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

NCT ID: NCT03659916

Last Updated: 2026-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-28
• Study Completion Date: 2025-12-02

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A4250

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"

Group Type: EXPERIMENTAL

A4250 (odevixibat)

Intervention Type: DRUG

A4250 is a small molecule and selective inhibitor of IBAT

Interventions

A4250 (odevixibat)

A4250 is a small molecule and selective inhibitor of IBAT

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Completion of the 24-week Treatment Period of Study A4250-005 or withdrawn from Study A4250-005 due to patient/caregiver judgment of intolerable symptoms after completing at least 12 weeks of treatment

2. Signed informed consent and assent as appropriate

3. Patients expected to have a consistent caregiver for the duration of the study

4. Caregivers (and age appropriate patients) must be willing and able to use an eDiary device as required by the study

1. 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.

2. Patient must have clinical genetic confirmation of PFIC

3. Patients with PFIC, excluding BRIC, must have elevated serum bile acid concentration,specifically measured to be ≥100 μmol/L, taken as the average of 2 samples at least 7 days apart (Visits S-1 and S-2) prior to the Screening/Inclusion Visit (Visit 1).

4. Patients with PFIC, excluding BRIC, must have history of significant pruritus and a caregiver-reported observed scratching or patient-reported itching (for patients >18 with no caregiver-reported observed scratching) in the eDiary average of ≥2 (on 0 to 4 scale) in the 2 weeks prior to the Screening/Inclusion Visit (Visit 1).

5. 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.

6. 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.

7. Age appropriate patients are expected to have a consistent caregiver for the duration of the study

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

Exclusion Criteria

1. Decompensated liver disease: coagulopathy, history, or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy

2. 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

3. Patients not compliant with treatment in study A4250-005

4. 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

1. Known pathologic variations of the ABCB11 gene that have been demonstrated to result in complete absence of the BSEP protein

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

3. Histopathology on liver biopsy is suggestive of alternate non-PFIC related etiology of cholestasis Note: Patients with clinically significant portal hypertension are allowed.

3. 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.

4. 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.

5. 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.

6. 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.

7. Patient has had a liver transplant, or a liver transplant is planned within 6 months of the Screening/Inclusion Visit.

8. Decompensated liver disease, coagulopathy, history, or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy

9. 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).

10. Serum ALT >10 × upper limit of normal (ULN) at Screening.

11. Serum ALT >15 × ULN at any time point during the last 6 months unless an alternate etiology was confirmed for the elevation.

12. Total bilirubin >10 × ULN at Screening.

13. Patient suffers from uncontrolled, recalcitrant pruritic condition other than PFIC.

Examples include, but not limited to, refractory atopic dermatitis or other primary pruritic skin diseases.

14. Any patient who is pregnant or lactating or who is planning to become pregnant within 72 weeks of the Screening/Inclusion Visit.

15. Sexually active males and females who are not using a reliable contraceptive method with ≤1% failure rate (such as hormonal contraception, intrauterine device, or complete abstinence) throughout the duration of the study and 90 days thereafter (from signed informed consent through 90 days after last dose of study drug).

16. Patient with a past medical history of alcohol or substance abuse will be excluded. Patient must agree to refrain from illicit drug and alcohol use during the study.

17. Administration of bile acid or lipid binding resins and medications that slow GI motility.

18. Patient has had investigational exposure to a drug, biologic agent, or medical device within 30 days prior to Screening, or 5 half-lives of the study agent, whichever is longer.

19. 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.

• Minimum Eligible Age: 0 Months
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Albireo, an Ipsen Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ipsen Medical Director

Role: STUDY_DIRECTOR

Ipsen

Locations

Children's Hospital Los Angeles

Los Angeles, California, United States

Children's Hospital Colorado

Denver, Colorado, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Riley Hospital for Children - Riley Children's Specialists

Indianapolis, Indiana, United States

Johns Hopkins School of Medicine

Baltimore, Maryland, United States

Washington University School of Medicine

St Louis, Missouri, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Columbia University Medical Center - Presbyterian Hospital Building

New York, New York, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Baylor College of Medicine - Texas Children's Liver Center

Houston, Texas, United States

The Royal Children's Hospital

Melbourne, , Australia

Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, , Belgium

The Hospital for Sick Children

Toronto, , Canada

University and Pediatric Hospital of Lyon

Bron, , France

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

Le Kremlin-Bicêtre, , France

Hospital De La Timone

Marseille, , France

Hospital Necker-Enfants Maladies

Paris, , France

Medizinische Hochschule Hannover

Hanover, , Germany

Kinderklinik Tubingen, Universitatsklinikum Tubingen

Tübingen, , Germany

Univesitatsklinikum Tubingen Klinik fur Kinder und Jugendmedizin

Tübingen, , Germany

Shaare-Zedek Mc

Jerusalem, , Israel

Schneider Children's Medical Center Of Israel

Petah Tikva, , Israel

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, , Italy

University Hospital Of Padova

Padua, , Italy

Ospedale Regina Margherita

Torino, , Italy

University Medical Center Groningen

Groningen, , Netherlands

Universitair Medisch Centrum (UMC) Utrecht

Utrecht, , Netherlands

Instytut Pomnik - Centrum Zarowia Dziecka

Warsaw, , Poland

King Faisal Specialist Hospital & Research Centre

Riyadh, , Saudi Arabia

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Astrid Lindgren Children's Hospital, Karolinska University Hospital

Solna, , Sweden

Gazi University

Ankara, , Turkey (Türkiye)

Hacettepe University Faculty of Medicine

Ankara, , Turkey (Türkiye)

Akdeniz University

Antalya, , Turkey (Türkiye)

Istanbul University Medical Faculty

Istanbul, , Turkey (Türkiye)

Inonu University Medical Faculty

Malatya, , Turkey (Türkiye)

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, , United Kingdom

Leeds General Infirmary

Leeds, , United Kingdom

Institute of Liver Studies - Kings College Hospital

London, , United Kingdom

Countries

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

References

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.

Reference Type: DERIVED

PMID: 37456676 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-002325-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

A4250-008

Identifier Type: -

Identifier Source: org_study_id