What side effects are associated with this type of intervention?

Mineralocorticoid Receptor Antagonists (MRAs) such as spironolactone and finerenone, used in the treatment of Chronic Kidney Disease (CKD), are associated with several side effects. Commonly reported adverse effects include hyperkalemia (elevated potassium levels), which can be significant and requires monitoring. Other potential side effects include hypotension, renal function deterioration, and, in the case of spironolactone, a theoretical risk of breast cancer, although no definitive evidence supports this. Additionally, spironolactone may cause feminization of male fetuses if taken during pregnancy.

What prior FDA approvals exist?

Mineralocorticoid Receptor Antagonists (MRAs) like spironolactone and eplerenone have been used in the management of conditions associated with chronic kidney disease, such as heart failure and hypertension. Spironolactone is commonly used for its potassium-sparing diuretic properties, while eplerenone is often chosen for its more selective action, reducing the risk of side effects related to androgen and progesterone receptors. These drugs help manage fluid retention and blood pressure, which are critical in CKD management. The FDA has approved these MRAs for heart failure and hypertension, which are common comorbidities in CKD patients, but their direct approval for CKD treatment is more limited. The ongoing study of KBP-5074 aims to further explore the efficacy and safety of MRAs specifically in CKD patients with uncontrolled hypertension.

What other types of research exist?

Finerenone is a promising novel alternative to KBP-5074 for CKD patients. It is a non-steroidal mineralocorticoid receptor antagonist that has shown efficacy and safety in reducing urinary albumin-to-creatinine ratio in patients with type 2 diabetes mellitus and diabetic nephropathy. Additionally, patiromer, a potassium binder, can be considered for managing hyperkalemia in CKD patients, which is a common issue with MRAs.

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KBP-5074 for High Blood Pressure and Chronic Kidney Disease (Clarion-CKD Trial)

Q: What is the mechanism of action of this treatment?

Common treatments for Chronic Kidney Disease (CKD) include angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs) like spironolactone and KBP-5074. MRAs work by blocking the action of aldosterone, a hormone that can cause sodium retention, potassium loss, and fibrosis in the kidneys. By inhibiting aldosterone, MRAs help reduce blood pressure, decrease proteinuria, and prevent further kidney damage. This is particularly important for CKD patients as it helps slow the progression of the disease and reduces the risk of cardiovascular events, which are common complications in this population.

Phase 3

Waitlist Available

Research Sponsored by KBP Biosciences

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

The participant must have Stage 3b (eGFR [EPI] ≥30 and ≤44 mL/min/1.73 m^2) or Stage 4 (eGFR [EPI] ≥15 and <30 mL/min/1.73 m^2) CKD.

Participant must have uncontrolled hypertension defined as meeting both of the following criteria: The participant has a resting seated trough cuff SBP ≥140 mm Hg at the Screening Visit (Visit 1), and at the start (Visit 2) and end (Visit 3) of the Run-In Period. The participant is taking 2 or more antihypertensive medications that have been titrated upward as tolerated to hypertension target doses per local SoC and have been stable (i.e., without any dose adjustments) from 4 weeks before the Screening Visit (Visit 1) through the end of the Run-In Period (Visit 3)

Must not have

Participant has taken an mineralocorticoid receptor antagonist (MRA), a potassium-sparing diuretic, or chronic potassium supplements during the 4 weeks before the Screening Visit (Visit 1)

Participant was not compliant with taking placebo during the Run-in Period or participant was not compliant with background antihypertensive medications during the Run-in Period as assessed at the Randomization Visit (Visit 3)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from baseline to week 12, week 24, and week 48

Awards & highlights

Pivotal Trial

Summary

This trial is testing KBP-5074, a new drug, in adults with severe kidney disease and high blood pressure. The goal is to see if it can better manage their blood pressure and improve kidney health compared to their current treatments.

Who is the study for?

Adults with stage 3b or 4 chronic kidney disease (CKD) and uncontrolled high blood pressure despite taking two or more antihypertensive medications. Participants should have a BMI between ≥19 to <45 kg/m^2, stable medication doses for at least four weeks, and systolic blood pressure between ≥140 and <180 mm Hg.

