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

Primary Purpose

Chronic Kidney Disease (CKD)

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

REGN5459

REGN5458

About this trial

This is an interventional treatment trial for Chronic Kidney Disease (CKD) focused on measuring kidney transplant, hemodialysis, desensitization

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

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

Key Exclusion Criteria:

Current or active malignancy not in remission for at least 1 year
Central nervous system (CNS) pathology or history of CNS neurodegenerative or movement disorders
Patients who have had their spleen removed, including patients with functional asplenia
Patients who have received a stem cell transplantation within 5 years
Use of investigational agents within 8 weeks or 5 half-lives of study drug administration (whichever is larger)
Hypogammaglobulinemia, defined as total plasma IgG <300 mg/dL at screening
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
Received a calcineurin inhibitor (eg, tacrolimus, cyclosporine) within 30 days of study drug administration
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
Prior treatment with any anti-BCMA antibody (including antibody drug conjugate or bsAb) or BCMA-directed CAR-T cell therapy
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

Sites / Locations

Cedars-Sinai Medical CenterRecruiting
University of California at San Francisco (UCSF) Connie Frank Transplant Center at UCSFRecruiting
Yale University School of Medicine Transplant SurgeryRecruiting
Northwestern University Comprehensive Transplant CenterRecruiting
New York University Langone Health - Transplant InstituteRecruiting
University of Pennsylvania-Penn Transplant InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

REGN5459

REGN5458

Arm Description

REGN5459 escalating dose

REGN5458 escalating dose

Outcomes

Primary Outcome Measures

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

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)

Secondary Outcome Measures

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

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

Percent change from baseline in the peak (immunodominant) MFI

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

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

Defined as peak anti-HLA alloantibody MFI <5,000 or ≥50% reduction

Maximum reduction in cPRA from baseline

Time to first clinically meaningful reduction in cPRA

Time to maximal reduction in cPRA from baseline

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

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

Duration of maximal reduction in cPRA by SAB assay

Serum concentration of Immunoglobulin(Ig) classes over time

Percent change from baseline of serum concentration of Ig classes

Concentration of REGN5458 in serum over time

Concentration of REGN5459 in serum over time

Incidence of treatment-emergent REGN5458 anti-drug antibodies (ADA) over time

Incidence of treatment-emergent REGN5459 ADA over time

Full Information

NCT ID

NCT05092347

First Posted

October 22, 2021

Last Updated

June 1, 2023

Sponsor

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT05092347

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 2, 2022 (Actual)

Primary Completion Date

October 21, 2025 (Anticipated)

Study Completion Date

October 21, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Kidney Disease (CKD)

Keywords

kidney transplant, hemodialysis, desensitization

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

REGN5459

Arm Type

Experimental

Arm Description

REGN5459 escalating dose

Arm Title

REGN5458

Arm Type

Experimental

Arm Description

REGN5458 escalating dose

Intervention Type

Drug

Intervention Name(s)

REGN5459

Other Intervention Name(s)

BCMAxCD3

Intervention Description

Administered by intravenous (IV) infusion

Intervention Type

Drug

Intervention Name(s)

REGN5458

Other Intervention Name(s)

BCMAxCD3, linvoseltamab

Intervention Description

Administered by intravenous (IV) infusion

Primary Outcome Measure Information:

Title

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

Time Frame

Up to approximately 4 weeks

Title

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

Description

TEAEs include adverse events of special interest (AESI) and serious adverse events (SAEs)

Time Frame

Up to 30 weeks

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Up to 30 weeks

Title

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

Time Frame

Up to 30 weeks

Title

Percent change from baseline in the peak (immunodominant) MFI

Time Frame

Up to 30 weeks

Title

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

Time Frame

Up to 30 weeks

Title

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

Description

Defined as peak anti-HLA alloantibody MFI <5,000 or ≥50% reduction

Time Frame

Up to 30 weeks

Title

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

Description

Defined as peak anti-HLA alloantibody MFI <5,000 or ≥50% reduction

Time Frame

Up to 30 weeks

Title

Maximum reduction in cPRA from baseline

Time Frame

Up to 30 weeks

Title

Time to first clinically meaningful reduction in cPRA

Time Frame

Up to 30 weeks

Title

Time to maximal reduction in cPRA from baseline

Time Frame

Up to 30 weeks

Title

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

Time Frame

Up to 30 weeks

Title

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

Time Frame

Up to 30 weeks

Title

Duration of maximal reduction in cPRA by SAB assay

Time Frame

Up to 30 weeks

Title

Serum concentration of Immunoglobulin(Ig) classes over time

Time Frame

Up to 30 weeks

Title

Percent change from baseline of serum concentration of Ig classes

Time Frame

Up to 30 weeks

Title

Concentration of REGN5458 in serum over time

Time Frame

Up to 30 weeks

Title

Concentration of REGN5459 in serum over time

Time Frame

Up to 30 weeks

Title

Incidence of treatment-emergent REGN5458 anti-drug antibodies (ADA) over time

Time Frame

Up to 30 weeks

Title

Incidence of treatment-emergent REGN5459 ADA over time

Time Frame

Up to 30 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: 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 Adequate hematologic and adequate hepatic function as defined in the protocol Willing and able to comply with clinic visits and study-related procedures Key Exclusion Criteria: Current or active malignancy not in remission for at least 1 year Central nervous system (CNS) pathology or history of CNS neurodegenerative or movement disorders Patients who have had their spleen removed, including patients with functional asplenia Patients who have received a stem cell transplantation within 5 years Use of investigational agents within 8 weeks or 5 half-lives of study drug administration (whichever is larger) Hypogammaglobulinemia, defined as total plasma IgG <300 mg/dL at screening 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 Received a calcineurin inhibitor (eg, tacrolimus, cyclosporine) within 30 days of study drug administration 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 Prior treatment with any anti-BCMA antibody (including antibody drug conjugate or bsAb) or BCMA-directed CAR-T cell therapy 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Clinical Trials Administrator

Phone

844-734-6643

clinicaltrials@regeneron.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trial Management

Organizational Affiliation

Regeneron Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Cedars-Sinai Medical Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90048

Country

United States

Individual Site Status

Recruiting

Facility Name

University of California at San Francisco (UCSF) Connie Frank Transplant Center at UCSF

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Individual Site Status

Recruiting

Facility Name

Yale University School of Medicine Transplant Surgery

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06519

Country

United States

Individual Site Status

Recruiting

Facility Name

Northwestern University Comprehensive Transplant Center

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Individual Site Status

Recruiting

Facility Name

New York University Langone Health - Transplant Institute

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Individual Site Status

Recruiting

Facility Name

University of Pennsylvania-Penn Transplant Institute

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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 URL

https://vivli.org/

Learn more about this trial

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

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