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Efficacy and safety of prolonged-release tacrolimus in stable pediatric allograft recipients converted from immediate-release tacrolimus - a Phase 2, open-label, single-arm, one-way crossover study.

Department of Nephrology, Kidney Transplantation and Hypertension, The Children's Memorial Health Institute, Warsaw, Poland. Pediatric Hepatology Unit, APHP-Hôpital Universitaire Necker, Paris, France. The Liver Unit, Birmingham Women's & Children's Hospital, Birmingham, UK. Pediatric Cardiology Unit, APHP-Hôpital Universitaire Necker, Paris, France. Department of Pediatric Nephrology, NIHR/Wellcome Trust Manchester Clinical Research Facility, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, University of Manchester, Manchester, UK. Department of Gastroenterology, Hepatology, Nutritional Disturbances and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland. Department of Pediatrics, Second School of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic. Department of Nephrology, Rheumatology, and Dermatology, Center for Rare Diseases, Civil Hospice of Lyon, 'Woman-Mother-Child' Hospital, Bron Cedex, France. Pediatric Hepatology, Gastroenterology and Transplantation, Civil Hospice of Lyon, Lyon, France. Department of Pediatrics, ISMETT-IRCCS, Palermo, Italy. Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany. Pediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy. Department of Pediatric Nephrology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK. Unité de Chirurgie et Transplantation Pédiatrique, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. BENKAZ Consulting Ltd, Cambridge, UK. Astellas Pharma Europe Ltd, Chertsey, UK.

Transplant international : official journal of the European Society for Organ Transplantation. 2019;(11):1182-1193
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Abstract

There are limited clinical data regarding prolonged-release tacrolimus (PR-T) use in pediatric transplant recipients. This Phase 2 study assessed the efficacy and safety of PR-T in stable pediatric kidney, liver, and heart transplant recipients (aged ≥5 to ≤16 years) over 1 year following conversion from immediate-release tacrolimus (IR-T), on a 1:1 mg total-daily-dose basis. Endpoints included the incidence of acute rejection (AR), a composite endpoint of efficacy failure (death, graft loss, biopsy-confirmed AR, and unknown outcome), and safety. Tacrolimus dose and whole-blood trough levels (target 3.5-15 ng/ml) were also evaluated. Overall, 79 patients (kidney, n = 48; liver, n = 29; heart, n = 2) were assessed. Following conversion, tacrolimus dose and trough levels remained stable; however, 7.6-17.7% of patients across follow-up visits had trough levels below the target range. Two (2.5%) patients had AR, and 3 (3.8%) had efficacy failure. No graft loss or deaths were reported. No new safety signals were identified. Drug-related treatment-emergent adverse events occurred in 28 patients (35.4%); most were mild, and all resolved. This study suggests that IR-T to PR-T conversion is effective and well tolerated over 1 year in pediatric transplant recipients and highlights the importance of therapeutic drug monitoring to maintain target tacrolimus trough levels.

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Publication Type : Clinical Trial ; Multicenter Study

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