SER150 vs Placebo in Diabetic Kidney Disease

Randomized, Double-blind, Placebo-controlled, Parallel Groups, Multicenter Pivotal Study Assessing the Efficacy and Safety of 15 mg Twice a Day (BID) of SER150 in Well-controlled Type 2 Diabetic Patients With Diabetic Kidney Disease and Macroalbuminuria in Treatment With an Angiotensin Converting Enzyme Inhibitor or an Angiotensin Receptor Antagonist

This study is to assess the efficacy, safety and pharmacokinetic (PK) of SER150 administered for 24 weeks as a 15 mg twice a day (BID) dose in participants with type 2 diabetes (T2D) and macroalbuminuria in treatment with either an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin receptor antagonist (ARB).

This is a randomized, double-blind, placebo-controlled, parallel groups, multicenter pivotal study assessing the efficacy and safety of 15 mg BID of SER150 in well-controlled adult T2D participants with stable concomitant medications, diabetic kidney disease (DKD) and macroalbuminuria in treatment with an ACEI or an ARB. The randomized treatment period will be 24 weeks followed by a 4-weeks follow-up.

The efficacy of 15 mg BID of SER150 with placebo will be compared in well controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB.

Efficacy of 15 mg BID of SER150 will be determined in well-controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB.

Efficacy of 15 mg BID of SER150 will be determined in well-controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB. eGFRcrea is defined as estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation and eGFRcys is defined as estimated glomerular filtration rate using the CKD-EPI cystatin C equation.

At Screening (up to 21 days before Day 1). Days 1, 2 (at discretion of PI), 28, 56, 84, 112, 140, 168 and Day 196 (follow up)

Efficacy of 15 mg BID of SER150 will be determined in well-controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB.

Efficacy of 15 mg BID of SER150 will be determined in well-controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB. eGFRcr-cys is defined as estimated glomerular filtration rate using CKD-EPI creatinine-cystatin C equation.

Number of participants with end stage renal disease, any serious cardiovascular events (stroke-acute myocardial infarction-cardiovascular death) and all-cause mortality

Efficacy of 15 mg BID of SER150 will be determined in well-controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB.

Safety/tolerability of 15 mg BID of SER150 will be determined in well-controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB.

Pharmacokinetics of 15 mg BID of SER150 will be determined in well-controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB.

Day 1 at 0 minutes (pre-dose), at 30 minutes post-dose, and at 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose, Day 2 at 24 hours post-dose and on Day 7, Day 28, Day 56, Day 84, Day 112, Day 140 and Day 168 pre-dose

Pharmacokinetics of 15 mg BID of SER150 will be determined in well-controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB.

Day 1 at 0 minutes (pre-dose), at 30 minutes post-dose, and at 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose, Day 2 at 24 hours post-dose and on Day 7, Day 28, Day 56, Day 84, Day 112, Day 140 and Day 168 pre-dose

Single-dose parameter: area under the concentration-time curve from time 0 to 6 hours after first dose (AUC0-6) for SER150

Pharmacokinetics of 15 mg BID of SER150 will be determined in well-controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB.

Day 1 at 0 minutes (pre-dose), at 30 minutes post-dose, and at 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose, Day 2 at 24 hours post-dose and on Day 7, Day 28, Day 56, Day 84, Day 112, Day 140 and Day 168 pre-dose

Single-dose parameter: area under the concentration-time curve from time zero to last quantifiable concentration after first dose (AUClast) for SER150

Pharmacokinetics of 15 mg BID of SER150 will be determined in well-controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB.

Day 1 at 0 minutes (pre-dose), at 30 minutes post-dose, and at 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose, Day 2 at 24 hours post-dose and on Day 7, Day 28, Day 56, Day 84, Day 112, Day 140 and Day 168 pre-dose

Pharmacokinetics of 15 mg BID of SER150 will be determined in well-controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB.

Day 1 at 0 minutes (pre-dose), at 30 minutes post-dose, and at 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose, Day 2 at 24 hours post-dose and on Day 7, Day 28, Day 56, Day 84, Day 112, Day 140 and Day 168 pre-dose

Pharmacokinetics of 15 mg BID of SER150 will be determined in well-controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB.

Day 1 at 0 minutes (pre-dose), at 30 minutes post-dose, and at 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose, Day 2 at 24 hours post-dose and on Day 7, Day 28, Day 56, Day 84, Day 112, Day 140 and Day 168 pre-dose

Repeat-dose parameter: area under the concentration-time curve from time 0 to 6 hours after last dose (AUC0-6_ss) for SER150

Pharmacokinetics of 15 mg BID of SER150 will be determined in well-controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB.

Day 1 at 0 minutes (pre-dose), at 30 minutes post-dose, and at 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose, Day 2 at 24 hours post-dose and on Day 7, Day 28, Day 56, Day 84, Day 112, Day 140 and Day 168 pre-dose

Repeat-dose parameter: area under the concentration-time curve from time zero to last quantifiable concentration after last dose (AUClast_ss) for SER150

Pharmacokinetics of 15 mg BID of SER150 will be determined in well-controlled type 2 diabetic participants with DKD, and macroalbuminuria in treatment with an ACEI or an ARB.

Day 1 at 0 minutes (pre-dose), at 30 minutes post-dose, and at 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose, Day 2 at 24 hours post-dose and on Day 7, Day 28, Day 56, Day 84, Day 112, Day 140 and Day 168 pre-dose

Inclusion Criteria: Participant has had stable T2D for 3 months prior to screening Participant has albuminuria defined by urine UACR ≥ 300 mg/g creatinine(macroalbuminuria) as a mean of three independent samples of first urine void of the day Participant is receiving stable antidiabetic treatment. Antidiabetic treatment includes all drugs given for the treatment of T2D Participant is in treatment with ACEI or ARB, with eGFRcrea lower than 75 mL/minute /1.73 m^2 and above 15 mL/minute/1.73 m^2 (CKD-EPI formula) and will not, in the opinion of the investigator, become a candidate for renal dialysis whilst on the study Participant is determined to be overtly healthy as determined by Investigator review of their medical history, physical examination, laboratory tests, and cardiac monitoring. It is anticipated that, whilst some of the participant's results may be different to that of a completely healthy individual, the Investigator will review the participant's individual results to ensure they are as healthy as can be expected give the participant's current health status Participant has ASA physical status, health class 2, 3 or 4 Participant has blood pressure ≤ 160 mmHg systolic, and ≤ 100 mmHg diastolic Participant has normal electrocardiogram Participant has glycosylated hemoglobin (HbA1c) ≤ 10% Participant has prothrombin within normal values Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies Exclusion Criteria: Acute myocardial infarction within the last 3 months Stroke within the last 3 months Any surgery within the last 3 months ACR ≤ 300 mg/g creatinine Urinary bladder infections within the last 3 months (all other urinary tract infections and vulvovaginitis are excluded) Recent history (within the last 6 months) or ongoing liver disease, including viral infections Participants with HIV Participants with known specific renal diseases different from DKD Any bleeding disorder or acute blood coagulation defect A history of gastric ulcers or any other organic lesion susceptible to bleeding Participant has had a confirmed COVID-19 infection by appropriate laboratory test (PCR or Rapid Antigen Test) within the last 4 weeks prior to screening or on admission Participant who had severe course of COVID-19 Any other condition or clinically relevant abnormal findings in physical examination, laboratory results or ECG during screening period that, in the opinion of the Investigator, may compromise the safety of the participant in the study, reduce the participant's ability to participate in the study, or interfere with evaluation of the study drug Change in antidiabetic treatment during last 3 months Chronic treatment with nonsteroidal anti-inflammatory drugs or other anti-inflammatory compounds during the last month Treatment with anticoagulant drugs Present participation in another clinical study or having participated in a clinical study 6 months prior to enrollment Alanine aminotransferase or aspartate aminotransferase values exceeding 2.5x upper limit of normal (ULN) Alkaline phosphatase and/or total bilirubin values exceeding 1.5 x ULN HbA1c > 10% eGFRcrea ≥75 mL/minute/1.73 m^2 and ≤ 15 mL/minute/1.73 m^2 Allergy to the active substance or any of the excipients of the drug product Pregnant or lactating women