Clinical trial NCT04373941: Part II: Granulocyte-Colony Stimulating Factor Adjunct Therapy for Biliary Atresia
Official title: Granulocyte-Colony Stimulating Factor Adjunct Therapy for Biliary Atresia: Part II of a Prospective, Randomized Controlled, Multi-Institutional Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Biliary Atresia
Lead sponsor: Holterman, Ai-Xuan, M.D.
Sponsor class: INDIV
Collaborators: name: T Rose Clinical, Inc.
name: Big Leap Research
name: Prometheus USA
First posted: 2020-05-05
Enrollment: 400
Sex: ALL
Minimum age (years): 14
Maximum age (years): 180
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: GCSF or No-GCSF
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: GCSF Response on Bile flow (KBA)
timeFrame: 3 months
measure: GCSF Response on transplant-free survival (NoK)
timeFrame: 24 months
Secondary outcomes:
measure: GCSF response on liver function and outcome (KBA)
timeFrame: 24 months
measure: GCSF response on liver function and outcome (KBA)
timeFrame: 24 months
measure: GCSF response on liver function and outcome (KBA)
timeFrame: 24 months
measure: GCSF response on liver function (NoK)
timeFrame: 24 months
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU)
state: Oregon
city: Karachi
country: Pakistan
facility: Aga Khan University
city: Hanoi
country: Vietnam
facility: Nation Children's Hospital
state: Dong Da District
city: Ho Chi Minh City
country: Vietnam
facility: Children Hospital 1
Study officials:
References:
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