A Study of Efficacy and Safety of Supaglutide in Type 2 Diabetes Patients On Metformin Treatment

Efficacy and Safety of Once-weekly Supaglutide Versus Placebo in Patients With Type 2 Diabetes Suboptimally Controlled on Metformin: A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial

This is a study to evaluate the efficacy and safety of Supaglutide injection in the treatment of type 2 diabetes patients with poor glycemic control after metformin treatment.

This trial includes dosage determination (Phase IIb) and efficacy confirmation stage(Phase III ). The primary outcome of the phase IIb period is to preliminarily evaluate the efficacy and safety of Supaglutide combined with metformin and to provide the recommended dosage for the Phase 3 period after 12-week treatment.

The primary outcome of the Phase III period is to evaluate the efficacy and safety of Supaglutide combined with metformin treatment after 24-week, double-blind treatment. The secondary outcome is to evaluate the efficacy and safety of Supaglutide combined with metformin during the 24-week, double-blinded plus 28-week, open-label treatment period.

Study Overview

• Status: Active, not recruiting
• Conditions: Type2 Diabetes
• Intervention / Treatment: Biological: supaglutide injection+metformin; Other: placebo+metformin

Detailed Description

This trial includes a 2-week screening period, a 4-week metformin titration and dose-stabilization period, a 4-week induction period, a 24-week double-blind treatment period and a 28-week open-label treatment period, followed by a 4-week follow-up period and a follow-up visit. We calculated that the sample size would need to be 632, including 120 subjects in the period of Phase IIb and 512 subjects in the period of Phase III. During the phase IIb period, subjects were randomly assigned to once-weekly subcutaneously injected Supaglutide 1mg plus metformin, 3mg plus metformin and placebo plus metformin at a ratio of 1:1:1.

When the number of participants who have completed the 12-week follow up reached 120, interim analyses will be performed and the results will be evaluated by Independent Data Monitoring Committee experts to determine the recommended phase 3 dosage.

During the phase III stage, subjects were randomly assigned 1:1 to the "recommended phase 3 dosage + metformin" group and the "placebo + metformin" group.

• Study Type: Interventional
• Enrollment (Actual): 620
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Hebei
    • Tianjin, Hebei, China, 300052
      • Tianjin Medical University General Hospital

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:

1. Male or female patients aged from 18 to 75;
2. Clinical diagnosed of Type 2 diabetes for at least 8 weeks ，receive metformin single treatment ；
3. During screening, HbA1c: 7.5% ≤ HbA1c ≤ 11% ，and before randomization 7.5% ≤ HbA1c ≤ 10.5%;
4. During screening and before randomization: FPG< 13.9 mmol/L； 5.18.5 kg/m2 ≤ BMI ≤ 35 kg/m2;

6. without birth plan and voluntarily take effective contraceptive measures; 7. fully understood the study, signed the informed consent；

Exclusion Criteria:

