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

2020年12月9日 更新者：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

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

61

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

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

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

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).

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：三倍

武器和干预

参与者组/臂
干预/治疗
安慰剂比较：安慰剂
药品：Part 1: Placebo
Matching placebo capsules administered once daily for 28 days
药品：Part 2: Placebo
Matching placebo to LJN452 administered once a day for 12 weeks
实验性的：LJN452
药品：Part 1: LJN452
LJN452 capsules administered once daily for 28 days
其他名称：
  • tropifexor
药品：Part 2: LJN452 Dose level 1
LJN452 capsules administered once a day for 12 weeks
其他名称：
  • tropifexor
药品：Part 2: LJN452 Dose level 2
LJN452
其他名称：
  • tropifexor

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Fold Change in Serum Gamma-glutamyl Transferase (GGT)
大体时间：Baseline to Day 28
Fold change in serum gamma-glutamyl transferase (GGT) from baseline to Day 28
Baseline to Day 28
Blood Pressure
大体时间：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
大体时间：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
大体时间：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
大体时间：Screening, Baseline, day 1, day 28
Electrocardiogram (ECG)
Screening, Baseline, day 1, day 28
ECG Intervals - PR Interval
大体时间：Screening, Baseline, day 1, day 28
Electrocardiogram (ECG)
Screening, Baseline, day 1, day 28
Haemoglobin
大体时间：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

次要结果测量

结果测量
措施说明
大体时间
Plasma PK Parameter - AUC 0-8h
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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)
大体时间：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

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Novartis Pharmaceuticals

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2015年9月9日

初级完成 (实际的)

2018年8月2日

研究完成 (实际的)

2018年8月2日

研究注册日期

首次提交

2015年8月4日

首先提交符合 QC 标准的

2015年8月4日

首次发布 (估计)

2015年8月6日

研究记录更新

最后更新发布 (实际的)

2021年1月5日

上次提交的符合 QC 标准的更新

2020年12月9日

最后验证

2019年10月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

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

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

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

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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