What is being tested?

The trial is testing the effectiveness of KBP-5074 compared to a placebo in managing hypertension in patients with moderate to severe CKD. It's a phase 3 study where participants are randomly assigned to either the drug or placebo group without knowing which one they receive.

What are the potential side effects?

While specific side effects of KBP-5074 aren't listed here, common ones may include changes in potassium levels, impacts on kidney function, dizziness due to lowered blood pressure, and potential interactions with other medications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney function is moderately to severely reduced.

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My high blood pressure is not controlled even though I am on two or more medications.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been taking a specific water pill or potassium supplement for the last 4 weeks.

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I did not follow the medication plan during the trial's initial phase.

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I have not taken strong CYP3A4 drugs in the week before my visit.

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I was hospitalized for high potassium levels within the last 3 months.

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My blood pressure was 180 or higher before starting the trial.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from baseline to week 12, week 24, and week 48

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from baseline to week 12, week 24, and week 48

This trial's timeline: 3 weeks for screening, Varies for treatment, and from baseline to week 12, week 24, and week 48 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in seated trough cuff SBP from Week 48 to Week 52

Change in seated trough cuff SBP from baseline to Week 12

Secondary study objectives

Change in UACR from Week 48 to Week 52

Change in seated trough cuff DBP from Week 48 to Week 52

Change in seated trough cuff SBP from baseline to Week 24

+8 more

Side effects data

From 2017 Phase 1 trial • 11 Patients • NCT02837237

fatigue

procedural hypotension

increased creatinine

hyperkalemia

metabolic acidosis

headache

100%

80%

60%

40%

20%

Study treatment Arm

KBP-5074

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: KBP-5074Experimental Treatment1 Intervention

Open-label Placebo Run-In period: All eligible participants will receive matching placebo, for approximately 2 weeks during the Open-label placebo Run-In period. Double-blind Treatment Period: All eligible participants will receive KBP-5074, from week 2 thru week 24 during the Double-blind Treatment Period Open-label Treatment Period: All eligible participants will receive KBP-5074, from week 24 thru week 48 during the Open label Treatment Period Randomized Double-blind Withdrawal Period: All eligible participants will be randomized to either continue their current KBP-5074 dose at the end of the Open-Label Treatment Period or receive matching placebo from week 48 thru week 52. Follow up Period: All participants will discontinue matching placebo/KBP-5074 and be followed for safety until end of study visit from week 52 to week 56.

Group II: PlaceboPlacebo Group1 Intervention

Open-label Placebo Run-In Period: All eligible participants will receive matching placebo, for approximately 2 weeks, during the Open-label placebo Run-In period. Double-blind Treatment Period: All eligible participants will receive matching placebo, from week 2 thru week 24 during the Double-blind treatment Period Open-label Treatment Period: All eligible participants will receive KBP-5074, from week 24 thru week 48 during the Open label Treatment Period Randomized Double-blind Withdrawal Period: All eligible participants will be randomized to either continue their current KBP-5074 dose at the end of the Open-Label Treatment Period or receive matching placebo from week 48 thru week 52. Follow up Period: All participants will discontinue matching placebo/KBP-5074 and be followed for safety until end of study visit from week 52 to week 56.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

KBP-5074

2020

Completed Phase 1

~130

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Chronic Kidney Disease (CKD) include angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs) like spironolactone and KBP-5074. MRAs work by blocking the action of aldosterone, a hormone that can cause sodium retention, potassium loss, and fibrosis in the kidneys. By inhibiting aldosterone, MRAs help reduce blood pressure, decrease proteinuria, and prevent further kidney damage. This is particularly important for CKD patients as it helps slow the progression of the disease and reduces the risk of cardiovascular events, which are common complications in this population.

Evidence-Based Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction and Chronic Kidney Disease.Aldosterone antagonists for people with chronic kidney disease requiring dialysis.Aldosterone Antagonists Reduce the Risk of Cardiovascular Mortality in Dialysis Patients: A Meta-Analysis.