1. Diabetes other than Type 2;
2. Any dipeptidyl peptidase IV and / or glucagon-like peptide-1 （GLP-1）analogues were used within 3 months before screening;
3. Continuous use of insulin for more than 14 days in the previous year;
4. C-Peptide <0.3 nmol/L;
5. Diabetic ketoacidosis, diabetic lactic acidosis or hyperosmolar non ketonic diabetic coma occurred within 6 months before screening;
6. Unstable proliferative retinopathy or macular lesion, severe diabetic neuropathy, intermittent claudication or diabetic foot occurred within 6 months before screening;
7. Severe hypoglycemia occurred within 6 months before screening
8. Severe trauma infection or operation within one month before screening;
9. Blood donation or massive blood loss or transfusion within 3 months ;
10. Suspected active infection ;
11. Growth hormone therapy was performed within 6 months before screening;
12. Patients having received corticosteroid continuous ≥ 7 days through within 2 months ;
13. use any drugs or surgery with weight control effect within 2 months;
14. weight change of more than 5% within 3 months;
15. mean systolic pressure (SBP) ≥ 160mmhg and / or diastolic pressure （DBP） ≥ 90 mmHg at screening, or new/changed antihypertensive drugs or adjusted dosage of antihypertensive drugs within 4 weeks before screening or before induction period
16. with a history of severe cardiovascular disease, high risk of stroke/stroke within 6 months before screening;
17. with a history of acute or chronic pancreatitis, symptomatic gallbladder , pancreatic injury and other risk factors for pancreatitis, or with blood amylase and/or blood lipase ≥1.5 times the upper limit of normal (ULN) at the time of screening or before randomization;
18. Calcitonin level ≥50 ng/L (pg/mL) during screening;
19. with a history of medullary thyroid cancer, multiple endocrine neoplasm (Men) 2A or 2B syndrome, or related family history;
20. with clinically significant abnormal gastric emptying , severe chronic gastrointestinal diseases , long-term use of drugs that have a direct impact on gastrointestinal peristalsis , or having undergone gastrointestinal surgery within 6 months before screening, are not suitable to participate in this clinical study according to the evaluation of the researchers;
21. suffering from hematological diseases or any disease causing hemolysis or erythrocyte instability ;
22. Uncontrolled hyperthyroidism or hypothyroidism;
23. with hemoglobinopathy that may affect the determination of HbA1c levels;
24. HBsAg, Hepatitis C antibody, HIV-Ab, Treponema pallidum antibody or Corona Virus Disease 2019 nucleic acid tested positive;
25. serious mental illness;
26. drinking more than 14 standard units weekly within 6 months before screening ;
27. a history of organ transplantation or other acquired or congenital immune system diseases;
28. allergic to the active ingredients (GLP-1 and GLP-1 analogues) of the study drug;
29. clear contraindications for the use of metformin;
30. clear contraindications for Empagliflozin；
31. Any of the following conditions: the pacemaker was installed when screened; no pacemaker was installed, but 12 lead ECG showed degree II or III atrioventricular block, long QT syndrome or QTc interval ≥ 450ms ; Patients with New York Heart Function Classification III or IV; Or other abnormal cardiac function with clinical significance that is not suitable for clinical research judged by researchers;
32. acute or chronic hepatitis, or whose laboratory examination indexes meet one of the following criteria at the time of screening or before randomization : alanine aminotransferase (ALT) level ≥ 2.5 fold ULN, aspartate aminotransferase (AST) ≥ 2.5 fold ULN, fasting triglyceride (TG) > 5.7 mmol/L or 500 mg/dl; the glomerular filtration rate (EGFR) < 60 ml/min/1.73 square meters was calculated by CKD-EPI (epi - (SCR)) formula;
33. participated in clinical trials of other drugs or devices within 3 months before screening;
34. Medication compliance in the metformin dosage stable period was < 80% or > 120%;
35. Supaglutide placebo injection compliance during the induction period was <75% or>125%, or metformin compliance <80% or >120%;
36. Any other situation that researchers think may affect the patients' informed consent or compliance with the trial protocol;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: supaglutide RP3D dose+metformin; Supaglutide Subcutaneous injection once a week for 52weeks,combined with metformin	Biological: supaglutide injection+metformin; supaglutide subcutaneous injection under RP3D dose combined with metformin treatment
Placebo Comparator: placebo+metformin; Placebo Subcutaneous injection once a week for 52weeks,,combined with metformin	Other: placebo+metformin; placebo subcutaneous injection combined with metformin treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	The change in mean HbA1c concentrations (%)from baseline with Supaglutide versus placebo	12 weeks for phase IIb; 24weeks and 52 weeks for phase III

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c<7.0% and <6.5%	The proportion of participants who achieved HbA1c target (HbA1c<7.0% and <6.5% Patient percentage)	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Fasting insulin	Fasting insulin changes（pmol/L) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
fasting C-peptide	Fasting C-peptide changes (nmol/L) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
fasting glucagon	fasting glucagon changes (pg/ml) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Area under the curve of insulin	Area under the curve of insulin (AUC0-120min,pmol/L) during the MMTT	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Area under the curve of C-peptide	Area under the curve of C-peptide (AUC0-120min,nmol/L) during the MMTT	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
weight	Weight change from baseline(kg)	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
salvage treatment	Percentage of subjects receiving salvage treatment(%)	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
fasting plasma glucose	Changes in fasting plasma glucose (mmol/L) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Area under the curve of blood glucose	Area under the curve of blood glucose (AUC0-120min,mmol/L) during the multi-maneuvering target tracking	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Total cholesterol	Changes in total cholesterol (mmol/L) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
low density lipoprotein	Changes in low density lipoprotein (mmol/L) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
High density lipoprotein	Changes in high density lipoprotein (mmol/L) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
triglyceride	Changes in triglyceride(mmol/L) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III

Collaborators and Investigators

• Sponsor: Shanghai Yinnuo Pharmaceutical Technology Co., Ltd.
• Investigators: Principal Investigator: Weiping Jia, M.D,Ph.D, Shanghai 6th people's hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2021
• Primary Completion (Anticipated): July 31, 2023
• Study Completion (Anticipated): August 28, 2023

Study Registration Dates

• First Submitted: July 28, 2021
• First Submitted That Met QC Criteria: August 8, 2021
• First Posted (Actual): August 10, 2021

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 16, 2023
• Last Verified: January 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; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: YN011-302

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