SER150 vs Placebo in Diabetic Kidney Disease

Sponsor

Serodus ASA (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04881123

Collaborator

(none)

100

Enrollment

Locations

Arms

21.9

Anticipated Duration (Months)

14.3

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is to assess the efficacy, safety and pharmacokinetic (PK) of SER150 administered for 12 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).

Condition or Disease	Intervention/Treatment	Phase
Diabetic Kidney Disease	Drug: SER150 Drug: Placebo	Phase 2/Phase 3

Detailed Description

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 12 weeks followed by a 4-weeks follow-up.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 18, 2021

Anticipated Primary Completion Date :

Jun 15, 2023

Anticipated Study Completion Date :

Jun 15, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SER150 Randomized participants will receive SER150, 15 mg, orally, BID.	Drug: SER150 Dosage Level(s): 30 mg (1 capsule of 15 mg twice a day - morning and evening)
Placebo Comparator: Placebo Randomized participants will receive matching placebo, orally, BID.	Drug: Placebo Dosage Level(s): Matched placebo (1 capsule twice a day - morning and evening)

Arm

Intervention/Treatment

Experimental: SER150

Randomized participants will receive SER150, 15 mg, orally, BID.

Drug: SER150

Dosage Level(s): 30 mg (1 capsule of 15 mg twice a day - morning and evening)

Placebo Comparator: Placebo

Randomized participants will receive matching placebo, orally, BID.

Drug: Placebo

Dosage Level(s): Matched placebo (1 capsule twice a day - morning and evening)

Outcome Measures

Primary Outcome Measures

A change of urine albumin-to-creatinine ratio (UACR) of > 30% from Baseline to Day 84 [Baseline, Day 84]
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.

Secondary Outcome Measures

Change of UACR from Baseline to Day 84 [Baseline, Day 84]
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.
Time to change of eGFRcrea and eGFRcys ≥ 0.50 mL/min/1.73 m^2 [At Screening (up to 21 days before Day 1), Days 1, 28, 56, 84, and at Follow-up (Day 112)]
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.
Number of participants with a change in eGFRcrea and eGFRcys from Baseline to Day 84 [Baseline, Day 84]
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.
Number of participants with a change in eGFRcr-cys from Baseline to Day 84 [Baseline, Day 84]
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 [From Screening (up to 21 days before Day 1) until the Follow-up (Day 112)]
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.
Number of participants with adverse events (AEs) [From Screening (up to 21 days before Day 1) until the Follow-up (Day 112)]
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.
Single-dose parameter: maximum observed concentration after first dose (Cmax) for SER150 [Day 1 and Day 84: 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 and on Day 7, Day 28, and Day 56 (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.
Single-dose parameter: time corresponding to occurrence of Cmax (tmax) for SER150 [Day 1 and Day 84: 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 and on Day 7, Day 28, and Day 56 (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.
Single-dose parameter: area under the concentration-time curve from time 0 to 6 hours after first dose (AUC0-6) for SER150 [Day 1 and Day 84: 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 and on Day 7, Day 28, and Day 56 (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.
Single-dose parameter: area under the concentration-time curve from time zero to last quantifiable concentration after first dose (AUClast) for SER150 [Day 1 and Day 84: 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 and on Day 7, Day 28, and Day 56 (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.
Repeat-dose parameter: maximum observed concentration after last dose (Cmax_ss) for SER150 [Day 1 and Day 84: 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 and on Day 7, Day 28, and Day 56 (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.
Repeat-dose parameter: time corresponding to occurrence of Cmax_ss (tmax_ss) for SER150 [Day 1 and Day 84: 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 and on Day 7, Day 28, and Day 56 (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.
Repeat-dose parameter: area under the concentration-time curve from time 0 to 6 hours after last dose (AUC0-6_ss) for SER150 [Day 1 and Day 84: 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 and on Day 7, Day 28, and Day 56 (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.
Repeat-dose parameter: area under the concentration-time curve from time zero to last quantifiable concentration after last dose (AUClast_ss) for SER150 [Day 1 and Day 84: 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 and on Day 7, Day 28, and Day 56 (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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 first morning spot urines
Participant is receiving stable antidiabetic treatment (no change over past 3 months). 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 25 mL/minute/1.73 m}2 (CKD-EPI formula)
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
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 clinical signs and symptoms consistent with coronavirus disease 2019 (COVID-19), e.g. fever, dry cough, dyspnea, sore throat, fatigue or confirmed infection by appropriate laboratory 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
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 ≤ 25 mL/minute/1.73 m}2
Pregnant or lactating women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Liverpool Hospital	Liverpool	New South Wales	Australia	2170
2	The AIM Centre (Hunter Diabetes Centre)	Merewether	New South Wales	Australia
3	Royal North Shore Hospital	Saint Leonards	New South Wales	Australia	2065
4	Southern Adelaide Diabetes and Endocrine Services	Adelaide	South Australia	Australia	5046
5	SA Endocrine Research	Keswick	South Australia	Australia	5035
6	St Vincent's Hospital	Fitzroy	Victoria	Australia	3065
7	Sunshine Hospital	Saint Albans	Victoria	Australia	3021