Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

A Multi-part, Double Blind Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in PBC Patients

9. december 2020 opdateret af: Novartis Pharmaceuticals

A Multi-part, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Efficacy of Tropifexor (LJN452) in Patients With Primary Biliary Cholangitis

A multi-part study to assess safety, tolerability and efficacy of tropifexor (LJN452) in patients with primary biliary cholangitis

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

61

Fase

  • Fase 2

Kontakter og lokationer

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

Studiesteder

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N1
        • Novartis Investigative Site
      • Edmonton, Alberta, Canada, T6G 2B7
        • Novartis Investigative Site
  • Den Russiske Føderation
      • Moscow, Den Russiske Føderation, 117198
        • Novartis Investigative Site
      • Saint-Petersburg, Den Russiske Føderation, 194044
        • Novartis Investigative Site
      • Samara, Den Russiske Føderation, 443011
        • Novartis Investigative Site
  • Det Forenede Kongerige
      • Cambridge, Det Forenede Kongerige, CB2 2QQ
        • Novartis Investigative Site
      • Hull, Det Forenede Kongerige, HU3 2JZ
        • Novartis Investigative Site
      • London, Det Forenede Kongerige, NW3 2PF
        • Novartis Investigative Site
      • Newcastle upon Tyne, Det Forenede Kongerige, NE1 4LP
        • Novartis Investigative Site
    • West Midlands
      • Birmingham, West Midlands, Det Forenede Kongerige, B15 2TH
        • Novartis Investigative Site
  • Forenede Stater
    • California
      • Rialto, California, Forenede Stater, 92377
        • Novartis Investigative Site
    • Florida
      • Miami, Florida, Forenede Stater, 33136
        • Novartis Investigative Site
    • Georgia
      • Atlanta, Georgia, Forenede Stater, 30308
        • Novartis Investigative Site
      • Marietta, Georgia, Forenede Stater, 30060
        • Novartis Investigative Site
    • Illinois
      • Chicago, Illinois, Forenede Stater, 60612
        • Novartis Investigative Site
    • New York
      • Manhasset, New York, Forenede Stater, 11030
        • Novartis Investigative Site
    • Texas
      • Dallas, Texas, Forenede Stater, 75390
        • Novartis Investigative Site
      • San Antonio, Texas, Forenede Stater, 78215
        • Novartis Investigative Site
    • Washington
      • Seattle, Washington, Forenede Stater, 98104
        • Novartis Investigative Site
  • Polen
      • Lodz, Polen, 91-347
        • Novartis Investigative Site
      • Myslowice, Polen, 41-400
        • Novartis Investigative Site
      • Warsaw, Polen, 02-097
        • Novartis Investigative Site
      • Wroclaw, Polen, 50-449
        • Novartis Investigative Site
  • Tyskland
      • Hamburg, Tyskland, 20246
        • Novartis Investigative Site
      • Hannover, Tyskland, 30625
        • Novartis Investigative Site
      • Heidelberg, Tyskland, 69120
        • Novartis Investigative Site
      • Muenchen, Tyskland, 81377
        • Novartis Investigative Site
      • Wuerzburg, Tyskland, 97080
        • Novartis Investigative Site

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

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Age ≥ 18 years

  • Diagnosis of PBC as demonstrated by the presence of at least 2 of the following 3 diagnostic criteria:

    • History of alkaline phosphatase (ALP) elevated above upper limit of normal (ULN) for at least 6 months
    • Positive antimitochondrial antibodies (AMA) titer or if AMA negative or in low titer (<1:80) PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components (PDC-E2, 2-oxo-glutaric acid dehydrogenase complex))
    • Previous liver biopsy findings consistent with PBC

  • At least 1 of the following markers of disease severity:

    • ALP ≥ 1.67 × ULN
    • Total bilirubin > ULN but < 1.5 × ULN

  • In addition, patients must meet the following biochemical criteria at enrollment:

    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 × ULN
    • Total bilirubin ≤ 1.5 × ULN
    • INR ≤ ULN
  • Taking UDCA for at least 12 months, or for at least 6 months and has reached maximal response to UDCA with a plateau in alkaline phosphatase, with no changes in dose for ≥ 3 months prior to Day 1.
  • Patients must weigh at least 40 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 40 kg/m2. BMI = Body weight (kg) / [Height (m)]2

Exclusion Criteria:

  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception for 30 days before randomization, during dosing and for 30 days following the end of treatment.

  • Presence of other concomitant liver diseases.

    • Cirrhosis with complications, including history or presence of:
    • Variceal bleed
    • Uncontrolled ascites
    • Encephalopathy
    • Spontaneous bacterial peritonitis
  • Significant hepatic impairment as defined by Child-Pugh classification of B or C, history of liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score ≥15.
  • History of conditions that may cause increases in ALP (e.g., Paget's disease).
  • Use of investigational drugs, or immunosuppressive drugs at the time of enrollment, or within 5 half-lives, or 30 days of randomization, whichever is longer; or longer if required by local regulations. Use of high dose oral steroids to treat co-morbid conditions (e.g., airways disease) will be allowed but must be properly documented as such in concomitant medications.
  • Currently taking obeticholic acid or have taken obeticholic acid within 30 days of randomization
  • Previous participation in CLJN452X2201 and received study medication within three months of randomization (or longer if required by local regulations).

