Efficacy and safety of bleselumab in kidney transplant recipients: A phase 2, randomized, open-label, noninferiority study

Robert C. Harland, Goran Klintmalm, Stephen Jensik, Harold Yang, Jonathan Bromberg, John Holman, Mysore S.A. Kumar, Vicki Santos, Tami J. Larson, Xuegong Wang

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

This study assessed the efficacy and safety of the anti-CD40 monoclonal antibody bleselumab (ASKP1240) in de novo kidney transplant recipients over 36 months posttransplant. Transplant recipients were randomized (1:1:1) to standard of care (SoC: 0.1 mg/kg per day immediate-release tacrolimus [IR-TAC]; target minimum blood concentration [Ctrough] 4-11 ng/mL plus 1 g mycophenolate mofetil [MMF] twice daily) or bleselumab (200 mg on days 0/7/14/28/42/56/70/90, and monthly thereafter) plus either MMF or IR-TAC (0.1 mg/kg per day; target Ctrough 4-11 ng/mL days 0-30, then 2-5 ng/mL). All received basiliximab induction (20 mg pretransplant and on days 3-5 posttransplant) and corticosteroids. One hundred thirty-eight transplant recipients received ≥1 dose of study drug (SoC [n = 48]; bleselumab + MMF [n = 46]; bleselumab + IR-TAC [n = 44]). For the primary endpoint (incidence of biopsy-proven acute rejection [BPAR] at 6 months), bleselumab + IR-TAC was noninferior to SoC (difference 2.8%; 95% confidence interval [CI] −8.1% to 13.8%), and bleselumab + MMF did not demonstrate noninferiority to SoC (difference 30.7%; 95% CI 15.2%-46.2%). BPAR incidence slightly increased through month 36 in all groups, with bleselumab + IR-TAC continuing to demonstrate noninferiority to SoC. Bleselumab had a favorable benefit–risk ratio. Most treatment-emergent adverse events were as expected for kidney transplant recipients (ClinicalTrials.gov NCT01780844).

Original languageEnglish (US)
Pages (from-to)159-171
Number of pages13
JournalAmerican Journal of Transplantation
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • clinical research/practice
  • immunosuppressant —fusion proteins and monoclonal antibodies
  • immunosuppressant—antiproliferative agent: mycophenolate mofetil
  • immunosuppressant—calcineurin inhibitor: tacrolimus
  • immunosuppression/immune modulation
  • kidney transplantation/nephrology
  • kidney transplantation: living donor
  • translational research/science

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Harland, R. C., Klintmalm, G., Jensik, S., Yang, H., Bromberg, J., Holman, J., Kumar, M. S. A., Santos, V., Larson, T. J., & Wang, X. (2020). Efficacy and safety of bleselumab in kidney transplant recipients: A phase 2, randomized, open-label, noninferiority study. American Journal of Transplantation, 20(1), 159-171. https://doi.org/10.1111/ajt.15591