m2 at screening and before randomization (V3).
7. Able to understand and willing to sign a written informed consent form (ICF) and comply with the study protocol.

Exclusion Criteria:

1. People diagnosed with type 1 diabetes or other types of diabetes.
2. Those who have used other hypoglycemic agents within 8 weeks prior to screening or prior to randomization (V3), or those who have used medications that may affect glucose metabolism, such as systemic glucocorticoids (except for inhalation or topical topical use), growth hormones, etc.
3. Acute complications of diabetes, such as diabetic ketoacidosis or hyperglycemic hyperosmolar state, within 6 months prior to screening or prior to randomization.
4. Severe chronic complications of diabetes mellitus (e.g., proliferative diabetic retinopathy, severe diabetic neuropathy, diabetic foot, etc.) within 6 months prior to screening, which are assessed by the investigator to be unsuitable for participation in this clinical study.
5. Persons who have had a severe trauma or serious infection within 1 month prior to screening or prior to randomization (V3) that may affect glycemic control, and persons who currently have a complicated or refractory urinary or genital tract infection.
6. Suffering from any condition at screening or prior to randomization (V3) that may cause hemolysis or red blood cell instability that would interfere with the measurement of HbA1c levels, such as hemolytic anemia.
7. Subjects who have abnormal thyroid function tests at Screening and require medication, or subjects who are being treated with thyroid-related medications whose thyroid function is still not well controlled at Screening.
8. Those with any of the following abnormalities on serologic testing at screening:

1）Positive human immunodeficiency virus antibodies or syphilis spirochete-specific antibodies; 2）Hepatitis C antibody positive; 3）Hepatitis B virus surface antigen (HBsAg) positive and hepatitis B viral load (HBV-DNA) above the lower limit of laboratory testing (HBV-DNA is added only if HBsAg is positive); 9. The subject has other conditions that, in the judgment of the investigator, make participation in this clinical study inappropriate.

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: Exendin-4 Fc fusion protein injection(1.2mg）; 1.2mg,Subcutaneous injection in the abdomen,Bi-weekly for 54 weeks.	Drug: Exendin-4 Fc fusion protein injection; 1.2mg, subcutaneous injection in the abdomen, biweekly, 54 weeks of treatment.; Other Names: JY09(1.2mg); Drug: Exendin-4 Fc fusion protein injection; The first dose of 1.2 mg was administered subcutaneously in the abdomen, and after two weeks, the dose was adjusted to 2.4 mg, followed by a continuation of treatment for 52 weeks.; Other Names: JY09(2.4mg)
Experimental: Exendin-4 Fc fusion protein injection(2.4mg）; The first dose of 1.2 mg of JY09 injection was administered, the dose was adjusted to 2.4 mg after two weeks, after which 2.4 mg was maintained to continue subcutaneous injection in the abdomen, bi-weekly treatment for 52 weeks.	Drug: Exendin-4 Fc fusion protein injection; 1.2mg, subcutaneous injection in the abdomen, biweekly, 54 weeks of treatment.; Other Names: JY09(1.2mg); Drug: Exendin-4 Fc fusion protein injection; The first dose of 1.2 mg was administered subcutaneously in the abdomen, and after two weeks, the dose was adjusted to 2.4 mg, followed by a continuation of treatment for 52 weeks.; Other Names: JY09(2.4mg)
Placebo Comparator: placebo(0.6ml）; JY09 placebo injection 0.6 ml, biweekly abdominal subcutaneous injection for 26 weeks, followed by randomization in a 1:1 ratio into JY09 (1.2 mg) and JY09 (2.4 mg) for 28 weeks, biweekly subcutaneous injections.	Drug: Placebo; 0.6 ml, placebo injection, biweekly subcutaneous abdominal injections for 26 weeks (core treatment period), after which placebo was randomized 1:1 to JY09 (1.2 mg) and JY09 (2.4 mg) continued subcutaneous abdominal injections biweekly for 28 weeks (extended treatment period).; Other Names: Injection mimetic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	Change in glycated hemoglobin (HbA1c) values relative to baseline after 26 weeks of treatment.	Baseline, Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of HbA1c <6.5% and <7%	Proportion of subjects with HbA1c <7% and HbA1c <6.5% after 26 and 54 weeks of treatment.	Baseline, Week 26,Week 54
HbA1c	Change in HbA1c relative to baseline after 6, 10, 14, 20, 38, and 54 weeks of treatment.	Baseline, Week 6,Week 10,Week 14,Week 20,Week 38,Week 54
fasting plasma glucose (FPG)	Change in fasting plasma glucose (FPG) relative to baseline after 6, 10, 14, 20, 38, and 54 weeks of treatment.	Baseline, Week 6,Week 10,Week 14,Week 20,Week 38,Week 54
fasting insulin	Change in fasting insulin relative to baseline after 14, 26, and 54 weeks of treatment.	Baseline, Week 14,Week 26,Week 54
Homeostatic Model Assessment of Insulin Resistance(HOMA-IR)	Change in HOMA-IR relative to baseline after 26 and 54 weeks of treatment.	Baseline,Week 26,Week 54
Health Survey Short Form (SF-36)	Value of change in Health Survey Short Form (SF-36) scores relative to baseline after 26 and 54 weeks of treatment.	Baseline,Week 26,Week 54
blood pressure	Change in blood pressure (sitting) relative to baseline after 26 and 54 weeks of treatment.	Baseline,Week 26,Week 54

Collaborators and Investigators

• Sponsor: Beijing Dongfang Biotech Co., Ltd.
• Investigators: Principal Investigator: Linong Ji, Doctor, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: February 3, 2024
• First Submitted That Met QC Criteria: February 9, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 17, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: T2DM
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: DFBT-JY09-DM-301

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