Filgrastim for Biliary Atresia

(BA_GCSF2b Trial)

Recruiting in Palo Alto (17 mi)

+3 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Holterman, Ai-Xuan, M.D.

Disqualifiers: Liver transplant, Cardiac malformations, CNS malformations, others

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests if a treatment can improve outcomes for newly diagnosed biliary atresia patients by helping their bodies produce more white blood cells. It includes patients who have had surgery and those who have not. The goal is to see if this treatment can help these patients fight infections and heal better.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What data supports the effectiveness of the drug Filgrastim for treating Biliary Atresia?

Filgrastim, a drug used to boost white blood cell production, has been effective in treating neutropenia (low white blood cell count) in cancer patients and those with congenital neutropenia. While there is no direct evidence for its use in Biliary Atresia, its ability to stimulate the immune system may offer potential benefits. ^{1 2 3 4 5}

Is Filgrastim generally safe for humans?

Filgrastim, also known as Neupogen and other names, has been used since 1991 and is generally considered safe, but it can cause side effects like fever, muscle pain, and bone pain. Different versions of the drug may have varying rates of these side effects. ^{2 6 7 8 9}

How does the drug Filgrastim differ from other treatments for biliary atresia?

Filgrastim is unique because it is a granulocyte colony-stimulating factor (G-CSF) that helps increase white blood cell production, which is not a standard approach for treating biliary atresia, a liver condition. This drug is typically used to treat neutropenia (low white blood cell count) in cancer patients, making its use in biliary atresia novel. ^{1 5 7 8 10}

Research Team

Eligibility Criteria

This trial is for infants over 14 days old diagnosed with Biliary Atresia, a liver condition. They must have specific blood test results and weigh more than 2 kg. It's not for those with major organ malformations, recent nutrition through IV, immediate need for a liver transplant, or certain blood conditions.

Inclusion Criteria

My weight at admission was over 2 kg.

My cholangiogram after Kasai surgery shows I have biliary atresia.

Preliminary work up for cholestasis suspected or inconclusive diagnosis of BA

Exclusion Criteria

Platelet count < 20,000 cells/uL or >1 million cells/uL

I have had sudden severe bruising or unexplained blood clots.

I do not have major heart, kidney, or brain malformations.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Eligible KBA and NoK subjects are randomized to receive GCSF or no-GCSF. GCSF is administered subcutaneously for 3 consecutive daily doses.

1 week

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including transplant-free survival and liver function, over a period of 24 months.

24 months

Regular visits at 6, 12, 18, and 24 months

Treatment Details

Interventions

• Filgrastim (Growth Factor)

Trial Overview The study tests if the drug Filgrastim can improve outcomes in babies with Biliary Atresia. Some had surgery (Kasai procedure), others didn't. Participants are monitored for two years to assess safety and effectiveness of this treatment.

Participant Groups

Group I: No Kasai GCSF Experimental Treatment 1 Intervention

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

Group II: Kasai GCSF Experimental Treatment 1 Intervention

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

Group III: Kasai no GCSF Active Control 1 Intervention

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

Group IV: No Kasai No GCSF Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

Holterman, Ai-Xuan, M.D.

Lead Sponsor

Trials

2

Recruited

410+

Big Leap Research

Collaborator

Trials

7

Recruited

2,100+

Prometheus USA

Collaborator

Trials

1

Recruited

400+

Big Leap Research

Collaborator

Trials

1

Recruited

400+

T Rose Clinical, Inc.

Collaborator

Trials

1

Recruited

400+

Findings from Research

In two patients with congenital neutropenia, treatment with filgrastim (G-CSF) was necessary to stimulate white blood cell production, highlighting its role in managing this condition.

The patients required higher doses of G-CSF due to poor initial bone marrow response, suggesting that individual sensitivity to treatment can vary significantly and may impact dosing strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of granulocyte colony-stimulating factor on granulopoiesis of congenital neutropenic children. Benkö, I., Maródi, L., Megyeri, A., et al.[2015]

Filgrastim significantly reduces the incidence of febrile neutropenia and severe neutropenia in patients undergoing chemotherapy, with relative risks of 0.63 and 0.50, respectively, based on a systematic review of 25 studies involving 1194 articles.

