What side effects are associated with this type of intervention?

Common treatments for Progressive Familial Intrahepatic Cholestasis (PFIC), such as bile acid sequestrants and selective inhibitors of ileal bile acid transporters like A4250, often have gastrointestinal side effects including constipation and nausea. They can also interfere with the absorption of other medications and lead to fat malabsorption and vitamin deficiencies, particularly vitamin K deficiency. Monitoring these side effects is essential to ensure patient safety and treatment effectiveness.

What prior FDA approvals exist?

The FDA has approved several treatments for Progressive Familial Intrahepatic Cholestasis (PFIC). One notable approval is for odevixibat (brand name Bylvay), which, like A4250, is a selective inhibitor of the ileal bile acid transporter (IBAT). This class of drugs works by reducing the reabsorption of bile acids in the intestines, thereby decreasing bile acid levels in the liver and alleviating cholestasis symptoms. Other treatments for PFIC may include ursodeoxycholic acid (UDCA), which helps improve bile flow, although it works through a different mechanism compared to IBAT inhibitors.

What other types of research exist?

Based on the provided context, there are no specific novel alternatives to A4250 mentioned for PFIC. However, treatments like ursodeoxycholic acid (UDCA) and oral budesonide have been used in related liver conditions and may be considered. It is essential to consult with a healthcare provider for the most current and personalized treatment options.

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Bile Acid Sequestrant

Odevixibat for PFIC

Phase 3

Waitlist Available

Research Sponsored by Albireo, an Ipsen Company

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Cohort 2: Patients with PFIC, excluding BRIC, must have elevated serum bile acid concentration, specifically measured to be ≥100 μmol/L, taken as the average of 2 samples at least 7 days apart (Visits S-1 and S-2) prior to the Screening/Inclusion Visit (Visit 1)

Cohort 2: Patient must have clinical genetic confirmation of PFIC

Must not have

Cohort 2: Patient has a confirmed past diagnosis of infection with human immunodeficiency virus or other present and active, clinically significant, acute, or chronic infection, or past medical history of any major episode of infection requiring hospitalization or treatment with parenteral anti-infective treatment within 4 weeks of treatment start (Study Day 1) or completion of oral anti-infective treatment within 2 weeks prior to start of Screening Period

Cohort 1: Decompensated liver disease: coagulopathy, history, or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from baseline to weeks 24, 48, and 72

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing A4250, a medication, to see if it is safe and effective for children with a rare liver disease called PFIC. The goal is to improve liver function and reduce symptoms over time.

Who is the study for?

This trial is for children with PFIC, a liver disorder causing severe itching and jaundice. Participants need genetic confirmation of PFIC, have had significant pruritus, weigh at least 5 kg, and can use an eDiary. They must have completed or partially completed a prior A4250 study. Those with episodic PFIC should be experiencing a flare-up.

What is being tested?

The trial tests the long-term safety and effectiveness of A4250 (odevixibat) in kids with PFIC. It's an open-label extension study meaning all participants receive the drug and are monitored over time to see how well it works and what side effects occur.

What are the potential side effects?

While specific side effects for A4250 aren't listed here, common issues may include gastrointestinal symptoms like diarrhea or abdominal pain due to its effect on bile acids.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have PFIC with bile acid levels ≥100 μmol/L, confirmed by 2 tests.

Select...

I have a genetic confirmation of PFIC.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have had a significant infection or HIV in the past, but it's currently under control.

Select...

I have severe liver disease with symptoms like bleeding, fluid buildup, or confusion.

Select...

I have a genetic variation in the ABCB11 gene leading to no BSEP protein.

Select...

I have had chronic diarrhea for over 3 months needing IV fluids or nutritional support.

Select...

I have severe liver issues, including bleeding, fluid buildup, or mental confusion.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from baseline to weeks 24, 48, and 72

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from baseline to weeks 24, 48, and 72

This trial's timeline: 3 weeks for screening, Varies for treatment, and from baseline to weeks 24, 48, and 72 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

US: Change in Pruritus

Secondary study objectives

All regions: Change in growth

Side effects data

From 2020 Phase 3 trial • 62 Patients • NCT03566238

26%

Pyrexia

26%

Upper respiratory tract infection

21%

Diarrhoea

16%

Alanine aminotransferase increased

16%

Vomiting

11%

Nasopharyngitis

11%

Otitis media

11%

Vitamin D deficiency

11%

Cough

11%

Splenomegaly

11%

Blood bilirubin increased

11%

Blood alkaline phosphatase increased

Respiratory tract infection

Cholelithiasis

Vitamin D decreased

Otorrhoea

Liver function test increased

Cardiac ablation

Urinary tract infection

Supraventricular tachycardia

Abdominal pain

Mouth ulceration

Viral infection

Vitamin A deficiency

Vitamin E deficiency

Cystitis haemorrhagic

Rhinitis allergic

Dehydration

Ear pain

Eye discharge

Abdominal discomfort

Gastroenteritis norovirus

Influenza

Aspartate aminotransferase increased

Platelet count increased

Blood creatine phosphokinase increased

Irritability

Genital rash

Epistaxis

Dermatitis allergic

Pruritus

Sinusitis bacterial

Abdominal pain upper

Dental caries

Hepatomegaly

Parotitis

Headache

Dizziness

100%

80%

60%

40%

20%

Study treatment Arm

A4250 High Dose

A4250 Low Dose

Placebo

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: A4250Experimental Treatment1 Intervention

Capsules for oral administration (40 or 120 µg/kg) once daily for 72 weeks, or 40 µg/kg/day for the first 12 weeks followed by 120 µg/kg/day for the remaining 60 weeks"

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

A4250 (odevixibat)

2018

Completed Phase 3

~70

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Progressive Familial Intrahepatic Cholestasis (PFIC) include selective inhibitors of the ileal bile acid transporter (IBAT) such as A4250. These inhibitors work by reducing the reabsorption of bile acids in the ileum, thereby decreasing the bile acid pool in the liver and reducing cholestasis. This mechanism is crucial for PFIC patients as it helps to alleviate symptoms like pruritus and liver damage caused by the accumulation of bile acids. Other treatments may include ursodeoxycholic acid (UDCA), which improves bile flow and reduces liver inflammation, and surgical options like partial external biliary diversion (PEBD) or liver transplantation in severe cases. These treatments aim to manage symptoms, improve quality of life, and prevent progression to liver failure.

Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3.