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

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ClinicalTrials.gov Identifier: NCT04373941
Recruitment Status : Recruiting
First Posted : May 5, 2020
Last Update Posted : May 5, 2020
Sponsor:
Collaborators:
T Rose Clinical, Inc.
Big Leap Research
Information provided by (Responsible Party):
Holterman, Ai-Xuan, M.D.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Biliary Atresia Drug: Filgrastim Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: GCSF or No-GCSF
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Granulocyte-Colony Stimulating Factor Adjunct Therapy for Biliary Atresia: Part II of a Prospective, Randomized Controlled, Multi-Institutional Trial
Estimated Study Start Date : June 1, 2020
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : October 31, 2024


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 Name: 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 Name: 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



Primary Outcome Measures :
  1. 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.

  2. 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


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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

  4. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   14 Days to 180 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04373941


Contacts
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Contact: AiXuan Holterman, MD 8473340230 Aithanh@uic.edu
Contact: Sherri J Boykin 9195596061 Sboykin@trclinical.com

Locations
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Pakistan
Aga Khan University Recruiting
Karachi, Pakistan
Contact: Saqib Qazi, MD    +923018233059    saqib.qazi@aku.edu   
Vietnam
Nation Children's Hospital Recruiting
Hanoi, Dong Da District, Vietnam
Contact: Pham Anh Hoa Nguyen, MD    +84 462738842    drhoanph@yahoo.com   
Contact: Thuy Trinh, MD    +84 984078256    bsthuya7@gmail.com   
Children Hospital 1 Enrolling by invitation
Ho Chi Minh City, Vietnam
Sponsors and Collaborators
Holterman, Ai-Xuan, M.D.
T Rose Clinical, Inc.
Big Leap Research
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Holterman, Ai-Xuan, M.D.
ClinicalTrials.gov Identifier: NCT04373941    
Other Study ID Numbers: HoltermanA
First Posted: May 5, 2020    Key Record Dates
Last Update Posted: May 5, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Biliary Atresia
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Digestive System Abnormalities
Congenital Abnormalities
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs