Trial Review

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/ct2/show/NCT03566238




Registration number
NCT03566238
Ethics application status
Date submitted
25/05/2018
Date registered
25/06/2018
Date last updated
5/09/2021

Titles & IDs
Public title
This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC Types 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 ileal bile acid transporter (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
Proportion of Positive Pruritus Assessments at the Participant Level Over the 24-week Treatment Period Based on the Albireo Observer-reported Outcome (ObsRO) Instrument (United States Primary Endpoint)
Timepoint [1] 0 0
Over 24 weeks of treatment
Primary outcome [2] 0 0
Percentage of Participants Experiencing at Least a 70% Reduction in Fasting s-BA Concentration From Baseline to the End of Treatment or Reaching a Level <= 70 µmol/L After 24 Weeks of Treatment (European Union and Rest of the World Primary Endpoint)
Timepoint [2] 0 0
Over 24 weeks of treatment

Eligibility
Key inclusion criteria
Key

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

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

- Participant must have elevated serum bile acid (s-BA) concentration

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

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

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

- Caregivers and age-appropriate participants (=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
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participant with pathologic variations of the ABCB11 gene that predict complete
absence of the bile salt export pump (BSEP) protein

- Participant 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

- Participant with past medical history or ongoing chronic diarrhea

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

- Participant 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

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

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

- Decompensated liver disease

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

- Participant 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 assessing the outcomes
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/05/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/07/2020
Sample size
Target
Accrual to date
Final
62
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 progressive
familial intrahepatic cholestasis (PFIC) types 1 and 2.
Trial website
https://clinicaltrials.gov/ct2/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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03566238