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

NCT01854827 | Completed Phase 1 Results DMC

• 2 other identifiers: P007 PRIMEU01DK062456
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 7

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.

Conditions

Biliary Atresia

Keywords

Biliary atresia; Hepatic portoenterostomy; Intravenous immunoglobulin

Outcome Measures

Primary Outcomes (5)

• 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

  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.

  60 days post-HPE

• Serious Adverse Events

  Percentage of subjects with any serious adverse events (SAEs) prior to liver transplant

  360 days post-HPE

• Level 3-5 Toxicity

  Percentage of subjects with any level 3, 4, or 5 toxicity (per NCI CTEP grading system)

  360 days post-HPE

• Adverse Events

  Percentage of subjects with other expected adverse events

  360 days post-HPE

Secondary Outcomes (5)

• Good Bile Drainage at 90 Days Post-HPE

  90 days post-HPE

• Good Bile Drainage at 180 Days Post-HPE

  180 days post-HPE

• Good Bile Drainage at 360 Days Post-HPE

  360 days post-HPE

• Transplant-free Survival

  360 days post-HPE

• Circulating Regulatory T-Cells, Inflammatory Cytokines, and Specific Autoantibodies.

  Over 360 days after HPE

Study Arms (1)

IVIG active treatment

EXPERIMENTAL

Intravenous immunoglobulin (IVIG) 10% 1 gm/kg body weight/dose Day 3-5,30, 60 post HPE

Drug: Intravenous immunoglobulin (IVIG)

Interventions

Intravenous immunoglobulin (IVIG) DRUG

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.

Also known as: Gamunex-C®, Gamunex®

IVIG active treatment

Eligibility Criteria

• Age: 3 Days - 120 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (7)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital at Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (1)

• Mack CL, Spino C, Alonso EM, Bezerra JA, Moore J, Goodhue C, Ng VL, Karpen SJ, Venkat V, Loomes KM, Wang K, Sherker AH, Magee JC, Sokol RJ; The ChiLDReN Network. A Phase I/IIa Trial of Intravenous Immunoglobulin Following Portoenterostomy in Biliary Atresia. J Pediatr Gastroenterol Nutr. 2019 Apr;68(4):495-501. doi: 10.1097/MPG.0000000000002256.

  PMID: 30664564 DERIVED

Related Links

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

MeSH Terms

Conditions

Biliary Atresia

Interventions

Immunoglobulins, Intravenous; Hizentra

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Digestive System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: DCC PI
• Organization: University of Michigan

mageej@med.umich.edu

734-936-3585

Study Officials

• Ronald Sokol, MD

  Children's Hospital Colorado

  STUDY CHAIR

• Ed Doo, MD

  National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

  STUDY DIRECTOR

• Averell Sherker, MD

  National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2012
• First Posted: May 16, 2013
• Study Start: October 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: October 1, 2019
• Results First Posted: May 11, 2018

Record last verified: 2019-09

Locations

US (6); CA (1)