Long Term Safety & Efficacy Study Evaluating The Effect of A4250 in Children With PFIC

NCT03659916 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: A4250-0082017-002325-38
• Study Type: interventional
• Target: 116
• Locations: 15 countries
• Sites: 41

Brief Summary

Open Label Extension Study to evaluate long term safety and persistence of effect of A4250 in children with PFIC.

Conditions

Progressive Familial Intrahepatic Cholestasis

Keywords

Pediatric; Cholestasis

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Serum Bile Acids

  Blood samples for analysis of fasting total serum bile acids were drawn at specified timepoints. Participants were to fast (water intake only) for at least 4 hours prior to the collection of samples for serum bile acids. Exceptions were made for infants \<12 months of age if unable to fast for the full 4 hours. Baseline for Cohort 1 placebo/odevixibat and Cohort 2 groups was defined as the average of last 2 values before the first dose of study treatment in the study. Baseline for Cohort 1 odevixibat/odevixibat group was defined as average of last 2 values before the first dose of study treatment in study A4250-005 (NCT03566238).

  Baseline and Week 72

• Proportion of Positive Pruritus Assessments at the Participant Level Over 72-Week Using the Albireo Observer-Reported Outcome (ObsRo) Instrument

  A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The proportion of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant.

  Baseline and Week 72

Secondary Outcomes (17)

• Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument From Weeks 0-4, 0-12, 0-22, 0-24, 0-36, 0-46, 0-48, 0-60, and 0-70

  Weeks 0-4, Weeks 0-12, Weeks 0-22, Weeks 0-24, Weeks 0-36, Weeks 0-46, Weeks 0-48, Weeks 0-60, and Weeks 0-70

• Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72

  Baseline and Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72

• Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument From Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 44-46, 47-48, 58-60, 68-70, 71-72, 73-76

  Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 44-46, 47-48, 58-60, 68-70, 71-72, 73-76

• Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score)

  Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 44-46, 47-48, 58-60, 68-70, 71-72, and 73-76

• Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score)

  Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 44-46, 47-48, 58-60, 68-70, 71-72, and 73-76

Study Arms (1)

A4250

EXPERIMENTAL

Capsules for oral administration (40 or 120 µg/kg) once daily for 72 weeks, or 40 µg/kg/day for the first 12 weeks followed by 120 µg/kg/day for the remaining 60 weeks"

Drug: A4250 (odevixibat)

Interventions

A4250 (odevixibat) DRUG

A4250 is a small molecule and selective inhibitor of IBAT

A4250

Eligibility Criteria

• Age: 0 Months - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Signed informed consent and assent as appropriate
• Patients expected to have a consistent caregiver for the duration of the study
• Caregivers (and age appropriate patients) must be willing and able to use an eDiary device as required by the study
• A male or female patient of any age, with a clinical diagnosis of PFIC, including episodic forms (i.e., BRIC), and with a body weight ≥5 kg at Visit S-1.
• Patient must have clinical genetic confirmation of PFIC
• Patients with episodic forms of PFIC (i.e., BRIC) must have an emerging flare characterized by clinically significant pruritus and elevated serum bile acid levels/cholestasis as judged by the investigator.
• Patient and/or legal guardian must sign informed consent (and assent) as appropriate. Patients who turn 18 years of age (or legal age per country) during the study will be required to re-consent in order to remain in the study.
• Age appropriate patients are expected to have a consistent caregiver 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

You may not qualify if:

• Decompensated liver disease: coagulopathy, history, or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy
• 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
• Patients not compliant with treatment in study A4250-005
• 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
• Known pathologic variations of the ABCB11 gene that have been demonstrated to result in 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:
• Biliary atresia of any kind
• Suspected or proven liver cancer or metastasis to the liver on imaging studies
• Histopathology on liver biopsy is suggestive of alternate non-PFIC related etiology of cholestasis Note: Patients with clinically significant portal hypertension are allowed.
• Patient with a past medical history or ongoing presence of any other disease or condition known to interfere with the absorption, distribution, metabolism (specifically bile acid metabolism), or excretion of drugs in the intestine, including but not limited to,inflammatory bowel disease.
• Patient with past medical history or ongoing chronic (i.e., \>3 months) diarrhea requiring intravenous fluid or nutritional intervention for treatment of the diarrhea and/or its sequelae.
• Patient has a confirmed past diagnosis of infection with human immunodeficiency virus or other present and active, clinically significant, acute, or chronic infection, or past medical history of any major episode of infection requiring hospitalization or treatment with parenteral anti-infective treatment within 4 weeks of treatment start (Study Day 1) or completion of oral anti-infective treatment within 2 weeks prior to start of Screening Period.
• Any patient with suspected or confirmed cancers except for basal cell carcinoma, and non-liver cancers treated at least 5 years prior to Screening with no evidence of recurrence.
• Decompensated liver disease, coagulopathy, history, or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy
• INR \>1.4 (the patient may be treated with Vitamin K intravenously, and if INR is ≤1.4 at resampling the patient may be included).

Sponsors & Collaborators

• Albireo, an Ipsen Company: lead

Study Sites (41)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Colorado

Denver, Colorado, 80045, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30329, United States

Location

Riley Hospital for Children - Riley Children's Specialists

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins School of Medicine

Baltimore, Maryland, 21287, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Medical Center - Presbyterian Hospital Building

New York, New York, 10032, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Baylor College of Medicine - Texas Children's Liver Center

Houston, Texas, 77030, United States

Location

The Royal Children's Hospital

Melbourne, Australia

Location

Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, Belgium

Location

The Hospital for Sick Children

Toronto, Canada

Location

University and Pediatric Hospital of Lyon

Bron, France

Location

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

Le Kremlin-Bicêtre, France

Location

Hospital De La Timone

Marseille, France

Location

Hospital Necker-Enfants Maladies

Paris, France

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Kinderklinik Tubingen, Universitatsklinikum Tubingen

Tübingen, Germany

Location

Univesitatsklinikum Tubingen Klinik fur Kinder und Jugendmedizin

Tübingen, Germany

Location

Shaare-Zedek Mc

Jerusalem, Israel

Location

Schneider Children's Medical Center Of Israel

Petah Tikva, Israel

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, Italy

Location

University Hospital Of Padova

Padova, Italy

Location

Ospedale Regina Margherita

Torino, Italy

Location

University Medical Center Groningen

Groningen, Netherlands

Location

Universitair Medisch Centrum (UMC) Utrecht

Utrecht, Netherlands

Location

Instytut Pomnik - Centrum Zarowia Dziecka

Warsaw, Poland

Location

King Faisal Specialist Hospital & Research Centre

Riyadh, Saudi Arabia

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Astrid Lindgren Children's Hospital, Karolinska University Hospital

Solna, Sweden

Location

Gazi University

Ankara, Turkey (Türkiye)

Location

Hacettepe University Faculty of Medicine

Ankara, Turkey (Türkiye)

Location

Akdeniz University

Antalya, Turkey (Türkiye)

Location

Istanbul University Medical Faculty

Istanbul, Turkey (Türkiye)

Location

Inonu University Medical Faculty

Malatya, Turkey (Türkiye)

Location

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, United Kingdom

Location

Leeds General Infirmary

Leeds, United Kingdom

Location

Institute of Liver Studies - Kings College Hospital

London, United Kingdom

Location

Related Publications (1)

• Thompson RJ, Artan R, Baumann U, Calvo PL, Czubkowski P, Dalgic B, D'Antiga L, Di Giorgio A, Durmaz O, Gonzales E, Grammatikopoulos T, Gupte G, Hardikar W, Houwen RHJ, Kamath BM, Karpen SJ, Lacaille F, Lachaux A, Lainka E, Loomes KM, Mack CL, Mattsson JP, McKiernan P, Ni Q, Ozen H, Rajwal SR, Roquelaure B, Shteyer E, Sokal E, Sokol RJ, Soufi N, Sturm E, Tessier ME, van der Woerd WL, Verkade HJ, Vittorio JM, Wallefors T, Warholic N, Yu Q, Horn P, Kjems L. Interim results from an ongoing, open-label, single-arm trial of odevixibat in progressive familial intrahepatic cholestasis. JHEP Rep. 2023 Apr 29;5(8):100782. doi: 10.1016/j.jhepr.2023.100782. eCollection 2023 Aug.

  PMID: 37456676 DERIVED

MeSH Terms

Conditions

Cholestasis, progressive familial intrahepatic 1; Cholestasis

Interventions

odevixibat

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Albireo, An Ipsen Company

clinical.trials@ipsen.com

see email

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2018
• First Posted: September 6, 2018
• Study Start: September 28, 2018
• Primary Completion: February 15, 2024
• Study Completion: December 2, 2025
• Last Updated: April 30, 2026
• Results First Posted: July 10, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

Locations

PL (1); IL (2); SA (1); DE (3); ES (2); US (11); GB (3); NL (2); TU (5); IT (3); CA (1); AU (1); FR (4); BE (1); SE (1)