Balcinrenone + Dapagliflozin for Chronic Kidney Disease

(MIRO-CKD Trial)

Recruiting at 104 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: MRA, Potassium sparing, CYP3A4

Disqualifiers: Uncontrolled hypertension, Type 1 diabetes, Hepatic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

324 Participants Needed

Trial Summary

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop all current medications, but you cannot use MRAs, potassium sparing diuretics, potassium binders, fludrocortisone, or strong/moderate CYP3A4 inducers or inhibitors within 4 weeks before screening and during treatment.

What data supports the idea that Balcinrenone + Dapagliflozin for Chronic Kidney Disease is an effective drug?

The available research shows that finerenone, a drug similar to Balcinrenone, has been effective in reducing the risk of kidney failure and heart complications in patients with chronic kidney disease and type 2 diabetes. In a study, finerenone reduced the occurrence of kidney failure and other serious kidney issues from 21.1% to 17.8%. It also showed a significant reduction in both kidney and heart-related problems when compared to a placebo. Although the research does not directly mention Balcinrenone + Dapagliflozin, the effectiveness of similar drugs like finerenone suggests potential benefits for this combination as well. ^{1 2 3 4 5}

What safety data exists for Balcinrenone + Dapagliflozin in treating chronic kidney disease?

The safety data for dapagliflozin, a component of the treatment, is well-documented. Dapagliflozin (Farxiga) is approved to reduce the risk of kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease. It has been studied extensively for its efficacy, safety, and tolerability in treating type 2 diabetes and heart failure with reduced ejection fraction. Dapagliflozin is generally well-tolerated, with a safety profile consistent across various indications, as observed in trials like DECLARE-TIMI 58 and DAPA-HF. However, specific safety data for the combination of Balcinrenone and Dapagliflozin is not detailed in the provided research. ^{6 7 8 9 10}

Is the drug dapagliflozin a promising treatment for chronic kidney disease?

Yes, dapagliflozin is a promising drug for chronic kidney disease. It is approved to reduce the risk of worsening kidney function, kidney failure, heart-related death, and hospital visits for heart failure in people with chronic kidney disease, whether or not they have type 2 diabetes. ^{2 3 6 11 12}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for adults with chronic kidney disease, specifically those who have protein in their urine (albuminuria). Participants should not be currently treated with Balcinrenone or Dapagliflozin. The study aims to find the best dose of a new combination drug.

Inclusion Criteria

I have chronic kidney disease with a specific kidney function level.

Serum potassium ≥ 3.5 mmol/L to ≤ 5.0 mmol/L

UACR > 100 mg/g (10 mg/mmol) to ≤ 5000 mg/g (500 mg/mmol)

Exclusion Criteria

I have not had a heart attack, stroke, or similar event in the last 3 months.

I haven't used specific heart or kidney medications in the last 4 weeks.

Hypotension defined as SBP < 100 mmHg

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 3 weeks

Treatment

Participants receive either balcinrenone/dapagliflozin or dapagliflozin alone to evaluate efficacy, safety, and tolerability

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• Balcinrenone/dapagliflozin
• Dapagliflozin

Trial Overview The study tests the effectiveness and safety of combining two drugs: Balcinrenone and Dapagliflozin, against using just Dapagliflozin. It's looking at how well this combo reduces protein levels in urine compared to the single drug.

Participant Groups

Group I: Balcinrenone/dapagliflozin 40 mg/10 mg Experimental Treatment 1 Intervention

Patients will be randomized 1:1:1 to either balcinrenone/dapagliflozin and matching placebo for dapagliflozin or dapagliflozin and matching placebo for balcinrenone/dapagliflozin

Group II: Balcinrenone/dapagliflozin 15 mg/10 mg Experimental Treatment 1 Intervention

Patients will be randomized 1:1:1 to either balcinrenone/dapagliflozin and matching placebo for dapagliflozin or dapagliflozin and matching placebo for balcinrenone/dapagliflozin

Group III: Dapagliflozin 10 mg Active Control 1 Intervention

Patients will be randomized 1:1:1 to either balcinrenone/dapagliflozin and matching placebo for dapagliflozin or dapagliflozin and matching placebo for balcinrenone/dapagliflozin

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

Finerenone is a first-in-class oral medication that selectively targets mineralocorticoid receptors, approved in the USA for reducing the risk of serious complications like kidney decline and heart issues in adults with chronic kidney disease related to type 2 diabetes.

It has shown efficacy in preventing sustained declines in kidney function and reducing cardiovascular risks, and is currently being studied in a phase III trial for heart failure with preserved ejection fraction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finerenone: First Approval. Frampton, JE.[2022]

In the phase 3 FIDELIO-DKD trial, finerenone significantly reduced the risk of kidney failure and related outcomes in patients with diabetic kidney disease, lowering the primary composite outcome from 21.1% to 17.8%.

Finerenone has a favorable safety profile and offers a different mechanism of action compared to other treatments like GLP-1 receptor agonists and SGLT-2 inhibitors, suggesting it could be an effective option for managing diabetic chronic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finerenone - are we there yet with a non-steroidal mineralocorticoid receptor antagonist for the treatment of diabetic chronic kidney disease? Doggrell, SA.[2022]

In a study of 5674 patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), finerenone significantly reduced urine albumin-to-creatinine ratio (UACR) regardless of whether patients were also using sodium-glucose cotransporter-2 inhibitors (SGLT-2i).

