A Study to Evaluate the Efficacy and Safety of SC0062 in the Treatment of Chronic Kidney Disease

Study Overview
=================
Brief Summary
-----------------
This is a phase II study to investigate the safety, preliminary efficacy and pharmacokinetics of SC0062 capsule in patients with chronic kidney disease (diabetic kidney disease and IgA nephropathy)with albuminuria compared to matching placebo.

Detailed Description
-----------------
This multicenter, randomized, double blind, placebo parallel controlled, 2 cohorts phase II study will contain 2 cohorts: Cohort 1: diabetic kidney disease Cohort 2: biopsy-proven IgAN In each cohort, approximately 120 patients will be randomized to receive SC0062 or placebo daily for 24 weeks. The objective of this study is to evaluate the preliminary efficacy and safety of SC0062 capsules compared to placebo in patients with chronic kidney disease (diabetic kidney disease and IgA nephropathy) with albuminuria who are treated with the maximum tolerated labeled dose renin-angiotensin system inhibitor (RASi).

Official Title
-----------------
A Randomized, Double Blind, Placebo Parallel Controlled, 2 Cohorts, Multicenter Phase II Study to Investigate the Safety and Efficacy of SC0062 Capsule in Patients With Chronic Kidney Disease With Albuminuria

Conditions
-----------------
Diabetic Kidney Disease, IgA Nephropathy

Intervention / Treatment
-----------------
* Drug: Placebo of SC0062
* Drug: SC0062 low dose
* Drug: SC0062 medium dose
* Drug: SC0062 high dose


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Sign the informed consent voluntarily, and fully understand and comply with the relevant procedures of the test; 2. Age range from 18 to 70 years old (including the critical value), gender is not limited; 3. Patients with chronic kidney disease (CKD) stage G2 G3a with albuminuria, requirements: eGFR ≥ 45 mL/min/1.73m^2 and < 90mL/min/1.73m^2 at Screening based on the CKD-EPI equation.. Receiving a maximally tolerated dose of RAS inhibitor therapy (ACEi or ARB) that has been stable for at least 12 weeks; If an SGLT2i is prescribed, the dose must be stable or only slight changes from 4 weeks prior before randomization to the end of treatment (per Investigator judgement) . Cohort 1: Diagnosed with type 2 diabetes mellitus and receiving at least one hypoglycemic agent in the 12 months prior to randomization; In accordance with the diagnostic criteria of DKD, urine albumin to creatinine ratio (UACR) ≥300 mg/g and < 1500 mg/g during at screening. Cohort 2: Biopsy-proven IgA nephropathy; Urine protein-creatinine ratio (UPCR) ≥0.5g/g and < 2.5 g/g at screening. 4. Laboratory parameters meet the following criteria: Serum albumin ≥30 g/L; Hemoglobin value ≥90 g/L; Platelet ≥80×10^9/L; Brain natriuretic peptide (BNP) ≤ 200 pg/mL; Blood potassium ≤ 5.5 mmol/L; Systolic blood pressure (SBP) ≤140 mmHg; Diastolic blood pressure (DBP) ≤90 mmHg; Hemoglobin A1c (HbA1c) ≤ 10% (cohort 1)/Hemoglobin A1c (HbA1c) < 6.5% (cohort 2); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2×ULN; Total bilirubin ≤1.5ULN; 5. All participants should follow protocol defined contraceptives procedures. Exclusion Criteria: Women who were pregnant or breastfeeding; A WOCBP who has a positive blood pregnancy test (within 72 hours) prior to randomization; Patients who are allergic to or are allergic to any component of the study drug (SC0062 capsules); Systemic use of corticosteroids or immunosuppressants within 3 months prior to randomization; Other causes of chronic kidney disease are also diagnosed; 5.1 Type diabetes or other specific types of diabetes; 6. Secondary IgA nephropathy; 7. Clinical suspicion of rapidly progressive glomerulonephritis (RPGN); 8. Diagnosed with nephrotic syndrome; 9. Have a history of pulmonary hypertension, pulmonary fibrosis or any lung disease requiring oxygen therapy (e.g., chronic obstructive pulmonary disease, emphysema, pulmonary edema, etc.); 10. Subjects who had received endothelin receptor antagonist in the past; 11. History of moderate or severe edema, non-traumatic facial edema, or myxoid edema within the 6 months prior to randomization; 12. History of orthostatic hypotension within 6 months prior to randomization; 13. History of clinically significant cirrhosis; 14. History of heart failure or previous hospital admissions due to fluid overload; 15. History of renal transplantation or other organ transplantation; 16. Hypothyroidism (except subclinical hypothyroidism or stable hypothyroidism after hormone replacement therapy); 17. Patients who have the potential to interfere with oral drug absorption, such as subtotal gastrectomy, clinically severe gastrointestinal disease, or certain types of bariatric surgery, such as gastric bypass surgery, that do not involve simply separating the stomach into a separate chamber, such as gastric banding surgery; 18. Use of potent CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin, phenobarbital, St. John's Burt) and potent CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, voriconazole, clarithromycin, telomycin, nefazodone, ritonavir, saquinavir) within 1 month before randomization; 19. Active hepatitis B; active hepatitis C; active syphilis; positive HIV serum reaction. 20. Malignancy within the past 5 years.; 21.Alcohol or drug abuse or dependence, or a history of psychological disorder; 22. Participants participated in clinical trials of other investigational drugs or medical devices within 3 months prior to randomization; 23. Any other clinically significant clinical condition, or medical history may interfere with the subject's safety, study evaluation, and/or study procedures per the judgment by the investigator; 24. The investigator believes that the subject has any other reasons for not being eligible to participate in this clinical study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SC0062 low dose group<br>Subjects will take two capsules daily for 24 weeks during the treatment period | Drug: SC0062 low dose<br>* Subjects will take two capsules daily of one of those which are SC0062 low dose, SC0062 medium dose, SC0062 high dose or placebo for 24 weeks during the treatment period<br>|
| Experimental: SC0062 medium dose group<br>Subjects will take two capsules daily for 24 weeks during the treatment period | Drug: Placebo of SC0062<br>* Subjects will take two capsules daily of one of those which are SC0062 low dose, SC0062 medium dose, SC0062 high dose or placebo for 24 weeks during the treatment period<br>Drug: SC0062 medium dose<br>* Subjects will take two capsules daily of one of those which are SC0062 low dose, SC0062 medium dose, SC0062 high dose or placebo for 24 weeks during the treatment period<br>|
| Experimental: SC0062 high dose group<br>Subjects will take two capsules daily for 24 weeks during the treatment period | Drug: SC0062 high dose<br>* Subjects will take two capsules daily of one of those which are SC0062 low dose, SC0062 medium dose, SC0062 high dose or placebo for 24 weeks during the treatment period<br>|
| Placebo Comparator: Placebo of SC0062 group<br>Subjects will take two capsules daily for 24 weeks during the treatment period | Drug: Placebo of SC0062<br>* Subjects will take two capsules daily of one of those which are SC0062 low dose, SC0062 medium dose, SC0062 high dose or placebo for 24 weeks during the treatment period<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urine albumin creatinine ratio (UACR) at Week 12 | Change from baseline to Week12 in urine albumin creatinine ratio (UACR) | Week 12 | 
| Changes in urine protein creatinine ratio (UPCR) at Week 12 | Change from baseline to Week12 in urine protein creatinine ratio (UPCR) | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urine albumin creatinine ratio (UACR) by visit | Change in urine albumin creatinine ratio (UACR) after treatment | Week 2, week 4, week 8, week 12, week 16, week 20, week 24 | 
| Change in urine protein creatinine ratio (UPCR) by visit | Change in urine protein creatinine ratio (UPCR) after treatment | Week 2, week 4, week 8, week 12, week 16, week 20, week 24 | 
| Changes in glomerular filtration rate (eGFR) | Change in glomerular filtration rate (eGFR) from baseline to end of study | Week 2, week 4, week 8, week 12, week 16, week 20, week 24 | 
| Change of 24-hour urine albumin excretion rate (UAER) | Change of 24-hour urine albumin excretion rate (UAER) at Week 12 and Week 24 | Week 12, week 24 | 
| Percentage of subjects achieving UACR ≥30%, ≥40%, and ≥50% reduction from baseline | Percentage of subjects achieving UACR ≥30%, ≥40%, and ≥50% reduction at Week 12 and Week 24 | Week 12, week 24 | 
| Percentage of subjects achieving UPCR ≥30%, ≥40%, and ≥50% reduction from baseline | Percentage of subjects achieving UPCR ≥30%, ≥40%, and ≥50% reduction at Week 12 and Week 24 | Week 12, week 24 |