Study for Desensitization of Chronic Kidney Disease in Adult Patients in Need of a Kidney Transplant Who Are Highly Sensitized to Human Leukocyte Antigen

A Dose Escalation and Proof-of-Concept Study of REGN5459 or REGN5458 (BCMA × CD3 Bispecific Antibodies) for Desensitization of Chronic Kidney Disease Patients in Need of Kidney Transplantation Who Are Highly Sensitized to Human Leukocyte Antigen

The primary objective of the study is to assess the safety and tolerability of REGN5459 (Part A) or REGN5458 (Part B) as monotherapy in patients with chronic kidney disease (CKD) who need kidney transplantation and are highly sensitized to human leukocyte antigen (HLA).

The secondary objectives of the study are to determine/assess the following for REGN5459 (Part A) or REGN5458 (Part B):

• Dose regimen(s) that result in a clinically meaningful reduction of anti-HLA alloantibody levels
• Effect on calculated panel-reactive antibody (cPRA) levels
• Time to maximal and clinically meaningful reduction in anti-HLA alloantibody levels
• Duration of the effect of study drug on the reduction of anti-HLA alloantibodies
• Effect on circulating immunoglobulin (Ig) classes (isotypes)
• Pharmacokinetics (PK) properties
• Immunogenicity

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Disease (CKD)
• Intervention / Treatment: Drug: REGN5458; Drug: REGN5459

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
    • Orange, California, United States, 92868
      • Recruiting
      • University of California, Irvine
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California at San Francisco (UCSF) Connie Frank Transplant Center at UCSF
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • Yale University School of Medicine Transplant Surgery
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University Comprehensive Transplant Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Johns Hopkins Hospital
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • New York University Langone Health - Transplant Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania-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
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. Hypogammaglobulinemia, defined as 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 6 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
11. Has received a COVID-19 vaccination within 1 week of planned start of study drug, or for which the planned COVID-19 vaccination would not be completed 1 week before start of study drug

Note: Other protocol defined inclusion / exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REGN5459; REGN5459 escalating dose	Drug: REGN5459; Administered by intravenous (IV) infusion; Other Names: BCMAxCD3
Experimental: REGN5458; REGN5458 escalating dose	Drug: REGN5458; Administered by intravenous (IV) infusion; Other Names: linvoseltamab; BCMAxCD3

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 4 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 30 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 30 weeks
Maximum reduction in the peak (immunodominant) MFI of anti-HLA alloantibodies from baseline		Up to 30 weeks
Percent change from baseline in the peak (immunodominant) MFI		Up to 30 weeks
Percent change from baseline in the sum of MFI of anti-HLA alloantibodies using the SAB assay		Up to 30 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 30 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 30 weeks
Maximum reduction in cPRA from baseline		Up to 30 weeks
Time to first clinically meaningful reduction in cPRA		Up to 30 weeks
Time to maximal reduction in cPRA from baseline		Up to 30 weeks
Duration of a reduction in peak anti-HLA alloantibody to MFI <5,000 or by ≥50% by SAB assay		Up to 30 weeks
Duration of maximal reduction in anti-HLA alloantibody MFI by SAB assay		Up to 30 weeks
Duration of maximal reduction in cPRA by SAB assay		Up to 30 weeks
Serum concentration of Immunoglobulin(Ig) classes over time		Up to 30 weeks
Percent change from baseline of serum concentration of Ig classes		Up to 30 weeks
Concentration of REGN5458 in serum over time		Up to 30 weeks
Concentration of REGN5459 in serum over time		Up to 30 weeks
Incidence of treatment-emergent REGN5458 anti-drug antibodies (ADA) over time		Up to 30 weeks
Incidence of treatment-emergent REGN5459 ADA over time		Up to 30 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2022
• Primary Completion (Estimated): October 21, 2025
• Study Completion (Estimated): October 21, 2025

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 (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: hemodialysis; kidney transplant; desensitization
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; 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: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data 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, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• 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