The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03566238




Registration number
NCT03566238
Ethics application status
Date submitted
25/05/2018
Date registered
25/06/2018
Date last updated
5/03/2020

Titles & IDs
Public title
This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC 1 or 2
Scientific title
A Double-Blind, Randomized, Placebo-Controlled, Phase 3 Study to Demonstrate Efficacy and Safety of A4250 in Children With Progressive Familial Intrahepatic Cholestasis Types 1 and 2 (PEDFIC 1)
Secondary ID [1] 0 0
A4250-005
Universal Trial Number (UTN)
Trial acronym
PEDFIC 1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
PFIC1 0 0
PFIC2 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)
Treatment: Drugs - Placebo

Experimental: A4250 low dose - Capsules for oral administration (40 ug/kg) once daily for 24 weeks

Experimental: A4250 high dose - Capsules for oral administration (120 ug/kg) once daily for 24 weeks

Placebo Comparator: Placebo - Capsules for oral administration (to match active) once daily for 24 weeks


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

Treatment: Drugs: Placebo
Placebo identical in appearance to active drug (A4250)

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

Outcomes
Primary outcome [1] 0 0
Change in pruritus (US) - Change in pruritus as indexed by caregiver-reported (Albireo ObsRO instrument) observed scratching compared to placebo
Timepoint [1] 0 0
From baseline over the last 5 months of the treatment period
Primary outcome [2] 0 0
Bile acid reduction (EU and rest of world) - Bile acid responder rate on treatment compared to the placebo group
Timepoint [2] 0 0
From baseline to Week 24
Secondary outcome [1] 0 0
Bile acid reduction (US) - Bile acid responder rate on treatment compared to the placebo group
Timepoint [1] 0 0
From baseline to Week 24
Secondary outcome [2] 0 0
Change in pruritus (EU and rest of world) - Change in pruritus as indexed by caregiver-reported (Albireo ObsRO instrument) observed scratching compared to placebo
Timepoint [2] 0 0
From baseline over the last 5 months of the treatment period
Secondary outcome [3] 0 0
Change in fasting serum bile acids (s-BA)
Timepoint [3] 0 0
From baseline to Week 24
Secondary outcome [4] 0 0
Change in serum ALT concentration
Timepoint [4] 0 0
From baseline to Week 24
Secondary outcome [5] 0 0
Change in growth - defined as the linear deficit (weight for age and body mass index) compared to the standard growth curves (Z-score, standard deviation from P50)
Timepoint [5] 0 0
From baseline to Week 24
Secondary outcome [6] 0 0
Proportion of patients achieving meaningful reduction in caregiver-reported observed scratching
Timepoint [6] 0 0
From baseline over the last 5 months of the treatment period
Secondary outcome [7] 0 0
Change in sleep disturbances - measured with the Albireo PRO instrument
Timepoint [7] 0 0
From baseline over the last 5 months of the treatment period
Secondary outcome [8] 0 0
Change in sleep disturbances, including number of awakenings - measured with the ObsRO instrument
Timepoint [8] 0 0
From baseline over the last 5 months of the treatment period
Secondary outcome [9] 0 0
Change in patient-reported itch severity - measured by the average daily score of the Albireo PRO instrument
Timepoint [9] 0 0
From baseline over the last 5 months of the treatment period
Secondary outcome [10] 0 0
Number of patients undergoing biliary diversion surgery or liver transplantation
Timepoint [10] 0 0
From randomization to week 24

Eligibility
Key inclusion criteria
Key

- A male or female patient with a clinical diagnosis of PFIC Type 1 or 2 and with a body
weight above 5 kg

- Patient must have clinical genetic confirmation of PFIC-1 or PFIC-2

- Patient must have elevated s-BA concentration

- Patient must have history of significant pruritus and a caregiver reported observed
scratching in the eDiary

- Patient and/or legal guardian must sign informed consent (and assent) as appropriate.

- Patients will be expected to have a consistent caregiver(s) for the duration of the
study

- Caregivers and age-appropriate patients (=8 years of age) must be willing and able to
use an eDiary device as required by the study

Key
Minimum age
6 Months
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patient with pathologic variations of the ABCB11 gene that predict complete absence of
the BSEP protein

- 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 s
BAs

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

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

- Patient with past medical history or ongoing chronic diarrhea

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

- Patient with a past medical history of chronic kidney disease with an impaired renal
function and a glomerular filtration rate <70 mL/min/1.73 m^2

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

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

- Decompensated liver disease

- Patient suffers from uncontrolled, recalcitrant pruritic condition other than PFIC

- Patient who has been previously treated with an IBAT inhibitor whose pruritus has not
responded to treatment

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not 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
Leuven
Country [11] 0 0
Belgium
State/province [11] 0 0
Woluwe-Saint-Lambert
Country [12] 0 0
Canada
State/province [12] 0 0
Toronto
Country [13] 0 0
Canada
State/province [13] 0 0
Vancouver
Country [14] 0 0
France
State/province [14] 0 0
Bron
Country [15] 0 0
France
State/province [15] 0 0
le Kremlin Bicetre
Country [16] 0 0
France
State/province [16] 0 0
Marseille
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
Germany
State/province [18] 0 0
Essen
Country [19] 0 0
Germany
State/province [19] 0 0
Hannover
Country [20] 0 0
Germany
State/province [20] 0 0
Tubingen
Country [21] 0 0
Israel
State/province [21] 0 0
Haifa
Country [22] 0 0
Israel
State/province [22] 0 0
Jerusalem
Country [23] 0 0
Israel
State/province [23] 0 0
Petach-Tikva
Country [24] 0 0
Italy
State/province [24] 0 0
Bergamo
Country [25] 0 0
Italy
State/province [25] 0 0
Padova
Country [26] 0 0
Italy
State/province [26] 0 0
Torino
Country [27] 0 0
Netherlands
State/province [27] 0 0
Groningen
Country [28] 0 0
Netherlands
State/province [28] 0 0
Utrecht
Country [29] 0 0
Poland
State/province [29] 0 0
Warsaw
Country [30] 0 0
Saudi Arabia
State/province [30] 0 0
Riyadh
Country [31] 0 0
Spain
State/province [31] 0 0
Barcelona
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid
Country [33] 0 0
Sweden
State/province [33] 0 0
Solna
Country [34] 0 0
Turkey
State/province [34] 0 0
Ankara
Country [35] 0 0
Turkey
State/province [35] 0 0
Antalya
Country [36] 0 0
Turkey
State/province [36] 0 0
Istanbul
Country [37] 0 0
Turkey
State/province [37] 0 0
Malatya
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Birmingham
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Leeds
Country [40] 0 0
United Kingdom
State/province [40] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
Double blind, randomized, placebo controlled, Phase 3 study to investigate the efficacy and
safety of low doses and high doses of A4250 compared to placebo in children with PFIC
(deficiencies of familial intrahepatic cholestasis-1 or bile salt export pump).
Trial website
https://clinicaltrials.gov/show/NCT03566238
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications