This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC Types 1 or 2

NCT ID: NCT03566238

Last Updated: 2025-11-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-16

Study Completion Date

2020-07-28

Brief Summary

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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.

Detailed Description

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Up to 50 sites in the following countries will take part in this study:

Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Poland, Spain, Sweden, Turkey, United Kingdom, United States, and Saudi Arabia

Conditions

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PFIC1 PFIC2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Double-Blind, Randomized, Placebo-Controlled
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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A4250 low dose

Capsules for oral administration (40 ug/kg) once daily for 24 weeks

Group Type EXPERIMENTAL

A4250 (odevixibat)

Intervention Type DRUG

A4250 is a small molecule and selective inhibitor of ileal bile acid transporter (IBAT).

A4250 high dose

Capsules for oral administration (120 ug/kg) once daily for 24 weeks

Group Type EXPERIMENTAL

A4250 (odevixibat)

Intervention Type DRUG

A4250 is a small molecule and selective inhibitor of ileal bile acid transporter (IBAT).

Placebo

Capsules for oral administration (to match active) once daily for 24 weeks

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo identical in appearance to active drug (A4250).

Interventions

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A4250 (odevixibat)

A4250 is a small molecule and selective inhibitor of ileal bile acid transporter (IBAT).

Intervention Type DRUG

Placebo

Placebo identical in appearance to active drug (A4250).

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

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
Minimum Eligible Age

6 Months

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Albireo

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Denver, Colorado, United States

Site Status

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status

Johns Hopkins School of Medicine

Baltimore, Maryland, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

Columbia University Medical Center - Presbyterian Hospital Building

New York, New York, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Baylor College of Medicine - Texas Children's Liver Center

Houston, Texas, United States

Site Status

The Royal Children's Hospital

Melbourne, , Australia

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, , Belgium

Site Status

The Hospital for Sick Children

Toronto, , Canada

Site Status

British Columbia Children's Hospital

Vancouver, , Canada

Site Status

University and Pediatric Hospital of Lyon

Bron, , France

Site Status

Universite Paris SUD - Hopitaux Universitaires Paris-Sud - Hopital Bicetre

Le Kremlin-Bicêtre, , France

Site Status

Hospital de la Timone

Marseille, , France

Site Status

Hospital Necker-Enfants maladies

Paris, , France

Site Status

Uniklinikum Essen- Kinderklinik II

Essen, , Germany

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Kinderklinik Tübingen, Universitätsklinikum Tübingen

Tübingen, , Germany

Site Status

Rambam Medical Centre

Haifa, , Israel

Site Status

Shaare-Zedek Mc

Jerusalem, , Israel

Site Status

Schneider Children's Medical Center Of Israel

Petah Tikva, , Israel

Site Status

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, , Italy

Site Status

University Hospital Of Padova

Padua, , Italy

Site Status

Ospedale Regina Margherita

Torino, , Italy

Site Status

University Medical Center Groningen

Groningen, , Netherlands

Site Status

Universitair Medisch Centrum (UMC) Utrecht

Utrecht, , Netherlands

Site Status

Instytut Pomnik - Centrum Zdrowia Dziecka

Warsaw, , Poland

Site Status

King Faisal Specialist Hospital & Research Centre

Riyadh, , Saudi Arabia

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Astrid Lindgren Children's Hospital, Karolinska University Hospital

Solna, , Sweden

Site Status

Gazi University

Ankara, , Turkey (Türkiye)

Site Status

Hacettepe University Faculty of Medicine

Ankara, , Turkey (Türkiye)

Site Status

Akdeniz University

Antalya, , Turkey (Türkiye)

Site Status

Istanbul University Medical Faculty

Istanbul, , Turkey (Türkiye)

Site Status

Inonu University Medical Faculty

Malatya, , Turkey (Türkiye)

Site Status

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, , United Kingdom

Site Status

Leeds General Infirmary

Leeds, , United Kingdom

Site Status

Institute of Liver Studies - Kings College Hospital

London, , United Kingdom

Site Status

Countries

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United States Australia Belgium Canada France Germany Israel Italy Netherlands Poland Saudi Arabia Spain Sweden Turkey (Türkiye) United Kingdom

References

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Gwaltney C, Ivanescu C, Karlsson L, Warholic N, Kjems L, Horn P. Validation of the PRUCISION Instruments in Pediatric Patients with Progressive Familial Intrahepatic Cholestasis. Adv Ther. 2022 Nov;39(11):5105-5125. doi: 10.1007/s12325-022-02262-7. Epub 2022 Sep 6.

Reference Type DERIVED
PMID: 36066745 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35780807 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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A4250-005

Identifier Type: -

Identifier Source: org_study_id

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