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Langsigtet undersøgelse af sikkerhed og effektivitet, der evaluerer effekten af ​​A4250 hos børn med PFIC

12. august 2026 opdateret af: Albireo, an Ipsen Company

En åben udvidelsesundersøgelse til evaluering af langsigtet effektivitet og sikkerhed af A4250 hos børn med progressiv familiær intrahepatisk kolestase type 1 og 2 (PEDFIC 2)

Open Label Extension Study for at evaluere langsigtet sikkerhed og vedvarende effekt af A4250 hos børn med PFIC.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

116

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Australien
      • Melbourne, Australien
        • The Royal Children's Hospital
  • Belgien
      • Woluwe-Saint-Lambert, Belgien
        • Cliniques universitaires Saint-Luc
  • Canada
      • Toronto, Canada
        • The Hospital for Sick Children
  • Det Forenede Kongerige
      • Birmingham, Det Forenede Kongerige
        • Birmingham Women's and Children's NHS Foundation Trust
      • Leeds, Det Forenede Kongerige
        • Leeds General Infirmary
      • London, Det Forenede Kongerige
        • Institute of Liver Studies - Kings College Hospital
  • Forenede Stater
    • California
      • Los Angeles, California, Forenede Stater, 90027
        • Children's Hospital Los Angeles
    • Colorado
      • Denver, Colorado, Forenede Stater, 80045
        • Children's Hospital Colorado
    • Georgia
      • Atlanta, Georgia, Forenede Stater, 30329
        • Emory University School of Medicine
    • Indiana
      • Indianapolis, Indiana, Forenede Stater, 46202
        • Riley Hospital for Children - Riley Children's Specialists
    • Maryland
      • Baltimore, Maryland, Forenede Stater, 21287
        • Johns Hopkins School of Medicine
    • Missouri
      • St Louis, Missouri, Forenede Stater, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, Forenede Stater, 10029
        • Icahn School of Medicine at Mount Sinai
      • New York, New York, Forenede Stater, 10032
        • Columbia University Medical Center - Presbyterian Hospital Building
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, Forenede Stater, 15224
        • Children's Hospital of Pittsburgh
    • Texas
      • Houston, Texas, Forenede Stater, 77030
        • Baylor College of Medicine - Texas Children's Liver Center
  • Frankrig
      • Bron, Frankrig
        • University and Pediatric Hospital of Lyon
      • Le Kremlin-Bicêtre, Frankrig
        • Universite Paris SUD - Hpitaux Universitaires Paris-Sud - Hopital Bicetre
      • Marseille, Frankrig
        • Hospital De La Timone
      • Paris, Frankrig
        • Hospital Necker-Enfants Maladies
  • Holland
      • Groningen, Holland
        • University Medical Center Groningen
      • Utrecht, Holland
        • Universitair Medisch Centrum (UMC) Utrecht
  • Israel
      • Jerusalem, Israel
        • Shaare-Zedek Mc
      • Petah Tikva, Israel
        • Schneider Children's Medical Center of Israel
  • Italien
      • Bergamo, Italien
        • Azienda Ospedaliera Papa Giovanni XXIII
      • Padova, Italien
        • University Hospital Of Padova
      • Torino, Italien
        • Ospedale Regina Margherita
  • Polen
      • Warsaw, Polen
        • Instytut Pomnik - Centrum Zarowia Dziecka
  • Saudi Arabien
      • Riyadh, Saudi Arabien
        • King Faisal Specialist Hospital & Research Centre
  • Spanien
      • Barcelona, Spanien
        • Hospital Universitari Vall d'Hebron
      • Madrid, Spanien
        • Hospital Universitario La Paz
  • Sverige
      • Solna, Sverige
        • Astrid Lindgren Children's Hospital, Karolinska University Hospital
  • Tyrkiet (Türkiye)
      • Ankara, Tyrkiet (Türkiye)
        • Gazi University
      • Ankara, Tyrkiet (Türkiye)
        • Hacettepe University Faculty of Medicine
      • Antalya, Tyrkiet (Türkiye)
        • Akdeniz University
      • Istanbul, Tyrkiet (Türkiye)
        • Istanbul University Medical Faculty
      • Malatya, Tyrkiet (Türkiye)
        • Inonu University Medical Faculty
  • Tyskland
      • Hanover, Tyskland
        • Medizinische Hochschule Hannover
      • Tübingen, Tyskland
        • Kinderklinik Tubingen, Universitatsklinikum Tubingen
      • Tübingen, Tyskland
        • Univesitatsklinikum Tubingen Klinik fur Kinder und Jugendmedizin

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

3 år til 96 år (Barn, Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Beskrivelse

Inklusionskriterier, kohorte 1:

  1. Afslutning af den 24-ugers behandlingsperiode for undersøgelse A4250-005 eller trukket tilbage fra undersøgelse A4250-005 på grund af patient/plejers vurdering af uacceptable symptomer efter at have afsluttet mindst 12 ugers behandling
  2. Underskrevet informeret samtykke og samtykke efter behov
  3. Patienter forventede at have en konsekvent omsorgsperson i hele undersøgelsens varighed
  4. Pårørende (og aldersbestemte patienter) skal være villige og i stand til at bruge en e-dagbogsanordning som krævet af undersøgelsen

Inklusionskriterier, kohorte 2:

  1. En mandlig eller kvindelig patient i enhver alder, med en klinisk diagnose af PFIC, inklusive episodiske former (dvs. BRIC), og med en kropsvægt ≥5 kg ved besøg S-1.
  2. Patienten skal have klinisk genetisk bekræftelse af PFIC
  3. Patienter med PFIC, eksklusive BRIC, skal have forhøjet galdesyrekoncentration i serum, specifikt målt til at være ≥100 μmol/L, taget som gennemsnittet af 2 prøver med mindst 7 dages mellemrum (besøg S-1 og S-2) før Screening/Inklusionsbesøg (besøg 1).
  4. Patienter med PFIC, ekskl. BRIC, skal have en anamnese med betydelig kløe og en plejer-rapporteret observeret krads eller patientrapporteret kløe (for patienter >18 uden plejer-rapporteret observeret kradse) i e-dagbogs gennemsnit på ≥2 (på 0 til 4) skala) i de 2 uger forud for screenings-/inklusionsbesøget (besøg 1).
  5. Patienter med episodiske former for PFIC (dvs. BRIC) skal have en ny opblussen karakteriseret ved klinisk signifikant kløe og forhøjede serumgaldesyreniveauer/kolestase som vurderet af investigator.
  6. Patient og/eller værge skal underskrive informeret samtykke (og samtykke) efter behov. Patienter, der fylder 18 år (eller lovlig alder pr. land) i løbet af undersøgelsen, skal give et nyt samtykke for at forblive i undersøgelsen.
  7. Aldersegnede patienter forventes at have en konsekvent omsorgsperson i hele undersøgelsens varighed
  8. Pårørende og alderssvarende patienter (≥8 år) skal være villige og i stand til at bruge en e-dagbog som krævet af undersøgelsen

Ekskluderingskriterier, kohorte 1:

  1. Dekompenseret leversygdom: koagulopati, historie eller tilstedeværelse af klinisk signifikant ascites, varicealblødning og/eller encefalopati
  2. Seksuelt aktive mænd og kvinder, der ikke bruger en pålidelig præventionsmetode med ≤1 % fejlrate (såsom hormonel prævention, intra-uterin enhed eller fuldstændig afholdenhed) i hele undersøgelsens varighed og 90 dage derefter
  3. Patienter, der ikke overholder behandlingen i undersøgelse A4250-005
  4. Enhver anden tilstand eller abnormitet, som efter investigatorens eller den medicinske monitors mening kan kompromittere patientens sikkerhed eller forstyrre patientens deltagelse i eller fuldførelse af undersøgelsen

Eksklusionskriterier, kohorte 2:

  1. Kendte patologiske variationer af ABCB11-genet, der har vist sig at resultere i fuldstændigt fravær af BSEP-proteinet

  2. Patient med tidligere sygehistorie eller vedvarende tilstedeværelse af andre typer leversygdom, herunder, men ikke begrænset til, følgende:

    1. Biliær atresi af enhver art
    2. Mistænkt eller påvist leverkræft eller metastasering til leveren på billeddiagnostiske undersøgelser
    3. Histopatologi på leverbiopsi tyder på alternativ ikke-PFIC-relateret ætiologi af kolestase. Bemærk: Patienter med klinisk signifikant portalhypertension er tilladt.
  3. Patient med en tidligere sygehistorie eller vedvarende tilstedeværelse af enhver anden sygdom eller tilstand, der vides at interferere med absorption, distribution, metabolisme (specifikt galdesyremetabolisme) eller udskillelse af lægemidler i tarmen, inklusive, men ikke begrænset til, inflammatorisk tarmsygdom.
  4. Patient med tidligere sygehistorie eller igangværende kronisk (dvs. >3 måneder) diarré, der kræver intravenøs væske eller ernæringsintervention til behandling af diarréen og/eller dens følgesygdomme.
  5. Patienten har en bekræftet tidligere diagnose af infektion med humant immundefektvirus eller anden tilstedeværende og aktiv, klinisk signifikant, akut eller kronisk infektion, eller tidligere sygehistorie med enhver større infektionsepisode, der kræver hospitalsindlæggelse eller behandling med parenteral anti-infektionsbehandling inden for 4 uger behandlingsstart (studiedag 1) eller afslutning af oral anti-infektionsbehandling inden for 2 uger før starten af ​​screeningsperioden.
  6. Enhver patient med mistænkt eller bekræftet cancer, undtagen basalcellekarcinom og ikke-levercancer behandlet mindst 5 år før screening uden tegn på tilbagefald.
  7. Patienten har fået en levertransplantation, eller en levertransplantation er planlagt inden for 6 måneder efter screenings-/inklusionsbesøget.
  8. Dekompenseret leversygdom, koagulopati, historie eller tilstedeværelse af klinisk signifikant ascites, varicealblødning og/eller encefalopati
  9. INR >1,4 (patienten kan behandles med K-vitamin intravenøst, og hvis INR er ≤1,4 ved ny prøvetagning, kan patienten inkluderes).
  10. Serum ALT >10 × øvre normalgrænse (ULN) ved screening.
  11. Serum ALT >15 × ULN på et hvilket som helst tidspunkt i løbet af de sidste 6 måneder, medmindre en alternativ ætiologi blev bekræftet for forhøjelsen.
  12. Total bilirubin >10 × ULN ved screening.

  13. Patienten lider af ukontrolleret, genstridig kløetilstand, bortset fra PFIC.

    Eksempler omfatter, men ikke begrænset til, refraktær atopisk dermatitis eller andre primære kløe hudsygdomme.

  14. Enhver patient, der er gravid eller ammer, eller som planlægger at blive gravid inden for 72 uger efter screenings-/inklusionsbesøget.
  15. Seksuelt aktive mænd og kvinder, der ikke bruger en pålidelig præventionsmetode med ≤1 % fejlrate (såsom hormonel prævention, intrauterin enhed eller fuldstændig afholdenhed) i hele undersøgelsens varighed og 90 dage derefter (fra underskrevet informeret samtykke til 90 dage). efter sidste dosis af undersøgelseslægemidlet).
  16. Patienter med en tidligere sygehistorie med alkohol- eller stofmisbrug vil blive udelukket. Patienten skal acceptere at afstå fra ulovligt stof- og alkoholbrug under undersøgelsen.
  17. Administration af galdesyre eller lipidbindende harpikser og medicin, der bremser GI-motiliteten.
  18. Patienten har haft undersøgelseseksponering for et lægemiddel, biologisk middel eller medicinsk udstyr inden for 30 dage før screening, eller 5 halveringstider af undersøgelsesmidlet, alt efter hvad der er længst.
  19. Alle andre tilstande eller abnormiteter, som efter investigatorens eller den medicinske monitors mening kan kompromittere patientens sikkerhed eller forstyrre patientens deltagelse i eller fuldende undersøgelsen.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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. Patients participating in the optional extension period will continue at the same dose as at the end of the 72-week treatment period.
Medicin: A4250 (odevixibat)
A4250 er et lille molekyle og selektiv hæmmer af ileal galdesyretransporter (IBAT).

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Percentage of Positive Pruritus Assessments at the Participant Level Over 72-Week Using the Albireo Observer-Reported Outcome (ObsRo) Instrument (AM and PM Score)
Tidsramme: Week 72
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 percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments recorded by each participant multiplied by 100.
Week 72

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change From Baseline in Serum Bile Acids at Week 72
Tidsramme: Baseline and Week 72
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 A4250-008 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
Percentage 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 (AM and PM Score)
Tidsramme: 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
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 percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments by each participant multiplied by 100.
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
Percentage 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, 0-70, and 0-72 (AM Score)
Tidsramme: Weeks 0-4, Weeks 0-12, Weeks 0-22, Weeks 0-24, Weeks 0-36, Weeks 0-46, Weeks 0-48, Weeks 0-60, Weeks 0-70, and Weeks 0-72
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 percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments by each participant multiplied by 100. AM score represents night-time itching/scratching and sleep disturbance.
Weeks 0-4, Weeks 0-12, Weeks 0-22, Weeks 0-24, Weeks 0-36, Weeks 0-46, Weeks 0-48, Weeks 0-60, Weeks 0-70, and Weeks 0-72
Percentage 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, 0-70, and 0-72 (PM Score)
Tidsramme: Weeks 0-4, Weeks 0-12, Weeks 0-22, Weeks 0-24, Weeks 0-36, Weeks 0-46, Weeks 0-48, Weeks 0-60, Weeks 0-70, and Weeks 0-72
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 percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments by each participant multiplied by 100. PM score represents daytime itching/scratching and tiredness.
Weeks 0-4, Weeks 0-12, Weeks 0-22, Weeks 0-24, Weeks 0-36, Weeks 0-46, Weeks 0-48, Weeks 0-60, Weeks 0-70, and Weeks 0-72
Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, 72 and Every 16 Weeks During the Optional Extension Period
Tidsramme: Baseline and Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, and 328
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 A4250-008 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 Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, and 328
Percentage 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, and 73-76 (AM and PM Score)
Tidsramme: 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
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 percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments in the time interval recorded by each participant multiplied by 100.
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
Percentage of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score)
Tidsramme: 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
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 percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments in the time interval recorded by each participant multiplied by 100. AM score represents night-time itching/scratching and sleep disturbance.
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
Percentage of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score)
Tidsramme: 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
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 percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments in the time interval recorded by each participant multiplied by 100. PM score represents daytime itching/scratching and tiredness.
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
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM Score)
Tidsramme: Weeks 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, 13-14, 15-16, 17-18, 19-20, 21-22, 23-24, 35-36, 47-48, 59-60, and 71-72
A responder is defined as a participant who reports a decrease in pruritus score from unrounded baseline equivalent to or greater than the threshold of meaningful change of 1.0 estimated from the blinded psychometric analysis. The averaged pruritus score was used to calculate the percentage of participants achieving meaningful reduction against the threshold value of 1.0 based on bi-weekly scores. ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with score from 0 to 4 where 0 is no scratching and 4 is worst possible scratching.
Weeks 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, 13-14, 15-16, 17-18, 19-20, 21-22, 23-24, 35-36, 47-48, 59-60, and 71-72
Percentage of Responders for Pruritus Assessments Monthly (AM and PM Score)
Tidsramme: Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 45-48, 58-60, and 68-72
A responder is defined as a participant who reports a decrease in pruritus score from unrounded baseline equivalent to or greater than the threshold of meaningful change of 1.0 estimated from the blinded psychometric analysis. The averaged pruritus score was used to calculate the percentage of participants achieving meaningful reduction against the thresholds value of 1.0 based on monthly scores. ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with score from 0 to 4 where 0 is no scratching and 4 is worst possible scratching.
Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 45-48, 58-60, and 68-72
Percentage of Participants Achieving a Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO (AM and PM Score)
Tidsramme: Week 72
The percentage of participants who achieved positive pruritus assessment for more than 50% of the time for Weeks 0-72 is reported. A positive pruritus assessment is defined as a scratching score of <=1 or at least a 1-point decrease from baseline on the Albireo ObsRO instrument based on rounded baseline and was calculated based on reported eDiary data. At each assessment, the AM score was compared to the baseline AM average, and the PM score was compared to the baseline PM average.
Week 72
Number of Participants Who Underwent Biliary Diversion Surgery and/or Liver Transplantation
Tidsramme: Weeks 24, 48, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, 328, 344, and 360
Participants who underwent BDS and/or liver transplantation are reported.
Weeks 24, 48, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, 328, 344, and 360
Change From Baseline in Height Z-Scores During Treatment Period and the Optional Extension Period
Tidsramme: Baseline and Weeks 12, 24, 36, 48, 60, 70, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, and 328
