Efficacy and Safety of SPH3127 Tablets on Treating the Diabetic Kidney Disease

Diabetic Kidney Disease Clinical Trial

Official title:

A Multicenter, Randomized, Double-blind, Active-controlled, Parallel, Dose-finding Phase 2 Clinical Study to Evaluate the Efficacy and Safety of SPH3127 Tablets in the Treatment of Diabetic Kidney Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05593575
• Other study ID #: SPH3127-202
• Status: Recruiting
• Phase: Phase 2
• Start date: March 22, 2023
• Est. completion date: March 31, 2025

Study information

• Verified date: November 2023
• Source: Shanghai Pharmaceuticals Holding Co., Ltd
• Contact: Limeng Chen
• Phone: 0086+15801391704
• Email: chenlimeng[@]pumch.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To preliminarily evaluate the efficacy and safety of the renin inhibitor (SPH3127 tablets) in reduction in proteinuria in patients with diabetic kidney disease with valsartan as the comparator, and determine the recommended dose.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. completion date: March 31, 2025
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Subjects who are diagnosed with type 2 diabetes who have been treated with at least one hypoglycemic therapy within 12 months prior to screening, with basically stable blood glucose level during screening;

2. During screening period, 120 mmHg = sitting SBP = 160 mmHg and sitting DBP < 110 mmHg;

3. Laboratory results before randomization should be: 1) at least twice the result of UCAR should be 30 mg/g = UACR < 3000mg/g at W-8, W-4, W-2, and W0; 2) EGFR = 45mL/min/1.73 m2 at W-4 and W0; 3) AST and ALT = 2 times the upper limit of normal (ULN), and total bilirubin = 1.5 times ULN at W0; 4) hemoglobin = 90 g/L at W0; 5) 3.5 mmol/L =Serum potassium = 4.8 mmol/L at W-4 and W0;

4. Subjects who agree to take effective contraceptive measures with their spouses throughout the study period and for up to 12 weeks after the last dose;

5. Subjects who thoroughly learn about the nature, significance, possible benefits, possible inconvenience and potential risks of the trial, and understand the study procedures and voluntarily sign the informed consent form prior to their participation in the trial.

Exclusion Criteria:

1. Sitting SBP >140 mmHg and/or sitting DBP >90 mmHg at baseline (W0);

2. Color ultrasonography of renal artery indicated renal artery stenosis;

3. ? Acute renal insufficiency? acute nephritic syndrome, polycystic kidney, kidney stone, nephrotic syndrome; ?there is evidence that proteinuria originates from primary and secondary renal diseases other than hypertensive renal damage; ? gross hematuria in the past one year.

4. During the screening/run-in period, major modifications need to be made to the subject's corresponding treatment regimen due to poor control of other underlying diseases based on the investigator's judgement;

5. Subjects with fundus lesions in malignant hypertensive, such as retinal hemorrhage and papilledema;

6. Subjects who need to continuously take glucocorticoids, anti-tumor chemical or biological agents, and non-steroidal anti-inflammatory drugs during the study period;

7. Subjects with a history of acute myocardial infarction, coronary artery revascularization, Class IV heart failure, acute cerebral infarction, cerebral hemorrhage and transient ischemic attack within 3 months prior to randomization;

8. Subjects who have abnormal thyroid function tests with clinically significance;

9. Subjects with poor control of diabetes: HbA1c = 9.0% at W0;

10. Subjects who have undergone major surgery within 3 months prior to screening or need to undergo major surgery during the trial;

11. Subjects whose medication adherence in the run-in period is < 80% or > 120%;

12. Subjects with a history of gastrointestinal surgery that may significantly change the absorption, distribution, metabolism and excretion of drugs;

13. Subjects who are known to be allergic to renin inhibitors, ARBs, ACEIs and their excipients, or those with hypersensitive constitution, or those who experience serious adverse reactions;

14. Women during pregnancy or lactating;

15. Subjects who need transplantation before randomization and during the trial;

16. Subjects with HIV infection, hepatitis B infection, hepatitis C infection, or other active infections;

17. Subjects who have a history of malignant tumor, and those who are suspected of malignant tumor;

18. Subjects with a past and current history of mental illness;

19. Subjects with a history of drug abuse or alcohol abuse within 2 years prior to screening;

20. Subjects who have participated in clinical trials of other drugs/devices as a subject within 3 months prior to screening;

