A Multi-part, Double Blind Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in PBC Patients
9 de dezembro de 2020 atualizado por: 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
Visão geral do estudo
Status
Concluído
Condições
Tipo de estudo
Intervencional
Inscrição (Real)
61
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Hamburg, Alemanha, 20246
- Novartis Investigative Site
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Hannover, Alemanha, 30625
- Novartis Investigative Site
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Heidelberg, Alemanha, 69120
- Novartis Investigative Site
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Muenchen, Alemanha, 81377
- Novartis Investigative Site
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Wuerzburg, Alemanha, 97080
- Novartis Investigative Site
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Alberta
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Calgary, Alberta, Canadá, T2N 4N1
- Novartis Investigative Site
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Edmonton, Alberta, Canadá, T6G 2B7
- Novartis Investigative Site
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California
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Rialto, California, Estados Unidos, 92377
- Novartis Investigative Site
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Florida
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Miami, Florida, Estados Unidos, 33136
- Novartis Investigative Site
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Georgia
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Atlanta, Georgia, Estados Unidos, 30308
- Novartis Investigative Site
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Marietta, Georgia, Estados Unidos, 30060
- Novartis Investigative Site
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Illinois
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Chicago, Illinois, Estados Unidos, 60612
- Novartis Investigative Site
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New York
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Manhasset, New York, Estados Unidos, 11030
- Novartis Investigative Site
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Texas
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Dallas, Texas, Estados Unidos, 75390
- Novartis Investigative Site
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San Antonio, Texas, Estados Unidos, 78215
- Novartis Investigative Site
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Washington
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Seattle, Washington, Estados Unidos, 98104
- Novartis Investigative Site
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Moscow, Federação Russa, 117198
- Novartis Investigative Site
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Saint-Petersburg, Federação Russa, 194044
- Novartis Investigative Site
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Samara, Federação Russa, 443011
- Novartis Investigative Site
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Lodz, Polônia, 91-347
- Novartis Investigative Site
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Myslowice, Polônia, 41-400
- Novartis Investigative Site
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Warsaw, Polônia, 02-097
- Novartis Investigative Site
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Wroclaw, Polônia, 50-449
- Novartis Investigative Site
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Cambridge, Reino Unido, CB2 2QQ
- Novartis Investigative Site
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Hull, Reino Unido, HU3 2JZ
- Novartis Investigative Site
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London, Reino Unido, NW3 2PF
- Novartis Investigative Site
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Newcastle upon Tyne, Reino Unido, NE1 4LP
- Novartis Investigative Site
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West Midlands
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Birmingham, West Midlands, Reino Unido, B15 2TH
- Novartis Investigative Site
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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).
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Triplo
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Comparador de 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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Experimental: LJN452
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LJN452 capsules administered once daily for 28 days
Outros nomes:
LJN452 capsules administered once a day for 12 weeks
Outros nomes:
LJN452
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Fold Change in Serum Gamma-glutamyl Transferase (GGT)
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Plasma PK Parameter - AUC 0-8h
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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)
Prazo: 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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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Publicações e links úteis
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Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
9 de setembro de 2015
Conclusão Primária (Real)
2 de agosto de 2018
Conclusão do estudo (Real)
2 de agosto de 2018
Datas de inscrição no estudo
Enviado pela primeira vez
4 de agosto de 2015
Enviado pela primeira vez que atendeu aos critérios de CQ
4 de agosto de 2015
Primeira postagem (Estimativa)
6 de agosto de 2015
Atualizações de registro de estudo
Última Atualização Postada (Real)
5 de janeiro de 2021
Última atualização enviada que atendeu aos critérios de controle de qualidade
9 de dezembro de 2020
Última verificação
1 de outubro de 2019
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- CLJN452X2201
- 2015-001590-41 (Número EudraCT)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Sim
Descrição do plano 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
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Sim
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Não
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .