Evidence map›Paper›PMID 37456676›Full record

ArticleJHEP reports : innovation in hepatology2023

Interim results from an ongoing, open-label, single-arm trial of odevixibat in progressive familial intrahepatic cholestasis.

Richard J Thompson, Reha Artan, Ulrich Baumann, Pier Luigi Calvo, Piotr Czubkowski, Buket Dalgic, Lorenzo D'Antiga, Angelo Di Giorgio, Özlem Durmaz, Emmanuel Gonzalès and 31 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JHEP reports : innovation in hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03659916 (An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of A4250 in Children With Progressive Familial Intrahepatic Cholestasis Types 1 and 2), which is not on this map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
8.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03659916 phase3completednot on this map

An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of A4250 in Children With Progressive Familial Intrahepatic Cholestasis Types 1 and 2 (PEDFIC 2)

TypeinterventionalSponsorAlbireo, an Ipsen CompanyRan2018 to 2025Enrolled116ConditionsProgressive Familial Intrahepatic CholestasisArmsA4250 (odevixibat)
3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

41 authors at 20 institutions in 12 countries.

Richard J ThompsonInstitute of Liver Studies, King's College London, London, UK.
Reha ArtanDepartment of Pediatric Gastroenterology, Akdeniz University, Antalya, Turkey.
Ulrich BaumannPediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany.
Pier Luigi CalvoPediatric Gastroenterology Unit, Regina Margherita Children's Hospital, Azienda Ospedaliera-Città della Salute e della Scienza di Torino, Turin, Italy.
Piotr CzubkowskiDepartment of Gastroenterology, Hepatology, Nutritional Disorders, and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland.
Buket DalgicDepartment of Pediatric Gastroenterology, Gazi University Faculty of Medicine, Ankara, Turkey.
Lorenzo D'AntigaPediatric Hepatology, Gastroenterology, and Transplantation, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
Angelo Di GiorgioPediatric Hepatology, Gastroenterology, and Transplantation, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
Özlem DurmazIstanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey.
Emmanuel GonzalèsHépatologie et Transplantation Hépatique Pédiatriques, Centre de Référence de l'Atrésie des Voies Biliaires et des Cholestases Génétiques, FSMR FILFOIE, ERN RARE LIVER, Hôpital Bicêtre, AP-HP, Université Paris-Saclay, Hépatinov, Inserm U 1193, Paris, France.
Tassos GrammatikopoulosInstitute of Liver Studies, King's College London, London, UK.
Girish GupteLiver Unit and Small Bowel Transplantation, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
Winita HardikarDepartment of Gastroenterology, Royal Children's Hospital, Melbourne, Australia.
Roderick H J HouwenDepartment of Pediatric Gastroenterology at the Wilhelmina Children's Hospital and University Medical Center, Utrecht, The Netherlands.
Binita M KamathDivision of Gastroenterology, Hepatology, and Nutrition, Hospital for Sick Children and the University of Toronto, Toronto, ON, Canada.
Saul J KarpenPediatrics Department, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA, USA.
Florence LacaillePediatric Gastroenterology-Hepatology-Nutrition Unit, Hôpital Universitaire Necker-Enfants Malades, Paris, France.
Alain LachauxHospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service D'hépatogastoentérologie et Nutrition Pédiatrique, Lyon, France.
Elke LainkaDepartment of Pediatric Gastroenterology, Hepatology, and Liver Transplantation, University Children's Hospital, Essen, Germany.
Kathleen M LoomesDepartment of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Cara L MackPediatric Gastroenterology, Hepatology, & Nutrition, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA.
Jan P MattssonAlbireo Pharma, Inc., Boston, MA, USA.
Patrick McKiernanLiver Unit and Small Bowel Transplantation, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
Quanhong NiAlbireo Pharma, Inc., Boston, MA, USA.
Hasan ÖzenDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Sanjay R RajwalChildren's Liver Unit, Leeds Teaching Hospitals NHS Trust, Leeds Children's Hospital, Leeds, UK.
Bertrand RoquelaureCHU, Hospital de la Timone, Marseille, France.
Eyal ShteyerFaculty of Medicine, Hebrew University of Jerusalem, Juliet Keidan Department of Pediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel.
Etienne SokalUniversité Catholique de Louvain, Cliniques St Luc, Brussels, Belgium.
Ronald J SokolUniversity of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO, USA.
Nisreen SoufiPediatrics Department, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Ekkehard SturmPediatric Gastroenterology and Hepatology, University Children's Hospital Tübingen, Tübingen, Germany.
Mary Elizabeth TessierDepartment of Pediatrics, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Baylor College of Medicine/Texas Children's Hospital, Houston, TX, USA.
Wendy L van der WoerdDepartment of Pediatric Gastroenterology at the Wilhelmina Children's Hospital and University Medical Center, Utrecht, The Netherlands.
Henkjan J VerkadeDepartment of Pediatrics, University of Groningen, Beatrix Children's Hospital/University Medical Center Groningen, Groningen, The Netherlands.
Jennifer M VittorioDepartment of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York, NY, USA.
Terese WalleforsAlbireo Pharma, Inc., Boston, MA, USA.
Natalie WarholicAlbireo Pharma, Inc., Boston, MA, USA.
Qifeng YuAlbireo Pharma, Inc., Boston, MA, USA.
Patrick HornAlbireo Pharma, Inc., Boston, MA, USA.
Lise KjemsAlbireo Pharma, Inc., Boston, MA, USA.
Birmingham Women’s and Children’s NHS Foundation Trust · GBKing's College London · GBOspedale Papa Giovanni XXIII · ITUniversity Medical Center Utrecht · NLAkdeniz University · TRAzienda Ospedaliera Citta' della Salute e della Scienza di Torino · ITBaylor College of Medicine · USChildren's Hospital Colorado · USChildren's Hospital of Los Angeles · USChildren's Hospital of Philadelphia · USChildren's Hospital of Wisconsin · USChildren's Memorial Health Institute · PLCliniques Universitaires Saint-Luc · BEColumbia University Irving Medical Center · USEmory University · USEssen University Hospital · DEGazi University · TRHacettepe University · TRHebrew University of Jerusalem · ILHôpital de la Timone · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background & Aims: PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis. Methods: PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age). We report data through 15 July 2020, with Week 24 of PEDFIC 2 the main time point analysed. This represents up to 48 weeks of cumulative exposure for patients treated with odevixibat from the 24-week PEDFIC 1 study (cohort 1A) and up to 24 weeks of treatment for those who initiated odevixibat in PEDFIC 2 (patients who received placebo in PEDFIC 1 [cohort 1B] or cohort 2 patients). Primary endpoints for this prespecified interim analysis were change from baseline to Weeks 22-24 in serum bile acids (sBAs) and proportion of positive pruritus assessments (≥1-point drop from PEDFIC 2 baseline in pruritus on a 0-4 scale or score ≤1) over the 24-week period. Safety monitoring included evaluating treatment-emergent adverse events (TEAEs). Results: In cohort 1A, mean change from PEDFIC 1 baseline to Weeks 22-24 of PEDFIC 2 in sBAs was -201 μmol/L ( Conclusions: Odevixibat in patients with progressive familial intrahepatic cholestasis was generally well tolerated and associated with sustained reductions in sBAs and pruritus. Clinical Trials Registration: This study is registered at ClinicalTrials.gov (NCT03659916). Impact and Implications: Disrupted bile flow is a hallmark feature of patients with progressive familial intrahepatic cholestasis and can result in build-up of bile constituents in the liver with spill over into the bloodstream; other effects that patients can experience include extremely itchy skin, and because not enough bile reaches the gut, patients can have problems digesting food, which may lead to poor growth. Odevixibat is an orally administered medication that shunts bile acids away from the liver. The current study, called PEDFIC 2, suggested that odevixibat can improve the problematic signs and symptoms of progressive familial intrahepatic cholestasis and was generally safe for patients.

Indexed as

Bile acids and saltsClinical trialEnterohepatic circulationLiver diseases

Identifiers

PMID37456676
PMCPMC10338319
OpenAlexW4367397117

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.