Height was measured using certified stadiometer. Change in growth parameters was assessed using linear growth (height) compared to standard growth curve (Z-score) calculated by using the software or methods from the Centers for Disease Control (CDC) website for participants with age >=2 years old and from the World Health Organization (WHO) website for participants with age <2 years old. A Z-score was not calculated for participants whose accurate age was not available. Baseline was the last available assessment prior to first dose of study treatment in the A4250-008 study. A Z-score indicates how many standard deviation's (SD) a participant's height measurement, was from the average for their age and sex. A Z-score of 0 represents the median or 50th percentile, while positive or negative values show how far above or below average a measurement was.
Baseline and Weeks 12, 24, 36, 48, 60, 70, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, and 328
Change From Baseline in Weight Z-Scores During Treatment Period and the Optional Extension Period
Tidsramme: Baseline and Weeks 12, 24, 36, 48, 60, 70, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, and 328
Weight was measured using certified weight scale. Change in growth parameters was assessed using linear growth (weight) compared to standard growth curve (Z-score), calculated by using the software or methods from the CDC website for participants with age >=2 years old and from the WHO website for participants with age <2 years old. A Z-score was not calculated for participants whose accurate age was not available. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study. The Z-score indicates how many SDs a participant's weight measurement, was from the average for their age and sex. A Z-score of 0 represents the median or 50th percentile, while positive or negative values show how far above or below the average a measurement was.
Baseline and Weeks 12, 24, 36, 48, 60, 70, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, and 328
Change From Baseline in Body Mass Index (BMI) Z-Scores During Treatment Period and the Optional Extension Period
Tidsramme: Baseline and Weeks 12, 24, 36, 48, 60, 70, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, and 328
BMI was calculated by weight (kg) / height (m)^2 which were measured by the standardized assessments. Change in growth parameters was assessed using linear growth (BMI) compared to standard growth curve (Z-score), calculated by using the software or methods from the CDC website for participants with age >=2 years old and from the WHO website for participants with age <2 years old. A Z-score was not calculated for participants whose accurate age was not available. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study. The Z-score indicates how many SDs a participant's BMI measurement, was from the average for their age and sex. A Z-score of 0 represents the median or 50th percentile, while positive or negative values show how far above or below the average a measurement was.
Baseline and Weeks 12, 24, 36, 48, 60, 70, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, and 328
Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72
Tidsramme: Weeks 24, 48, and 72
The number of participants with use of UDCA and/or rifampicin are reported.
Weeks 24, 48, and 72
Change From Baseline to Week 72 During Treatment Period and During the Optional Extension Period in Pediatric End-Stage Liver Disease (PELD) Score
Tidsramme: Baseline and Weeks 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, and 312
The PELD score was calculated for children under 12 years of age, ranged across negative to positive values. Calculation of PELD score was done by converting the laboratory parameters: total bilirubin in milligram/deciliter (mg/dL), albumin in gram (g)/dL, and creatinine in mg/dL laboratory parameters were converted to units. PELD score was calculated as 4.80*ln (total bilirubin)+18.57*ln [international normalized ratio (INR)] - 6.87*ln (albumin) + 4.36 (if participant <1 year: scores for participants listed for liver transplantation before the participant's first birthday continued to include the value assigned for age (<1 year) until the participant reached the age of 24 months)+6.67 (if the participant has growth failure [<-2 SD]). The laboratory values <1.0 were set to 1.0 for the calculation of PELD score. Lower scores represent less severe hepatic disease. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study.
Baseline and Weeks 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, and 312
Change From Baseline to Week 72 During Treatment Period and During the Optional Extension Period in Model for End-stage Liver Disease (MELD) Score for Children 12 Years of Age or Older
Tidsramme: Baseline and Weeks 72, 88, 104, and 120
MELD score was calculated for children 12 years of age or older ranges from 6 to 40. Calculation of MELD score was done by converting the laboratory parameters in the following units: total bilirubin in mg/dL, albumin in g/dL, and creatinine in mg/dL laboratory parameters were converted to units. MELD score was calculated as 9.57*ln (creatinine)+3.78*ln (total bilirubin)+11.2 *ln (INR)+6.43. Laboratory values <1.0 were set to 1.0 and serum creatinine values >4.0 mg/dL were set to 4.0 for calculation of the MELD score. Lower scores represent less severe hepatic disease. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study. All assessments after intercurrent events (premature treatment discontinuation, death, or initiation of rescue treatments such as biliary diversion surgery or liver transplantation) or follow-up assessments (>= last dose day+15 days) were excluded from analysis.
Baseline and Weeks 72, 88, 104, and 120
Change From Baseline to Week 72 in Aspartate Aminotransferase (AST) to Platelet Ratio Index (APRI) Score
Tidsramme: Baseline and Week 72
The AST to APRI score was calculated as [(AST in units per liter {U/L})/ (AST upper limit of normal {ULN} in U/L)] * 100/ (platelets in 10^9/L). The APRI score is a way to assess fibrosis of the liver. The lower the APRI score (< 0.5), the greater the negative predictive value and ability to rule out cirrhosis; the higher the value (> 1.5) the greater the positive predictive value and ability to rule in cirrhosis. Lower values indicate less severe hepatic fibrosis. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study.
Baseline and Week 72
Change From Baseline to Week 72 in Fibrosis-4 (Fib-4) Score
Tidsramme: Baseline and Week 72
Fib-4 score was calculated as (age * AST in U/L)/ (platelets in 10^9/L *√ ( alanine aminotransferase [ALT] in U/L). The FIB-4 score estimates the amount of scarring in the liver. A FIB-4 score <1.45 has a negative predictive value of 90% for advanced fibrosis (Ishak fibrosis score 4-6 which includes early bridging fibrosis to cirrhosis). In contrast, a FIB-4 score > 3.25 would have a 97% specificity and a positive predictive value of 65% for advanced fibrosis. Lower values indicate less severe hepatic fibrosis. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study.
Baseline and Week 72

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Albireo, an Ipsen Company

Efterforskere

  • Studieleder: Ipsen Medical Director, Ipsen

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

28. september 2018

Primær færdiggørelse (Faktiske)

15. februar 2024

Studieafslutning (Faktiske)

2. december 2025

Datoer for studieregistrering

Først indsendt

24. august 2018

Først indsendt, der opfyldte QC-kriterier

4. september 2018

Først opslået (Faktiske)

6. september 2018

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

3. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

12. august 2026

Sidst verificeret

1. august 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • A4250-008
  • 2017 (U.S. NIH-bevilling/kontrakt)
  • 2017-002325-38 (EudraCT nummer)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

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Eventuelle anmodninger skal sendes til www.vivli.org til vurdering af et uafhængigt videnskabeligt bedømmelsesudvalg.

IPD-delingstidsramme

Hvor det er relevant, er data fra kvalificerede undersøgelser tilgængelige 6 måneder efter, at den undersøgte medicin og indikation er blevet godkendt i USA og EU, eller efter at det primære manuskript, der beskriver resultaterne, er blevet accepteret til offentliggørelse, alt efter hvad der er senere.

IPD-delingsadgangskriterier

Yderligere detaljer om Ipsens delingskriterier, kvalificerede undersøgelser og proces for deling er tilgængelige her (https://vivli.org/members/ourmembers/).

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

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