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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetic Kidney Disease
• Intervention / Treatment: Drug: SPH3127+SPH3127matching placebo+valsartan matching placebo; Drug: SPH3127+SPH3127matching placebo+valsartan matching placebo; Drug: SPH3127+valsartan matching placebo; Drug: SPH3127 matching placebo+valsartan

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Limeng Chen; Phone Number: 0086+15801391704; Email: chenlimeng@pumch.cn

Study Locations

• China
  • Beijin, China
    • Recruiting
    • Beijing Tsinghua Changgeng Hospital
    • Contact: Yuehong Li
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Limeng Chen; Phone Number: 0086-15801391704; Email: chenlimeng@pumch.cn
  • Beijing, China
    • Recruiting
    • Beijing Anzhen Hospital，Capital Medical University
    • Contact: Hong Cheng
  • Beijing, China
    • Recruiting
    • Beijing Tiantan Hospital,Capital Medical University
    • Contact: Yilun Zhou
  • Beijing, China
    • Recruiting
    • Beijing Tongren Hospital
    • Contact: Guojuan Zhang
    • Contact: Jianbo Zhou
  • Changsha, China
    • Recruiting
    • Xiangya Hospital Central South University
    • Contact: Hui Xu
  • Chengdu, China
    • Recruiting
    • West China Hospital of Sichuan University
    • Contact: Ping Fu
  • Chengdu, China
    • Recruiting
    • Sichuan Provincial People's Hospital
    • Contact: Yurong Zou
  • Haikou, China
    • Recruiting
    • The Second Affiliated Hospital of Hainan Medical University
    • Contact: Bing Li
    • Contact: maoxiong Fu
  • Jinan, China
    • Recruiting
    • Qilu Hospital of Shandong University
    • Contact: Zhao Hu
  • Jinan, China
    • Recruiting
    • The First Affiliated Hospital of Shandong First Medical University
    • Contact: Wenbin Li
  • Ningbo, China
    • Recruiting
    • Ningbo No.2 Hospital
    • Contact: Qun Luo
  • Shanghai, China
    • Recruiting
    • Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
    • Contact: Xiaonong Chen
  • Shanghai, China
    • Recruiting
    • Shanghai Fengxian District Central Hospital
    • Contact: Xuemei Yu
  • Shanghai, China
    • Recruiting
    • Shanghai Minhang District Central Hospital
    • Contact: Jialin Yang
  • Shenyang, China
    • Recruiting
    • The First Affiliated Hospital of China Medical University
    • Contact: Li Yao
  • Shenyang, China
    • Recruiting
    • Sheng Jing Hospital of China Medical University
    • Contact: Hua Zhou
  • Shenzhen, China
    • Recruiting
    • The Seventh Affiliated Hospital，Sun Yat-sen University
    • Contact: Zhihua Zheng
  • Taiyuan, China
    • Recruiting
    • Second Hospital of Shanxi Medical University
    • Contact: Lihua Wang
  • Wuhan, China
    • Recruiting
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
    • Contact: Chun Zhang
  • Xi'an, China
    • Recruiting
    • The First Affiliated Hospital of Xi'an Jiaotong University
    • Contact: Aiping Yin
  • Anhui
    • Hefei, Anhui, China
      • Recruiting
      • The Second Hospital of Anhui Medical University
      • Contact: Deguang Wang
  • Fujian
    • Fuzhou, Fujian, China
      • Recruiting
      • The 900 Hospital of the Joint Service Support Force of the People's Liberation Army of China
      • Contact: Yongze Zhuang
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
      • Contact: Qiongqiong Yang
    • Guangzhou, Guangdong, China
      • Recruiting
      • The First Affiliated Hospital，Sun Yat sen University
      • Contact: Wei Chen
  • Guangxi
    • Nanning, Guangxi, China
      • Recruiting
      • The First Affiliated Hospital of Guangxi Medical University
      • Contact: Zhenhua Yang
  • Guizhou
    • Guiyang, Guizhou, China
      • Recruiting
      • Guizhou Provincial People's Hospital
      • Contact: Yan Zha
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Recruiting
      • Harbin Medical University Affiliated Fourth Hospital
      • Contact: Zhifeng Cheng
  • Henan
    • Luoyang, Henan, China
      • Recruiting
      • Luoyang Third People's Hospital
      • Contact: Junhang Tian
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Renmin Hospital of Wuhan University
      • Contact: Huiming Wang
      • Contact: Chongyuan Wen
    • Wuhan, Hubei, China
      • Recruiting
      • The Third Hospital of Wuhan
      • Contact: Xiangqun Liu
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • The Third Xiangya Hospital of Central South University
      • Contact: Zhaohui Mo
  • Jilin
    • Chang chun, Jilin, China
      • Recruiting
      • The Second Norman Bethune Hospital of Jilin University
      • Contact: Ping Luo
  • Ningxia
    • Yinchuan, Ningxia, China
      • Recruiting
      • The First People's Hospital of Yinchuan
      • Contact: Peng Zhang
  • Qinghai
    • Xining, Qinghai, China
      • Recruiting
      • Qinghai University Affiliated Hospital
      • Contact: Feng Mei
  • Shanxi
    • Xi'an, Shanxi, China
      • Recruiting
      • Xi'an Daxing Hospital
      • Contact: Ying Xing
  • Sichuan
    • Chengdu, Sichuan, China
      • Recruiting
      • ChengDu Second People's Hospital
      • Contact: Haoming Tian
    • Suining, Sichuan, China
      • Recruiting
      • Suining Central Hospital
      • Contact: Yan Wu
    • Zigong, Sichuan, China
      • Recruiting
      • Zigong Fourth People's Hospital
      • Contact: Chunying Deng
  • Xinjiang
    • Ürümqi, Xinjiang, China
      • Recruiting
      • The First Affiliated Hospital of Xinjiang Medical University
      • Contact: Jing Li
  • Zhejiang
    • Taizhou, Zhejiang, China
      • Recruiting
      • Taizhou Municipal hospital
      • Contact: Fei He

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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. ① Acute renal insufficiency② acute nephritic syndrome, polycystic kidney, kidney stone, nephrotic syndrome; ③there is evidence that proteinuria originates from primary and secondary renal diseases other than hypertensive renal damage; ④ 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SPH3127-1; 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	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; Drug: 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
Experimental: SPH3127-2; 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	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; Drug: 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
Experimental: SPH3127-3; 4 tablet of SPH3127 (50 mg) ，1 capsule of valsartan matching placebo, orally, once daily for 12 consecutive weeks	Drug: SPH3127+valsartan matching placebo; 4 tablet of SPH3127 (50 mg) ， 1 capsule of valsartan matching placebo, orally, once daily for 12 consecutive weeks
Experimental: SPH3127-4; 4 tablets of SPH3127 (50mg)matching placebo， 1 capsule of valsartan , orally, once daily for 12 consecutive weeks	Drug: SPH3127 matching placebo+valsartan; 4 tablets of SPH3127 (50mg)matching placebo， 1 capsule of valsartan, orally, once daily for 12 consecutive weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Shanghai Pharmaceuticals Holding Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2023
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: October 20, 2022
• First Submitted That Met QC Criteria: October 24, 2022
• First Posted (Actual): October 25, 2022

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Diabetic Nephropathies; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan
• Other Study ID Numbers: SPH3127-202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No