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

Holterman, Ai-Xuan, M.D.

Status and phase: Enrolling; Phase 2

Conditions: Biliary Atresia

Treatments: Drug: Filgrastim

Study type: Interventional

Funder types: Other

Identifiers

NCT04373941

HoltermanA

Details and patient eligibility

About

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.

Full 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.

Enrollment: 400 estimated patients

Sex: All

Ages: 14 to 180 days old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 4 patient groups

Kasai GCSF

Experimental group

Description:

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

Treatment:

Drug: Filgrastim

Kasai no GCSF

No Intervention group

Description:

The no GCSF group will not receive GCSF and receives the standard of care

No Kasai GCSF

Experimental group

Description:

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

Treatment:

Drug: Filgrastim

No Kasai No GCSF

No Intervention group

Description:

The No Kasai No GCSF group will receive the standard of care and will not receive GCSF