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

NCT ID: NCT01854827

Last Updated: 2019-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2016-07-31

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 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.

Conditions

Biliary Atresia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IVIG active treatment

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

Group Type: EXPERIMENTAL

Intravenous immunoglobulin (IVIG)

Intervention Type: 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.

Interventions

Intravenous immunoglobulin (IVIG)

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.

Intervention Type: DRUG

Other Intervention Names

Gamunex-C®; Gamunex®

Eligibility 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

• Minimum Eligible Age: 3 Days
• Maximum Eligible Age: 120 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ronald Sokol, MD

Role: STUDY_CHAIR

Children's Hospital Colorado

Ed Doo, MD

Role: STUDY_DIRECTOR

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

Averell Sherker, MD

Role: STUDY_DIRECTOR

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

Locations

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

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

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 30664564 (View on PubMed)

Related Links

https://childrennetwork.org/

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

Other Identifiers

U01DK062456

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P007 PRIME

Identifier Type: -

Identifier Source: org_study_id