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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/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
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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)
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Secondary ID [1]
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A4250-005
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Universal Trial Number (UTN)
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Trial acronym
PEDFIC 1
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
PFIC1
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PFIC2
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Condition category
Condition code
Oral and Gastrointestinal
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Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
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Intervention/exposure
Study type
Interventional
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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).
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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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)
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Assessment method [1]
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ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with score from 0 to 4 where 0 is no scratching and 4 is worst possible scratching. A positive pruritus assessment was defined as a scratching score of \<= 1 or at least one point drop from baseline. At each post baseline assessment over the 24-week treatment period, the AM score was compared to the baseline AM average and the PM score was compared to the baseline PM average. Both AM and PM pruritus assessments were included in the analysis. Any intermittently missing assessment or missing planned assessment after premature treatment discontinuation, death, or initiation of rescue treatment was classified as negative assessment. Proportion of positive pruritus assessments at the participant level over the 24-week was then calculated. Full analysis set was used for the analysis.
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Timepoint [1]
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Over 24 weeks of treatment
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Primary outcome [2]
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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)
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Assessment method [2]
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Fasting s-BA baseline was calculated as the average of the last 2 values prior to the first dose. The end value was the average of the values at Weeks 22 and 24 after the start of double-blind treatment. Participants who had at least 70% reduction in Fasting s-BA from baseline to the end of treatment or reached \<=70 µmol/L after 24 weeks of treatment were considered as responder. Participants with missing average at the end of treatment were classified as non-responder. Full analysis set was used for the analysis.
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Timepoint [2]
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Over 24 weeks of treatment
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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
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Minimum age
6
Months
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Maximum age
18
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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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
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
16/05/2018
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
28/07/2020
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Sample size
Target
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Accrual to date
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Final
62
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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The Royal Children's Hospital - Melbourne
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Recruitment postcode(s) [1]
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- Melbourne
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Recruitment outside Australia
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United States of America
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California
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Colorado
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Georgia
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Leuven
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Woluwe-Saint-Lambert
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Bron
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France
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le Kremlin Bicetre
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France
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Essen
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Israel
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Israel
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Istanbul
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Malatya
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Birmingham
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Leeds
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London
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Albireo
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Address
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/study/NCT03566238
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Trial related presentations / publications
Thompson RJ, Arnell H, Artan R, Baumann U, Calvo PL, Czubkowski P, Dalgic B, D'Antiga L, Durmaz O, Fischler B, Gonzales E, Grammatikopoulos T, Gupte G, Hardikar W, Houwen RHJ, Kamath BM, Karpen SJ, Kjems L, Lacaille F, Lachaux A, Lainka E, Mack CL, Mattsson JP, McKiernan P, Ozen H, Rajwal SR, Roquelaure B, Shagrani M, Shteyer E, Soufi N, Sturm E, Tessier ME, Verkade HJ, Horn P. Odevixibat treatment in progressive familial intrahepatic cholestasis: a randomised, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2022 Sep;7(9):830-842. doi: 10.1016/S2468-1253(22)00093-0. Epub 2022 Jul 1.
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Public notes
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Contacts
Principal investigator
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/38/NCT03566238/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/38/NCT03566238/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT03566238
Download to PDF