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| Name | Class |
|---|---|
| T Rose Clinical, Inc. | UNKNOWN |
| Big Leap Research | OTHER |
| Prometheus USA | UNKNOWN |
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The Investigators propose to test the hypothesis that GCSF enhances the clinical outcome of biliary atresia in a multi-institutional Phase 2 trial to prospectively evaluate the safety and efficacy of GCSF in each of the 2 groups of newly diagnosed BA patients: KBA (i.e., Kasai-operated) or NoK (i.e., patients who did not undergo Kasai surgery). Subjects who participate in the trial will be followed for 2 years.
This is a prospective, randomized, multi-institutional trial in KBA and NoK subjects to be conducted under a Food and Drug Administration approved Investigational New Drug application.
The KBA group is composed of just operated Kasai patients with intraoperative liver biopsy-confirmed BA. Their clinical characteristics have been described in the previously completed Phase 1 study under CR00005169 (ie. inclusion and exclusion criteria as described below)
The NoK group will be composed of newly diagnosed BA patients, including the following:
Having met the same inclusion and exclusion criteria as the Kasai KBS group,
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Kasai GCSF | Experimental | The Kasai GCSF group will receive the standard of care PLUS 3 consecutive daily doses of 10 ug/kg of GCSF to be administered subcutaneously by day 3 post Kasai surgery |
|
| Kasai no GCSF | No Intervention | The no GCSF group will not receive GCSF and receives the standard of care | |
| No Kasai GCSF | Experimental | The No Kasai GCSF group will receive the standard of care PLUS 3 consecutive daily doses of 10 ug/kg of GCSF to be administered subcutaneously once the diagnosis of BA is established |
|
| No Kasai No GCSF | No Intervention | The No Kasai No GCSF group will receive the standard of care and will not receive GCSF |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Filgrastim | Drug | G-CSF is a glycoprotein produced by monocytes, fibroblasts, and endothelial cells. Filgrastim is a human granulocyte colony stimulating factor (G-CSF) produced by recombinant DNA technology with NEUPOGEN® as the Amgen Inc. trademark for filgrastim. G-CSF regulates the production, proliferation and differentiation of neutrophils and hematopoietic stem cell precursors within the bone marrow leading to dose-dependent increase in circulating neutrophils and hematopoietic stem cells in the blood. It is indicated to reduce the incidence of infection in patients with severe neutropenia, for neutrophil recovery in neutropenic patients with bone marrow depletion, to mobilize hematopoietic progenitor stem cell for collection by leukapheresis in hematopoietic stem cell transplantation. |
| Measure | Description | Time Frame |
|---|---|---|
| GCSF Response on Bile flow (KBA) | For KBA subjects: Bile flow as measured by the percentage of subjects with total bilirubin< 2 mg/dL at 3 months post-Kasai. | 3 months |
| GCSF Response on transplant-free survival (NoK) | For NoK subjects: Changes at 6, 12, 18 and 24 months-transplant free survival | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| GCSF response on liver function and outcome (KBA) | KBA subjects: Pediatric end-stage liver disease (PELD) score at 6, 12, 18, and 24 months after GCSF treatment. | 24 months |
| GCSF response on liver function and outcome (KBA) |
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Inclusion criteria
Exclusion criteria
Patients having access to liver transplantation for immediate liver failure
Prior Kasai patients
Major cardiac, renal, central nervous system (CNS) malformations
Intracranial hemorrhage
History of recent total parenteral nutrition (TPN) use within the last 2 weeks
Gl tract obstruction
For Kasai-operated subjects: Type 1 or 2 biliary atresia anatomy
Current systemic infection
WBC > 20,000 cells/uL
Platelet count < 20,000 cells/uL or >1 million cells/uL
Concurrent respiratory, metabolic, neurological, cardiovascular, metabolic, and renal illness
Elevated serum creatinine > 1 mg/dL
Purpura fulminans or unexplained vascular thrombosis
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| AiXuan Holterman, MD | Contact | 8473340230 | Aithanh@uic.edu | |
| Sherri J Boykin | Contact | 9195596061 | Sboykin@trclinical.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Oregon Health & Science University (OHSU) | Not yet recruiting | Portland | Oregon | 97239 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29604222 | Background | Bezerra JA, Wells RG, Mack CL, Karpen SJ, Hoofnagle JH, Doo E, Sokol RJ. Biliary Atresia: Clinical and Research Challenges for the Twenty-First Century. Hepatology. 2018 Sep;68(3):1163-1173. doi: 10.1002/hep.29905. | |
| 24027727 | Background | Chaudhuri J, Mitra S, Mukhopadhyay D, Chakraborty S, Chatterjee S. Granulocyte Colony-stimulating Factor for Preterms with Sepsis and Neutropenia: A Randomized Controlled Trial. J Clin Neonatol. 2012 Oct;1(4):202-6. doi: 10.4103/2249-4847.105993. |
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| ID | Term |
|---|---|
| D001656 | Biliary Atresia |
| ID | Term |
|---|---|
| D001649 | Bile Duct Diseases |
| D001660 | Biliary Tract Diseases |
| D004066 | Digestive System Diseases |
| D004065 | Digestive System Abnormalities |
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| ID | Term |
|---|---|
| D000069585 | Filgrastim |
| D016179 | Granulocyte Colony-Stimulating Factor |
| ID | Term |
|---|---|
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
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GCSF or No-GCSF
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|
|
KBA subjects: Percentage of patients with transplant-free survival at 6, 12, 18 and 24 months
| 24 months |
| GCSF response on liver function and outcome (KBA) | KBA subjects: Percentage of patients with cholangitis-free transplant-free survival at 6, 12, 18 and 24 months | 24 months |
| GCSF response on liver function (NoK) | NoK subjects: Changes in Pediatric end-stage liver disease (PELD) score at 6, 12, 18, and 24 months after GCSF treatment. | 24 months |
| Aga Khan University | Not yet recruiting | Karachi | Pakistan |
|
| Nation Children's Hospital | Recruiting | Hanoi | Dong Da District | Vietnam |
|
| Children Hospital 1 | Enrolling by invitation | Ho Chi Minh City | Vietnam |
| 26725209 | Background | Shneider BL, Magee JC, Karpen SJ, Rand EB, Narkewicz MR, Bass LM, Schwarz K, Whitington PF, Bezerra JA, Kerkar N, Haber B, Rosenthal P, Turmelle YP, Molleston JP, Murray KF, Ng VL, Wang KS, Romero R, Squires RH, Arnon R, Sherker AH, Moore J, Ye W, Sokol RJ; Childhood Liver Disease Research Network (ChiLDReN). Total Serum Bilirubin within 3 Months of Hepatoportoenterostomy Predicts Short-Term Outcomes in Biliary Atresia. J Pediatr. 2016 Mar;170:211-7.e1-2. doi: 10.1016/j.jpeds.2015.11.058. Epub 2015 Dec 24. |
| 25749502 | Background | Kedarisetty CK, Anand L, Bhardwaj A, Bhadoria AS, Kumar G, Vyas AK, David P, Trehanpati N, Rastogi A, Bihari C, Maiwall R, Garg HK, Vashishtha C, Kumar M, Bhatia V, Sarin SK. Combination of granulocyte colony-stimulating factor and erythropoietin improves outcomes of patients with decompensated cirrhosis. Gastroenterology. 2015 Jun;148(7):1362-70.e7. doi: 10.1053/j.gastro.2015.02.054. Epub 2015 Mar 4. |
| 31335841 | Background | Fanna M, Masson G, Capito C, Girard M, Guerin F, Hermeziu B, Lachaux A, Roquelaure B, Gottrand F, Broue P, Dabadie A, Lamireau T, Jacquemin E, Chardot C. Management of Biliary Atresia in France 1986 to 2015: Long-term Results. J Pediatr Gastroenterol Nutr. 2019 Oct;69(4):416-424. doi: 10.1097/MPG.0000000000002446. |
| 29278428 | Background | Verma N, Kaur A, Sharma R, Bhalla A, Sharma N, De A, Singh V. Outcomes after multiple courses of granulocyte colony-stimulating factor and growth hormone in decompensated cirrhosis: A randomized trial. Hepatology. 2018 Oct;68(4):1559-1573. doi: 10.1002/hep.29763. Epub 2018 Jul 25. |
| 18537187 | Background | Spahr L, Lambert JF, Rubbia-Brandt L, Chalandon Y, Frossard JL, Giostra E, Hadengue A. Granulocyte-colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial. Hepatology. 2008 Jul;48(1):221-9. doi: 10.1002/hep.22317. |
| 21460243 | Background | Korbling M, Freireich EJ. Twenty-five years of peripheral blood stem cell transplantation. Blood. 2011 Jun 16;117(24):6411-6. doi: 10.1182/blood-2010-12-322214. Epub 2011 Apr 1. |
| 35391541 | Derived | Nguyen HPA, Ren J, Butler M, Li H, Qazi S, Sadiq K, Dao HT, Holterman A. Study protocol of Phase 2 open-label multicenter randomized controlled trial for granulocyte-colony stimulating factor (GCSF) in post-Kasai Type 3 biliary atresia. Pediatr Surg Int. 2022 Jul;38(7):1019-1030. doi: 10.1007/s00383-022-05115-0. Epub 2022 Apr 7. |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D016298 |
| Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |