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

NCT03566238 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: A4250-005
• Study Type: interventional
• Target: 62
• Locations: 15 countries
• Sites: 45

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.

Conditions

PFIC1; PFIC2

Keywords

Pediatric; Cholestasis

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With at Least a 70% Reduction in Fasting Serum Bile Acid (s-BA) Concentration From Baseline to the End of Treatment or Reaching a Level <=70 Micromoles Per Liter (Mcmol/L) After 24 Weeks of Treatment

  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 mcmol/L after 24 weeks of treatment were considered as responder. Participants with missing average at the end of treatment were classified as non-responder. Percentages are rounded to hundredth decimal.

  From Baseline (Day 1) up to Week 24

• Percentage of Positive Pruritus Assessments at the Participant Level Based on the Albireo Observer-Reported Outcome (ObsRO) Instrument Over the 24-Week Treatment Period

  A positive pruritus assessment was defined as a scratching score of \<=1 or at least 1 point drop from baseline. The percentage 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 multiplied by 100.

  From Baseline (Day 1) up to Week 24

Secondary Outcomes (11)

• Change From Baseline in Fasting Serum Bile Acid at Weeks 12 and 24

  Baseline (Day 1) and Weeks 12 and 24

• Change From Baseline in Serum Alanine Aminotransferase (ALT) Concentration at Weeks 12 and 24

  Baseline (Day 1) and Weeks 12 and 24

• Change From Baseline in Growth Parameters at Weeks 12 and 24

  Baseline (Day 1) and Weeks 12 and 24

• Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24

  Weeks 12 and 24

• Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period

  Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24

Study Arms (3)

A4250 low dose

EXPERIMENTAL

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

Drug: A4250 (odevixibat)

A4250 high dose

EXPERIMENTAL

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

Drug: A4250 (odevixibat)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

A4250 (odevixibat) DRUG

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

A4250 high dose; A4250 low dose

Placebo DRUG

Placebo identical in appearance to active drug (A4250).

Placebo

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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:
• Biliary atresia of any kind
• Benign recurrent intrahepatic cholestasis, indicated by any history of normal s BAs
• Suspected or proven liver cancer or metastasis to the liver on imaging studies
• 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

Sponsors & Collaborators

• Albireo: lead

Study Sites (45)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Denver, Colorado, 80045, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30329, 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

Cleveland Clinic

Cleveland, Ohio, 44195, 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

UZ Leuven

Leuven, Belgium

Location

Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, Belgium

Location

The Hospital for Sick Children

Toronto, Canada

Location

British Columbia Children's Hospital

Vancouver, Canada

Location

University and Pediatric Hospital of Lyon

Bron, France

Location

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

Le Kremlin-Bicêtre, France

Location

Hospital de la Timone

Marseille, France

Location

Hospital Necker-Enfants maladies

Paris, France

Location

Uniklinikum Essen- Kinderklinik II

Essen, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Kinderklinik Tübingen, Universitätsklinikum Tübingen

Tübingen, Germany

Location

Rambam Medical Centre

Haifa, Israel

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

Padua, 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 Zdrowia Dziecka

Warsaw, Poland

Location

King Faisal Specialist Hospital & Research Centre

Riyadh, 11211, 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 (2)

• 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.

  PMID: 36066745 DERIVED

• 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.

  PMID: 35780807 DERIVED

MeSH Terms

Conditions

Cholestasis

Interventions

odevixibat

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Results Point of Contact

• Title: Patrick Horn, MD, PhD
• Organization: Albireo AB

medinfo@albireopharma.com

+1 (857) 378- 2035

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-Blind, Randomized, Placebo-Controlled

Study Record Dates

• First Submitted: May 25, 2018
• First Posted: June 25, 2018
• Study Start: May 16, 2018
• Primary Completion: July 27, 2020
• Study Completion: July 28, 2020
• Last Updated: November 28, 2025
• Results First Posted: September 5, 2021

Record last verified: 2025-11

Locations

DE (3); ES (2); US (12); BE (2); SA (1); CA (2); PL (1); AU (1); SE (1); IL (3); TU (5); NL (2); GB (3); IT (3); FR (4)