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: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Tredobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Placebo komparator: Placebo
Medicin: Part 1: Placebo
Matching placebo capsules administered once daily for 28 days
Medicin: Part 2: Placebo
Matching placebo to LJN452 administered once a day for 12 weeks
Eksperimentel: LJN452
Medicin: Part 1: LJN452
LJN452 capsules administered once daily for 28 days
Andre navne:
  • tropifexor
Medicin: Part 2: LJN452 Dose level 1
LJN452 capsules administered once a day for 12 weeks
Andre navne:
  • tropifexor
Medicin: Part 2: LJN452 Dose level 2
LJN452
Andre navne:
  • tropifexor

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Fold Change in Serum Gamma-glutamyl Transferase (GGT)
Tidsramme: Baseline to Day 28
Fold change in serum gamma-glutamyl transferase (GGT) from baseline to Day 28
Baseline to Day 28
Blood Pressure
Tidsramme: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
Vital signs - Systolic Blood pressure
Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
Pulse Rate
Tidsramme: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
Vital signs
Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
Body Temperature
Tidsramme: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
Vital signs
Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
ECG - Heart Rate
Tidsramme: Screening, Baseline, day 1, day 28
Electrocardiogram (ECG)
Screening, Baseline, day 1, day 28
ECG Intervals - PR Interval
Tidsramme: Screening, Baseline, day 1, day 28
Electrocardiogram (ECG)
Screening, Baseline, day 1, day 28
Haemoglobin
Tidsramme: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
Hematology panel for safety laboratory assessments.
Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Plasma PK Parameter - AUC 0-8h
Tidsramme: Day 1, Day 28
Tropifexor levels were determined in plasma using a validated LC-MS/MS method. AUC0-t=The area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration [mass x time / volume]
Day 1, Day 28
Plasma PK Parameter - Cmax
Tidsramme: Day 1, Day 28
Tropifexor levels were determined in plasma using a validated LC-MS/MS method. Cmax=The observed maximum plasma concentration following drug administration [mass /volume]
Day 1, Day 28
Plasma PK Parameter - Tmax
Tidsramme: Day 1, Day 28
Tropifexor levels were determined in plasma using a validated LC-MS/MS method. Tmax = The time to reach the maximum concentration after drug administration [time]
Day 1, Day 28
Changes From Baseline in Total PBC-40 Score
Tidsramme: Baseline, Day 28, Day 56, Day 84
Baseline is defined as the latest available predose value. The PBC-40 is a paper-based, patient-derived, disease-specific health-related quality of life (HRQOL) patient reported outcome (PRO) measure which was developed and validated for use in PBC patients (Jacoby et al 2005). It consists of 40 questions arranged in 6 domains with between 3 and 11 questions in each domain. Each question is scored from 1 to 5 in increasing order of severity. All questions within a domain are summed and all domain totals are summed to obtain a total score. The total score range is between a minimum of 40 and a maximum of 200. Higher scores represent a poorer quality of life. The median difference from baseline in total sum score for each treatment group is presented.
Baseline, Day 28, Day 56, Day 84
Change From Baseline in Itch Subdomain of PBC-40 Score
Tidsramme: Baseline, Day 28, Day 56, Day 84
Baseline is defined as the latest available predose value. The PBC-40 is a paper-based, patient-derived, disease-specific health-related quality of life (HRQOL) patient reported outcome (PRO) measure which was developed and validated for use in PBC patients (Jacoby et al 2005). It consists of 40 questions arranged in 6 domains with between 3 and 11 questions in each domain. Each question is scored from 1 to 5 in increasing order of severity. This dataset focuses on the itch subdomain which consists of 3 questions. These 3 questions within the itch subdomain are summed to obtain a total score for the itch subdomain. The total score range is between a minimum of 3 and a maximum of 15. Higher scores represent a poorer quality of life. The median change from baseline in total itch subdomain score in each treatment group is presented.
Baseline, Day 28, Day 56, Day 84
Change From Baseline in Global Itch Visual Analogue Scale (VAS)
Tidsramme: Day 7, Day 14, Day 21, Day 28, Day 56, and Day 84
Baseline is defined as the latest available predose value. The Global Itch Visual Analogue Scale, a 100 mm visual analogue scale (VAS), was used to assess the severity of patients itch (ranging from 0 = none at all to 100 = the worst imaginable itch). The score range is between a minimum of 0 and a maximum of 100. The score (distance in mm from left) on the VAS was recorded by the patient marking with a line and used to test for an effect of tropifexor over placebo. The mean change from baseline in itch VAS score in each treatment group is presented.
Day 7, Day 14, Day 21, Day 28, Day 56, and Day 84

Samarbejdspartnere og efterforskere

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

Sponsor

Novartis Pharmaceuticals

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

Hjælpsomme links

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)

9. september 2015

Primær færdiggørelse (Faktiske)

2. august 2018

Studieafslutning (Faktiske)

2. august 2018

Datoer for studieregistrering

Først indsendt

4. august 2015

Først indsendt, der opfyldte QC-kriterier

4. august 2015

Først opslået (Skøn)

6. august 2015

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

5. januar 2021

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

9. december 2020

Sidst verificeret

1. oktober 2019

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CLJN452X2201
  • 2015-001590-41 (EudraCT nummer)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

Ja

IPD-planbeskrivelse

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Primær biliær kolangitis

Kliniske forsøg med Part 1: LJN452

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Ecuador

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner