A Multi-part, Double Blind Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in PBC Patients
9 décembre 2020 mis à jour par: 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
Aperçu de l'étude
Statut
Complété
Les conditions
Type d'étude
Interventionnel
Inscription (Réel)
61
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Hamburg, Allemagne, 20246
- Novartis Investigative Site
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Hannover, Allemagne, 30625
- Novartis Investigative Site
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Heidelberg, Allemagne, 69120
- Novartis Investigative Site
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Muenchen, Allemagne, 81377
- Novartis Investigative Site
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Wuerzburg, Allemagne, 97080
- Novartis Investigative Site
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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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Moscow, Fédération Russe, 117198
- Novartis Investigative Site
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Saint-Petersburg, Fédération Russe, 194044
- Novartis Investigative Site
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Samara, Fédération Russe, 443011
- Novartis Investigative Site
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Lodz, Pologne, 91-347
- Novartis Investigative Site
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Myslowice, Pologne, 41-400
- Novartis Investigative Site
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Warsaw, Pologne, 02-097
- Novartis Investigative Site
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Wroclaw, Pologne, 50-449
- Novartis Investigative Site
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Cambridge, Royaume-Uni, CB2 2QQ
- Novartis Investigative Site
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Hull, Royaume-Uni, HU3 2JZ
- Novartis Investigative Site
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London, Royaume-Uni, NW3 2PF
- Novartis Investigative Site
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Newcastle upon Tyne, Royaume-Uni, NE1 4LP
- Novartis Investigative Site
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West Midlands
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Birmingham, West Midlands, Royaume-Uni, B15 2TH
- Novartis Investigative Site
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California
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Rialto, California, États-Unis, 92377
- Novartis Investigative Site
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Florida
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Miami, Florida, États-Unis, 33136
- Novartis Investigative Site
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Georgia
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Atlanta, Georgia, États-Unis, 30308
- Novartis Investigative Site
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Marietta, Georgia, États-Unis, 30060
- Novartis Investigative Site
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Illinois
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Chicago, Illinois, États-Unis, 60612
- Novartis Investigative Site
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New York
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Manhasset, New York, États-Unis, 11030
- Novartis Investigative Site
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Texas
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Dallas, Texas, États-Unis, 75390
- Novartis Investigative Site
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San Antonio, Texas, États-Unis, 78215
- Novartis Investigative Site
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Washington
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Seattle, Washington, États-Unis, 98104
- Novartis Investigative Site
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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).
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Comparateur placebo: 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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Expérimental: LJN452
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LJN452 capsules administered once daily for 28 days
Autres noms:
LJN452 capsules administered once a day for 12 weeks
Autres noms:
LJN452
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Fold Change in Serum Gamma-glutamyl Transferase (GGT)
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Plasma PK Parameter - AUC 0-8h
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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)
Délai: 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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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
9 septembre 2015
Achèvement primaire (Réel)
2 août 2018
Achèvement de l'étude (Réel)
2 août 2018
Dates d'inscription aux études
Première soumission
4 août 2015
Première soumission répondant aux critères de contrôle qualité
4 août 2015
Première publication (Estimation)
6 août 2015
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
5 janvier 2021
Dernière mise à jour soumise répondant aux critères de contrôle qualité
9 décembre 2020
Dernière vérification
1 octobre 2019
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- CLJN452X2201
- 2015-001590-41 (Numéro EudraCT)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Oui
Description du régime IPD
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
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Oui
Étudie un produit d'appareil réglementé par la FDA américaine
Non
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .