Clinical trial NCT05593575: Efficacy and Safety of SPH3127 Tablets on Treating the Diabetic Kidney Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Kidney Disease
Lead sponsor: Shanghai Pharmaceuticals Holding Co., Ltd
Sponsor class: INDUSTRY
First posted: 2022-10-25
Enrollment: 305
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage change from baseline in UACR
timeFrame: at the end of Week 12 of treatment
Secondary outcomes:
measure: Percentage change from baseline in UACR
timeFrame: at the end of Weeks 2, 4 and 8 of treatment
measure: Percentage change from baseline in UPCR
timeFrame: at the end of Weeks 2, 4, 8 and 12 of treatment
measure: The change trend of eGFR
timeFrame: from baseline to the end of Weeks 2, 4, 8 and 12 of treatment
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Fuzhou
country: China
facility: The 900 Hospital of the Joint Service Support Force of the People's Liberation Army of China
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital，Sun Yat sen University
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Harbin
country: China
facility: Harbin Medical University Affiliated Fourth Hospital
state: Heilongjiang
city: Luoyang
country: China
facility: Luoyang Third People's Hospital
state: Henan
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: The Third Hospital of Wuhan
state: Hubei
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Chang chun
country: China
facility: The Second Norman Bethune Hospital of Jilin University
state: Jilin
city: Yinchuan
country: China
facility: The First People's Hospital of Yinchuan
state: Ningxia
city: Xining
country: China
facility: Qinghai University Affiliated Hospital
state: Qinghai
city: Xi'an
country: China
facility: Xi'an Daxing Hospital
state: Shanxi
city: Chengdu
country: China
facility: Chengdu Second People's Hospital
state: Sichuan
city: Suining
country: China
facility: Suining Central Hospital
state: Sichuan
city: Zigong
country: China
facility: Zigong Fourth People's Hospital
state: Sichuan
city: Ürümqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Taizhou
country: China
facility: Taizhou Municipal Hospital
state: Zhejiang
city: Beijing
country: China
facility: Beijing Anzhen Hospital，Capital Medical University
city: Beijing
country: China
facility: Beijing Tiantan Hospital，Capital Medical University
city: Beijing
country: China
facility: Beijing Tongren Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijin
country: China
facility: Beijing Tsinghua Changgeng Hospital
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Chengdu
country: China
facility: Chengdu Seventh People's Hospital
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
city: Foshan
country: China
facility: Shunde Hospital of Southern Medical University
city: Haikou
country: China
facility: The Second Affiliated Hospital of Hainan Medical University
city: Huizhou
country: China
facility: Huizhou First Hospital
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
city: Jinan
country: China
facility: The First Affiliated Hospital of Shandong First Medical University
city: Ningbo
country: China
facility: Ningbo No.2 Hospital
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University，Qingpu Branch
city: Shanghai
country: China
facility: Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine
city: Shanghai
country: China
facility: Shanghai Fengxian District Central Hospital
city: Shanghai
country: China
facility: Shanghai Minhang District Central Hospital
city: Shenyang
country: China
facility: Sheng Jing Hospital of China Medical University
city: Shenyang
country: China
facility: The First Affiliated Hospital of China Medical University
city: Shenzhen
country: China
facility: The Seventh Affiliated Hospital，Sun Yat-sen University
city: Taiyuan
country: China
facility: Second Hospital of Shanxi Medical University
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
Study officials:
References: