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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary: 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.
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Current Primary Outcome:

  • Feasibility of IVIG treatment [ Time Frame: 60 days post-HPE ]
    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
  • Acceptability of IVIG [ Time Frame: 60 days post-HPE ]
    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.
  • Serious Adverse Events [ Time Frame: 360 days post-HPE ]
    Percentage of subjects with any serious adverse events (SAEs)
  • Level 3-5 toxicity [ Time Frame: 360 days post-HPE ]
    Percentage of subjects with any level 3, 4, or 5 toxicity (per NCI CTEP grading system)
  • Adverse events [ Time Frame: 360 days post-HPE ]
    Percentage of subjects with other expected adverse events


Original Primary Outcome:

  • Feasibility of IVIG treatment [ Time Frame: 60 days post-HPE ]
    Percentage of subjects for whom administration of IVIG is feasible, defined as the successful administration (at least 80% of each dose) of at least 3 of the 4 doses of IVIG
  • Acceptability of IVIG [ Time Frame: 60 days post-HPE ]
    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.
  • Serious Adverse Events [ Time Frame: 360 days post-HPE ]
    Percentage of subjects with any serious adverse events (SAEs)
  • Level 3-5 toxicity [ Time Frame: 360 days post-HPE ]
    Percentage of subjects with any level 3, 4, or 5 toxicity (per NCI CTEP grading system)
  • Adverse events [ Time Frame: 360 days post-HPE ]
    Percentage of subjects with other expected adverse events


Current Secondary Outcome:

  • Good bile drainage at 90 days post-HPE [ Time Frame: 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
  • Good bile drainage at 180 days post-HPE [ Time Frame: 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
  • Good bile drainage at 360 days post-HPE [ Time Frame: 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
  • Transplant-free survival [ Time Frame: 360 days post-HPE ]
    Percentage of subjects who survive with their native liver at 360 days after HPE.
  • Circulating regulatory T-Cells, inflammatory cytokines, and specific autoantibodies. [ Time Frame: Over 360 days after HPE ]
    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)


Original Secondary Outcome: Same as current

Information By: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Dates:
Date Received: September 27, 2012
Date Started: October 2013
Date Completion:
Last Updated: August 5, 2016
Last Verified: August 2016