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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01854827
Recruitment Status : Completed
First Posted : May 16, 2013
Results First Posted : May 11, 2018
Last Update Posted : October 1, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Description
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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.

Condition or disease Intervention/treatment Phase
Biliary Atresia Drug: Intravenous immunoglobulin (IVIG) Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2A Trial of Intravenous Immunoglobulin (IVIG) Therapy Following Portoenterostomy in Infants With Biliary Atresia
Study Start Date : October 2013
Actual Primary Completion Date : July 2016
Actual Study Completion Date : July 2016

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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-C®
  • Gamunex®


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. 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.

  3. Serious Adverse Events [ Time Frame: 360 days post-HPE ]
    Percentage of subjects with any serious adverse events (SAEs) prior to liver transplant

  4. 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)

  5. Adverse Events [ Time Frame: 360 days post-HPE ]
    Percentage of subjects with other expected adverse events


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. Transplant-free Survival [ Time Frame: 360 days post-HPE ]
    Percentage of subjects who survive with their native liver at 360 days after HPE.

  5. 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)


Eligibility Criteria
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Ages Eligible for Study:   up to 120 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01854827


Locations
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United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Georgia
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30322
United States, Ohio
Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital at Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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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)
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT01854827    
Other Study ID Numbers: P007 PRIME
U01DK062456 ( U.S. NIH Grant/Contract )
First Posted: May 16, 2013    Key Record Dates
Results First Posted: May 11, 2018
Last Update Posted: October 1, 2019
Last Verified: September 2019
Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Biliary atresia
Hepatic portoenterostomy
Intravenous immunoglobulin
Additional relevant MeSH terms:
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Biliary Atresia
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Digestive System Abnormalities
Congenital Abnormalities
Immunoglobulins
 Immunoglobulins, Intravenous
Antibodies
gamma-Globulins
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs