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
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Kidney Disease (CKD) focused on measuring kidney transplant, hemodialysis, desensitization
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
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
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
No
Data Monitoring Committee
No
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
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 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
No
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
Email
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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