21. Subjects with other diseases or conditions that the investigator considers not suitable for this trial.

Related Conditions & MeSH terms

• Diabetic Kidney Disease
• Diabetic Nephropathies
• Kidney Diseases

Intervention

Drug:
• SPH3127+SPH3127matching placebo+valsartan matching placebo
1 tablet of SPH3127 (50 mg) ,3 tablets of SPH3127 (50mg)matching placebo, 1 capsule of valsartan matching placebo, orally, once daily for 12 consecutive weeks
• SPH3127+SPH3127matching placebo+valsartan matching placebo
2 tablet of SPH3127 (50 mg) ,2 tablets of SPH3127 (50mg)matching placebo, 1 capsule of valsartan matching placebo, orally, once daily for 12 consecutive weeks
• SPH3127+valsartan matching placebo
4 tablet of SPH3127 (50 mg) , 1 capsule of valsartan matching placebo, orally, once daily for 12 consecutive weeks
• SPH3127 matching placebo+valsartan
4 tablets of SPH3127 (50mg)matching placebo, 1 capsule of valsartan, orally, once daily for 12 consecutive weeks

Locations

Country	Name	City	State
China	Beijing Tsinghua Changgeng Hospital	Beijin
China	Beijing Anzhen Hospital,Capital Medical University	Beijing
China	Beijing Tiantan Hospital,Capital Medical University	Beijing
China	Beijing Tongren Hospital	Beijing
China	Peking Union Medical College Hospital	Beijing
China	The Second Norman Bethune Hospital of Jilin University	Chang chun	Jilin
China	The Third Xiangya Hospital of Central South University	Changsha	Hunan
China	Xiangya Hospital Central South University	Changsha
China	Chengdu Second People's Hospital	Chengdu	Sichuan
China	Sichuan Provincial People's Hospital	Chengdu
China	West China Hospital of Sichuan University	Chengdu
China	The 900 Hospital of the Joint Service Support Force of the People's Liberation Army of China	Fuzhou	Fujian
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital,Sun Yat sen University	Guangzhou	Guangdong
China	Guizhou Provincial People's Hospital	Guiyang	Guizhou
China	The Second Affiliated Hospital of Hainan Medical University	Haikou
China	Harbin Medical University Affiliated Fourth Hospital	Harbin	Heilongjiang
China	The Second Hospital of Anhui Medical University	Hefei	Anhui
China	Qilu Hospital of Shandong University	Jinan
China	The First Affiliated Hospital of Shandong First Medical University	Jinan
China	Luoyang Third People's Hospital	Luoyang	Henan
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Ningbo No.2 Hospital	Ningbo
China	Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine	Shanghai
China	Shanghai Fengxian District Central Hospital	Shanghai
China	Shanghai Minhang District Central Hospital	Shanghai
China	Sheng Jing Hospital of China Medical University	Shenyang
China	The First Affiliated Hospital of China Medical University	Shenyang
China	The Seventh Affiliated Hospital,Sun Yat-sen University	Shenzhen
China	Suining Central Hospital	Suining	Sichuan
China	Second Hospital of Shanxi Medical University	Taiyuan
China	Taizhou Municipal Hospital	Taizhou	Zhejiang
China	The First Affiliated Hospital of Xinjiang Medical University	Ürümqi	Xinjiang
China	Renmin Hospital of Wuhan University	Wuhan	Hubei
China	The Third Hospital of Wuhan	Wuhan	Hubei
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an
China	Xi'an Daxing Hospital	Xi'an	Shanxi
China	Qinghai University Affiliated Hospital	Xining	Qinghai
China	The First People's Hospital of Yinchuan	Yinchuan	Ningxia
China	Zigong Fourth People's Hospital	Zigong	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Pharmaceuticals Holding Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage change from baseline in UACR	Percentage change from baseline in log-transformed UACR at the end of Week 12 of treatment	at the end of Week 12 of treatment
Secondary	Percentage change from baseline in UACR	Percentage change from baseline in log-transformed UACR at the end of Weeks 2, 4 and 8 of treatment	at the end of Weeks 2, 4 and 8 of treatment
Secondary	Percentage change from baseline in UPCR	Percentage change from baseline in log-transformed UPCR at the end of Weeks 2, 4, 8 and 12 of treatment	at the end of Weeks 2, 4, 8 and 12 of treatment
Secondary	The change trend of eGFR	The change trend of eGFR from baseline to the end of Weeks 2, 4, 8 and 12 of treatment	from baseline to the end of Weeks 2, 4, 8 and 12 of treatment