The most common adverse effect reported with filgrastim treatment is bone pain, which has a relative risk of 2.61, indicating it is a notable side effect to consider when using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic literature review of the efficacy, effectiveness, and safety of filgrastim. Dale, DC., Crawford, J., Klippel, Z., et al.[2022]

A study comparing the originator filgrastim (Neupogen) with three EU-approved biosimilars showed that all products maintained a high level of similarity in quality attributes, including protein content and impurity levels, up to 5 years post-approval.

The biological activity of the biosimilars was comparable to the reference standard, indicating that they are equally effective in treating neutropenia-related conditions in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analytical Comparison of the Originator Granulocyte-colony Stimulating Factor Filgrastim and its Biosimilars. Orlik, G., Khan, MA., Grieb, P.[2019]

A retrospective study of adverse drug reactions from 1991 to 2018 found that filgrastim biosimilars, such as Grasin® and Zarzio®, reported higher rates of specific side effects compared to the originator Neupogen®, indicating potential differences in safety profiles.

The study revealed that some biosimilars, like Zarzio® and Tevagrastim®, had significant reports of drug ineffectiveness, suggesting that their efficacy may not match that of the original filgrastim, highlighting the need for further large-scale studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards a comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars in treating chemotherapy associated febrile neutropenia: Trends from decades of data. Rastogi, S., Shukla, S., Sharma, AK., et al.[2020]

This study identified and quantified low-level product-related variants in filgrastim products, including newly discovered variants, using advanced mass spectrometry techniques.

Despite the presence of these variants in some filgrastim products, they are mostly found at levels below 1% and are not expected to have any significant clinical impact on their efficacy or safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Low-Level Product-Related Variants in Filgrastim Products Presently Available in Highly Regulated Markets. Hausberger, A., Lamanna, WC., Hartinger, M., et al.[2017]

In a study of 386 patients undergoing chemotherapy, biosimilar filgrastim was found to be effective and well-tolerated, with 95.6% of patients not needing a change in chemotherapy dose due to febrile neutropenia (FN).

Only 29.8% of patients experienced adverse events potentially related to biosimilar filgrastim, indicating a favorable safety profile for its use in both primary and secondary prophylaxis against FN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compatibility of Biosimilar Filgrastim with Cytotoxic Chemotherapy during the Treatment of Malignant Diseases (VENICE): A Prospective, Multicenter, Non-Interventional, Longitudinal Study. Fruehauf, S., Otremba, B., Stötzer, O., et al.[2018]

In a study involving 348 breast cancer patients undergoing chemotherapy, the new G-CSF XM02 was found to significantly reduce the duration of severe neutropenia compared to a placebo, with a mean duration of 1.1 days for both XM02 and Neupogen, versus 3.9 days for placebo.

XM02 demonstrated similar safety profiles to Neupogen, indicating that it is an effective alternative for managing chemotherapy-induced neutropenia without increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy. del Giglio, A., Eniu, A., Ganea-Motan, D., et al.[2022]

References

1. Hungary pubmed.ncbi.nlm.nih.gov

Effect of granulocyte colony-stimulating factor on granulopoiesis of congenital neutropenic children. [2015]

2. Germany pubmed.ncbi.nlm.nih.gov

A systematic literature review of the efficacy, effectiveness, and safety of filgrastim. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Monitoring Effects of Excipients, Formulation Parameters and Mutations on the High Order Structure of Filgrastim by NMR. [2018]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Analytical Comparison of the Originator Granulocyte-colony Stimulating Factor Filgrastim and its Biosimilars. [2019]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Effectiveness of Leukostim, a Russian preparation of granulocyte colony-stimulating factor, in the treatment of chemotherapy-induced neutropenia in patients with malignant tumors]. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Towards a comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars in treating chemotherapy associated febrile neutropenia: Trends from decades of data. [2020]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Identification of Low-Level Product-Related Variants in Filgrastim Products Presently Available in Highly Regulated Markets. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

Compatibility of Biosimilar Filgrastim with Cytotoxic Chemotherapy during the Treatment of Malignant Diseases (VENICE): A Prospective, Multicenter, Non-Interventional, Longitudinal Study. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Preclinical and clinical phase I studies of a new recombinant Filgrastim (BK0023) in comparison with Neupogen®. [2021]

10. England pubmed.ncbi.nlm.nih.gov

XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy. [2022]