Efficacy and safety of bleselumab in kidney transplant recipients: A phase 2, randomized, open-label, noninferiority study
Autor: | Tami Jo Larson, Jonathan S. Bromberg, Stephen Jensik, Goran B. Klintmalm, Vicki Santos, Xuegong Wang, Robert C. Harland, Mysore S Anil Kumar, Harold Yang, John Holman |
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Rok vydání: | 2018 |
Předmět: |
Graft Rejection
Male medicine.medical_specialty Basiliximab Urology Equivalence Trials as Topic 030230 surgery Antibodies Monoclonal Humanized Kidney transplant Tacrolimus 03 medical and health sciences 0302 clinical medicine Postoperative Complications Risk Factors Clinical endpoint medicine Immunology and Allergy Humans Pharmacology (medical) Adverse effect Transplantation business.industry Incidence (epidemiology) Graft Survival Middle Aged Mycophenolic Acid Prognosis Kidney Transplantation Confidence interval Transplant Recipients Kidney Failure Chronic Female Open label business Immunosuppressive Agents medicine.drug Follow-Up Studies |
Zdroj: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant SurgeonsREFERENCES. 20(1) |
ISSN: | 1600-6143 |
Popis: | 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). |
Databáze: | OpenAIRE |
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