An Investigation of the Safety and Efficacy of Odevixibat in Patients with Alagille syndrome

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2020-004011-28-FR
• Date of registration: 25/11/2020
• Prospective Registration: Yes
• Primary sponsor: Albireo AB
• Public title: An Investigation of the Safety and Efficacy of Odevixibat in Patients with Alagille syndrome
• Scientific title: A Phase 3 Double-blind, Randomized, Placebo-controlled Study of the Safety and Efficacy of Odevixibat (A4250) in Patients with Alagille Syndrome (ASSERT)
• Date of first enrolment: 09/02/2021
• Target sample size: 63
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004011-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, Denmark, France, Germany, Italy, Netherlands, Poland, United Kingdom, United States

Contacts

• Name: Clinical Operations Department
• Affiliation: Albireo AB

• Name: Clinical Operations Department
• Affiliation: Albireo AB

Key inclusion & exclusion 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 pruritus score at an average of =2 (on 0 to 4 scale), as measured by the Albireo ObsRO instrument (for patients <18 years of age) or the PRO 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 =1% failure rate (such as hormonal contraception, intrauterine device, or complete abstinence) throughout the duration of the study and 90 days thereafter (from signed informed consent through 90 days after last dose of study drug)
Are the trial subjects under 18? yes
Number of subjects for this age range: 45
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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
b) Progressive Familial Intrahepatic Cholestasis (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 <70 mL/min/1.73 m2

9. Patient with surgical history of disruption of the enterohepatic circulation (biliary diversion surgery) within 6 months prior to start of Screening Period

10. Patient has had a liver transplant or a liver transplant is planned within 6 months of randomization

11. Decompensated liver disease, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy

12. International normalized ratio (INR) >1.4 (the patient may be treated with Vitamin K intravenously, and if INR is =1.4 at resampling the patient may be randomized)

13. Serum alanine aminotransferase (ALT) >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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Alagille Syndrome
MedDRA version: 20.0 Level: PT Classification code 10053870 Term: Alagille syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Product Name: Odevixibat
Product Code: A4250
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Odevixibat
CAS Number: 501692-44-0
Current Sponsor code: A4250
Other descriptive name: A4250
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Odevixibat
Product Code: A4250
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Odevixibat
CAS Number: 501692-44-0
Current Sponsor code: A4250
Other descriptive name: A4250
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Odevixibat
Product Code: A4250
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Odevixibat
CAS Number: 501692-44-0
Current Sponsor code: A4250
Other descriptive name: A4250
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Odevixibat
Product Code: A4250
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Odevixibat
CAS Number: 501692-44-0
Current Sponsor code: A4250
Other descriptive name: A4250
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 1200-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To assess the impact of odevixibat on serum bile acid levels in patients with ALGS.
To evaluate the safety and tolerability of odevixibat in patients with ALGS.

Timepoint(s) of evaluation of this end point: Change from baseline in scratching to Month 6 (Weeks 21 to 24)

Primary end point(s): Change from baseline in scratching to Month 6 (Weeks 21 to 24) as measured by the Albireo ObsRO caregiver instrument

Main Objective: The primary objective is to demonstrate the efficacy of repeated daily doses of 120 µg/kg/day odevixibat in relieving pruritus in patients with ALGS.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: From baseline to the average of Week 20 and Week 24

Secondary end point(s): Change in serum bile acid levels from baseline to the average of Week 20 and Week 24

Secondary ID(s)

A4250-012

Source(s) of Monetary Support

Albireo AB

Ethics review

Status: Approved
Approval date: 09/02/2021
Contact: