A Phase I/IIa Trial of Intravenous Immunoglobulin Following Portoenterostomy in Biliary Atresia

and The ChiLDReN Network

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

OBJECTIVES: Biliary atresia (BA) is a progressive neonatal fibroinflammatory cholangiopathy. We hypothesized that intravenous immunoglobulin (IVIg) would be safe, feasible, acceptable, and efficacious for the treatment of BA. The primary objective of this study was to establish the feasibility, acceptability, and safety profile of IVIg administration after hepatoportoenterostomy (HPE) in BA. The secondary objective was to determine the treatment efficacy of IVIg based on good bile drainage and survival with the native liver. METHODS: A multicenter, prospective, open-labeled, phase I/IIA trial of IVIg was conducted, with 1 g/kg/dose of IVIg infused at 3-5, 30, and 60 days post-HPE, and subjects followed for 360 days post-HPE. Twenty-nine participants completed the study. RESULTS: Administration of IVIg infusions was feasible and acceptable in 79%. None of the serious adverse events (SAEs) were directly related to IVIg infusions; however, 90% of participants had an SAE. Compared with a historical placebo-arm group, there was no significant increase in the proportion of IVIg participants with a serum total bilirubin <1.5 mg/dL at 90, 180, or 360 days post-HPE. Survival with the native liver in the IVIg participants showed no significant benefit over the historical placebo arm, with a difference at 360 days of -11.9% (IVIg: 58.6%, placebo: 70.5%; 90% UCB: 2.1%; P > 0.05). CONCLUSIONS: Although IVIg infusions in infants with BA post-HPE were feasible, acceptable and safe, there was no trend to lower bilirubin levels or improved 360-day survival with the native liver. CLINICAL TRIAL: Safety Study of Intravenous Immunoglobulin Post-Portoenterostomy in Biliary Atresia; #NCT01854827.

Original languageEnglish (US)
Pages (from-to)495-501
Number of pages7
JournalJournal of pediatric gastroenterology and nutrition
Volume68
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

Biliary Atresia
Intravenous Immunoglobulins
Intravenous Infusions
Bilirubin
Safety
Liver
Bile
Intravenous Administration
Drainage
Placebos

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Gastroenterology

Cite this

@article{5dc26e60470341738cdffc02879c427c,
title = "A Phase I/IIa Trial of Intravenous Immunoglobulin Following Portoenterostomy in Biliary Atresia",
abstract = "OBJECTIVES: Biliary atresia (BA) is a progressive neonatal fibroinflammatory cholangiopathy. We hypothesized that intravenous immunoglobulin (IVIg) would be safe, feasible, acceptable, and efficacious for the treatment of BA. The primary objective of this study was to establish the feasibility, acceptability, and safety profile of IVIg administration after hepatoportoenterostomy (HPE) in BA. The secondary objective was to determine the treatment efficacy of IVIg based on good bile drainage and survival with the native liver. METHODS: A multicenter, prospective, open-labeled, phase I/IIA trial of IVIg was conducted, with 1 g/kg/dose of IVIg infused at 3-5, 30, and 60 days post-HPE, and subjects followed for 360 days post-HPE. Twenty-nine participants completed the study. RESULTS: Administration of IVIg infusions was feasible and acceptable in 79{\%}. None of the serious adverse events (SAEs) were directly related to IVIg infusions; however, 90{\%} of participants had an SAE. Compared with a historical placebo-arm group, there was no significant increase in the proportion of IVIg participants with a serum total bilirubin <1.5 mg/dL at 90, 180, or 360 days post-HPE. Survival with the native liver in the IVIg participants showed no significant benefit over the historical placebo arm, with a difference at 360 days of -11.9{\%} (IVIg: 58.6{\%}, placebo: 70.5{\%}; 90{\%} UCB: 2.1{\%}; P > 0.05). CONCLUSIONS: Although IVIg infusions in infants with BA post-HPE were feasible, acceptable and safe, there was no trend to lower bilirubin levels or improved 360-day survival with the native liver. CLINICAL TRIAL: Safety Study of Intravenous Immunoglobulin Post-Portoenterostomy in Biliary Atresia; #NCT01854827.",
author = "{and The ChiLDReN Network} and Mack, {Cara L.} and Cathie Spino and Alonso, {Estella M} and Bezerra, {Jorge A.} and Jeffrey Moore and Catherine Goodhue and Ng, {Vicky L.} and Karpen, {Saul J.} and Veena Venkat and Loomes, {Kathleen M.} and Kasper Wang and Sherker, {Averell H.} and Magee, {John C.} and Sokol, {Ronald J.}",
year = "2019",
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doi = "10.1097/MPG.0000000000002256",
language = "English (US)",
volume = "68",
pages = "495--501",
journal = "Journal of Pediatric Gastroenterology and Nutrition",
issn = "0277-2116",
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number = "4",

}

A Phase I/IIa Trial of Intravenous Immunoglobulin Following Portoenterostomy in Biliary Atresia. / and The ChiLDReN Network.

In: Journal of pediatric gastroenterology and nutrition, Vol. 68, No. 4, 01.04.2019, p. 495-501.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Phase I/IIa Trial of Intravenous Immunoglobulin Following Portoenterostomy in Biliary Atresia

AU - and The ChiLDReN Network

AU - Mack, Cara L.

AU - Spino, Cathie

AU - Alonso, Estella M

AU - Bezerra, Jorge A.

AU - Moore, Jeffrey

AU - Goodhue, Catherine

AU - Ng, Vicky L.

AU - Karpen, Saul J.

AU - Venkat, Veena

AU - Loomes, Kathleen M.

AU - Wang, Kasper

AU - Sherker, Averell H.

AU - Magee, John C.

AU - Sokol, Ronald J.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - OBJECTIVES: Biliary atresia (BA) is a progressive neonatal fibroinflammatory cholangiopathy. We hypothesized that intravenous immunoglobulin (IVIg) would be safe, feasible, acceptable, and efficacious for the treatment of BA. The primary objective of this study was to establish the feasibility, acceptability, and safety profile of IVIg administration after hepatoportoenterostomy (HPE) in BA. The secondary objective was to determine the treatment efficacy of IVIg based on good bile drainage and survival with the native liver. METHODS: A multicenter, prospective, open-labeled, phase I/IIA trial of IVIg was conducted, with 1 g/kg/dose of IVIg infused at 3-5, 30, and 60 days post-HPE, and subjects followed for 360 days post-HPE. Twenty-nine participants completed the study. RESULTS: Administration of IVIg infusions was feasible and acceptable in 79%. None of the serious adverse events (SAEs) were directly related to IVIg infusions; however, 90% of participants had an SAE. Compared with a historical placebo-arm group, there was no significant increase in the proportion of IVIg participants with a serum total bilirubin <1.5 mg/dL at 90, 180, or 360 days post-HPE. Survival with the native liver in the IVIg participants showed no significant benefit over the historical placebo arm, with a difference at 360 days of -11.9% (IVIg: 58.6%, placebo: 70.5%; 90% UCB: 2.1%; P > 0.05). CONCLUSIONS: Although IVIg infusions in infants with BA post-HPE were feasible, acceptable and safe, there was no trend to lower bilirubin levels or improved 360-day survival with the native liver. CLINICAL TRIAL: Safety Study of Intravenous Immunoglobulin Post-Portoenterostomy in Biliary Atresia; #NCT01854827.

AB - OBJECTIVES: Biliary atresia (BA) is a progressive neonatal fibroinflammatory cholangiopathy. We hypothesized that intravenous immunoglobulin (IVIg) would be safe, feasible, acceptable, and efficacious for the treatment of BA. The primary objective of this study was to establish the feasibility, acceptability, and safety profile of IVIg administration after hepatoportoenterostomy (HPE) in BA. The secondary objective was to determine the treatment efficacy of IVIg based on good bile drainage and survival with the native liver. METHODS: A multicenter, prospective, open-labeled, phase I/IIA trial of IVIg was conducted, with 1 g/kg/dose of IVIg infused at 3-5, 30, and 60 days post-HPE, and subjects followed for 360 days post-HPE. Twenty-nine participants completed the study. RESULTS: Administration of IVIg infusions was feasible and acceptable in 79%. None of the serious adverse events (SAEs) were directly related to IVIg infusions; however, 90% of participants had an SAE. Compared with a historical placebo-arm group, there was no significant increase in the proportion of IVIg participants with a serum total bilirubin <1.5 mg/dL at 90, 180, or 360 days post-HPE. Survival with the native liver in the IVIg participants showed no significant benefit over the historical placebo arm, with a difference at 360 days of -11.9% (IVIg: 58.6%, placebo: 70.5%; 90% UCB: 2.1%; P > 0.05). CONCLUSIONS: Although IVIg infusions in infants with BA post-HPE were feasible, acceptable and safe, there was no trend to lower bilirubin levels or improved 360-day survival with the native liver. CLINICAL TRIAL: Safety Study of Intravenous Immunoglobulin Post-Portoenterostomy in Biliary Atresia; #NCT01854827.

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U2 - 10.1097/MPG.0000000000002256

DO - 10.1097/MPG.0000000000002256

M3 - Article

VL - 68

SP - 495

EP - 501

JO - Journal of Pediatric Gastroenterology and Nutrition

JF - Journal of Pediatric Gastroenterology and Nutrition

SN - 0277-2116

IS - 4

ER -