A Phase 3 Study to Evaluate the Efficacy of JY09 Compared With Dulaglutide in Combination Therapy Diabetes Mellitus Type 2 Patients With Metformin

A Phase 3, Multi-center, Open-label, Randomized Study to Evaluate the Efficacy and Safety of JY09 Versus Dulaglutide in Patients With T2DM Inadequately Controlled by Metformin

The aim of the study is to compare the efficacy and safety of two JY09 doses versus dulaglutide as add-on therapy to metformin in participants with type 2 diabetes mellitus (T2DM)

Study Overview

• Status: Not yet recruiting
• Conditions: Type2 Diabetes Mellitus
• Intervention / Treatment: Drug: Exendin-4 Fc fusion protein injection(1.2mg）; Drug: Metformin; Drug: Exendin-4 Fc fusion protein injection（2.4mg）; Drug: Dulaglutide

Detailed Description

This study was designed as a multicenter, randomized, open, parallel, positively 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 who have poor glycemic control after metformin treatment only.

The proposed plan is to enroll 600 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=200 subjects), 2.4 mg JY09 injection group (n=200 subjects) and dulaglutide injection group (n=200 subjects) in a 1:1:1 ratio.

The trial was divided into 4 phases, i.e., a screening period of 2 weeks, an 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. A total of 64 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 600
• 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, 100034
      • Peking University First Hospital
      • Contact: Junqing Zhang, Doctor; Phone Number: 010-83572386; Email: junqing.zhang@pkufh.com

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. Received a stable dose of metformin monotherapy with a metformin dose ≥1500 mg/day or a maximally tolerated dose (<1500 mg/day but ≥1000 mg/day) on the basis of dietary and exercise interventions during 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 (V4).
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 glucose-lowering drugs other than metformin within 8 weeks prior to screening or prior to randomization (V3), or those who have used drugs that may affect glucose metabolism, such as systemic glucocorticosteroids (except for inhalation or topical topical use) and growth hormone.
3. Those who have used glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon-like peptide-1 (GLP-1) receptor agonists (including single-target, multi-target agonists, and insulin-containing GLP-1 combinations) prior to screening.
4. More than 14 days of continuous insulin use in the 6 months prior to screening.
5. Acute complications of diabetes such as diabetic ketoacidosis or hyperglycemic hyperosmolar state within 6 months prior to screening or prior to randomization .
6. 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.
7. Individuals who have had severe gastrointestinal disease (e.g., active ulcer, gastroparesis, pyloric obstruction, inflammatory bowel disease, etc.) or have undergone gastrointestinal surgery within 6 months prior to screening or prior to randomization or who have been using long-term medications for chronic gastrointestinal disease that have a direct effect on gastrointestinal motility are not suitable for participation in this clinical study, as assessed by the investigator.
8. Other conditions that, in the judgment of the investigator, make the subject unsuitable 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: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exendin-4 Fc fusion protein injection(1.2mg）+Metformin; 1.2mg,Subcutaneous injection in the abdomen,Bi-weekly for 54 weeks.	Drug: Exendin-4 Fc fusion protein injection(1.2mg）; 1.2mg, subcutaneous injection in the abdomen, biweekly, 54 weeks of treatment.; Other Names: JY09(1.2mg); Drug: Metformin; Metformin hydrochloride tablets, oral administration, 54 weeks of treatment
Experimental: Exendin-4 Fc fusion protein injection(2.4mg）+Metformin; 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: Metformin; Metformin hydrochloride tablets, oral administration, 54 weeks of treatment; Drug: Exendin-4 Fc fusion protein injection（2.4mg）; 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)
Active Comparator: Dulaglutide+Metformin; 1.5 mg dulaglutide injection subcutaneously once a week for 26 weeks.	Drug: Metformin; Metformin hydrochloride tablets, oral administration, 54 weeks of treatment; Drug: Dulaglutide; 1.5 mg dulaglutide injection subcutaneously once a week for 54 weeks.

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
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
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

Collaborators and Investigators

• Sponsor: Beijing Dongfang Biotech Co., Ltd.
• Investigators: Principal Investigator: Junqing Zhang, Doctor, Peking University First Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: February 6, 2024
• First Posted (Estimated): February 14, 2024

Study Record Updates

• Last Update Posted (Estimated): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 6, 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; Dulaglutide; Metformin; Exenatide
• Other Study ID Numbers: DFBT-JY09-DM-302

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