Efficacy, Safety and Tolerability of Balcinrenone/Dapagliflozin Compared to Dapagliflozin in Adults With Chronic Kidney Disease (MIRO-CKD)

A Phase IIb, Multicenter, Randomised, Double-Blind, Dose-finding Study to Evaluate the Efficacy, Safety and Tolerability of Balcinrenone in Combination With Dapagliflozin Compared With Dapagliflozin in Patients With Chronic Kidney Disease and Albuminuria

The purpose of the study is to evaluate the efficacy, safety and tolerability of balcinrenone/dapagliflozin compared with dapagliflozin alone on patients with chronic kidney disease (CKD) and albuminuria. This study will evaluate the effect of the balcinrenone/dapagliflozin on urinary albumin-to-creatinine ratio (UACR), compared with dapagliflozin in patients with CKD. This is a dose-finding study aiming to identify an optimal dose of balcinrenone/dapagliflozin for a future Phase III study in patients with CKD.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: Balcinrenone/dapagliflozin 15 mg/10 mg and matching placebo for dapagliflozin 10 mg; Drug: Balcinrenone/dapagliflozin 40 mg/10 mg and matching placebo for dapagliflozin 10 mg; Drug: Dapagliflozin 10 mg and matching placebo for balcinrenone/dapa gliflozin

Detailed Description

This is a Phase IIb, multicentre, randomised, double-blind, dose-finding, parallel group, double-dummy study aiming to determine the effect on albuminuria, as well as safety and tolerability, of balcinrenone/dapagliflozin compared with dapagliflozin, when given once daily on top of other Standard of Care (SoC) to patients with CKD and albuminuria.

Study population will include participants with CKD (eGFR ≥ 25 to < 60 mL/min/1.73 m2) and UACR > 100 mg/g to ≤ 5000 mg/g. Participants with or without a diagnosis of T2DM and with or without an SGLT2 inhibitor treatment at screening are eligible for the study.

The study will be conducted at approximately 110 sites in approximately 16 countries globally.

At least 300 participants will be randomised in order to have 300 evaluable participants.

Participants will be randomised to one of 3 treatment arms in a 1:1:1 ratio:

• Balcinrenone/dapagliflozin 15 mg/10 mg
• Balcinrenone/dapagliflozin 40 mg/10 mg
• Dapagliflozin 10 mg

For each participant, the total duration of participation will be approximately 23 weeks: an up to 3-week screening period followed by a 12-week treatment period, and an 8-week follow-up period after end of investigational medicinal product (IMP) treatment.

• Study Type: Interventional
• Enrollment (Actual): 324
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, 4021
    • Research Site
  • St. Pölten, Austria, 3100
    • Research Site
  • Vienna, Austria, A-1090
    • Research Site
  • Wels, Austria, 4600
    • Research Site
  • Wien, Austria, 1130
    • Research Site
  • Wien, Austria, 1030
    • Research Site
  • Wien, Austria, 1190
    • Research Site
• Brazil
  • Porto Alegre, Brazil, 90020-090
    • Research Site
  • Sao Paulo, Brazil, 05403-9000
    • Research Site
  • Sao Paulo, Brazil, 01228-000
    • Research Site
  • São Paulo, Brazil, 04012-909
    • Research Site
  • São Paulo, Brazil, 04038-031
    • Research Site
• Bulgaria
  • Burgas, Bulgaria, 8018
    • Research Site
  • Dobrich, Bulgaria, 9300
    • Research Site
  • Pleven, Bulgaria, 5800
    • Research Site
  • Plovdiv, Bulgaria, 4000
    • Research Site
  • Sofia, Bulgaria, 1680
    • Research Site
• Canada
  • Quebec, Canada, G1R 2J6
    • Research Site
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Research Site
    • Waterloo, Ontario, Canada, N2T 0C1
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Research Site
• China
  • Changchun, China, 130021
    • Research Site
  • Changzhou, China, 213004
    • Research Site
  • Shanghai, China, 200032
    • Research Site
  • Shanghai, China, 200050
    • Research Site
  • Tianjin, China, 300050
    • Research Site
• Italy
  • Bari, Italy, 70124
    • Research Site
  • Bologna, Italy, 40138
    • Research Site
  • Genoa, Italy, 16132
    • Research Site
  • Novara, Italy, 28100
    • Research Site
  • Pavia, Italy, 27100
    • Research Site
• Japan
  • Ageo, Japan, 362-8588
    • Research Site
  • Fujisawa-shi, Japan, 251-0041
    • Research Site
  • Fukuoka-shi, Japan, 810-8563
    • Research Site
  • Koga-shi, Japan, 306-0232
    • Research Site
  • Koshigaya-shi, Japan, 343-8577
    • Research Site
  • Kumamoto-shi, Japan, 860-0008
    • Research Site
  • Nagasaki-shi, Japan, 852-8034
    • Research Site
  • Nagoya, Japan, 451-8511
    • Research Site
  • Okinawa-shi, Japan, 904-2143
    • Research Site
  • Takamatsu-shi, Japan, 760-0076
    • Research Site
  • Zentsuji-shi, Japan, 765-8507
    • Research Site
• Malaysia
  • Ipoh, Malaysia, 30990
    • Research Site
  • Johor Bahru, Malaysia, 80100
    • Research Site
  • Kajang, Malaysia, 43000
    • Research Site
  • Kota Bharu, Malaysia, 15586
    • Research Site
  • Kuala Terengganu, Malaysia, 20400
    • Research Site
• Poland
  • Białystok, Poland, 15-481
    • Research Site
  • Grodzisk Mazowiecki, Poland, 05-825
    • Research Site
  • Leżajsk, Poland, 37-300
    • Research Site
  • Szczecin, Poland, 70-111
    • Research Site
  • Warszawa, Poland, 02-798
    • Research Site
  • Żywiec, Poland, 34-300
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Research Site
  • Barcelona, Spain, 08036
    • Research Site
  • Córdoba, Spain, 14004
    • Research Site
  • Palma de Mallorca, Spain, 07010
    • Research Site
  • Valencia, Spain, 46026
    • Research Site
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Research Site
  • New Taipei City, Taiwan, 220
    • Research Site
  • Taichung, Taiwan, 40201
    • Research Site
  • Tainan, Taiwan, 710
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
  • Taipei, Taiwan, 11490
    • Research Site
  • Taipei City, Taiwan, 110
    • Research Site
  • Taipei City, Taiwan, 11217
    • Research Site
• Turkey
  • Ankara, Turkey, 06340
    • Research Site
  • Gaziantep, Turkey, 27310
    • Research Site
  • Kahramanmaras, Turkey, 46100
    • Research Site
  • Kayseri, Turkey, 38039
    • Research Site
  • Kocaeli, Turkey, 41380
    • Research Site
• United Kingdom
  • Dundee, United Kingdom, DDS 1SY
    • Research Site
  • London, United Kingdom, N18 1QX
    • Research Site
  • Newquay, United Kingdom, TR7 1RU
    • Research Site
  • Nottingham, United Kingdom, NG9 6DX
    • Research Site
• United States
  • Alabama
    • Sheffield, Alabama, United States, 35660
      • Research Site
  • California
    • Glendale, California, United States, 91206
      • Research Site
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Research Site
  • Florida
    • Hialeah, Florida, United States, 33012
      • Research Site
    • Miami Lakes, Florida, United States, 33014
      • Research Site
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Research Site
  • North Carolina
    • New Bern, North Carolina, United States, 28562
      • Research Site
  • Texas
    • El Paso, Texas, United States, 79935
      • Research Site
    • Houston, Texas, United States, 77099
      • Research Site
    • Houston, Texas, United States, 77079
      • Research Site
    • San Antonio, Texas, United States, 78212
      • Research Site
  • Utah
    • Ogden, Utah, United States, 84405
      • Research Site
    • Salt Lake City, Utah, United States, 84124
      • Research Site
    • Salt Lake City, Utah, United States, 84115
      • Research Site
  • Virginia
    • Norfolk, Virginia, United States, 23504
      • Research Site
• Vietnam
  • Hai Phong, Vietnam, 180000
    • Research Site
  • Ho Chi Minh, Vietnam, 700000
    • Research Site
  • Hochiminh city, Vietnam, 700000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: - Age ≥ 18 years old - Diagnosis of CKD and eGFR ≥ 25 to < 60 mL/min/1.73 m2. - UACR > 100 mg/g (10 mg/mmol) to ≤ 5000 mg/g (500 mg/mmol). - Serum potassium ≥ 3.5 mmol/L to ≤ 5.0 mmol/L. - Stable RAAS inhibitors treatment for 4 weeks before screening. Participants who cannot tolerate or are not treated with RAAS inhibitors can also participate in the study. Exclusion criteria: - Uncontrolled arterial hypertension (SBP > 160 mmHg or DBP > 100 mmHg). - Hypotension defined as SBP < 100 mmHg. - Autosomal dominant polycystic kidney disease, lupus nephritis or ANCA-associated vasculitis or other nephropathies that are unstable or progress rapidly. - Cytotoxic or immunomodulatory therapy within 6 months prior to screening, or current, or planned within 6 months following randomization. - History of solid organ or bone marrow transplantation - Recent (90 d prior to screening) or ongoing dialysis, or likely need for dialysis within 3 months following randomization. - Myocardial infarction, acute coronary syndrome, stroke or transient ischaemic attack within the previous 12 weeks. - Type 1 diabetes mellitus (DM) or uncontrolled type 2 DM. - Hepatic disease, including active hepatitis, and/or hepatic impairment (Child-Pugh class B-C; or any of AST or ALT > 3 × ULN; or TBL > 2 × ULN. - Serum HCO3 < 18 mmol/L at screening. - Adrenal insufficiency (eg, Addison's disease, prolonged use of glucocorticoids). - Any use of the following within 4 weeks prior to screening: - MRA (or planned initiation of MRA treatment), potassium sparing diuretic, potassium binders, fludrocortisone. - Strong or moderate CYP3A4 inducers or inhibitors prohibited at least 1 week prior to randomisation and during treatment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Balcinrenone/dapagliflozin 15 mg/10 mg; Patients will be randomized 1:1:1 to either balcinrenone/dapagliflozin and matching placebo for dapagliflozin or dapagliflozin and matching placebo for balcinrenone/dapagliflozin	Drug: Balcinrenone/dapagliflozin 15 mg/10 mg and matching placebo for dapagliflozin 10 mg; 1 capsule of balcinrenone/dapagliflozin 15 mg/10 mg and 1 tablet of matching placebo for dapagliflozin 10 mg once daily, oral use
Experimental: Balcinrenone/dapagliflozin 40 mg/10 mg; Patients will be randomized 1:1:1 to either balcinrenone/dapagliflozin and matching placebo for dapagliflozin or dapagliflozin and matching placebo for balcinrenone/dapagliflozin	Drug: Balcinrenone/dapagliflozin 40 mg/10 mg and matching placebo for dapagliflozin 10 mg; 1 capsule of balcinrenone/dapagliflozin 40 mg/10 mg and 1 tablet of matching placebo for dapagliflozin 10 mg once daily, oral use
Active Comparator: Dapagliflozin 10 mg; Patients will be randomized 1:1:1 to either balcinrenone/dapagliflozin and matching placebo for dapagliflozin or dapagliflozin and matching placebo for balcinrenone/dapagliflozin	Drug: Dapagliflozin 10 mg and matching placebo for balcinrenone/dapa gliflozin; 1 tablet of dapagliflozin 10 mg and 1 capsule of matching placebo for balcinrenone/dapagliflozin once daily, oral use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change in UACR from baseline to Week 12	Evaluating the effect of balcinrenone/dapagliflozin compared with dapagliflozin alone on UACR.	Baseline (Day 1) until Week 12 (Day 85)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Actual): May 9, 2025
• Study Completion (Actual): May 9, 2025

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 5, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2025
• Last Update Submitted That Met QC Criteria: May 15, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: D6405C00002; 2023-509709-63-00 (Registry Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No