GCSF Adjunct Therapy for Biliary Atresia

NCT03395028 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: CR00005169IND 119679-0007
• Study Type: interventional
• Target: 6
• Locations: 2 countries
• Sites: 2

Brief Summary

The Investigators propose to test the hypothesis that GCSF therapy enhances the clinical outcome of Kasai operated Biliary Atresia (BA) patients. In this study, Investigators will conduct a dose determination for GCSF use in post Kasai subjects to support a future phase 2 efficacy study. The first 3 post Kasai BA subjects with liver biopsy-confirmed BA will be given 5 ug/kg/d of GCSF in 3 daily subcutaneous doses starting on post Kasai day 3. A second group of 3 subjects will be assigned to the 10 ug/Kg/d dose after the 5ug/kg/d dose has been proven to be safe. The levels of circulating hematopoietic stem cells and a 1-month safety profile will be analyzed.

Conditions

Biliary Atresia

Keywords

Biliary Atresia; Granulocyte Colony Stimulating Factor; GCSF

Outcome Measures

Primary Outcomes (1)

• Dose determination GCSF

  To determine the maximum tolerated dose of GCSF based on GCSF dose limiting toxicity and the extent of peripheral blood stem cell mobilization as measured by increases in CD34+cells with upper levels limited by white blood cells (WBCs) less than 50,000 per microliter (mcL) of blood.

  13 months

Interventions

Granulocyte Colony-Stimulating Factor 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.

Also known as: Filgrastim

Eligibility Criteria

• Age: 2 Weeks - 180 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Completed the preliminary work up for cholestasis with suspected or inconclusive diagnosis of BA
• Gestational Age \> 36wks
• Weight \> 2 Kg
• Age \>-2 weeks-\<180 days at diagnosis
• Serum Direct Bilirubin \> 2 mg/dL GGT \> 100 U/L
• Kasai operated patients for Type 3 or 4 anatomy of BA
• Cholangiogram/porta hepatis findings diagnostic of BA
• Liver biopsy supporting BA diagnosis

You may not qualify if:

• Having access to liver transplantation for immediate Kasai failure
• Prior Kasai patients
• Major cardiac, renal, CNS malformations with poor prognosis
• Intracranial hemorrhage
• History of recent TPN use within the last 2 weeks of surgery
• GI tract obstruction
• Laparoscopic Kasai repair

Sponsors & Collaborators

• Holterman, Ai-Xuan, M.D.: lead
• T. Rose Clinical, Inc., United States: collaborator
• Children's National Research Institute: collaborator
• Big Leap Research: collaborator

Study Sites (2)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

National Childrens Hospital

Hanoi, Vietnam

Location

Related Publications (6)

• Davenport M. Biliary atresia: clinical aspects. Semin Pediatr Surg. 2012 Aug;21(3):175-84. doi: 10.1053/j.sempedsurg.2012.05.010.

  PMID: 22800970 BACKGROUND

• Panopoulos AD, Watowich SS. Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and 'emergency' hematopoiesis. Cytokine. 2008 Jun;42(3):277-88. doi: 10.1016/j.cyto.2008.03.002. Epub 2008 Apr 8.

  PMID: 18400509 BACKGROUND

• Yannaki E, Athanasiou E, Xagorari A, Constantinou V, Batsis I, Kaloyannidis P, Proya E, Anagnostopoulos A, Fassas A. G-CSF-primed hematopoietic stem cells or G-CSF per se accelerate recovery and improve survival after liver injury, predominantly by promoting endogenous repair programs. Exp Hematol. 2005 Jan;33(1):108-19. doi: 10.1016/j.exphem.2004.09.005.

  PMID: 15661404 BACKGROUND

• Takami T, Terai S, Sakaida I. Stem cell therapy in chronic liver disease. Curr Opin Gastroenterol. 2012 May;28(3):203-8. doi: 10.1097/MOG.0b013e3283521d6a.

  PMID: 22395569 BACKGROUND

• Prajapati R, Arora A, Sharma P, Bansal N, Singla V, Kumar A. Granulocyte colony-stimulating factor improves survival of patients with decompensated cirrhosis: a randomized-controlled trial. Eur J Gastroenterol Hepatol. 2017 Apr;29(4):448-455. doi: 10.1097/MEG.0000000000000801.

  PMID: 27930386 BACKGROUND

• 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.

  PMID: 35391541 DERIVED

MeSH Terms

Conditions

Biliary Atresia

Interventions

Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Digestive System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Evan P Nadler, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Model Details: Dose determination for GCSF

Study Record Dates

• First Submitted: December 22, 2017
• First Posted: January 9, 2018
• Study Start: January 15, 2018
• Primary Completion: January 31, 2020
• Study Completion: January 31, 2020
• Last Updated: February 17, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); VN (1)