Efficacy and safety of bleselumab in kidney transplant recipients: A phase 2, randomized, open‐label, noninferiority study. Issue 1 (19th October 2019)

• Record Type: Journal Article
• Authors: Harland, Robert C.; Klintmalm, Goran; Jensik, Stephen; Yang, Harold; Bromberg, Jonathan; Holman, John; Kumar, Mysore S. A.; Santos, Vicki; Larson, Tami J.; Wang, Xuegong
• Is Part Of: American journal of transplantation. Volume 20:Issue 1(2020)
• Page Start: 159
• Page End: 171
• Publication Date: 2019-10-19
• Subjects: clinical research/practice -- immunosuppressant—antiproliferative agent: mycophenolate mofetil -- immunosuppressant—calcineurin inhibitor: tacrolimus -- immunosuppressant —fusion proteins and monoclonal antibodies -- immunosuppression/immune modulation -- kidney transplantation/nephrology -- kidney transplantation: living donor -- translational research/science; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.15591
• Languages: English
• ISSNs: 1600-6135

Abstract

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). Abstract : In this phase 2a, randomized, open‐label study in kidney transplant recipients, bleselumab (a nondepleting, fully human, anti‐CD40 monoclonal antibody) + immediate‐release tacrolimus demonstrates noninferiority, but bleselumab + mycophenolate mofetil does not, versus the standard of care (immediate‐release tacrolimus + mycophenolate mofetil) for the prevention of biopsy‐proven acute rejection, but both bleselumab groups demonstrate a favorable benefit–risk ratio, with safety profiles that are as expected for this patient population. See the related article by Vincenti et al on page 172 .