Alagille Syndrome
Conditions
Interventions
Patients will be randomized 2:1 to receive odevixibat 120 µg/kg/day or placebo.
Sponsors
Albireo AB
Eligibility
Age
2 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. A male or female patient (of any age) with genetically confirmed diagnosis of ALGS. A patient may be randomized based on genetic testing results in the medical record. If genetic testing results are not available, testing will be performed at Screening Visit 1, and the patient may not be randomized until the genetic diagnosis is confirmed 2. Patient must have a history of significant pruritus and a caregiver reported observed scratching or a patient-reported itching score at an average of >=2 (on 0 to 4 scale), as measured by the Albireo ObsRO instrument (for patients 18 years of age) in the 14 days prior to randomization. For each AM and PM weekly assessment a minimum of 4 out of 7 expected scores must be recorded. The mean of the weekly AM and the mean of the weekly PM scores will be averaged to determine the pruritus score as measured by ObsRO or PRO, if the patient is >=18 years of age 3. Patient must have an elevated baseline serum bile acid level. Each of the serum bile acid levels obtained at Screening Visit 1 and Screening Visit 2 must be greater than the upper limit of normal (>ULN) 4. Patient and/or legal guardian must sign informed consent (and assent) as appropriate. Patients who turn 18 years of age (or legal age per country) during the study will be required to re-consent in order to remain in the study 5. Caregivers must be willing and able to use an eDiary device as required by the study and patients >=8 years of age must be willing to use an eDiary if able to do so 6. Sexually active males and females must agree to use a reliable contraceptive method with
Exclusion criteria
Exclusion criteria: 1. Patient with past medical history or ongoing presence of other types of liver disease including, but not limited to, the following: a) Biliary atresia of any kind b) PFIC c) Benign recurrent intrahepatic cholestasis d) Suspected or proven liver cancer or metastasis to the liver on imaging studies 2. Patient with a past medical history or ongoing presence of any other disease or condition known to interfere with the absorption, distribution, metabolism (specifically bile acid metabolism), or excretion of drugs in the intestine, including but not limited to, inflammatory bowel disease 3. Patient with past medical history or ongoing chronic (i.e. >3 months) diarrhea requiring intravenous fluid or nutritional intervention for treatment of the diarrhea and/or its sequelae 4. Patient has a confirmed past diagnosis of infection with human immunodeficiency virus or other present and active, clinically significant chronic infection 5. Recent infection requiring hospitalization or treatment with parenteral anti-infective within 4 weeks of randomization (Study Day 1) or completion of oral anti-infective treatment within 2 weeks prior to start of Screening Period 6. Cancer within the last 5 years except for basal cell carcinoma 7. Cancer >5 years prior to screening except for non-liver cancers with no evidence of recurrence 8. Chronic kidney disease with an impaired renal function and a glomerular filtration rate 1.4 (the patient may be treated with Vitamin K intravenously, and if INR is 10 × ULN at Screening 14. Serum ALT >15 × ULN at any time point during the last 6 months unless an alternate etiology was confirmed for the elevation 15. Total bilirubin >15 × ULN at Screening 16. Patient suffers from uncontrolled, recalcitrant pruritic condition other than ALGS. Examples include, but not limited to, refractory atopic dermatitis or other primary pruritic skin diseases 17. Any patient who is pregnant or lactating or who is planning to become pregnant within 24 weeks of randomization 18. Patient with a past medical history of alcohol or substance abuse. Patient must agree to refrain from illicit drug and alcohol use during the study 19. Administration of bile acid or lipid binding resins and medications that slow gastrointestinal motility 20. Patient has had investigational exposure to a drug, biologic agent, or medical device within 30 days prior to Screening, or 5 half-lives of the study agent, whichever is longer 21. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in scratching to Month 6 (Weeks 21 to 24) as measured by the Albireo ObsRO caregiver instrument. | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in serum bile acid levels from baseline to the average of Week 20 and Week 24 | — |
Countries
Netherlands
Outcome results
None listed