Clinical trial NCT06350123: Efficacy, Safety and Tolerability of Balcinrenone/Dapagliflozin Compared to Dapagliflozin in Adults With Chronic Kidney Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Kidney Disease
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-04-05
Enrollment: 324
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre, randomised, double-blind, dose-finding, parallel group, double-dummy
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Relative change in UACR from baseline to Week 12
timeFrame: Baseline (Day 1) until Week 12 (Day 85)
Secondary outcomes:
Other outcomes:
Locations:
city: Sheffield
country: United States
facility: Research Site
state: Alabama
city: Glendale
country: United States
facility: Research Site
state: California
city: Waterbury
country: United States
facility: Research Site
state: Connecticut
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Miami Lakes
country: United States
facility: Research Site
state: Florida
city: Annapolis
country: United States
facility: Research Site
state: Maryland
city: New Bern
country: United States
facility: Research Site
state: North Carolina
city: El Paso
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Ogden
country: United States
facility: Research Site
state: Utah
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Norfolk
country: United States
facility: Research Site
state: Virginia
city: Linz
country: Austria
facility: Research Site
city: St. Pölten
country: Austria
facility: Research Site
city: Vienna
country: Austria
facility: Research Site
city: Wels
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Burgas
country: Bulgaria
facility: Research Site
city: Dobrich
country: Bulgaria
facility: Research Site
city: Pleven
country: Bulgaria
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: London
country: Canada
facility: Research Site
state: Ontario
city: Waterloo
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changzhou
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Genoa
country: Italy
facility: Research Site
city: Novara
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Ageo
country: Japan
facility: Research Site
city: Fujisawa-shi
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Koga-shi
country: Japan
facility: Research Site
city: Koshigaya-shi
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
facility: Research Site
city: Nagasaki-shi
country: Japan
facility: Research Site
city: Nagoya
country: Japan
facility: Research Site
city: Okinawa-shi
country: Japan
facility: Research Site
city: Takamatsu-shi
country: Japan
facility: Research Site
city: Zentsuji-shi
country: Japan
facility: Research Site
city: Ipoh
country: Malaysia
facility: Research Site
city: Johor Bahru
country: Malaysia
facility: Research Site
city: Kajang
country: Malaysia
facility: Research Site
city: Kota Bharu
country: Malaysia
facility: Research Site
city: Kuala Terengganu
country: Malaysia
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Grodzisk Mazowiecki
country: Poland
facility: Research Site
city: Leżajsk
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Żywiec
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Córdoba
country: Spain
facility: Research Site
city: Palma de Mallorca
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: New Taipei City
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Gaziantep
country: Turkey
facility: Research Site
city: Kahramanmaras
country: Turkey
facility: Research Site
city: Kayseri
country: Turkey
facility: Research Site
city: Kocaeli
country: Turkey
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Newquay
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Hai Phong
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Hochiminh city
country: Vietnam
facility: Research Site
Study officials:
References: