Clinical trial NCT05687890: A Study to Evaluate the Efficacy and Safety of SC0062 in the Treatment of Chronic Kidney Disease
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Diabetic Kidney Disease
IgA Nephropathy
Lead sponsor: Biocity Biopharmaceutics Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-01-18
Enrollment: 255
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Sign the informed consent voluntarily, and fully understand and comply with the relevant procedures of the test;
2. Age of ≥ 18 years old, gender is not limited;
3. Patients with chronic kidney disease (CKD) stage G1\~G3 with albuminuria, requirements:

   1. eGFR ≥ 30 mL/min/1.73m\^2 at Screening based on the CKD-EPI equation (2009).
   2. RAS inhibitor therapy (ACEi and/or ARB) has been administered for at least 12 weeks and the maximally tolerated dose has been stable for at least 4 weeks prior to randomization; If an SGLT2i is prescribed, the dose must be stable for at least 8 weeks prior to randomization.
   3. 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 before randomization.
   4. Cohort 2: Biopsy-proven IgA nephropathy; Urine protein-creatinine ratio (UPCR) ≥0.75 g/g or urine protein excretion rate ≥ 1.0 g/24h before randomization.
4. Laboratory parameters meet the following criteria:

   1. Serum albumin ≥30 g/L;
   2. Hemoglobin value ≥90 g/L; Platelet ≥80×10\^9/L;
   3. Brain natriuretic peptide (BNP) ≤ 200 pg/mL or N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≤ 600 pg/mL;
   4. Blood potassium ≤ 5.5 mmol/L;
   5. Systolic blood pressure (SBP) ≤140 mmHg; Diastolic blood pressure (DBP) ≤90 mmHg;
   6. Hemoglobin A1c (HbA1c) ≤ 10% (cohort 1)/Hemoglobin A1c (HbA1c) \< 6.5% (cohort 2);
   7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2×ULN; Total bilirubin ≤1.5ULN;
5. All participants should follow protocol defined contraceptives procedures.

Exclusion Criteria:

1. Women who were pregnant or breastfeeding; A WOCBP who has a positive blood pregnancy test prior to randomization;
2. Patients who are allergic to or are allergic to any component of the study drug (SC0062 capsules);
3. Systemic use of corticosteroids or immunosuppressants for more than 2 weeks within 3 months prior to randomization; with exceptions as follows: Topical or intra-articular, intranasal, and inhaled glucocorticoids; on stable doses of hydroxychloroquine for at least 8 weeks.
4. Type 1 diabetes or other specific types of diabetes;
5. Secondary IgA nephropathy;
6. Clinical suspicion of rapidly progressive glomerulonephritis (RPGN);
7. Diagnosed with nephrotic syndrome;
8. Have a history of pulmonary hypertension (WHO Group 1), idiopathic pulmonary fibrosis or any lung disease requiring oxygen therapy (e.g., chronic obstructive pulmonary disease, emphysema, pulmonary edema, etc.);
9. Subjects who had received endothelin receptor antagonist in the past;
10. History of moderate or severe edema, non-traumatic facial edema, or myxoid edema within the 6 months prior to randomization;
11. History of orthostatic hypotension within 6 months prior to randomization;
12. History of clinically significant cirrhosis;
13. History of heart failure NYHA Class III\~IV; exacerbation heart failure or acute coronary syndrome within 6 months prior to randomization;
14. History of renal transplantation or other organ transplantation;
15. Hypothyroidism (except subclinical hypothyroidism or stable hypothyroidism after hormone replacement therapy);
16. 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;
17. 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;
18. Active hepatitis B; active hepatitis C; active syphilis; positive HIV serum reaction.
19. Malignancy within the past 5 years (Except for treated basal cell carcinoma of the skin, effectively resected squamous cell carcinoma of the skin, colon polyps, or cervical cancer in situ that do not require ongoing treatment);
20. Alcohol or drug abuse or dependence, or a history of psychological disorder;
21. Participants participated in clinical trials of other investigational drugs or medical devices within 3 months prior to randomization;
22. 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;
23. The investigator believes that the subject has any other reasons for not being eligible to participate in this clinical study.

Primary outcomes:
measure: Change in urine albumin creatinine ratio (UACR)
timeFrame: Week 12
measure: Changes in urine protein creatinine ratio (UPCR)
timeFrame: Week 12
Secondary outcomes:
measure: Change in urine albumin creatinine ratio (UACR) by visit
timeFrame: Week 2, week 4, week 8, week 12, week 16, week 20, week 24
measure: Change in urine protein creatinine ratio (UPCR) by visit
timeFrame: Week 2, week 4, week 8, week 12, week 16, week 20, week 24
measure: Changes in glomerular filtration rate (eGFR)
timeFrame: Week 2, week 4, week 8, week 12, week 16, week 20, week 24
measure: Change of 24-hour urine albumin excretion rate (UAER)
timeFrame: Week 12, week 24
measure: Change of 24-hour urine protein excretion rate (UPER)
timeFrame: Week 12, week 24
measure: Percentage of subjects achieving UACR ≥30%, ≥40%, and ≥50% reduction from baseline
timeFrame: Week 12, week 24
measure: Percentage of subjects achieving UPCR ≥30%, ≥40%, and ≥50% reduction from baseline
timeFrame: Week 12, week 24
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: 79 Qingchun Rd.,Shangcheng District
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: Jianghua Chen, Prof
role: PRINCIPAL_INVESTIGATOR
References: