A4250, an IBAT Inhibitor in Pediatric Cholestasis

Study Overview
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Brief Summary
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This study will evaluate A4250 (IBATinhibitor) as a treatment option in pediatric patients with chronic cholestasis with main emphasis on safety evaluation and on effects on pruritus

Detailed Description
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The primary aims of this Phase II exploratory study in patients treated with A4250 due to cholestasis induced pruritus are to: Assess the safety and tolerability of A4250, orally administered first as a single dose and then during a four week treatment period, as determined by the occurrence of treatment-emergent SAEs Explore changes in serum total bile acids after a four week treatment period Secondary safety aims include assessment of the safety and tolerability of A4250, orally administered first as a single dose and then during a four week treatment period, as determined by the occurrence of treatment-emergent AEs and changes in safety parameters including laboratory tests and vital signs Secondary efficacy aims are to: Demonstrate the efficacy of A4250, orally administered during a four week treatment period, on liver biochemistry variables and on pruritus parameters Evaluate the pharmacokinetic properties of A4250 orally administered first as a single dose and then after a four week treatment period Evaluate changes in VAS-itching score after a four week treatment period

Official Title
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An Exploratory Phase II Study to Demonstrate the Safety and Efficacy of A4250 in Children With Cholestatic Pruritus

Conditions
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Pediatric Cholestasis

Intervention / Treatment
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* Drug: A4250


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of pruritus due to chronic cholestasis based on history and investigator judgment. This will include but will not be restricted to patients with Progressive familial intrahepatic cholestasis (PFIC), Alagille syndrome (ALGS), Biliary Atresia and Sclerosing Cholangitis Exclusion Criteria: Any condition that in the opinion of the investigator constitutes a risk for the patient or a contraindication for participation and completion of the study, or could interfere with study objectives, conduct, or evaluations Clinical or biochemical signs of decompensated liver disease Liver transplantation

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A4250 1<br>Dose I | Drug: A4250<br>* A4250<br>|
| Active Comparator: A4250 2<br>Dose 2 | Drug: A4250<br>* A4250<br>|
| Active Comparator: A4250 3<br>Dose 3 | Drug: A4250<br>* A4250<br>|
| Active Comparator: A4250 4<br>Dose 4 | Drug: A4250<br>* A4250<br>|
| Active Comparator: A4250 5<br>Dose 5 | Drug: A4250<br>* A4250<br>|
| Active Comparator: A4250 6<br>Dose 6 | Drug: A4250<br>* A4250<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AE evaluation | Treatment-emergent SAEs Adverse events | 4 wks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bile acid changes | Evaluation of bile acids | 4 weeks |