A Study to Learn How Safe and Tolerable Vonsetamig is in Adult Patients With Chronic Kidney Disease (CKD) Who Need Kidney Transplantation and Are Highly Sensitized to Human Leukocyte Antigen (HLA)

A Dose Escalation and Proof-of-Concept Study of Vonsetamig (BCMA × CD3 Bispecific Antibody) for Desensitization of Chronic Kidney Disease Patients in Need of Kidney Transplantation Who Are Highly Sensitized to Human Leukocyte Antigen

The purpose of this study is to determine whether vonsetamig will safely decrease anti-HLA antibodies to allow for kidney transplantation.

Vonsetamig is being studied for treatment of patients in need of kidney transplantation who are highly sensitized to HLA.

The study is looking at several other research questions, including:

• Side effects that may be experienced from taking vonsetamig
• How vonsetamig works in the body
• How much vonsetamig is present in the blood
• If vonsetamig works to lower levels of antibodies to HLA

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Kidney Disease (CKD)
• Intervention / Treatment: Drug: Vonsetamig

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Orange, California, United States, 92868
      • University of California Irvine
    • San Francisco, California, United States, 94143
      • Connie Frank Transplant Center at UCSF
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University of Medicine
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Medstar Georgetown Transplant Institute - 2-PHC
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Comprehensive Transplant Center
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • John Hopkins Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New York
    • New York, New York, United States, 10016
      • New York University Langone Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Transplant Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. 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, as defined in the protocol
2. Adequate hematologic and adequate hepatic function as defined in the protocol
3. Willing and able to comply with clinic visits and study-related procedures

Key Exclusion Criteria:

1. Current or active malignancy not in remission for at least 1 year
2. Central nervous system (CNS) pathology or history of CNS neurodegenerative or movement disorders
3. Patients who have had their spleen removed, including patients with functional asplenia
4. Patients who have received a stem cell transplantation within 5 years
5. Use of investigational agents within 8 weeks or 5 half-lives of study drug administration (whichever is larger)
6. Total plasma IgG <300 mg/dL at screening
7. Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone (or anti-inflammatory equivalent) within 72 hours of start of study drug administration
8. Received a calcineurin inhibitor (eg, tacrolimus, cyclosporine) within 30 days of study drug administration
9. Received cyclophosphamide, rituximab, obinutuzumab, other anti-CD20 or B cell-depleting agents, or proteasome inhibitors or anti-CD38 therapies (eg, isatuximab, daratumumab) within 12 months of study drug administration
10. Prior treatment with any anti-BCMA antibody (including antibody drug conjugate or bsAb) or BCMA-directed CAR-T cell therapy, as described in the protocol
11. Has received a COVID-19 vaccination, as described in the protocol

Note: Other protocol defined inclusion / exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vonsetamig	Drug: Vonsetamig; Administered by intravenous (IV) infusion; Other Names: BCMAxCD3; REGN5459

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse event(s) of interest (AEI) from the first dose through end of the safety observation period		Up to approximately 6 weeks
Incidence and severity of treatment-emergent adverse events (TEAE)s from the first study drug dose up to the end of the study	TEAEs include adverse events of special interest (AESI) and serious adverse events (SAEs)	Up to 78 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants with a clinically meaningful reduction in anti-HLA alloantibodies	Clinically meaningful reduction in anti-HLA alloantibodies are defined as either: Reduction in Calculated panel-reactive antibody (cPRA) from baseline, or; Reduction in the peak (immunodominant) anti-HLA mean fluorescence intensity (MFI) to <5,000, or by ≥50% by Single antigen bead (SAB) assay	Up to 78 weeks
Maximum reduction in the peak (immunodominant) MFI of anti-HLA alloantibodies from baseline		Up to 78 weeks
Percent change from baseline in the peak (immunodominant) MFI		Up to 78 weeks
Percent change from baseline in the sum of MFI of anti-HLA alloantibodies using the SAB assay		Up to 78 weeks
Time to first clinically meaningful reduction in anti-HLA alloantibody levels by SAB assay	Defined as peak anti-HLA alloantibody MFI <5,000 or ≥50% reduction	Up to 78 weeks
Time to maximal reduction in anti-HLA alloantibody levels by SAB assay	Defined as peak anti-HLA alloantibody MFI <5,000 or ≥50% reduction	Up to 78 weeks
Maximum reduction in cPRA from baseline		Up to 78 weeks
Time to first clinically meaningful reduction in cPRA		Up to 78 weeks
Time to maximal reduction in cPRA from baseline		Up to 78 weeks
Duration of a reduction in peak anti-HLA alloantibody to MFI <5,000 or by ≥50% by SAB assay		Up to 78 weeks
Duration of maximal reduction in anti-HLA alloantibody MFI by SAB assay		Up to 78 weeks
Duration of maximal reduction in cPRA by SAB assay		Up to 78 weeks
Serum concentration of Immunoglobulin (Ig) classes over time		Up to 78 weeks
Percent change from baseline of serum concentration of Ig classes		Up to 78 weeks
Concentration of vonsetamig in serum over time		Up to 78 weeks
Incidence of treatment-emergent anti-drug antibodies (ADAs) to vonsetamig over time		Up to 78 weeks

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Karam S, Boudhabhay I, Jhaveri KD. Bispecific Antibodies for Glomerular Diseases: Are We Ready for Prime Time? J Am Soc Nephrol. 2026 Apr 14. doi: 10.1681/ASN.0000001120. Online ahead of print. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2022
• Primary Completion (Estimated): November 22, 2027
• Study Completion (Estimated): November 22, 2027

Study Registration Dates

• First Submitted: October 22, 2021
• First Submitted That Met QC Criteria: October 22, 2021
• First Posted (Actual): October 25, 2021

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Hemodialysis; Kidney Transplant; Desensitization; Human Leukocyte Antigen (HLA)
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Renal Insufficiency, Chronic
• Other Study ID Numbers: R5459-RT-1944

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No