BI 690517 + Empagliflozin for Chronic Kidney Disease

Recruiting at 280 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Must not be taking: MRAs, Dual RAS inhibitors

Disqualifiers: High potassium, Liver cirrhosis, Dialysis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 10

11000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the medication BI 690517, combined with empagliflozin (a drug for type 2 diabetes), can slow the progression of chronic kidney disease and reduce related heart problems. Participants will receive either the actual treatment or a placebo (a look-alike pill with no active ingredients) for comparison. People with chronic kidney disease, regardless of whether they have type 2 diabetes, may qualify if they already take certain blood pressure or diabetes medications, or even if they don't. The trial will track how often participants experience worsening kidney disease or heart issues over several years. Regular check-ups will monitor health and any side effects. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications if you are on ACE inhibitors or ARBs, as you can continue these throughout the study. However, if you are on more than one Renin-Angiotensin System inhibitor or certain other medications like MRAs, you may not be eligible to participate.

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

Previous studies have tested both BI 690517 and empagliflozin for safety. Research has shown that BI 690517 is generally well-tolerated. In a study with 586 patients, BI 690517 significantly reduced signs of kidney damage and was safe, with no major side effects reported.

Empagliflozin, already approved for treating type 2 diabetes, has been studied in people with chronic kidney disease. Safety data from these studies showed that empagliflozin was well-tolerated. Common side effects might include urinary tract infections or low blood sugar, but these were usually mild.

Since this trial is in a late stage (Phase 3), earlier phases demonstrated that the treatments were safe enough for testing on more people. Researchers will closely monitor participants for any unwanted effects to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for chronic kidney disease?

Unlike the standard treatments for chronic kidney disease, which often include ACE inhibitors or angiotensin II receptor blockers (ARBs), the combination of BI 690517 and empagliflozin acts on different mechanisms. BI 690517 is designed to specifically target pathways that may help protect kidney function, while empagliflozin, a well-known SGLT2 inhibitor, helps lower blood sugar and may have beneficial effects on kidney health. Researchers are excited about these treatments because they could offer enhanced kidney protection and potentially slow disease progression more effectively than current options. This dual-action approach is what sets it apart and fuels optimism about its potential benefits.

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

Research shows that using BI 690517 with empagliflozin may help treat chronic kidney disease. In this trial, participants will receive either the combination of BI 690517 and empagliflozin or a placebo. One study found that patients taking BI 690517 experienced up to a 39.5% reduction in albuminuria, a sign of kidney damage, compared to those on a placebo. Another important finding revealed that up to 70% of patients on BI 690517 saw a significant drop in their urinary albumin-to-creatinine ratio (UACR), which measures kidney function. Additionally, empagliflozin is known to slow kidney disease and lower the risk of heart-related death in these patients. These results suggest that this combination could effectively manage and slow the progression of kidney disease. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with chronic kidney disease, including those with or without type 2 diabetes. It's open to patients taking ACEi or ARB medications and those not on any SGLT2 inhibitors like empagliflozin. Participants must have a certain level of kidney function (eGFR) and may have protein in their urine.

Inclusion Criteria

Evidence of chronic kidney disease (CKD) at risk of kidney disease progression is defined on the basis of local laboratory results recorded at least 3 months before and at the time of the Screening visit, and requires:

My kidney function is low but not extremely severe.

I don't need, nor is it inappropriate for me to take, medications for hormone control.

Exclusion Criteria

Blood potassium of >5.2 mmol/L at screening visit

Blood Alanine Transaminase (ALT) or Aspartate Transaminase (AST) >3x Upper Limit of Normal (ULN) at Screening visit

I have been diagnosed with liver cirrhosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Eligible participants receive placebo matching BI 690517 + empagliflozin

6 weeks

4 visits (in-person) within the first 6 months

Randomized Treatment

Participants are divided into two groups: one receives BI 690517 and the other receives placebo, both in addition to empagliflozin

3-4 years

Every 6 months after the initial 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BI 690517
• Empagliflozin
• Placebo matching BI 690517

Trial Overview The study tests if BI 690517 combined with empagliflozin can protect against kidney disease progression compared to placebo. Initially, all participants receive empagliflozin or placebo for at least six weeks; then they're randomly assigned to add either BI 690517 or a placebo tablet daily.

How Is the Trial Designed?

Group I: Part 2: Randomized treatment, follow-up period, treatment group Experimental Treatment 2 Interventions

Group II: Part 1: Run-in period (all participants) Experimental Treatment 2 Interventions

Eligible participants will enter a Run-in period during which they will receive placebo matching BI 690517 + empagliflozin.

Group III: Part 2: Follow-up period, placebo group Placebo Group 2 Interventions

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

Empagliflozin (Jardiance) has been associated with a significant reduction in cardiovascular mortality among patients with type 2 diabetes and established cardiovascular disease, although the exact mechanism for this benefit is not yet understood.

There is uncertainty regarding whether empagliflozin may also increase the risk of fractures, a concern raised with another SGLT2 inhibitor, canagliflozin (Invokana), and all SGLT2 inhibitors are noted to have only modest effectiveness in managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2 inhibitors: new reports. [2019]

The EMPA-KIDNEY trial is a large-scale study involving 6609 participants with chronic kidney disease (CKD) to assess the efficacy and safety of empagliflozin in reducing the risk of kidney disease progression and cardiovascular death.

Participants included individuals with varying degrees of kidney function and both diabetic and non-diabetic patients, making the results applicable to a broad population at risk for CKD complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial. [2023]

Empagliflozin effectively lowers blood sugar levels in patients with type 2 diabetes by inhibiting glucose reabsorption in the kidneys, resulting in an average reduction of HbA1c by approximately 0.8% without causing hypoglycemia, except in those already on insulin or sulphonylureas.

In addition to improving glycemic control, empagliflozin promotes weight loss (about 2 kg) and lowers blood pressure (systolic by approximately 4 mm Hg), while also providing cardiovascular protection, as demonstrated in the EMPA-REG OUTCOME trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. Scheen, AJ.[2022]

Empagliflozin, when administered to 15,081 patients with type 2 diabetes and moderate to severe chronic kidney disease (CKD), showed no new safety concerns, with similar rates of serious adverse events compared to placebo.

The treatment was associated with significantly lower risks of hyperkalemia and edema, suggesting potential benefits for patients with advanced CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. Tuttle, KR., Levin, A., Nangaku, M., et al.[2022]

Empagliflozin effectively reduces blood sugar levels in patients with type 2 diabetes by preventing glucose reabsorption, leading to a loss of about 70 grams of glucose per day, which also contributes to weight loss.

In addition to its blood sugar-lowering effects, empagliflozin has been shown to slightly decrease blood pressure and has been approved for use in the European Union since May 2014, often in combination with other diabetes medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Empagliflozin - the new representative of SGLT2 transporter inhibitors for the treatment of patients with diabetes 2 type]. Prázný, M., Slíva, J.[2018]

The EMPA-KIDNEY study evaluated the effects of empagliflozin in patients with chronic kidney disease, demonstrating significant benefits in slowing the progression of kidney disease.

This study involved a large cohort of patients, providing robust evidence for the efficacy of empagliflozin as a treatment option for chronic kidney disease, highlighting its potential to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In CKD, once-daily empagliflozin reduced progression of kidney disease or CV death at 2 y. Kwong, YD., Hsu, CY.[2023]

The EMPEROR-Reduced trial demonstrated that empagliflozin significantly improves heart failure outcomes in patients with reduced ejection fraction, showing benefits across various levels of kidney function.

Empagliflozin not only helps in managing heart failure symptoms but also provides protective effects on kidney function, making it a dual-action treatment for patients with both heart and kidney issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In HFrEF, adding empagliflozin to medical therapy reduced a composite outcome, regardless of CKD status. Santos-Gallego, CG., Van Spall, HGC.[2021]

In the EMPEROR-Reduced study involving over 3700 participants with chronic heart failure and reduced ejection fraction, empagliflozin significantly reduced the risk of hospitalization for heart failure complications (13.2% vs. 18.3% for placebo) over an average of 16 months.

Empagliflozin also showed a lower incidence of serious kidney problems (1.6% vs. 3.1% for placebo), indicating its potential safety and efficacy in managing heart failure, although it was associated with a higher rate of genital tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. Zannad, F., Macari, S.[2023]

Empagliflozin (Jardiance) is now approved for reducing the risk of cardiovascular death and hospitalization in adults with heart failure, even in those without diabetes, highlighting its expanded therapeutic use.

Healthcare providers, including nurses and nurse practitioners, should closely monitor patients for potential adverse effects, particularly fluid deficits, to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. Aschenbrenner, DS.[2023]

Citations

1. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/chronic-kidney-disease/promising-phase-ii-results-chronic-kidney-disease

Promising phase II results in chronic kidney disease Phase II results demonstrated significant albuminuria reductions by up to 39.5% vs. placebo when BI 690517, a novel selective aldosterone ...

2. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/chronic-kidney-disease/easi-kidney-phase-iii-trial-people-ckd

EASi-KIDNEY™ Phase III trial for people with CKD The combined use of vicadrostat with empagliflozin has already shown promising results in a Phase II trial in chronic kidney disease in 2023, with full data ...

3. withpower.com withpower.com/trial/phase-3-renal-insufficiency-chronic-7-2024-002d9

BI 690517 + Empagliflozin for Chronic Kidney Disease Empagliflozin has been shown to reduce the progression of kidney disease and the risk of cardiovascular death in patients with chronic kidney disease. It is ...

4. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2021-001434-19/DK

Clinical Trials Register ... combination with empagliflozin improve kidney function in people with chronic kidney disease ... The trial will compare 3 doses of BI 690517 ...

5. firstwordpharma.com firstwordpharma.com/story/5797383

Boehringer's aldosterone synthase inhibitor shows promise ... A clinically meaningful ≥30% reduction in UACR, a key secondary endpoint, was achieved by up to 70% of patients treated with BI 690517 on top of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39533115/

a rationale for the EASi-KIDNEY trial Phase II data from 586 patients with albuminuric CKD have shown that 10 mg of an ASi, vicadrostat (BI 690517), reduced urine albumin-to- ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S014067362302408X

Efficacy and safety of aldosterone synthase inhibition with ... This phase 2 clinical trial assessed BI 690517, an aldosterone synthase inhibitor, for efficacy, safety, and dose selection.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05182840

NCT05182840 | A Study to Test Whether Different Doses of ... The purpose of this study is to find out whether a medicine called BI 690517 improves kidney function in people with chronic kidney disease when taken alone or ...

9. academic.oup.com academic.oup.com/ndt/article/40/6/1175/7896419

potential for improving cardio-renal outcomes in chronic ... Safety of empagliflozin in patients with type 2 diabetes and chronic kidney disease: pooled analysis of placebo-controlled clinical trials.