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Am J Transplant. 2019 Sep 11. doi: 10.1111/ajt.15591. [Epub ahead of print]

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

Author information

1
Department of Surgery, University of Arizona, Tucson, Arizona.
2
Department of Transplantation Services, Annette C. and Harold C. Simmons Transplant Institute, Dallas, Texas.
3
Department of Surgery, Rush University, Chicago, Illinois.
4
Department of Surgery, Pinnacle Health Transplant Associates, Harrisburg, Pennsylvania.
5
Department of Surgery, University of Maryland, Baltimore, Maryland.
6
Astellas Pharma Global Development, Inc., Northbrook, Illinois.

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).

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

PMID:
31509331
DOI:
10.1111/ajt.15591

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