Clinical trial NCT01854827: Safety Study of Intravenous Immunoglobulin (IVIG) Post-Portoenterostomy in Infants With Biliary Atresia
Official title: A Phase 1/2A Trial of Intravenous Immunoglobulin (IVIG) Therapy Following Portoenterostomy in Infants With Biliary Atresia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Biliary Atresia
Keywords: Biliary atresia
Hepatic portoenterostomy
Intravenous immunoglobulin
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
First posted: 2013-05-16
Enrollment: 30
Sex: ALL
Minimum age (years): 3
Maximum age (years): 120
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Feasibility of IVIG Treatment
timeFrame: 60 days post-HPE
measure: Acceptability of IVIG
timeFrame: 60 days post-HPE
measure: Serious Adverse Events
timeFrame: 360 days post-HPE
measure: Level 3-5 Toxicity
timeFrame: 360 days post-HPE
measure: Adverse Events
timeFrame: 360 days post-HPE
Secondary outcomes:
measure: Good Bile Drainage at 90 Days Post-HPE
timeFrame: 90 days post-HPE
measure: Good Bile Drainage at 180 Days Post-HPE
timeFrame: 180 days post-HPE
measure: Good Bile Drainage at 360 Days Post-HPE
timeFrame: 360 days post-HPE
measure: Transplant-free Survival
timeFrame: 360 days post-HPE
measure: Circulating Regulatory T-Cells, Inflammatory Cytokines, and Specific Autoantibodies.
timeFrame: Over 360 days after HPE
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital at Pittsburgh
state: Pennsylvania
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Children's Hospital Colorado
name: Ronald Sokol, MD
role: STUDY_CHAIR
affiliation: National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
name: Ed Doo, MD
role: STUDY_DIRECTOR
affiliation: National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
name: Averell Sherker, MD
role: STUDY_DIRECTOR
References:
citation: 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.