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

September 20, 2019 updated by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Children's Hospital Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15213
        • Children's Hospital at Pittsburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

3 days to 3 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: IVIG active treatment
Intravenous immunoglobulin (IVIG) 10% 1 gm/kg body weight/dose Day 3-5,30, 60 post HPE
Drug: 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.
Other Names:
  • Gamunex®
  • Gamunex-C®

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
60 days post-HPE
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.
60 days post-HPE
Serious Adverse Events
Time Frame: 360 days post-HPE
Percentage of subjects with any serious adverse events (SAEs) prior to liver transplant
360 days post-HPE
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)
360 days post-HPE
Adverse Events
Time Frame: 360 days post-HPE
Percentage of subjects with other expected adverse events
360 days post-HPE

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
90 days post-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
180 days post-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
360 days post-HPE
Transplant-free Survival
Time Frame: 360 days post-HPE
Percentage of subjects who survive with their native liver at 360 days after HPE.
360 days post-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)
Over 360 days after HPE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Ronald Sokol, MD, Children's Hospital Colorado
  • Study Director: 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)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 27, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 13, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 16, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 1, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 20, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P007 PRIME
  • U01DK062456 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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