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 language | English (US) |
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Pages (from-to) | 159-171 |
Number of pages | 13 |
Journal | American Journal of Transplantation |
Volume | 20 |
Issue number | 1 |
DOIs | |
State | Published - 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)