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

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.

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