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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
All participants will receive the same dose of IVIG at the same intervals in an open-label fashion as long as the subject does not have any increased risk for toxicity for any IVIG infusion. IVIG will be initiated on day 3 (up to day 5) after HPE surgery (HPE is day 0) at a dose of 1 gm/kg body weight by slow intravenous infusion over at least 4 hours. The same dose (1 gm/kg) and duration of infusion will be repeated on day 30 and day 60 after HPE.
Children's Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, United States
Children's Hospital Medical Center
Cincinnati, Ohio, United States
Feasibility of IVIG Treatment
Percentage of subjects for whom administration of IVIG is feasible, defined as the successful administration (at least 80% of each dose) of all 3 doses of IVIG
Time frame: 60 days post-HPE
Acceptability of IVIG
Percentage of subjects for whom the study is acceptable, defined as the ability of the subject's family or guardian to allow intravenous line placements, blood draws, and other study procedures for the study subjects.
Time frame: 60 days post-HPE
Serious Adverse Events
Percentage of subjects with any serious adverse events (SAEs) prior to liver transplant
Time frame: 360 days post-HPE
Level 3-5 Toxicity
Percentage of subjects with any level 3, 4, or 5 toxicity (per NCI CTEP grading system)
Time frame: 360 days post-HPE
Adverse Events
Percentage of subjects with other expected adverse events
Time frame: 360 days post-HPE
Good Bile Drainage at 90 Days Post-HPE
Percentage of subjects who survive 90 days after HPE with both their native liver and serum total bilirubin \<1.5 mg/dL at 90 days after HPE
Time frame: 90 days post-HPE
Good Bile Drainage at 180 Days Post-HPE
Percentage of subjects who survive 180 days after HPE with both their native liver and serum total bilirubin \<1.5 mg/dL at 180 days after HPE
Time frame: 180 days post-HPE
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Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital at Pittsburgh
Pittsburgh, Pennsylvania, United States
Hospital for Sick Children
Toronto, Ontario, Canada
Good Bile Drainage at 360 Days Post-HPE
Percentage of subjects who survive 360 days after HPE with both their native liver and serum total bilirubin \<1.5 mg/dL at 360 days after HPE
Time frame: 360 days post-HPE
Transplant-free Survival
Percentage of subjects who survive with their native liver at 360 days after HPE.
Time frame: 360 days post-HPE
Circulating Regulatory T-Cells, Inflammatory Cytokines, and Specific Autoantibodies.
Percentage and absolute number of Tregs (CD4+CD25+FoxP3+), CD3/4 T cells, CD3/8 T cells, NK cells (CD56), NK T cells (CD3/56), CD19/20 B cells, macrophages (CD14/11b), and neutrophils; plasma levels of anti-enolase antibody; and plasma cytokine levels (Th1/Th2 multiplex and IL17)
Time frame: Over 360 days after HPE