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)

Phase 2RecruitingNCT05092347

Regeneron Pharmaceuticals56 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Chronic Kidney Disease (CKD)

Interventions

Vonsetamig

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (10)

Cedars-Sinai Medical Center

Los Angeles, California, United States

RECRUITING

University of California Irvine

Orange, California, United States

RECRUITING

Connie Frank Transplant Center at UCSF

San Francisco, California, United States

RECRUITING

Yale University of Medicine

New Haven, Connecticut, United States

RECRUITING

Medstar Georgetown Transplant Institute - 2-PHC

Washington D.C., District of Columbia, United States

RECRUITING

Comprehensive Transplant Center

Chicago, Illinois, United States

RECRUITING

John Hopkins Hospital

Baltimore, Maryland, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

RECRUITING

New York University Langone Health

New York, New York, United States

RECRUITING

Penn Transplant Institute

Philadelphia, Pennsylvania, United States

RECRUITING

Outcomes

Primary Outcomes

Incidence of adverse event(s) of interest (AEI) from the first dose through end of the safety observation period

Time frame: 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)

Time frame: Up to 78 weeks

Secondary Outcomes

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

Time frame: Up to 78 weeks

Maximum reduction in the peak (immunodominant) MFI of anti-HLA alloantibodies from baseline

Time frame: Up to 78 weeks

Percent change from baseline in the peak (immunodominant) MFI

Time frame: Up to 78 weeks

Percent change from baseline in the sum of MFI of anti-HLA alloantibodies using the SAB assay

Time frame: 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

Time frame: 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

Time frame: Up to 78 weeks

Maximum reduction in cPRA from baseline

Time frame: Up to 78 weeks

Time to first clinically meaningful reduction in cPRA

Time frame: Up to 78 weeks

Time to maximal reduction in cPRA from baseline

Time frame: Up to 78 weeks

Duration of a reduction in peak anti-HLA alloantibody to MFI <5,000 or by ≥50% by SAB assay

Time frame: Up to 78 weeks

Duration of maximal reduction in anti-HLA alloantibody MFI by SAB assay

Time frame: Up to 78 weeks

Duration of maximal reduction in cPRA by SAB assay

Time frame: Up to 78 weeks

Serum concentration of Immunoglobulin (Ig) classes over time

Time frame: Up to 78 weeks

Percent change from baseline of serum concentration of Ig classes

Time frame: Up to 78 weeks

Concentration of vonsetamig in serum over time

Time frame: Up to 78 weeks

Incidence of treatment-emergent anti-drug antibodies (ADAs) to vonsetamig over time

Time frame: Up to 78 weeks

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)

Overview

Conditions

Interventions

Eligibility

Locations (10)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts