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Langtidsstudie om sikkerhet og effektivitet som evaluerer effekten av A4250 hos barn med PFIC

12. august 2026 oppdatert av: Albireo, an Ipsen Company

En åpen utvidelsesstudie for å evaluere langsiktig effekt og sikkerhet av A4250 hos barn med progressiv familiær intrahepatisk kolestase type 1 og 2 (PEDFIC 2)

Open Label Extension Study for å evaluere langsiktig sikkerhet og vedvarende effekt av A4250 hos barn med PFIC.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Faktiske)

116

Fase

  • Fase 3

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

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

Tar imot friske frivillige

Nei

Beskrivelse

Inkluderingskriterier Kohort 1:

  1. Fullføring av den 24-ukers behandlingsperioden for studie A4250-005 eller trukket tilbake fra studie A4250-005 på grunn av pasient/omsorgspersons vurdering av utålelige symptomer etter å ha fullført minst 12 ukers behandling
  2. Signert informert samtykke og samtykke etter behov
  3. Pasienter forventet å ha en konsekvent omsorgsperson under hele studien
  4. Omsorgspersoner (og aldersbestemte pasienter) må være villige og i stand til å bruke en eDiary-enhet som kreves av studien

Inkluderingskriterier Kohort 2:

  1. En mannlig eller kvinnelig pasient i alle aldre, med en klinisk diagnose av PFIC, inkludert episodiske former (dvs. BRIC), og med en kroppsvekt ≥5 kg ved besøk S-1.
  2. Pasienten må ha klinisk genetisk bekreftelse på PFIC
  3. Pasienter med PFIC, unntatt BRIC, må ha forhøyet gallesyrekonsentrasjon i serum, spesifikt målt til å være ≥100 μmol/L, tatt som gjennomsnittet av 2 prøver med minst 7 dagers mellomrom (besøk S-1 og S-2) før Screening/inkluderingsbesøk (besøk 1).
  4. Pasienter med PFIC, unntatt BRIC, må ha en historie med betydelig kløe og en omsorgsrapportert observert kløe eller pasientrapportert kløe (for pasienter >18 uten omsorgsrapportert observert skraping) i eDiary-gjennomsnittet på ≥2 (på 0 til 4) skala) i de 2 ukene før screening/inkluderingsbesøket (besøk 1).
  5. Pasienter med episodiske former for PFIC (dvs. BRIC) må ha en ny oppblussing karakterisert ved klinisk signifikant kløe og forhøyede gallesyrenivåer/kolestase i serum som bedømt av etterforskeren.
  6. Pasient og/eller verge må signere informert samtykke (og samtykke) etter behov. Pasienter som fyller 18 år (eller lovlig alder per land) under studien vil bli pålagt å gi nytt samtykke for å forbli i studien.
  7. Alderstilpassede pasienter forventes å ha en konsekvent omsorgsperson under hele studien
  8. Omsorgspersoner og alderstilpassede pasienter (≥8 år) må være villige og i stand til å bruke en eDiary-enhet som kreves av studien

Ekskluderingskriterier Kohort 1:

  1. Dekompensert leversykdom: koagulopati, historie eller tilstedeværelse av klinisk signifikant ascites, varicealblødning og/eller encefalopati
  2. Seksuelt aktive menn og kvinner som ikke bruker en pålitelig prevensjonsmetode med ≤1 % feilrate (som hormonell prevensjon, intrauterin enhet eller fullstendig avholdenhet) gjennom hele studiens varighet og 90 dager etterpå
  3. Pasienter som ikke samsvarer med behandling i studie A4250-005
  4. Eventuelle andre tilstander eller abnormiteter som, etter etterforskerens eller medisinsk monitors oppfatning, kan kompromittere sikkerheten til pasienten, eller forstyrre pasienten som deltar i eller fullfører studien

Ekskluderingskriterier Kohort 2:

  1. Kjente patologiske variasjoner av ABCB11-genet som har vist seg å resultere i fullstendig fravær av BSEP-proteinet

  2. Pasient med tidligere medisinsk historie eller pågående tilstedeværelse av andre typer leversykdom, inkludert, men ikke begrenset til, følgende:

    1. Biliær atresi av noe slag
    2. Mistenkt eller påvist leverkreft eller metastasering til leveren på bildeundersøkelser
    3. Histopatologi på leverbiopsi tyder på alternativ ikke-PFIC-relatert etiologi av kolestase. Merk: Pasienter med klinisk signifikant portalhypertensjon er tillatt.
  3. Pasient med en tidligere medisinsk historie eller pågående tilstedeværelse av annen sykdom eller tilstand som er kjent for å forstyrre absorpsjon, distribusjon, metabolisme (spesifikt gallesyremetabolisme), eller utskillelse av legemidler i tarmen, inkludert, men ikke begrenset til, inflammatorisk tarmsykdom.
  4. Pasient med tidligere sykehistorie eller pågående kronisk (dvs. >3 måneder) diaré som krever intravenøs væske eller ernæringsintervensjon for behandling av diaréen og/eller dens følgetilstander.
  5. Pasienten har en bekreftet tidligere diagnose av infeksjon med humant immunsviktvirus eller annen nåværende og aktiv, klinisk signifikant, akutt eller kronisk infeksjon, eller tidligere medisinsk historie med en alvorlig infeksjonsepisode som krever sykehusinnleggelse eller behandling med parenteral anti-infeksjonsbehandling innen 4 uker behandlingsstart (studiedag 1) eller fullføring av oral anti-infeksjonsbehandling innen 2 uker før starten av screeningsperioden.
  6. Alle pasienter med mistenkt eller bekreftet kreft, bortsett fra basalcellekarsinom, og ikke-leverkreft behandlet minst 5 år før screening uten bevis for tilbakefall.
  7. Pasienten har hatt en levertransplantasjon, eller en levertransplantasjon er planlagt innen 6 måneder etter screening/inkluderingsbesøket.
  8. Dekompensert leversykdom, koagulopati, historie eller tilstedeværelse av klinisk signifikant ascites, varicealblødning og/eller encefalopati
  9. INR >1,4 (pasienten kan behandles med vitamin K intravenøst, og hvis INR er ≤1,4 ved ny prøvetaking kan pasienten inkluderes).
  10. Serum ALT >10 × øvre normalgrense (ULN) ved screening.
  11. Serum ALT >15 × ULN på et hvilket som helst tidspunkt i løpet av de siste 6 månedene med mindre en alternativ etiologi ble bekreftet for forhøyelsen.
  12. Totalt bilirubin >10 × ULN ved screening.

  13. Pasienten lider av ukontrollert, gjenstridig kløetilstand annet enn PFIC.

    Eksempler inkluderer, men ikke begrenset til, refraktær atopisk dermatitt eller andre primære kløe hudsykdommer.

  14. Enhver pasient som er gravid eller ammer eller planlegger å bli gravid innen 72 uker etter screening/inkluderingsbesøket.
  15. Seksuelt aktive menn og kvinner som ikke bruker en pålitelig prevensjonsmetode med ≤1 % feilrate (som hormonell prevensjon, intrauterin enhet eller fullstendig avholdenhet) gjennom hele studiens varighet og 90 dager deretter (fra signert informert samtykke til 90 dager) etter siste dose studiemedisin).
  16. Pasienter med tidligere sykehistorie med alkohol- eller rusmisbruk vil bli ekskludert. Pasienten må godta å avstå fra ulovlig bruk av narkotika og alkohol under studien.
  17. Administrering av gallesyre eller lipidbindende harpikser og medisiner som bremser GI-motiliteten.
  18. Pasienten har vært eksponert for et legemiddel, biologisk middel eller medisinsk utstyr innen 30 dager før screening, eller 5 halveringstider av studiemiddelet, avhengig av hva som er lengst.
  19. Eventuelle andre tilstander eller abnormiteter som etter etterforskerens eller den medisinske monitorens oppfatning kan kompromittere sikkerheten til pasienten, eller forstyrre pasienten som deltar i eller fullfører studien.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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.
Legemiddel: A4250 (odevixibat)
A4250 er et lite molekyl og selektiv hemmer av ileal gallesyretransportør (IBAT).

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
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
Tiltaksbeskrivelse
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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Albireo, an Ipsen Company

Etterforskere

  • Studieleder: Ipsen Medical Director, Ipsen

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

28. september 2018

Primær fullføring (Faktiske)

15. februar 2024

Studiet fullført (Faktiske)

2. desember 2025

Datoer for studieregistrering

Først innsendt

24. august 2018

Først innsendt som oppfylte QC-kriteriene

4. september 2018

Først lagt ut (Faktiske)

6. september 2018

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

3. september 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

12. august 2026

Sist bekreftet

1. august 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

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

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

Kvalifiserte forskere kan be om tilgang til data på pasientnivå og relaterte studiedokumenter, inkludert den kliniske studierapporten, studieprotokollen med eventuelle endringer, kommentert saksrapportskjema, statistisk analyseplan og datasettspesifikasjoner. Data på pasientnivå vil anonymiseres og studiedokumenter vil bli redigert for å beskytte personvernet til studiedeltakerne.

Eventuelle forespørsler skal sendes til www.vivli.org for vurdering av en uavhengig vitenskapelig vurderingskomité.

IPD-delingstidsramme

Der det er aktuelt, er data fra kvalifiserte studier tilgjengelige 6 måneder etter at den studerte medisinen og indikasjonen er godkjent i USA og EU eller etter at primærmanuskriptet som beskriver resultatene er akseptert for publisering, avhengig av hva som kommer senere.

Tilgangskriterier for IPD-deling

Ytterligere detaljer om Ipsens delingskriterier, kvalifiserte studier og prosess for deling er tilgjengelig her (https://vivli.org/members/ourmembers/).

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere