Efficacy, Safety and Tolerability of Balcinrenone/Dapagliflozin Compared to Dapagliflozin in Adults With Chronic Kidney Disease.

Chronic Kidney Disease Clinical Trial

— MIRO-CKD  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06350123
• Other study ID #: D6405C00002
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 6, 2024
• Est. completion date: January 13, 2026

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: January 13, 2026
• Est. primary completion date: January 13, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
Austria	Research Site	Linz
Austria	Research Site	St. Pölten
Austria	Research Site	Vienna
Austria	Research Site	Wels
Austria	Research Site	Wien
Austria	Research Site	Wien
Austria	Research Site	Wien
Bulgaria	Research Site	Burgas
Bulgaria	Research Site	Dobrich
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Waterloo	Ontario
Italy	Research Site	Bari
Italy	Research Site	Bologna
Italy	Research Site	Genoa
Italy	Research Site	Parma
Italy	Research Site	Pavia
Malaysia	Research Site	Ipoh
Malaysia	Research Site	Kota Bahru
Malaysia	Research Site	Kuala Lumpur
Poland	Research Site	Bialystok
Poland	Research Site	Gdansk
Poland	Research Site	Grodzisk Mazowiecki
Poland	Research Site	Lezajsk
Poland	Research Site	Lódz
Poland	Research Site	Ruda Slaska
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Poland	Research Site	Zywiec
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Cordoba
Spain	Research Site	Palma de Mallorca
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	New Taipei City
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taipei City
United States	Research Site	Hialeah	Florida
United States	Research Site	Norfolk	Virginia
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Carlos	California
United States	Research Site	Waterbury	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Austria,  Bulgaria,  Canada,  Italy,  Malaysia,  Poland,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)