What side effects are associated with this type of intervention?

Common treatments for kidney failure include dialysis, kidney transplantation, and medications such as ACE inhibitors, ARBs, and immunosuppressants. Dialysis can cause side effects like low blood pressure, infections, and muscle cramps. Kidney transplantation may lead to rejection, infections, and complications from immunosuppressive drugs. Treatments similar to Belzutifan, such as other HIF inhibitors, can cause side effects including fatigue, anemia, and gastrointestinal issues. Additionally, these treatments may have specific renal-related side effects like changes in kidney function and electrolyte imbalances.

What other types of research exist?

Promising novel alternatives to Belzutifan for kidney failure patients include: 1) Mycophenolate mofetil combined with benazapril, which has shown potential in delaying tubulointerstitial fibrosis. 2) Traditional Chinese medicine Alisma orientale Juzepzuk, which has demonstrated lipid-lowering and anti-fibrotic effects. 3) TRF-budesonide, which has shown efficacy in reducing proteinuria and stabilizing eGFR in patients with IgA nephropathy. These alternatives target different aspects of kidney disease and may offer new therapeutic options in 2024.

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HIF-2alpha Inhibitor

Belzutifan for Kidney Failure

Q: What prior FDA approvals exist?

The FDA has approved several treatments for kidney failure, though specific approvals for HIF-2α inhibitors like Belzutifan are limited. Traditional treatments include erythropoiesis-stimulating agents (ESAs) such as epoetin alfa and darbepoetin alfa, which address anemia associated with chronic kidney disease. Additionally, drugs like angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are commonly used to manage hypertension and slow the progression of kidney disease. While Belzutifan represents a novel approach by targeting the HIF pathway, most current FDA-approved treatments focus on managing symptoms and slowing disease progression rather than directly targeting hypoxia pathways.

Phase 1

Waitlist Available

Research Sponsored by Merck Sharp & Dohme Corp.

Eligibility Criteria Checklist

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

Must have

For Participants With ESRD: Female participants must be of nonchildbearing potential

For Participants With Healthy Renal Function: Female participants must be of nonchildbearing potential

Must not have

For Participants With Healthy Renal Function: Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit

Participants With ESRD: Has required frequent emergent HD (≥3) within a year prior to the initial dose of study intervention

Timeline

Screening 3 weeks

Treatment Varies

Follow Up predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose

Awards & highlights

No Placebo-Only Group

Summary

This trial tests how a pill called belzutifan is processed in people with severe kidney disease who are on dialysis. It also checks if dialysis affects the medication's effectiveness.

Who is the study for?

This trial is for adults with end-stage renal disease (ESRD) on stable hemodialysis and healthy individuals as controls. Participants must be in good health aside from kidney issues, not planning to conceive, and agree to use contraception. Exclusions include recent major surgery, blood donation, cancer history, significant medical conditions, or positive tests for hepatitis B/C or HIV.

What is being tested?

The study is testing the drug Belzutifan at a single oral dose of 120 mg. It aims to compare how the drug behaves in the bloodstream of patients with ESRD before and after dialysis versus healthy participants. The removal of Belzutifan by dialysis will also be assessed.

What are the potential side effects?

While specific side effects are not listed here, safety and tolerability of Belzutifan will be evaluated during the trial which typically includes monitoring for any adverse reactions such as nausea, headaches, allergic reactions or other potential side effects.

Eligibility Criteria

Inclusion Criteria

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

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I am a woman with ESRD and cannot become pregnant.

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I am a woman who cannot become pregnant.

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I have end-stage renal disease and have been on a stable dialysis schedule of at least 3 times a week for the last 3 months.

Exclusion Criteria

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

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I have not had major surgery or donated/lost significant blood in the last 4 weeks.

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I have needed emergency dialysis 3 or more times in the last year.

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I have ESRD and tested positive for HBsAg, hepatitis C, or HIV.

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I have kidney failure and a history of cancer.

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I have had cancer before and my kidneys are healthy.

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I have healthy kidneys but test positive for hepatitis B, C, or HIV.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose

This trial's timeline: 3 weeks for screening, Varies for treatment, and predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Apparent terminal half-life (t½) of plasma belzutifan

Area under the plasma concentration time curve of belzutifan from hour 0 to 24 (AUC0-24)

Area under the plasma concentration time curve of belzutifan from hour 0 to infinity (AUC0-inf)

+2 more

Secondary study objectives

Dialysis clearance of belzutifan based on plasma (CLD, plasma)

Number of participants who discontinued from the study due to an AE

Number of participants who experienced an adverse event (AE)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Belzutifan in Participants with ESRDExperimental Treatment1 Intervention

Participants with ESRD will receive a single dose of belzutifan 120 mg orally on Day 1 of a 4-day treatment period (Period 1), followed by a ≥7 day washout period. Participants receive another single dose of belzutifan 120 mg orally on Day 1 of a 4-day treatment period (Period 2).

Group II: Belzutifan in Healthy ParticipantsExperimental Treatment1 Intervention

Participants in the healthy matched control group will receive a single dose of belzutifan 120 mg orally on Day 1 of a 4-day treatment period (Period 1).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Belzutifan

2018

Completed Phase 1

~50

0 / 9Eligibility 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

Belzutifan, an inhibitor of Hypoxia-Inducible Factor-2α (HIF-2α), works by targeting pathways involved in cellular response to low oxygen levels, which can protect against hypoxia-induced renal damage. This is particularly relevant for kidney failure patients as hypoxia and subsequent inflammation are key contributors to renal injury and fibrosis. Other common treatments for kidney failure include angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), which help reduce proteinuria and control blood pressure, thereby slowing the progression of kidney disease. Immunosuppressive therapies, such as glucocorticoids and cyclophosphamide, are also used to manage underlying autoimmune conditions that may contribute to kidney damage. These treatments are crucial as they address different aspects of kidney failure, from reducing inflammation and fibrosis to managing blood pressure and proteinuria, ultimately aiming to preserve kidney function and delay the need for dialysis or transplantation.

Newer insights into cisplatin nephrotoxicity.Uric acid lowering for slowing CKD progression after the CKD-FIX trial: a solved question or still a dilemma?Endothelial HIF-2 mediates protection and recovery from ischemic kidney injury.