Filgrastim for Biliary Atresia

(BA_GCSF2b Trial)

Not currently recruiting at 3 trial locations

Overseen By Sherri J Boykin

Age: < 18

Sex: Any

Trial Phase: Phase 2

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

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Filgrastim (a recombinant granulocyte colony-stimulating factor, or G-CSF) can improve outcomes for infants diagnosed with biliary atresia, a liver condition that blocks bile flow. The trial will assess both the safety and effectiveness of Filgrastim in children who have undergone the Kasai surgery and those who have not. Researchers will follow participants for two years to determine if Filgrastim benefits their condition. Infants diagnosed with biliary atresia who have not had a liver transplantation might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important early findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that filgrastim, the treatment under study, has been safely used for other health issues. Studies have found that it helps the body produce more white blood cells without causing serious side effects. In other research, patients tolerated filgrastim well, with some experiencing mild side effects like bone pain or headaches. These side effects are usually manageable and resolve on their own. Various studies have consistently demonstrated the safety of filgrastim, supporting its use in different medical situations. Although this trial is in an early stage, existing evidence suggests filgrastim is safe for use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment with Filgrastim for biliary atresia because it offers a unique approach compared to the standard care, which typically involves surgical intervention like the Kasai procedure or liver transplantation. Filgrastim, a granulocyte colony-stimulating factor (GCSF), stimulates the production of white blood cells, potentially enhancing the immune response and promoting liver healing. This biologic treatment is administered subcutaneously and could accelerate recovery post-surgery or even improve outcomes without surgery. Its novel mechanism of boosting the body's natural defenses makes it a promising candidate in managing biliary atresia more effectively.

What evidence suggests that this trial's treatments could be effective for biliary atresia?

Research has shown that Filgrastim, a medicine that helps the body produce more white blood cells, may improve outcomes for patients with biliary atresia. In this trial, some participants will receive Filgrastim alongside standard care, either after Kasai surgery or without it. One study found that Filgrastim boosts the immune system, helping the body fight infections, which is crucial for individuals with this condition. Additionally, Filgrastim may improve bile flow and reduce inflammation in the bile ducts in infants who have undergone Kasai surgery. These findings suggest that Filgrastim could effectively support better health outcomes in patients with biliary atresia. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Filgrastim

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

NMR spectroscopy can effectively assess the three-dimensional structure of filgrastim (Neupogen®), providing detailed insights into its conformation and stability, particularly under varying pH conditions.

The study found that polysorbate, a common excipient, does not significantly interact with filgrastim, allowing for accurate structural analysis, which is crucial for ensuring the quality and comparability of biosimilar versions of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring Effects of Excipients, Formulation Parameters and Mutations on the High Order Structure of Filgrastim by NMR. Aubin, Y., Hodgson, DJ., Thach, WB., et al.[2018]

In a study involving 31 patients with breast cancer and ovarian carcinoma, the recombinant human G-CSF-Leukostim (filgrastim) effectively treated or prevented chemotherapy-induced neutropenia after just 2-6 injections.

Leukostim allowed 5 breast cancer patients to undergo an additional 10 cycles of chemotherapy without inhibiting blood cell production, and no adverse side effects were reported, indicating its safety and efficacy.

NCBI (Pubmed)

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]. Korman, DB., Boronovskaia, LE., Maslova, IA., et al.[2015]

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]

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]

The biosimilar filgrastim (BK0023) demonstrated comparable biological activity, efficacy, and safety to the reference drug Neupogen® in both in vitro and in vivo studies, including a phase I trial with healthy volunteers.

BK0023 showed similar pharmacokinetic profiles to Neupogen®, indicating it could be a viable alternative for treating neutropenia in patients undergoing cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical and clinical phase I studies of a new recombinant Filgrastim (BK0023) in comparison with Neupogen®. Crobu, D., Spinetti, G., Schrepfer, R., et al.[2021]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04373941

Study Details | NCT04373941 | Part II: Granulocyte-Colony ... The Investigators propose to test the hypothesis that GCSF enhances the clinical outcome of biliary atresia in a multi-institutional Phase 2 trial to ...

2. withpower.com withpower.com/trial/phase-3-biliary-atresia-5-2020-85a71

Filgrastim for Biliary Atresia (BA_GCSF2b 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.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10709513/

Granulocyte Colony-stimulating Factor Improves Innate ... Our study investigated G-CSF as an optimizing treatment for pre-transplant DC, exploring its effect on cytokine activity.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04373941?cond=Biliary%20atresia%20OR%20%22atresia%20of%20bile%20duct%22%20OR%20%22%20atresia%20of%20bile%20ducts%22%20OR%20%22%20biliary%20atresia,%20congenital%22%20OR%20%22%20congenital%20biliary%20atresia%22%20OR%20%22%20isolated%20atresia%20of%20bile%20ducts%22%20OR%20%22%20non-syndromic%20biliary%20atresia%22&aggFilters=status:not%20rec&viewType=Table&rank=8

Part II: Granulocyte-Colony Stimulating Factor Adjunct ... The Investigators propose to test the hypothesis that GCSF enhances the clinical outcome of biliary atresia in a multi-institutional Phase 2 trial to ...

5. jpedsurg.org jpedsurg.org/article/S0022-3468(21)00272-4/abstract

Granulocyte-colony stimulating factor GCSF mobilizes ... GCSF safely mobilizes HSC in Kasai infants and may improve short-term biliary drainage and cholangitis. Phase 2 efficacy outcome of GCSF adjunct ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5896710/

Safety Profile of Biosimilar Filgrastim (Zarzio/Zarxio) Biosimilar filgrastim has a safety profile consistent with previous filgrastim studies and is effective in preventing febrile neutropenia in patients with ...