A Phase 3 Study of Bardoxolone Methyl in Patients With Diabetic Kidney Disease; AYAME Study

RTA 402 Phase 3 Clinical Trial (A Randomized, Double-blind, Placebo-controlled Clinical Trial in Patients With Diabetic Kidney Disease)

The purpose of this study is to demonstrate the efficacy of multiple oral doses of RTA 402 (5, 10, or 15 mg) administered once daily in patients with diabetic kidney disease (DKD) using the time to onset of a ≥ 30% decrease in estimated glomerular filtration rate calculated from serum creatinine (eGFR) from baseline or end-stage renal disease (ESRD) as an indicator in a randomized, double-blind, placebo-controlled study; the safety of RTA 402 will also be evaluated.

Study Overview

• Status: Terminated
• Conditions: Diabetic Kidney Disease
• Intervention / Treatment: Drug: Bardoxolone methyl; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1323
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Miyagi
    • Sendai, Miyagi, Japan, 981-3281
      • Japan Community Health care Organization Sendai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with DKD
• Mean eGFR ≥ 15 and < 60 mL/min/1.73 m²
• Albumin/creatinine ratio (ACR) ≤ 3500 mg/g Cr
• Treatment with an angiotensin converting enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (ARB) with no change in dosage or medication etc.

Exclusion Criteria:

• Diabetes mellitus that is neither type 1 nor type 2
• Decreased renal function mainly attributed to a non-diabetic cause
• History of renal transplantation or upcoming preemptive renal transplantation
• Confirmed mean systolic blood pressure > 160 mmHg or a confirmed mean diastolic blood pressure > 90 mmHg during the 8-week period before screening
• Hemoglobin A1c level > 10.0% during screening
• Serum albumin level ≤ 3.0 g/dL during screening
• Cardiovascular disease specified in the study protocol
• History of cardiac failure
• BNP level > 200 pg/mL during screening etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RTA 402(Bardoxolone methyl); Patients will receive multiple oral doses of bardoxolone methyl once daily. The starting dose of bardoxolone methyl will be 5 mg. The maximum dose will be 15 mg, and the dose will be increased by 5 mg.	Drug: Bardoxolone methyl; Bardoxolone methyl 5 mg capsules; Other Names: RTA 402
Placebo Comparator: Placebo; Patients randomized to placebo will remain on placebo throughout the study, undergoing sham titration.	Drug: Placebo; Capsules containing an inert placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to onset of a ≥ 30% decrease in eGFR from baseline or ESRD	Through double-blind part completion, approximately 3 to 4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to onset of a ≥ 40% decrease in eGFR from baseline or ESRD	Through double-blind part completion, approximately 3 to 4 years
Time to onset of a ≥ 53% decrease in eGFR from baseline or ESRD	Through double-blind part completion, approximately 3 to 4 years
Time to onset of ESRD	Through double-blind part completion, approximately 3 to 4 years
Change in eGFR from baseline at each evaluation time point	Through double-blind part completion, approximately 3 to 4 years

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2018
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: May 14, 2018
• First Submitted That Met QC Criteria: June 7, 2018
• First Posted (Actual): June 8, 2018

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; Kidney Diseases; Diabetic Kidney Disease; Bardoxolone Methyl
• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: RTA 402-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No