Balcinrenone + Dapagliflozin for Chronic Kidney Disease

(MIRO-CKD Trial)

No longer recruiting at 122 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medications, balcinrenone (an experimental treatment) and dapagliflozin, to determine if they work better together than dapagliflozin alone for individuals with chronic kidney disease (CKD) and high levels of protein in their urine. Researchers aim to identify the optimal dose for future studies. The trial seeks participants with CKD who struggle to maintain stable kidney function, particularly those who have experienced these symptoms for an extended period. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that balcinrenone, when combined with dapagliflozin, is being tested for safety and effectiveness in treating chronic kidney disease (CKD). Previous studies have found that patients generally tolerate this combination well.

Dapagliflozin, already approved by the FDA for other uses, has a strong safety record. It is widely used and known for having a low risk of serious side effects.

Balcinrenone is newer, so researchers are still gathering safety information. However, earlier studies have not identified any major safety concerns. As this is a Phase 2 study, the treatment has already passed initial safety tests. This suggests it is likely safe, but more data is needed for confirmation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for chronic kidney disease focus on managing symptoms and slowing progression, mainly using drugs like ACE inhibitors and angiotensin II receptor blockers. But balcinrenone/dapagliflozin is unique because it combines two active ingredients: balcinrenone, a new mineralocorticoid receptor antagonist, and dapagliflozin, a well-known SGLT2 inhibitor. This combination targets the disease from two angles, aiming to provide better kidney protection and potentially improve heart health. Researchers are excited about this treatment because it could offer a more comprehensive approach to managing chronic kidney disease, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for chronic kidney disease?

Research has shown that using balcinrenone with dapagliflozin may be more effective than dapagliflozin alone for treating chronic kidney disease (CKD). In this trial, participants will receive either the combination of balcinrenone and dapagliflozin or dapagliflozin alone. One study found that this combination significantly reduces albuminuria, a condition where excess protein leaks into the urine, commonly seen in CKD. Lowering albuminuria can help protect the kidneys over time. Patients who have used this combination demonstrated promising results with fewer kidney problems. The trial aims to determine the optimal dose of this combination to maximize its benefits for CKD patients. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40623005/

Efficacy and safety of balcinrenone and dapagliflozin for CKD The MIRO-CKD study tests the hypothesis that balcinrenone with dapagliflozin is superior to dapagliflozin alone in reducing albuminuria in patients with CKD.

2. academic.oup.com academic.oup.com/ndt/advance-article-abstract/doi/10.1093/ndt/gfaf119/8191252

Efficacy and safety of balcinrenone and dapagliflozin for CKD The MIRO-CKD study tests the hypothesis that balcinrenone with dapagliflozin is superior to dapagliflozin alone in reducing albuminuria in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06350123

Study Details | NCT06350123 | Efficacy, Safety and ... This study will evaluate the effect of the balcinrenone/dapagliflozin on urinary albumin-to-creatinine ratio (UACR), compared with dapagliflozin in patients ...

4. journals.lww.com journals.lww.com/jasn/fulltext/2024/10001/a_phase_2b_dose_finding_study_to_evaluate_effects.4516.aspx

A Phase 2b Dose-Finding Study to Evaluate Effects of... The MIRO-CKD study will assess efficacy, safety and tolerability of the combination of balcinrenone and dapagliflozin with the aim to identify an optimal ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ejhf.3294

Balcinrenone plus dapagliflozin in patients with heart ... We investigated the efficacy and safety of the novel mineralocorticoid receptor modulator balcinrenone in combination with dapagliflozin in a phase 2b study.

6. academic.oup.com academic.oup.com/ndt/advance-article/doi/10.1093/ndt/gfaf119/8191252

design and baseline characteristics of the MIRO-CKD trial The MIRO-CKD study tests the hypothesis that balcinrenone with dapagliflozin is superior to dapagliflozin alone in reducing albuminuria in patients with CKD.