Efficacy and safety of bleselumab in kidney transplant recipients: A phase 2, randomized, open-label, noninferiority study.Harland, R. C., Klintmalm, G. et al. (2019).
American Journal of Transplantation [record in progress].
This study aimed to assess the efficacy and safety of the anti-CD40 monoclonal antibody bleselumab (ASKP1240) in de novo kidney transplant recipients over 36 months post-transplant.
Transplant recipients were randomized (1:1:1) to standard of care (SoC: 0.1 mg/kg/day immediate-release tacrolimus [IR-TAC]] 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/day; target Ctrough 4–11 ng/mL days 0–30, then 2–5 ng/mL).
149 de novo kidney transplant recipients (>18 years of age; men and women) were randomized in this study.
Primary outcomes were reported as the proportion of kidney transplant recipients with biopsy-proven acute (T- or B-cell) rejection (BPAR; Banff grade ≥1). Secondary endpoints of this study, through 6 months, were the estimated glomerular filtration rate (eGFR), kidney transplant recipient survival, and graft survival. Other endpoints were also included, including efficacy failure (defined as death, graft loss, BPAR, or lost to follow-up), time to first BPAR, time to first clinically-treated BPAR and incidence of transplant recipients experiencing multiple rejection episodes.
Bleselumab is an human anti-CD40 monoclonal antibody. This phase II non-inferiority study compared 3 immunosuppressive regimens in de-novo renal transplant recipients: (1) tacrolimus (target 4-11 ng/ml) and MMF, (2) bleselumab and MMF and (3) bleselumab and tacrolimus (target 2-5 ng/ml). All patients received basiliximb induction and corticosteroids. The primary endpoint, biopsy-proven acute rejection, was seen in 6.3% of standard-care patients, 9.1% of bleselumab and Tac patients, and 37% of bleselumab and MMF patients. Renal function and graft survival did not differ significantly between groups. Safety profiles differed, with more derangements of hepatic function seen in the bleselumab arms and slightly higher incidences of malignancy and BK virus infection in the bleselumab and tacrolimus arm. Bleselumab shows some promise as an alternative immunosuppressant to be used in conjunction with tacrolimus. Whilst trough tacrolimus levels were consistently lower in the bleselumab group, they did not reach the target of <5 ng/ml until around month 6 post-transplant. It is therefore not certain to what degree bleselumab allows CNI sparing. Further, larger studies will also be required to investigate the impact on infection and malignancy risk compared to standard care.
ClinicalTrials.gov - NCT01780844