Safety Study of Intravenous Immunoglobulin (IVIG) Post-Portoenterostomy in Infants With Biliary Atresia

Condition(s) targeted: Biliary Atresia

Intervention: Intravenous immunoglobulin (IVIG) (Drug)

Phase: Phase 1/Phase 2

Status: Enrolling by invitation

Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Official(s) and/or principal investigator(s):
Ronald Sokol, MD, Study Chair, Affiliation: Children's Hospital Colorado
Ed Doo, MD, Study Director, Affiliation: National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
Averell Sherker, MD, Study Director, Affiliation: National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

The Children Liver Disease Research and Education Network (ChiLDREN) is conducting a clinical trial to determine the feasibility, acceptability, tolerability and safety profile of IVIG treatment administered to infants after hepatic portoenterostomy (HPE) for biliary atresia, as well as investigate preliminary evidence of activity and explore mechanisms of action.

Official title: A Phase 1/2A Trial of Intravenous Immunoglobulin (IVIG) Therapy Following Portoenterostomy in Infants With Biliary Atresia

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Feasibility of IVIG treatment

Acceptability of IVIG

Serious Adverse Events

Level 3-5 toxicity

Adverse events

Secondary outcome:

Good bile drainage at 90 days post-HPE

Good bile drainage at 180 days post-HPE

Good bile drainage at 360 days post-HPE

Transplant-free survival

Circulating regulatory T-Cells, inflammatory cytokines, and specific autoantibodies.

Detailed description: In this multicenter prospective phase 1/2A open label trial, the feasibility, tolerability and safety of intravenous immunoglobulin (IVIG) therapy following hepatic portoenterostomy (HPE) will be assessed in 29 infants with biliary atresia (BA), efficacy will be estimated and exploratory mechanistic research studies will be performed. After written consent is obtained from the parent or guardian, the subject will be enrolled and will receive three intravenous doses of IVIG at designated intervals over the first 60 days following HPE and will be followed for 360 days after enrollment. Blood will also be obtained during this study to assess potential mechanisms by which the IVIG may alter or reduce bile duct inflammation and injury and improve bile flow. All infants in this trial will also be treated with standardized doses of other routine standard-of-care treatments for BA during this trial (ursodeoxycholic acid, trimethoprim-sulfamethoxasole, and fat-soluble vitamin supplements). This routine clinical care will not be modified by participation in this study. Subjects in this study will not receive corticosteroid therapy for treatment of biliary atresia, as this is of unproven benefit at the present time.

Minimum age: N/A. Maximum age: 120 Days. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Infant under 120 days old with established diagnosis of BA. Subjects in this trial

must start treatment within 3-5 days of the Kasai procedure and be part of a prospective study of the natural history of biliary atresia also being conducted by ChiLDREN (http://www. clinicaltrials. gov/ct/show/NCT00061828?order=3).

- Standard HPE operation has been performed for BA within the previous 3 days

- Post-conception age ≥ 36 weeks at time of enrollment

- Weight at enrolment ≥ 2000 gm

- Written informed consent to participate in the study obtained within 3 days of

completion of HPE. Exclusion Criteria:

- Laparoscopic HPE or "gall bladder Kasai" (cholecysto-portostomy) surgery was

performed

- Biliary atresia splenic malformation syndrome (presence of asplenia, polysplenia or

double spleen)

- History of a hypercoagulable disorder

- Renal Disease defined as serum creatinine > 1. 0 mg/dl prior to enrollment or

presence of complex renal anomalies found on imaging

- Evidence of congestive heart failure or fluid overload

- Presence of significant systemic hypertension for age (defined as persistent systolic

blood pressure ≥112 mmHg measured on at least 3 occasions following HPE)

- Infants whose mother is known to have human immunodeficiency virus infection

- Infants whose mother is known to be serum HBsAg or hepatitis C virus antibody

positive

- Previous treatment with intravenous immunoglobulin therapy or corticosteroid therapy

- Previous treatment with any other investigational agent

- History of allergic reaction to any human blood product infusion

- Infants with other severe concurrent illnesses, such as neurological, cardiovascular,

pulmonary, metabolic, endocrine, and renal disorders, that would interfere with the conduct and results of the study

- Any other clinical condition that is a contraindication to the use of IVIG

Children's Hospital Los Angeles, Los Angeles, California 90027, United States

Children's Hospital Colorado, Aurora, Colorado 80045, United States

Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States

Ann and Peter H. Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, United States

Children's Hospital Medical Center, Cincinnati, Ohio 45229, United States

Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States

Children's Hospital at Pittsburgh, Pittsburgh, Pennsylvania 15213, United States

Click here for more information about the Children Liver Disease Research and Education Network (ChiLDREN)

Starting date: October 2013
Last updated: September 15, 2014