Odevixibat for Biliary Atresia

(BOLD-EXT Trial)

Enrolling by invitation at 38 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Albireo, an Ipsen Company

Disqualifiers: Non-compliance, Hypersensitivity, Liver transplant, others

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

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the long-term effects and safety of odevixibat for children with biliary atresia, a liver condition affecting bile flow. Participants will take odevixibat capsules daily for two years. The trial seeks children who have completed a previous study with odevixibat and wish to continue treatment. It is crucial that these children have consistently taken their medication and are not expecting a liver transplant soon. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of this treatment for more children.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that Odevixibat is likely to be safe for humans?

A previous study tested odevixibat on children with liver diseases and showed positive results in reducing symptoms like itching. The study found that odevixibat was generally well-tolerated, with most side effects being mild, such as stomach aches or diarrhea. No serious side effects were directly linked to the treatment.

Another study tested odevixibat for a different liver condition and confirmed that it helped lower certain harmful substances in the blood without causing major side effects. Odevixibat is already approved in Japan for some liver conditions, indicating its safety in those cases.

Since this current study is in a later stage, earlier studies have shown the treatment to be safe enough to continue testing. This should reassure participants considering joining the trial about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Odevixibat is unique because it represents a new approach for treating biliary atresia, a condition where bile ducts are blocked or absent. Unlike current treatments that often focus on surgical intervention or liver transplantation, Odevixibat is a non-surgical option that works by inhibiting the ileal bile acid transporter (IBAT), which can reduce bile acid buildup and liver damage. Researchers are excited about this treatment because it offers a potentially less invasive and more manageable treatment option, with the convenience of being taken orally once daily. This could significantly improve the quality of life for patients and their families.

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

Research has shown that odevixibat, which participants in this trial will receive, can help children with liver problems feel better. One study found that this treatment likely reduces itching, a common issue in liver diseases like biliary atresia, within four weeks. Odevixibat is already approved in Japan for treating a rare liver disease, which is promising for similar conditions. These findings suggest that odevixibat may help manage symptoms for children with biliary atresia, although researchers are gathering more long-term information to confirm its effectiveness. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for children with Biliary Atresia who completed a previous 104-week study of Odevixibat. They must have consent from a caregiver and cannot join if they're allergic to Odevixibat, need an imminent liver transplant, were non-compliant in the prior study, or have conditions that may risk their safety or study participation.

Inclusion Criteria

Signed informed consent by caregiver

Completion of the 104-week Treatment Period of Study A4250-011

Exclusion Criteria

Any conditions or abnormalities which, in the opinion of the investigator, may compromise the safety of the patient, or interfere with the patient participating in or completing the study

Patients who were not compliant with study drug treatment or procedures in Study A4250-011 as per the investigator's discretion

You are in need of a liver transplant or are scheduled to receive one soon according to the investigator's judgement.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive odevixibat for 104 weeks to evaluate long-term efficacy and safety

104 weeks

Regular visits as per study protocol

Safety Follow-up

Participants are monitored for safety after the treatment period

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Odevixibat

Trial Overview The trial tests the long-term effects and safety of Odevixibat on children with Biliary Atresia. It's an extension of a prior study where participants continue to receive this medication under open-label conditions, meaning both researchers and participants know what treatment is being given.

How Is the Trial Designed?

Group I: Odevixibat (A4250) Experimental Treatment 1 Intervention

Capsules for oral administration 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

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]

Odevixibat is a novel treatment for cholestatic diseases like progressive familial intrahepatic cholestasis (PFIC), approved in the EU and USA in 2021, that works by inhibiting the ileal bile acid transporter, leading to significant reductions in bile acid levels in the body.

In clinical studies, a daily dose of 3 mg of odevixibat resulted in a 56% reduction in bile acid levels, demonstrating its efficacy in managing cholestatic pruritus and liver disease development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Odevixibat: A Review of a Bioactive Compound for the Treatment of Pruritus Approved by the FDA. Porwal, M., Kumar, A., Rastogi, V., et al.[2023]

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. 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).

3. 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 ... Odevixibat is also in late-stage development in an ongoing Phase III clinical trial (BOLD) for the treatment of biliary atresia. About ...

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK604832/?report=reader

Pharmacoeconomic Review - Odevixibat (Bylvay) Conclusions. Evidence from the PEDFIC 1 trial indicates that odevixibat 40 mcg/kg likely improves pruritus within 4 weeks, and this improvement is likely to ...

5. 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.

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

Odevixibat: First Approval - PMC Odevixibat continues to be assessed for PFIC in an ongoing open-label, phase III extension study for long term safety and efficacy, and is also ...

7. trial.medpath.com trial.medpath.com/clinical-trial/d698c59471257a60/odevixibat-efficacy-safety-biliary-atresia

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 ...

8. 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 ...