A Multi-part, Double Blind Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in PBC Patients
9 december 2020 bijgewerkt door: 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
Studie Overzicht
Toestand
Voltooid
Conditie
Studietype
Ingrijpend
Inschrijving (Werkelijk)
61
Fase
- Fase 2
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Alberta
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Calgary, Alberta, Canada, T2N 4N1
- Novartis Investigative Site
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Edmonton, Alberta, Canada, T6G 2B7
- Novartis Investigative Site
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Hamburg, Duitsland, 20246
- Novartis Investigative Site
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Hannover, Duitsland, 30625
- Novartis Investigative Site
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Heidelberg, Duitsland, 69120
- Novartis Investigative Site
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Muenchen, Duitsland, 81377
- Novartis Investigative Site
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Wuerzburg, Duitsland, 97080
- Novartis Investigative Site
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Lodz, Polen, 91-347
- Novartis Investigative Site
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Myslowice, Polen, 41-400
- Novartis Investigative Site
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Warsaw, Polen, 02-097
- Novartis Investigative Site
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Wroclaw, Polen, 50-449
- Novartis Investigative Site
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Moscow, Russische Federatie, 117198
- Novartis Investigative Site
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Saint-Petersburg, Russische Federatie, 194044
- Novartis Investigative Site
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Samara, Russische Federatie, 443011
- Novartis Investigative Site
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Cambridge, Verenigd Koninkrijk, CB2 2QQ
- Novartis Investigative Site
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Hull, Verenigd Koninkrijk, HU3 2JZ
- Novartis Investigative Site
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London, Verenigd Koninkrijk, NW3 2PF
- Novartis Investigative Site
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Newcastle upon Tyne, Verenigd Koninkrijk, NE1 4LP
- Novartis Investigative Site
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West Midlands
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Birmingham, West Midlands, Verenigd Koninkrijk, B15 2TH
- Novartis Investigative Site
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California
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Rialto, California, Verenigde Staten, 92377
- Novartis Investigative Site
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Florida
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Miami, Florida, Verenigde Staten, 33136
- Novartis Investigative Site
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Georgia
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Atlanta, Georgia, Verenigde Staten, 30308
- Novartis Investigative Site
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Marietta, Georgia, Verenigde Staten, 30060
- Novartis Investigative Site
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Illinois
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Chicago, Illinois, Verenigde Staten, 60612
- Novartis Investigative Site
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New York
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Manhasset, New York, Verenigde Staten, 11030
- Novartis Investigative Site
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Texas
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Dallas, Texas, Verenigde Staten, 75390
- Novartis Investigative Site
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San Antonio, Texas, Verenigde Staten, 78215
- Novartis Investigative Site
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Washington
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Seattle, Washington, Verenigde Staten, 98104
- Novartis Investigative Site
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
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).
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verdrievoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Placebo-vergelijker: Placebo
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Matching placebo capsules administered once daily for 28 days
Matching placebo to LJN452 administered once a day for 12 weeks
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Experimenteel: LJN452
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LJN452 capsules administered once daily for 28 days
Andere namen:
LJN452 capsules administered once a day for 12 weeks
Andere namen:
LJN452
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Fold Change in Serum Gamma-glutamyl Transferase (GGT)
Tijdsspanne: Baseline to Day 28
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Fold change in serum gamma-glutamyl transferase (GGT) from baseline to Day 28
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Baseline to Day 28
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Blood Pressure
Tijdsspanne: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
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Vital signs - Systolic Blood pressure
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Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
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Pulse Rate
Tijdsspanne: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
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Vital signs
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Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
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Body Temperature
Tijdsspanne: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
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Vital signs
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Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
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ECG - Heart Rate
Tijdsspanne: Screening, Baseline, day 1, day 28
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Electrocardiogram (ECG)
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Screening, Baseline, day 1, day 28
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ECG Intervals - PR Interval
Tijdsspanne: Screening, Baseline, day 1, day 28
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Electrocardiogram (ECG)
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Screening, Baseline, day 1, day 28
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Haemoglobin
Tijdsspanne: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
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Hematology panel for safety laboratory assessments.
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Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Plasma PK Parameter - AUC 0-8h
Tijdsspanne: Day 1, Day 28
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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]
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Day 1, Day 28
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Plasma PK Parameter - Cmax
Tijdsspanne: Day 1, Day 28
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Tropifexor levels were determined in plasma using a validated LC-MS/MS method.
Cmax=The observed maximum plasma concentration following drug administration [mass /volume]
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Day 1, Day 28
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Plasma PK Parameter - Tmax
Tijdsspanne: Day 1, Day 28
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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]
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Day 1, Day 28
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Changes From Baseline in Total PBC-40 Score
Tijdsspanne: Baseline, Day 28, Day 56, Day 84
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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.
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Baseline, Day 28, Day 56, Day 84
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Change From Baseline in Itch Subdomain of PBC-40 Score
Tijdsspanne: Baseline, Day 28, Day 56, Day 84
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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.
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Baseline, Day 28, Day 56, Day 84
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Change From Baseline in Global Itch Visual Analogue Scale (VAS)
Tijdsspanne: Day 7, Day 14, Day 21, Day 28, Day 56, and Day 84
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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.
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Day 7, Day 14, Day 21, Day 28, Day 56, and Day 84
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
9 september 2015
Primaire voltooiing (Werkelijk)
2 augustus 2018
Studie voltooiing (Werkelijk)
2 augustus 2018
Studieregistratiedata
Eerst ingediend
4 augustus 2015
Eerst ingediend dat voldeed aan de QC-criteria
4 augustus 2015
Eerst geplaatst (Schatting)
6 augustus 2015
Updates van studierecords
Laatste update geplaatst (Werkelijk)
5 januari 2021
Laatste update ingediend die voldeed aan QC-criteria
9 december 2020
Laatst geverifieerd
1 oktober 2019
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- CLJN452X2201
- 2015-001590-41 (EudraCT-nummer)
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Ja
Beschrijving IPD-plan
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
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Ja
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Nee
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .