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

Description

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

Trial Eligibility

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 Info

Interventions

Locations Recruiting

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