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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03659916




Registration number
NCT03659916
Ethics application status
Date submitted
24/08/2018
Date registered
6/09/2018
Date last updated
21/01/2020

Titles & IDs
Public title
Long Term Safety & Efficacy Study Evaluating The Effect of A4250 in Children With PFIC
Scientific title
An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of A4250 in Children With Progressive Familial Intrahepatic Cholestasis Types 1 and 2 (PEDFIC 2)
Secondary ID [1] 0 0
A4250-008
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Progressive Familial Intrahepatic Cholestasis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - A4250 (odevixibat)

Experimental: A4250 - Capsules for oral administration (120 ug/kg) once daily for 72 weeks


Treatment: Drugs: A4250 (odevixibat)
A4250 is a small molecule and selective inhibitor of IBAT

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in Pruritus - Change in pruritus as indexed by caregiver-reported (Albireo ObsRO instrument) observed scratching
Timepoint [1] 0 0
From baseline over 72 weeks
Primary outcome [2] 0 0
Change in serum bile acids
Timepoint [2] 0 0
From baseline up to week 72
Secondary outcome [1] 0 0
All-cause mortality
Timepoint [1] 0 0
From baseline to weeks 24, 48, and 72
Secondary outcome [2] 0 0
Number of patients undergoing biliary diversion surgery
Timepoint [2] 0 0
From baseline to weeks 24, 48, and 72
Secondary outcome [3] 0 0
Number of patients undergoing liver transplantation
Timepoint [3] 0 0
From baseline to weeks 24, 48, and 72
Secondary outcome [4] 0 0
Change in growth - The linear growth deficit compared to the standard growth curve
Timepoint [4] 0 0
From baseline to weeks 24, 48, and 72
Secondary outcome [5] 0 0
Change in AST to platelet ratio idex (APRI) score
Timepoint [5] 0 0
From baseline to week 72
Secondary outcome [6] 0 0
Change in Fib-4 score
Timepoint [6] 0 0
From baseline to week 72
Secondary outcome [7] 0 0
Change in pediatric end-stage liver disease (PELD)/model for end-stage liver disease (MELD) score
Timepoint [7] 0 0
From baseline to week 72
Secondary outcome [8] 0 0
Change in use of antipruritic medication
Timepoint [8] 0 0
From baseline to weeks 24, 48, and 72

Eligibility
Key inclusion criteria
Inclusion Criteria Cohort 1:

1. Completion of the 24-week Treatment Period of Study A4250-005 or withdrawn from Study
A4250-005 due to patient/caregiver judgment of intolerable symptoms after completing
at least 12 weeks of treatment

2. Signed informed consent and assent as appropriate

3. Patients expected to have a consistent caregiver for the duration of the study

4. Caregivers (and age appropriate patients) must be willing and able to use an eDiary
device as required by the study

Inclusion Criteria Cohort 2:

1. A male or female patient with a clinical diagnosis of PFIC and with a body weight =5
kg

2. Patient must have clinical genetic confirmation of PFIC

3. Patient must have elevated serum bile acid levels

4. Patient must have history of significant pruritus

5. Age appropriate patients are expected to have a consistent caregiver for the duration
of the study

6. Caregivers and age-appropriate patients (=8 years of age) must be willing and able to
use an eDiary device as required by the study
Minimum age
No limit
Maximum age
100 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria Cohort 1:

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

2. Sexually active males and females who are not using a reliable contraceptive method
with =1% failure rate (such as hormonal contraception, intra-uterine device, or
complete abstinence) throughout the duration of the study and 90 days thereafter

3. Patients not compliant with treatment in study A4250-005

4. Any other conditions or abnormalities which, in the opinion of the investigator or
Medical Monitor, may compromise the safety of the patient, or interfere with the
patient participating in or completing the study

Exclusion Criteria Cohort 2:

1. Known pathologic variations of the ABCB11 gene that have been demonstrated to result
in complete absence of the BSEP protein

2. Patient with past medical history or ongoing presence of other types of liver disease
including, but not limited to, the following:

1. Biliary atresia of any kind

2. Benign recurrent intrahepatic cholestasis, indicated by any history of normal
serum bile acids

3. Suspected or proven liver cancer or metastasis to the liver on imaging studies

4. Histopathology on liver biopsy is suggestive of alternate non-PFIC related
etiology of cholestasis

3. Patient with past medical history or ongoing chronic (i.e., >3 months) diarrhea

4. Any patient with suspected or confirmed cancers except for basal cell carcinoma

5. Patient has had a liver transplant, or a liver transplant is planned within 6 months
of the Screening/Inclusion Visit

6. Decompensated liver disease

7. Patient suffers from uncontrolled, recalcitrant pruritic condition other than PFIC

8. Patient previously treated with an IBAT inhibitor and whose pruritus did not respond
to treatment

9. Sexually active males and females who are not using a reliable contraceptive method
with =1% failure rate (such as hormonal contraception, intra-uterine device, or
complete abstinence) throughout the duration of the study and 90 days thereafter

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The Royal Children's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Belgium
State/province [10] 0 0
Woluwe-Saint-Lambert
Country [11] 0 0
Canada
State/province [11] 0 0
Toronto
Country [12] 0 0
France
State/province [12] 0 0
Bron
Country [13] 0 0
France
State/province [13] 0 0
Le Kremlin-Bicêtre
Country [14] 0 0
France
State/province [14] 0 0
Marseille
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
Germany
State/province [16] 0 0
Hannover
Country [17] 0 0
Germany
State/province [17] 0 0
Tübingen
Country [18] 0 0
Israel
State/province [18] 0 0
Jerusalem
Country [19] 0 0
Israel
State/province [19] 0 0
Petach-Tikva
Country [20] 0 0
Italy
State/province [20] 0 0
Bergamo
Country [21] 0 0
Italy
State/province [21] 0 0
Padova
Country [22] 0 0
Italy
State/province [22] 0 0
Torino
Country [23] 0 0
Netherlands
State/province [23] 0 0
Groningen
Country [24] 0 0
Netherlands
State/province [24] 0 0
Utrecht
Country [25] 0 0
Poland
State/province [25] 0 0
Warsaw
Country [26] 0 0
Spain
State/province [26] 0 0
Madrid
Country [27] 0 0
Sweden
State/province [27] 0 0
Solna
Country [28] 0 0
Turkey
State/province [28] 0 0
Ankara
Country [29] 0 0
Turkey
State/province [29] 0 0
Antalya
Country [30] 0 0
Turkey
State/province [30] 0 0
Istanbul
Country [31] 0 0
Turkey
State/province [31] 0 0
Malatya
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Birmingham
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Leeds
Country [34] 0 0
United Kingdom
State/province [34] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Albireo
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Open Label Extension Study to evaluate long term safety and persistence of effect of A4250 in
children with PFIC.
Trial website
https://clinicaltrials.gov/show/NCT03659916
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Albireo Pharma
Address 0 0
Country 0 0
Phone 0 0
(857) 378-2035
Fax 0 0
Email 0 0
medinfo@albireopharma.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03659916