Odevixibat for Alagille Syndrome

(ASSERT-EXT Trial)

Recruiting at 41 trial locations

Overseen By Ipsen Recruitment enquiries

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Albireo, an Ipsen Company

Must not be taking: Bile acid resins

Disqualifiers: Decompensated liver disease, Cancer, 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: 20

Duration: 72 weeks (cohort 1) or 12 weeks (cohort 2)

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term safety and effectiveness of odevixibat (Bylvay) for individuals with Alagille syndrome (ALGS), a rare genetic condition affecting the liver and other organs. ALGS often causes severe itching, yellowing of the skin, and poor growth in children. Participants who completed a prior study on this treatment or infants under 12 months with a confirmed ALGS diagnosis are suitable for this trial. As a Phase 3 trial, this study is the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications that slow gastrointestinal motility or bind bile acids or lipids are excluded, so you may need to discuss your current medications with the study team.

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

Research shows that odevixibat is generally safe for people with Alagille syndrome. Studies have found it can help reduce severe itching and lower bile acids in the blood, which is important because high bile acids can lead to liver problems.

Some people using odevixibat have reported side effects like diarrhea, stomach pain, easy bruising, and weight loss. These are the most common issues, but not everyone experiences them. The U.S. Food and Drug Administration has approved odevixibat for treating itching in young children with Alagille syndrome, confirming its safety in these patients.

Discuss any concerns with a doctor, especially if considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alagille syndrome?

Unlike the standard treatments for Alagille Syndrome, which often focus on managing symptoms like itching with medications such as ursodeoxycholic acid or cholestyramine, Odevixibat offers a novel approach. It works by inhibiting the ileal bile acid transporter (IBAT), which can help reduce the accumulation of bile acids that cause liver damage and severe itching. Researchers are excited about Odevixibat because it is taken orally once daily and has the potential to address the root cause of the symptoms rather than just providing temporary relief. This could significantly improve the quality of life for patients with Alagille Syndrome.

What is the effectiveness track record for odevixibat in treating Alagille syndrome?

Research has shown that odevixibat, which participants in this trial will receive, can help treat Alagille syndrome (ALGS). Studies have found it reduces severe itching and lowers bile acid levels in the blood, common problems for ALGS patients. Evidence also suggests it can improve growth in height and weight for those taking the medication. The FDA has approved odevixibat for treating itching related to ALGS in infants over 12 months old. These findings suggest that odevixibat is a promising option for managing ALGS symptoms. ^{2 3 6 7 8}

Who Is on the Research Team?

Ipsen Medical Director

Principal Investigator

Ipsen

Are You a Good Fit for This Trial?

This trial is for patients with Alagille Syndrome who completed a previous 24-week study. They must be able to use an eDiary and agree to reliable contraception if sexually active. It's not for those with severe liver issues, non-compliance in the prior study, or hypersensitivity to odevixibat.

Inclusion Criteria

Caregivers (and age-appropriate patients) must be willing and able to use an electronic diary (eDiary) device as required by the study

I agree to use effective birth control or abstain from sex during and 90 days after the study.

I have signed the consent form and will re-consent if I turn 18 during the study.

Exclusion Criteria

You did not follow the instructions for taking the study drug or participating in the procedures in a previous study.

Any other 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

I do not have severe liver problems or symptoms like fluid in the abdomen, bleeding veins in my esophagus, or confusion.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive odevixibat daily for 72 weeks (cohort 1) or 12 weeks (cohort 2) with clinic visits every 4 to 12 weeks

72 weeks (cohort 1) or 12 weeks (cohort 2)

Clinic visits every 4 to 12 weeks

Optional extension

Participants may continue receiving odevixibat with visits every 16 weeks until the drug is commercially available

Visits every 16 weeks

Safety follow-up

Participants are monitored for safety after treatment for 4 weeks (cohort 1) or 2 weeks (cohort 2), unless they continue in the optional extension

4 weeks (cohort 1) or 2 weeks (cohort 2)

What Are the Treatments Tested in This Trial?

Interventions

• Odevixibat

Trial Overview

The trial tests the long-term safety and effectiveness of Odevixibat in individuals with Alagille Syndrome. It's an open-label extension meaning everyone knows they're getting Odevixibat and there’s no placebo group.

How Is the Trial Designed?

Group I: Odevixibat (A4250) Experimental Treatment 1 Intervention

Capsules for oral administration once daily for 72 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

Adefovir dipivoxil (ADV) treatment for 156 weeks significantly reduced HBV DNA levels and normalized serum ALT in patients with HBeAg-positive chronic hepatitis B, demonstrating its efficacy.

The treatment was found to be safe, with no renal toxic effects reported, indicating that ADV can be a reliable long-term option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Three year adefovir dipivoxil treatment for hepatitis B e antigen-positive chronic hepatitis B patients]. Ling, N., Zhou, Z., Zhang, DZ., et al.[2013]

In a study involving 42 healthy volunteers aged 19 to 26, a single oral dose of adefovir dipivoxil up to 60 mg was found to be safe and well-tolerated, with no significant adverse effects related to dosage.

While some mild gastrointestinal symptoms and slight elevations in liver enzymes were observed, these were not linked to the dosage levels, indicating a favorable safety profile for adefovir dipivoxil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and tolerance study of single oral dose of adefovir dipivoxil tablets in healthy volunteers]. Wang, HS., Sun, DQ., Fan, XP., et al.[2013]

In a study analyzing 794 suspected adverse drug reactions (ADRs) related to oral anticoagulants from 2010 to 2015, it was found that 78% of these reports were associated with non-vitamin K antagonist oral anticoagulants (NOACs), indicating a growing concern about their safety.

The study revealed that while the overall incidence of NOAC-related ADRs decreased after 2012, there was a significant increase in reports of nervous system disorders linked to NOACs, suggesting a need for ongoing monitoring and evaluation of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suspected adverse drug reaction reports with oral anticoagulants in Portugal: a pharmacovigilance study. Caldeira, D., Rodrigues, R., Abreu, D., et al.[2018]

In a study of 54 patients with HBeAg positive chronic hepatitis, treatment with generic adefovir dipivoxil (ADV) for 96 weeks significantly reduced ALT levels and HBV-DNA compared to placebo, indicating its efficacy in managing the disease.

However, after stopping ADV treatment, 100% of patients experienced a relapse in HBV-DNA levels, and 88.24% developed abnormal liver function, highlighting the need for ongoing monitoring and potential long-term treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and durability of generic adefovir dipivoxil in patients with HBeAg positive chronic hepatitis]. Dong, PL., Wang, DM., Zhang, XM., et al.[2013]

Adefovir dipivoxil (ADV) treatment for 48 weeks in patients with chronic hepatitis B showed significant reductions in serum HBV DNA levels, with a median decrease of 2.8 log10 copies/ml at 12 weeks for those receiving ADV compared to only 0.3 log10 copies/ml for the placebo group.

The treatment was found to be safe, with only 5.56% of patients experiencing mild to moderate adverse events, and no significant changes in serum creatinine levels, indicating good renal safety during the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A clinical study of adefovir dipivoxil, made in China, for treatment of hepatitis B e antigen-positive patients with chronic hepatitis B]. Lin, XH., Si, CW., Yu, YY., et al.[2013]

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]

A pediatric patient diagnosed with Alagille syndrome showed significant improvement in liver function and reduction in pruritus after treatment with odevixibat, which was initially used for progressive familial intrahepatic cholestasis.

Odevixibat led to normalization of serum bile acid levels within weeks, suggesting it may be an effective off-label treatment for Alagille syndrome, a condition characterized by similar symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Odevixibat Treatment of Alagille Syndrome: A Case Report. Ganschow, R., Maucksch, C.[2023]

Maralixibat is the first FDA-approved treatment specifically for cholestatic pruritus in children with Alagille syndrome, showing significant efficacy in clinical trials with follow-up of up to 4 years.

A case report highlights a patient who experienced complete resolution of pruritus for over 7 years after starting maralixibat, allowing her to stop all other antipruritic medications, demonstrating the long-term effectiveness of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resolution of Pruritus in a Child With Alagille Syndrome Treated With Maralixibat for Seven Years: Durable Response and Discontinuation of Other Medications. Garcia, A., Hsu, E., Lin, HC.[2023]

Dabigatran, dosed using a pediatric-specific algorithm, was found to be non-inferior to standard anticoagulant treatments in children with venous thromboembolism, with similar efficacy in achieving complete thrombus resolution and preventing recurrence.

The safety profile of dabigatran was comparable to standard care, with similar rates of bleeding events and serious adverse effects, suggesting it could be a viable alternative for anticoagulation in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabigatran etexilate for the treatment of acute venous thromboembolism in children (DIVERSITY): a randomised, controlled, open-label, phase 2b/3, non-inferiority trial. Halton, J., Brandão, LR., Luciani, M., et al.[2021]

Dabigatran etexilate is an effective oral anticoagulant that offers a safer and more convenient alternative to warfarin for patients with nonvalvular atrial fibrillation, as it does not require blood monitoring and has fixed dosing.

In a large phase 3 trial, dabigatran etexilate (150 mg twice daily) was found to be superior to warfarin in preventing strokes and systemic embolism, with similar rates of major bleeding, although it may cause side effects like dyspepsia and gastrointestinal bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology and therapeutic use of dabigatran etexilate. Sarah, S.[2015]

In a post-marketing surveillance study of 6148 Japanese patients with nonvalvular atrial fibrillation, dabigatran showed a favorable safety profile, with low rates of serious adverse events such as myocardial infarction (0.06 per 100 patient-years) and serious hemorrhage (0.55 per 100 patient-years).

The study also indicated high treatment adherence, with 92% of patients taking dabigatran as prescribed, supporting its effectiveness in long-term management of atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing surveillance on the long-term use of dabigatran in Japanese patients with nonvalvular atrial fibrillation: Preliminary report of the J-dabigatran surveillance. Inoue, H., Uchiyama, S., Atarashi, H., et al.[2022]

Dabigatran etexilate, an oral direct thrombin inhibitor, can lead to serious complications such as hemorrhagic gastritis, especially in patients with chronic renal insufficiency, as demonstrated in a case involving an 85-year-old man.

In this case, fresh frozen plasma was used to manage the dabigatran-induced coagulopathy, highlighting the need for awareness of potential bleeding risks and treatment options for patients on dabigatran.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemorrhagic gastritis with dabigatran in a patient with renal insufficiency. Fellows, SE., Rosini, JM., Curtis, JA., et al.[2015]

Dabigatran etexilate is an effective oral anticoagulant for preventing strokes in patients with non-valvular atrial fibrillation, showing at least equal or often superior efficacy and safety compared to warfarin based on clinical trials and real-world studies.

While dabigatran etexilate has pharmacokinetic and pharmacodynamic advantages over warfarin, it is not suitable for patients with prosthetic heart valves or end-stage chronic kidney disease, highlighting important safety considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Warfarin versus dabigatran etexilate: an assessment of efficacy and safety in patients with atrial fibrillation. Dzeshka, MS., Lip, GY.[2022]

Maralixibat, a bile acid transport inhibitor, demonstrated significant and lasting improvements in serum bile acid levels and pruritus in children with Alagille syndrome, marking it as the first effective treatment for this condition.

In a study involving 31 children, those who continued maralixibat maintained their treatment benefits over 204 weeks, with the medication being generally safe and well tolerated, primarily causing mild gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of maralixibat treatment in patients with Alagille syndrome and cholestatic pruritus (ICONIC): a randomised phase 2 study. Gonzales, E., Hardikar, W., Stormon, M., et al.[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

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ipsen.com/press-releases/bylvay-odevixibat-data-shows-sustained-improvement-in-severe-itch-and-serum-bile-acid-levels-in-patients-with-pfic-and-algs-2982434/

Bylvay® (odevixibat) data shows sustained improvement in ...

Sustained efficacy data and improvements in height, weight and sleep measures were observed for patients treated with Bylvay for at least 72 weeks in both rare ...

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thelancet.com/journals/langas/article/PIIS2468-1253(24)00074-8/fulltext

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 ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12421396/

Odevixibat improves pruritus and bile acid level in Alagille ...

We report the effects of odevixibat treatment in a patient Alagille syndrome over 12 months. This case demonstrates the use of ileal bile acid ...

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clinicaltrials.gov/study/NCT05035030

Long-term Safety and Efficacy of Odevixibat in Patients ...

The purpose of this study is to assess the long-term safety and effectiveness of odevixibat in participants with Alagille syndrome (ALGS).

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Explore Bylvay® (odevixibat) efficacy in ALGS pruritus

An open-label study to evaluate the long-term safety and efficacy of odevixibat (A4250) in patients with Alagille syndrome (ASSERT-EXT). NCT05035030. Updated ...

6.

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The primary efficacy endpoint was change in caregiver-reported scratching score (on the PRUCISION instrument; range 0-4) from baseline to weeks 21-24. The ...

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Alagille syndrome home | Bylvay® (odevixibat) - Patient site

The most common side effects of BYLVAY treatment in patients with ALGS are diarrhea, abdominal pain, abnormal bleeding, such as bruising, and decreased weight.

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ipsen.com/us/press-releases/bylvay-odevixibat-data-shows-sustained-improvement-in-severe-itch-and-serum-bile-acid-levels-in-patients-with-pfic-and-algs-2982434/

Bylvay® (odevixibat) data shows sustained improvement in ...

Sustained efficacy data and improvements in height, weight and sleep measures were observed for patients treated with Bylvay for at least 72 weeks in both rare ...