Odevixibat for Biliary Atresia

Not currently recruiting at 85 trial locations

Overseen By Ipsen Clinical Study Enquiries

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Albireo, an Ipsen Company

Disqualifiers: Intractable ascites, Ileal resection, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 13

Duration: 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called odevixibat for children with biliary atresia, a liver condition that blocks bile flow. The researchers aim to determine if odevixibat can improve symptoms and is safe compared to a placebo (a non-active treatment). Children who have undergone a Kasai procedure (a type of surgery for this condition) and can start the trial within three weeks post-surgery might be suitable candidates. Participants will take capsules daily for about two years. The goal is to find a better way to manage biliary atresia symptoms and improve quality of life. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications. Please consult with the study team for guidance on your specific situation.

Is there any evidence suggesting that odevixibat is likely to be safe for children with biliary atresia?

Research has shown that odevixibat has been tested for safety in various situations. Studies have found it to be generally well-tolerated by children. In trials for other liver conditions, patients mostly experienced mild to moderate side effects, such as diarrhea and stomach pain, which are common and manageable.

Odevixibat is already approved in Japan for treating a rare liver disease called PFIC (progressive familial intrahepatic cholestasis). This approval suggests that the treatment is considered reasonably safe when used as directed for that condition. While this does not guarantee safety for biliary atresia, it offers some reassurance about its overall safety.

In summary, while no treatment is without risk, existing evidence suggests that odevixibat is generally safe for children, with manageable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Odevixibat is unique for treating biliary atresia because it targets the way bile is processed in the body. Unlike current treatments, which often involve surgery or liver transplants, Odevixibat works by inhibiting the ileal bile acid transporter (IBAT), reducing bile acid build-up and potentially easing liver damage. Researchers are excited because this oral medication could offer a less invasive, long-term solution for managing this challenging condition.

What evidence suggests that odevixibat might be an effective treatment for biliary atresia?

Studies have shown that odevixibat, which participants in this trial may receive, effectively improves liver conditions in children with certain rare diseases. In past research, it significantly helped children with PFIC, a liver disorder, by reducing bile acid levels in the blood. Odevixibat aids the body in eliminating bile acids, preventing harmful buildup in the liver. The EU and Japan have approved it for treating PFIC, demonstrating strong evidence of its effectiveness. While specific data for biliary atresia is still under study, its success in similar conditions suggests promising potential. ^{1 3 4 6 7}

Who Is on the Research Team?

Ipsen Medical Director

Principal Investigator

Ipsen

Are You a Good Fit for This Trial?

This trial is for children with Biliary Atresia who've had a Kasai procedure before they were 90 days old. They should be able to start treatment within 3 weeks post-surgery and weigh more than 3.5kg. Children with severe liver issues, relying solely on IV nutrition, or having certain other conditions are not eligible.

Inclusion Criteria

I have been diagnosed with biliary atresia.

I can start the study treatment within 3 weeks after my Kasai procedure.

I had the Kasai procedure done before I was 3 months old.

Exclusion Criteria

I do not have any major health issues that could affect my safety or participation in the study.

I have severe, untreatable fluid buildup in my abdomen.

ALT ≥10× upper limit of normal (ULN) at screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either odevixibat or placebo capsules for oral administration once daily

104 weeks

Regular visits for monitoring at Weeks 13, 26, 52, and 104

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Odevixibat
• Placebo

Trial Overview The study tests the effectiveness and safety of Odevixibat versus a placebo in kids after Kasai surgery for Biliary Atresia. It's a Phase 3 trial where participants are randomly assigned to either the drug or placebo without knowing which one they receive.

How Is the Trial Designed?

Group I: Odevixibat (A4250) Experimental Treatment 1 Intervention

Capsules for oral administration once daily for 104 weeks.

Group II: Placebo Placebo Group 1 Intervention

Capsules for oral administration (to match active) once daily for 104 weeks.

Odevixibat is already approved in United States for the following indications:

Approved in United States as Bylvay for:

• Cholestatic pruritus in infants with Alagille syndrome (ALGS) over 12 months of age
• Pruritus in patients with progressive familial intrahepatic cholestasis (PFIC)

Who Is Running the Clinical Trial?

Albireo, an Ipsen Company

Lead Sponsor

Trials

5

Recruited

640+

Albireo

Lead Sponsor

Trials

17

Recruited

1,200+

Published Research Related to This Trial

Combining ursodeoxycholic acid (UDCA) with bezafibrate significantly improves liver biochemistry markers in patients with primary biliary cholangitis (PBC) who do not respond adequately to UDCA alone, based on a meta-analysis of 10 trials involving 369 patients.

The combination therapy effectively reduces levels of alanine aminotransferase, alkaline phosphatase, and other liver-related markers without increasing the risk of adverse effects compared to UDCA monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of bezafibrate and ursodeoxycholic acid in patients with primary biliary cholangitis: a meta-analysis of randomized controlled trials. Agrawal, R., Majeed, M., Attar, BM., et al.[2022]

The 0.19 mg fluocinolone acetonide implant was successfully used in a 20-year-old woman with juvenile idiopathic arthritis (JIA) and chronic uveitis, showing significant improvements in visual acuity and reduction in central retinal thickness over a 12-month follow-up period.

This case suggests that the fluocinolone implant can be a safe and effective long-term treatment option for JIA-associated uveitis, particularly for patients who do not respond well to traditional corticosteroids or have compliance issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral 0.19 mg Fluocinolone Acetonide Intravitreal Implant in the Successful Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis and Secondary Macular Oedema: A Case Report and Review of Intravitreal Therapies. Ansari, AS., Amir, Z., Williams, GS.[2021]

Odevixibat (Bylvay™) is an approved treatment for progressive familial intrahepatic cholestasis (PFIC) in patients as young as 6 months in the EU and 3 months in the USA, highlighting its safety and efficacy for this specific cholestatic disease.

The drug is also being investigated for other cholestatic conditions, such as Alagille syndrome and biliary atresia, indicating its potential broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Odevixibat: First Approval. Deeks, ED.[2022]

In a study of 28 children with juvenile idiopathic arthritis-associated uveitis (JIA-U), adalimumab was found to be well tolerated, and most participants (92%) resumed treatment after initial withdrawal due to active disease.

However, the remission achieved with adalimumab did not last after stopping the medication, indicating that ongoing treatment may be necessary to maintain control of JIA-U.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab in Juvenile Idiopathic Arthritis-Associated Uveitis: 5-Year Follow-up of the Bristol Participants of the SYCAMORE Trial. Horton, S., Jones, AP., Guly, CM., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04336722

Efficacy and Safety of Odevixibat in Children With Biliary ... Double-blind, randomized, placebo-controlled, Phase 3 study to investigate the efficacy and safety of odevixibat compared to placebo in children with biliary ...

2. ipsen.com ipsen.com/press-releases/bylvay-odevixibat-approved-in-japan-for-rare-liver-disease-pfic-3153114/

Bylvay® (odevixibat) approved in Japan for rare liver ... The study evaluated the efficacy and safety of odevixibat in pediatric patients with PFIC types 1 and 2 and confirmed improvements in serum ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8550539/

Odevixibat: First Approval - PMC In July 2021, odevixibat received its first approval in the EU for the treatment of PFIC in patients aged ≥ 6 months, followed shortly by its approval in the ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2589555924003136

Real-world experience with odevixibat in children ... Data on the efficacy of odevixibat in patients with rarer forms of PFIC are scant; only two patients with PFIC-6 have been reported in two different cohorts.

5. gastrojournal.org gastrojournal.org/article/S0016-5085(23)00567-X/fulltext

Odevixibat Treatment Induces Biliary Bile Acid Secretion in ... Odevixibat treatment induces biliary bile acid secretion in responsive patients with bile salt export pump deficiency.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05426733

Study Details | NCT05426733 | An Open-label Extension ... This is a Phase 3, multi-center, open-label extension study to evaluate the long-term efficacy and safety of odevixibat in patients with Biliary Atresia (BA).

7. sciencedirect.com sciencedirect.com/science/article/pii/S2468125324000748

Efficacy and safety of odevixibat in patients with Alagille ... Data from ASSERT indicate that odevixibat can improve pruritus and reduce serum bile acids in patients with Alagille syndrome. These effects on pruritus and ...