Part II: Granulocyte-Colony Stimulating Factor Adjunct Therapy for Biliary Atresia (BA_GCSF2b)

September 7, 2023 updated by: Holterman, Ai-Xuan, M.D.

Granulocyte-Colony Stimulating Factor Adjunct Therapy for Biliary Atresia: Part II of a Prospective, Randomized Controlled, Multi-Institutional Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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:

  • surgical patients in whom the Kasai was not performed for intraoperative technical reasons or due to advanced liver disease, who also have no option for rescue liver transplantation.
  • Unoperated patients whose family refuses surgery or who are not operative candidates

Having met the same inclusion and exclusion criteria as the Kasai KBS group,

  • eligible KBA subjects will be randomized to GCSF vs. no-GCSF at the 10 ug/kg/d dose to be given subcutaneously for 3 consecutive daily doses on the third day following the Kasai procedure.
  • eligible NoK subjects will be randomized to GCSF vs. no-GCSF at the 10 ug/kg/d dose to be given subcutaneously for 3 consecutive daily doses on the third day following diagnostic liver biopsy.

Study Type

Interventional

Enrollment (Estimated)

400

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: AiXuan Holterman, MD
  • Phone Number: 8473340230
  • Email: Aithanh@uic.edu

Study Contact Backup

Study Locations

  • Pakistan
      • Karachi, Pakistan
        • Not yet recruiting
        • Aga Khan University
        • Contact:
  • United States
    • Oregon
      • Portland, Oregon, United States, 97239
        • Not yet recruiting
        • Oregon Health & Science University (OHSU)
        • Contact:
        • Contact:
  • Vietnam
      • Ho Chi Minh City, Vietnam
        • Enrolling by invitation
        • Children Hospital 1
    • Dong Da District
      • Hanoi, Dong Da District, Vietnam
        • Recruiting
        • Nation Children's Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 weeks to 5 months (Child)

Accepts Healthy Volunteers

No

Description

Inclusion criteria

  1. preliminary work up for cholestasis suspected or inconclusive diagnosis of BA.
  2. Serum Direct bilirubin > 2 mg/dl,GGT> 100 U/L
  3. Male or female infants with a gestational age> 36 weeks
  4. Admission weight > 2 kg
  5. Age > 14 days - 180 days at diagnosis
  6. For Kasai operated subjects, Type 3 or 4 anatomy of BA
  7. For Kasai operated subjects, cholangiogram (if performed) diagnostic of BA
  8. Liver biopsy supporting BA diagnosis

Exclusion criteria

  1. Patients having access to liver transplantation for immediate liver failure
  2. Prior Kasai patients
  3. Major cardiac, renal, central nervous system (CNS) malformations
  4. Intracranial hemorrhage
  5. History of recent total parenteral nutrition (TPN) use within the last 2 weeks

  6. Gl tract obstruction

    For Kasai-operated subjects: Type 1 or 2 biliary atresia anatomy

  7. Current systemic infection
  8. WBC > 20,000 cells/uL
  9. Platelet count < 20,000 cells/uL or >1 million cells/uL
  10. Concurrent respiratory, metabolic, neurological, cardiovascular, metabolic, and renal illness
  11. Elevated serum creatinine > 1 mg/dL
  12. Purpura fulminans or unexplained vascular thrombosis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Kasai GCSF
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
Drug: Filgrastim
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.
Other Names:
  • Neupogen, granulocyte colony stimulating factor
No Intervention: Kasai no GCSF
The no GCSF group will not receive GCSF and receives the standard of care
Experimental: No Kasai GCSF
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
Drug: Filgrastim
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.
Other Names:
  • Neupogen, granulocyte colony stimulating factor
No Intervention: No Kasai No GCSF
The No Kasai No GCSF group will receive the standard of care and will not receive GCSF

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
GCSF Response on Bile flow (KBA)
Time Frame: 3 months
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)
Time Frame: 24 months
For NoK subjects: Changes at 6, 12, 18 and 24 months-transplant free survival
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
GCSF response on liver function and outcome (KBA)
Time Frame: 24 months
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)
Time Frame: 24 months
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)
Time Frame: 24 months
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)
Time Frame: 24 months
NoK subjects: Changes in Pediatric end-stage liver disease (PELD) score at 6, 12, 18, and 24 months after GCSF treatment.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Holterman, Ai-Xuan, M.D.

Collaborators

T Rose Clinical, Inc.
Big Leap Research
Prometheus USA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2023

Primary Completion (Estimated)

August 31, 2024

Study Completion (Estimated)

October 31, 2025

Study Registration Dates

First Submitted

August 13, 2019

First Submitted That Met QC Criteria

May 1, 2020

First Posted (Actual)

May 5, 2020

Study Record Updates

Last Update Posted (Actual)

September 8, 2023

Last Update Submitted That Met QC Criteria

September 7, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HoltermanA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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