Biliary AtresiaPhase 1/2PRIMENCT01854827
Safety Study of Intravenous Immunoglobulin (IVIG) Post-Portoenterostomy in Infants With Biliary Atresia
A Phase 1/2 study testing Intravenous immunoglobulin (IVIG) in people with Biliary Atresia, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 7 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 3 to 120 days
- Conditions the study is for
- Biliary Atresia
- What is being tested?
- Intravenous immunoglobulin (IVIG)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Oct 2013to Jul 2016
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 120 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States6 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Children's Hospital Los Angeles
Los Angeles, California, 90027
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital at Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: 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.
Read the 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
- Being tested
- Intravenous immunoglobulin (IVIG)
- Keywords
- Biliary atresia, Hepatic portoenterostomy, Intravenous immunoglobulin
- Medical subject headings
- Biliary Atresia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous immunoglobulin (IVIG)Drug
Also called Gamunex-C®, Gamunex®
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.
| Study group | Role | What they receive |
|---|---|---|
| IVIG active treatment | Experimental | Intravenous immunoglobulin (IVIG) 10% 1 gm/kg body weight/dose Day 3-5,30, 60 post HPE Receives: Drug: Intravenous immunoglobulin (IVIG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 60 days post-HPE
Serious Adverse Events
Percentage of subjects with any serious adverse events (SAEs) prior to liver transplant
Measured: 360 days post-HPE
Level 3-5 Toxicity
Percentage of subjects with any level 3, 4, or 5 toxicity (per NCI CTEP grading system)
Measured: 360 days post-HPE
Adverse Events
Percentage of subjects with other expected adverse events
Measured: 360 days post-HPE
Secondary outcomes (5)
Good Bile Drainage at 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
Measured: 90 days post-HPE
Good Bile Drainage at 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
Measured: 180 days post-HPE
Good Bile Drainage at 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
Measured: 360 days post-HPE
Transplant-free Survival
Percentage of subjects who survive with their native liver at 360 days after HPE.
Measured: 360 days post-HPE
Circulating Regulatory T-Cells, Inflammatory Cytokines, and Specific Autoantibodies.
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)
Measured: Over 360 days after HPE
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2013 (estimated)
- Study startOct 2013
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Biliary AtresiaStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ronald Sokol, MD, Study chair, Children's Hospital ColoradoEd Doo, MD, Study director, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)Averell Sherker, MD, Study director, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01854827
- Sponsor's protocol ID
- P007 PRIME
- Other IDs
- U01DK062456
- Acronym
- PRIME
- Status last verified
- Sep 2019
- First submitted
- 27 Sep 2012
- Last updated
- 1 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 30664564