Clinical trial NCT04998032: A Study of Efficacy and Safety of Supaglutide in Type 2 Diabetes Patients On Metformin Treatment(SUPER-2)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Type2 Diabetes
Lead sponsor: Shanghai Yinnuo Pharmaceutical Technology Co., Ltd.
Sponsor class: OTHER
First posted: 2021-08-10
Enrollment: 620
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This clinical trial includes dosage determination (Phase IIb) and efficacy confirmation stage(Phase III ). During the phase IIb, subjects were randomly assigned to Supaglutide 1mg + metformin, Supaglutide 3mg + metformin and placebo + metformin according to a 1:1:1 ratio.

When 120 subjects complete the 12 weeks of follow-up, Interim analysis will be performed and the results be evaluated by IDMC to confirm the RP3D dose.

And then during the phase III, subjects were randomly assigned to Supaglutide RP3D + metformin, placebo + metformin group according to a 1:1 ratio.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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;

Primary outcomes:
measure: HbA1c
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary outcomes:
measure: fasting plasma glucose
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
measure: HbA1c<7.0% and <6.5%
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
measure: Fasting insulin
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
measure: fasting C-peptide
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
measure: fasting glucagon
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
measure: Area under the curve of blood glucose
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
measure: Area under the curve of insulin
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
measure: Area under the curve of C-peptide
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
measure: Total cholesterol
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
measure: low density lipoprotein
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
measure: High density lipoprotein
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
measure: triglyceride
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
measure: weight
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
measure: salvage treatment
timeFrame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Boai Hospital
city: Beijing
country: China
facility: Beijing Pinggu Hospital
city: Beijing
country: China
facility: Emergency General Hospital
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
city: Cangzhou
country: China
facility: Cangzhou Hospital of Integrated TCM-WM Hebei
city: Changchun
country: China
facility: The Second Hospital of Jilin University
city: Changde
country: China
facility: First People's Hospital of Changde
city: Changsha
country: China
facility: Changsha Hopital Affiliated to Hunan University
city: Changsha
country: China
facility: The Fourth Hospital of Changsha
city: Chengdu
country: China
facility: Chengdu Fifth People's Hospital
city: Chenzhou
country: China
facility: Chenzhou First People's Hospital
city: Chongqing
country: China
facility: Chongqing Ninth People's Hospital
city: Dalian
country: China
facility: Dalian Municipal Central Hospital
city: Daqing
country: China
facility: Daqing People's Hospital
city: Gongzhuling
country: China
facility: Jilin Guowen Hospital
city: Handan
country: China
facility: Handan First Hospital
city: Harbin
country: China
facility: The Fourth Affiliated Hospital of Harbin Medical University
city: Heze
country: China
facility: Heze Municipal Hospital
city: Huai'an
country: China
facility: Huai'an First People's Hospital
city: Huai'an
country: China
facility: Huai'an Second People's Hospital
city: Huizhou
country: China
facility: Huizhou Central Hospital
city: Jilin
country: China
facility: Jilin People's Hospital
city: Jinan
country: China
facility: Jinan Central Hospital Affiliated to Shandong First Medical University
city: Jincheng
country: China
facility: Jincheng General Hospital
city: Jingzhou
country: China
facility: Jingzhou Central Hospital
city: Kunming
country: China
facility: The Second Affiliated Hospital of Kunming Medical University
city: Lianyungang
country: China
facility: The Second People's Hospital of Lianyungang
city: Linfen
country: China
facility: Linfen People's Hospital
city: Linyi
country: China
facility: First People's Hospital of Tancheng
city: Liuzhou
country: China
facility: Liuzhou People's Hospital
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University
city: Meihekou
country: China
facility: Meihekou Central Hospital
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
city: Nanjing
country: China
facility: Nanjing First Hospital
city: Nanjing
country: China
facility: Nanjing Jiangning Hospital
city: Nanjing
country: China
facility: Sir Run Run Hospital of Nanjing Medical University
city: Nanyang
country: China
facility: Nanyang First People's Hospital
city: Nanyang
country: China
facility: Nanyang Second General Hospital
city: Nanyang
country: China
facility: The First Affiliated Hospital of Nanyang Medical College
city: Puyang
country: China
facility: Puyang Oilfield General Hospital
city: Qinhuangdao
country: China
facility: The First Hospital of Qinhuangdao
city: Qiqihar
country: China
facility: The First Hospital of Qiqihar
city: Shanghai
country: China
facility: Changhai Hospital
city: Shanghai
country: China
facility: Huadong Hospital
city: Shanghai
country: China
facility: Shanghai Pudong New Area People's Hospital
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University
city: Shanghai
country: China
facility: Shanghai Tongren Hospital
city: Siping
country: China
facility: Siping Central Hospital
city: Taiyuan
country: China
facility: Second Hospital of Shanxi Medical University
city: Tanan
country: China
facility: The Second Affiliated Hospital of Shandong First Medical University
city: Tianjing
country: China
facility: Tianjin Medical University General Hospital
city: Tianjin
country: China
facility: The Second Hospital of Tanjin Medical University
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
city: Wuxi
country: China
facility: Jiangyin People's Hospital
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
city: Xuzhou
country: China
facility: Xuzhou Cancer Hospital
city: Yibin
country: China
facility: The Second People's Hospital of Yibin
city: Yichun
country: China
facility: Yichun People's Hospital
city: Yiyang
country: China
facility: Yiyang Central Hospital
city: Zhengzhou
country: China
facility: The Second Affiliated Hospital of Zhengzhou University
city: Zunyi
country: China
facility: First People's Hospital of Zunyi
Study officials:
affiliation: Shanghai 6th People's Hospital
name: Weiping Jia, M.D,Ph.D
role: PRINCIPAL_INVESTIGATOR
References: