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

Mack, Cara L.*; Spino, Cathie; Alonso, Estella M.; Bezerra, Jorge A.§; Moore, Jeffrey; Goodhue, Catherine||; Ng, Vicky L.; Karpen, Saul J.#; Venkat, Veena**; Loomes, Kathleen M.††; Wang, Kasper||; Sherker, Averell H.‡‡; Magee, John C.; Sokol, Ronald J.* and The ChiLDReN Network

Journal of Pediatric Gastroenterology and Nutrition: April 2019 - Volume 68 - Issue 4 - p 495–501
doi: 10.1097/MPG.0000000000002256
Clinical Trials: Hepatology
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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.

*Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO

University of Michigan, Ann Arbor, MI

Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL

§Cincinnati Children's Hospital Medical Center, Cincinnati, OH

||Children's Hospital Los Angeles, Los Angeles, CA

The Hospital for Sick Children, University of Toronto, Toronto, Canada

#Emory University School of Medicine, Atlanta, GA

**Children's Hospital of Pittsburgh, Pittsburgh

††Children's Hospital of Philadelphia, Philadelphia, PA

‡‡National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MA.

Address correspondence and reprint requests to Cara L. Mack, MD, Children's Hospital Colorado, University of Colorado School of Medicine, 13123 E. 16th Avenue, B290, Aurora, CO 80045 (e-mail: cara.mack@childrenscolorado.org).

Received 5 August, 2018

Accepted 26 November, 2018

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org).

This work was supported by U01 grants from the National Institute of Diabetes, Digestive and Kidney Diseases (DK 62497 to J.A.B.; DK 62470 to S.J.K.; DK 62481 to K.M.L.; DK 62456 to C.S.; DK 62466 to V.V.; DK 62453 to R.J.S.; DK 84538 to K.W.; DK 62436 to E.M.A.; and DK 642453 to V.L.N). In addition, the project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, UL1 TR001878 (The Children's Hospital of Philadelphia), Clinical Translational Science AwardsUL1 TR002535 (University of Colorado Denver) and the Cincinnati Center for Translational Science and Training (Cincinnati Children's Hospital). FFF Enterprises (Temecula, California) supplied and shipped the IVIg.

Clinical Trial Registration: Safety Study of Intravenous Immunoglobulin (IVIG) Post-Portoenterostomy in Infants with Biliary Atresia (PRIME); #NCT01854827; https://clinicaltrials.gov/ct2/show/NCT01854827.

The authors report no conflicts of interest.

© 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,