Efficacy and Safety of Odevixibat in Patients With Alagille Syndrome

Study Overview
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Brief Summary
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Double-blind, randomized, placebo-controlled, Phase 3 study to investigate the efficacy and safety of odevixibat compared to placebo in Patients with Alagille Syndrome.

Detailed Description
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Approximately 35 sites will be initiated for this study in North America, Europe, Middle East, and Asia Pacific.

Official Title
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A Phase 3 Double-blind, Randomized, Placebo-controlled Study of the Safety and Efficacy of Odevixibat (A4250) in Patients With Alagille Syndrome (ASSERT)

Conditions
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Alagille Syndrome

Intervention / Treatment
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* Drug: Odevixibat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Genetically confirmed diagnosis of Alagille syndrome History of significant pruritus as measured by the Albireo Observer or Patient Reported Outcome instrument Elevated serum bile acid level Key Exclusion Criteria: History or ongoing presence of other types of liver disease (eg. biliary atresia, progressive familial intrahepatic cholestasis, hepatocellular carcinoma) History of liver transplant, or a liver transplant is planned within 6 months of randomization ALT >10× upper limit of normal (ULN) at screening Total bilirubin >15 × ULN at screening Patient suffers from uncontrolled, recalcitrant pruritic condition other than Alagille syndrome
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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Odevixibat (A4250)<br>Capsules for oral administration once daily for 24 weeks. | Drug: Odevixibat<br>* Odevixibat is a small molecule and selective inhibitor of IBAT.<br>* Other names: A4250;|
| Placebo Comparator: Placebo<br>Capsules for oral administration (to match active) once daily for 24 weeks. | Drug: Placebo<br>* Placebo identical in appearance to experimental drug (odevixibat).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Scratching Score | Change from baseline in average AM (measured after waking up) and PM (measured before bedtime) scratching score to Month 6 as measured by the Albireo Observer-Reported Outcome (ObsRO) Instrument. The ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with scores from 0 to 4 where 0 is no scratching and 4 is worst possible scratching. | Change from baseline for each four-week average pruritis score to Month 6 (Weeks 21 to 24), in which baseline was calculated based on the 14 days before the start of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Bile Acid Levels | Change in serum bile acid levels (μmol/L) from baseline to average of week 20 and 24 | Change from baseline to average of week 20 and 24, where baseline was calculated by averaging the last two values preceding start of treatment, and average of Week 20 and Week 24 was defined as the average of Week 20 and Week 24 values. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALGS, Alagille syndrome