Finerenone demonstrated consistent benefits on kidney and cardiovascular outcomes compared to placebo, with improved safety profile, particularly showing fewer hyperkalemia events in patients using SGLT-2i.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finerenone in Predominantly Advanced CKD and Type 2 Diabetes With or Without Sodium-Glucose Cotransporter-2 Inhibitor Therapy. Rossing, P., Filippatos, G., Agarwal, R., et al.[2023]

Finerenone significantly reduces the risk of both cardiovascular and renal outcomes in patients with type 2 diabetes and chronic kidney disease, as shown in combined analyses of the FIDELIO-DKD and FIGARO-DKD trials, with hazard ratios indicating a strong efficacy compared to placebo.

While finerenone has an excellent safety profile, it does carry a risk of increased serum potassium levels, necessitating careful patient selection and monitoring, especially when used alongside other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Finerenone (Kerendia®), a new weapon against the chronic kidney disease of a patient with type 2 diabetes]. Scheen, A., Delanaye, P.[2023]

Recent large trials involving over 12,000 participants indicate that finerenone, when added to existing treatments for diabetic kidney disease, can modestly improve kidney and cardiovascular outcomes, particularly in patients with proteinuria.

While there is a concern about hyperkalaemia (high potassium levels), finerenone appears to have a lower incidence of this side effect compared to other treatments, and new potassium-binding agents may help further reduce this risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finerenone: a new mineralocorticoid receptor antagonist to beat chronic kidney disease. Raj, R.[2023]

Dapagliflozin (Farxiga) is approved for reducing the risk of declining kidney function and kidney failure in adults with chronic kidney disease, regardless of whether they have type 2 diabetes.

It also helps lower the risk of cardiovascular death and hospitalization for heart failure, highlighting its efficacy in managing both kidney and heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. Aschenbrenner, DS.[2023]

Dapagliflozin is an effective treatment for type 2 diabetes, proven through multiple controlled clinical trials that assess its efficacy, safety, and tolerability.

It is approved by the FDA for use as a standalone therapy or in combination with other glucose-lowering medications, including insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. Davis, PN., Ndefo, UA., Oliver, A.[2021]

The fixed-dose combination of dapagliflozin and saxagliptin (QTERN) effectively reduces hemoglobin A1C levels in patients with uncontrolled type 2 diabetes when used alongside metformin, showing a significant difference in A1C reduction compared to other combinations.

QTERN is generally well tolerated, but its use may be limited by cost and modest efficacy in A1C reduction, highlighting the need for further research on its long-term effects on diabetes complications and cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin/Saxagliptin Fixed-Dose Tablets: A New Sodium-Glucose Cotransporter 2 and Dipeptidyl Peptidase 4 Combination for the Treatment of Type 2 Diabetes. Coppenrath, VA., Hydery, T.[2022]

Dapagliflozin, an SGLT2 inhibitor, has been shown to significantly reduce the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF), regardless of whether they have type 2 diabetes.

In the DAPA-HF trial, dapagliflozin was well tolerated and demonstrated a lower risk of worsening heart failure or cardiovascular death compared to placebo, making it a valuable treatment option for adults with symptomatic HFrEF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. Blair, HA.[2022]

Dapagliflozin (DAPA) is an effective SGLT2 inhibitor for treating type 2 diabetes, showing favorable pharmacokinetics and pharmacodynamics that help lower blood sugar levels while having beneficial effects on other metabolic risk factors.

While DAPA is generally safe, it carries an increased risk of genital and urinary infections, and concerns about bladder cancer and cardiovascular safety remain, prompting the FDA to seek further data on these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. Maranghi, M., Carnovale, A., Durante, C., et al.[2021]

Dapagliflozin has been shown to be effective in improving outcomes for patients with chronic kidney disease, as highlighted in the commentary on a study involving diverse patient populations.

The commentary emphasizes the importance of dapagliflozin's mechanism of action, which includes reducing the risk of kidney disease progression and cardiovascular events, making it a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin in people with chronic kidney disease. Sylvester, RD., Khong, TK.[2023]

Dapagliflozin has been shown to significantly improve kidney outcomes in patients with chronic kidney disease, demonstrating its efficacy in reducing the risk of kidney disease progression.

The study involved a large cohort of patients, providing robust evidence for the safety and effectiveness of dapagliflozin in managing chronic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In CKD, dapagliflozin reduced a composite of eGFR decline, end-stage kidney disease, or CV or renal mortality. Molony, DA., LeMaistre, FI.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Finerenone: First Approval. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Finerenone - are we there yet with a non-steroidal mineralocorticoid receptor antagonist for the treatment of diabetic chronic kidney disease? [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Finerenone in Predominantly Advanced CKD and Type 2 Diabetes With or Without Sodium-Glucose Cotransporter-2 Inhibitor Therapy. [2023]

4. Belgium pubmed.ncbi.nlm.nih.gov

[Finerenone (Kerendia®), a new weapon against the chronic kidney disease of a patient with type 2 diabetes]. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Finerenone: a new mineralocorticoid receptor antagonist to beat chronic kidney disease. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Dapagliflozin/Saxagliptin Fixed-Dose Tablets: A New Sodium-Glucose Cotransporter 2 and Dipeptidyl Peptidase 4 Combination for the Treatment of Type 2 Diabetes. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Dapagliflozin in people with chronic kidney disease. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

In CKD, dapagliflozin reduced a composite of eGFR decline, end-stage kidney disease, or CV or renal mortality. [2021]