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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Diabetic Kidney Disease

Intervention / Treatment
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* Drug: SPH3127+SPH3127matching placebo+valsartan matching placebo
* Drug: SPH3127+SPH3127matching placebo+valsartan matching placebo
* Drug: SPH3127+valsartan matching placebo
* Drug: SPH3127 matching placebo+valsartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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; During screening period, 120 mmHg ≤ sitting SBP ≤ 160 mmHg and sitting DBP < 110 mmHg; 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; 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; 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: Sitting SBP >140 mmHg and/or sitting DBP >90 mmHg at baseline (W0); Renal artery stenosis ≥ 50% on one or both sides by color renal artery ultrasound; ① Acute renal insufficiency: a change ≥ 30% in eGFR during the screening period; ② acute nephritic syndrome, polycystic kidney, kidney stone (confirmed by B-mode ultrasound), 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. 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; Subjects with fundus lesions in malignant hypertensive, such as retinal hemorrhage and papilledema; Subjects who need to continuously take glucocorticoids, anti-tumor chemical or biological agents, and non-steroidal anti-inflammatory drugs during the study period; 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; Subjects who have abnormal thyroid function tests with clinically significance; Subjects with poor control of diabetes: HbA1c ≥ 9.0% at W0; Subjects who have undergone major surgery within 3 months prior to screening or need to undergo major surgery during the trial; Subjects whose medication adherence in the run-in period is < 80% or > 120%; Subjects with a history of gastrointestinal surgery that may significantly change the absorption, distribution, metabolism and excretion of drugs; 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; Women during pregnancy or lactating; Subjects who need transplantation before randomization and during the trial; Subjects with HIV infection, hepatitis B infection, hepatitis C infection, or other active infections; Subjects who have a history of malignant tumor, and those who are suspected of tumor; Subjects with a past and current history of mental illness; Subjects with a history of drug abuse or alcohol abuse within 2 years prior to screening; Subjects who have participated in clinical trials of other drugs/devices as a subject within 3 months prior to screening; Subjects with other diseases or conditions that the investigator considers not suitable for this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |