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

Sponsor
Regeneron Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05092347
Collaborator
(none)
60
3
2
38.6
20
0.5

Study Details

Study Description

Brief Summary

The primary objective of the study is to assess the safety and tolerability of REGN5459 (Part

  1. 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

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Aug 2, 2022
Anticipated Primary Completion Date :
Oct 21, 2025
Anticipated Study Completion Date :
Oct 21, 2025

Arms and Interventions

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:
  • BCMAxCD3
  • Outcome Measures

    Primary Outcome Measures

    1. Incidence of adverse event(s) of interest (AEI) from the first dose through end of the safety observation period [Up to 28 weeks]

    2. Incidence and severity of treatment-emergent adverse events (TEAE)s from the first study drug dose up to the end of the study [Up to 28 weeks]

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

    Secondary Outcome Measures

    1. Proportion of Participants with a clinically meaningful reduction in anti-HLA alloantibodies [Up to 28 weeks]

      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

    2. Maximum reduction in the peak (immunodominant) MFI of anti-HLA alloantibodies from baseline [Up to 28 weeks]

    3. Percent change from baseline in the peak (immunodominant) MFI [Up to 28 weeks]

    4. Percent change from baseline in the sum of MFI of anti-HLA alloantibodies using the SAB assay [Up to 28 weeks]

    5. Time to first clinically meaningful reduction in anti-HLA alloantibody levels by SAB assay [Up to 28 weeks]

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

    6. Time to maximal reduction in anti-HLA alloantibody levels by SAB assay [Up to 28 weeks]

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

    7. Maximum reduction in cPRA from baseline [Up to 28 weeks]

    8. Time to first clinically meaningful reduction in cPRA [Up to 28 weeks]

    9. Time to maximal reduction in cPRA from baseline [Up to 28 weeks]

    10. Duration of a reduction in peak anti-HLA alloantibody to MFI <5,000 or by ≥50% by SAB assay [Up to 28 weeks]

    11. Duration of maximal reduction in anti-HLA alloantibody MFI by SAB assay [Up to 28 weeks]

    12. Duration of maximal reduction in cPRA by SAB assay [Up to 28 weeks]

    13. Serum concentration of Immunoglobulin(Ig) classes over time [Up to 28 weeks]

    14. Percent change from baseline of serum concentration of Ig classes [Up to 28 weeks]

    15. Concentration of REGN5458 in serum over time [Up to 28 weeks]

    16. Concentration of REGN5459 in serum over time [Up to 28 weeks]

    17. Incidence of treatment-emergent REGN5458 anti-drug antibodies (ADA) over time [Up to 28 weeks]

    18. Incidence of treatment-emergent REGN5459 ADA over time [Up to 28 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Yale University School of Medicine Transplant Surgery New Haven Connecticut United States 06519
    2 New York University Langone Health - Transplant Institute New York New York United States 10016
    3 University of Pennsylvania-Penn Transplant Institute Philadelphia Pennsylvania United States 19104

    Sponsors and Collaborators

    • Regeneron Pharmaceuticals

    Investigators

    • Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Regeneron Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT05092347
    Other Study ID Numbers:
    • R5459-RT-1944
    First Posted:
    Oct 25, 2021
    Last Update Posted:
    Aug 19, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Regeneron Pharmaceuticals
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 19, 2022