What side effects are associated with this type of intervention?

Common treatments for Chronic Kidney Disease (CKD) include immunosuppressive therapies, such as glucocorticoids and other immunosuppressive agents. Known side effects of these treatments can include increased risk of infections, liver enzyme elevation, pancreatitis, bone marrow suppression, and gastrointestinal issues like diarrhea. Specifically, for treatments aimed at reducing anti-HLA alloantibodies, such as those being studied in the trial REGN5459 or REGN5458, potential side effects may include hypersensitivity reactions, changes in circulating immunoglobulin levels, and other immunologic effects. It is important to monitor these side effects closely to manage and mitigate risks effectively.

What prior FDA approvals exist?

There is limited specific information provided about prior FDA approvals for treatments directly targeting the reduction of anti-HLA alloantibodies in Chronic Kidney Disease (CKD). However, treatments for CKD often involve immunosuppressive therapies to manage immune responses, such as glucocorticoids and other immunosuppressive agents. The study of REGN5459 and REGN5458 focuses on reducing anti-HLA alloantibodies, which is a novel approach in the context of highly sensitized patients needing kidney transplantation. This indicates ongoing research and development in this specific area of CKD treatment.

What other types of research exist?

Promising alternatives to REGN5459 or REGN5458 for CKD patients include the use of daratumumab, a monoclonal antibody targeting CD38, which has shown efficacy in reducing alloantibodies and improving transplant outcomes. Additionally, belatacept, a costimulation blocker, and bortezomib, a proteasome inhibitor, are being explored for their potential to reduce anti-HLA antibodies and enhance desensitization protocols.

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Monoclonal Antibodies

REGN5459 + REGN5458 for Transplant-Ready Chronic Kidney Disease

Phase 1 & 2

Recruiting

Research Sponsored by Regeneron Pharmaceuticals

Eligibility Criteria Checklist

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

Must have

Has Chronic Kidney Disease (CKD) requiring hemodialysis, and awaiting kidney transplant on the United Network for Organ Sharing (UNOS), with a cPRA ≥99.9%, or those with a cPRA >98% (98.1% to 99.8%) who have spent 5 years or longer on the waitlist

Be older than 18 years old

Must not have

Prior treatment with any anti-BCMA antibody (including antibody drug conjugate or bsAb) or BCMA-directed CAR-T cell therapy

Central nervous system (CNS) pathology or history of CNS neurodegenerative or movement disorders

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 30 weeks

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the safety of two experimental drugs, REGN5459 and REGN5458, in kidney disease patients who need a transplant but have high antibody levels that make finding a donor difficult. The drugs work by lowering these antibodies to improve donor compatibility.

Who is the study for?

This trial is for adults with chronic kidney disease who need a kidney transplant and are highly sensitized to human leukocyte antigen (HLA). They must be on hemodialysis, have been waiting for a transplant with a cPRA ≥99.9%, or have a cPRA >98% if they've been on the waitlist for over 5 years. Participants should not have active cancer, history of certain treatments, recent vaccinations, or specific medical conditions.

What is being tested?

The study tests REGN5459 (Part A) and REGN5458 (Part B) as potential treatments to reduce anti-HLA alloantibody levels in patients awaiting kidney transplants. It aims to find effective doses, understand how long the drugs work, their impact on immune system proteins, and overall safety.

What are the potential side effects?

While specific side effects aren't listed here, common ones may include reactions at the injection site, changes in blood counts or liver enzymes indicating organ inflammation or damage; allergic reactions; fatigue; headaches; and possible impacts on immune function.

Eligibility Criteria

Inclusion Criteria

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

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I have severe CKD, need dialysis, am on the UNOS waitlist for a kidney, and have a high cPRA score.

Exclusion Criteria

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

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I have not had treatments targeting BCMA for my cancer.

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I have no history of brain disorders or movement issues.

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I have had my spleen removed or it doesn't work properly.

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I have had a stem cell transplant in the last 5 years.

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My cancer has not been in remission for at least a year.

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I haven't taken more than 10 mg of prednisone or equivalent daily within 3 days before starting the study drug.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 30 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 30 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 30 weeks for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Incidence and severity of treatment-emergent adverse events (TEAE)s from the first study drug dose up to the end of the study

Secondary study objectives

Proportion of Participants with a clinically meaningful reduction in anti-HLA alloantibodies

Time to first clinically meaningful reduction in anti-HLA alloantibody levels by SAB assay

Time to maximal reduction in anti-HLA alloantibody levels by SAB assay

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: REGN5459Experimental Treatment1 Intervention

REGN5459 escalating dose

Group II: REGN5458Experimental Treatment1 Intervention

REGN5458 escalating dose

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 immunosuppressive therapies, plasmapheresis, and targeted biologic agents. Immunosuppressive therapies, such as cyclophosphamide and prednisone, work by reducing the immune system's activity to prevent further kidney damage. Plasmapheresis removes harmful antibodies from the blood, which is crucial for conditions like anti-GBM disease. Targeted biologic agents, such as those studied in the trial REGN5459 or REGN5458, aim to reduce anti-HLA alloantibodies, which are important for patients awaiting kidney transplants as they can improve transplant compatibility and outcomes. These treatments are vital for CKD patients as they help manage the immune response, reduce inflammation, and improve the chances of successful kidney transplantation.

Therapies Targeting Epigenetic Alterations in Acute Kidney Injury-to-Chronic Kidney Disease Transition.Molecular characterization of the transition from acute to chronic kidney injury following ischemia/reperfusion.Cytokines: Names and Numbers You Should Care About.