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
調査の概要
状態
完了
条件
研究の種類
介入
入学 (実際)
61
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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California
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Rialto、California、アメリカ、92377
- Novartis Investigative Site
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Florida
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Miami、Florida、アメリカ、33136
- Novartis Investigative Site
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Georgia
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Atlanta、Georgia、アメリカ、30308
- Novartis Investigative Site
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Marietta、Georgia、アメリカ、30060
- Novartis Investigative Site
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Illinois
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Chicago、Illinois、アメリカ、60612
- Novartis Investigative Site
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New York
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Manhasset、New York、アメリカ、11030
- Novartis Investigative Site
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Texas
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Dallas、Texas、アメリカ、75390
- Novartis Investigative Site
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San Antonio、Texas、アメリカ、78215
- Novartis Investigative Site
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Washington
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Seattle、Washington、アメリカ、98104
- Novartis Investigative Site
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Cambridge、イギリス、CB2 2QQ
- Novartis Investigative Site
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Hull、イギリス、HU3 2JZ
- Novartis Investigative Site
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London、イギリス、NW3 2PF
- Novartis Investigative Site
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Newcastle upon Tyne、イギリス、NE1 4LP
- Novartis Investigative Site
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West Midlands
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Birmingham、West Midlands、イギリス、B15 2TH
- Novartis Investigative Site
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Alberta
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Calgary、Alberta、カナダ、T2N 4N1
- Novartis Investigative Site
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Edmonton、Alberta、カナダ、T6G 2B7
- Novartis Investigative Site
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Hamburg、ドイツ、20246
- Novartis Investigative Site
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Hannover、ドイツ、30625
- Novartis Investigative Site
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Heidelberg、ドイツ、69120
- Novartis Investigative Site
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Muenchen、ドイツ、81377
- Novartis Investigative Site
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Wuerzburg、ドイツ、97080
- Novartis Investigative Site
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Lodz、ポーランド、91-347
- Novartis Investigative Site
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Myslowice、ポーランド、41-400
- Novartis Investigative Site
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Warsaw、ポーランド、02-097
- Novartis Investigative Site
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Wroclaw、ポーランド、50-449
- Novartis Investigative Site
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Moscow、ロシア連邦、117198
- Novartis Investigative Site
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Saint-Petersburg、ロシア連邦、194044
- Novartis Investigative Site
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Samara、ロシア連邦、443011
- Novartis Investigative Site
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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).
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
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プラセボコンパレーター：プラセボ
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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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実験的：LJN452
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LJN452 capsules administered once daily for 28 days
他の名前：
LJN452 capsules administered once a day for 12 weeks
他の名前：
LJN452
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Fold Change in Serum Gamma-glutamyl Transferase (GGT)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Plasma PK Parameter - AUC 0-8h
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2015年9月9日
一次修了 (実際)
2018年8月2日
研究の完了 (実際)
2018年8月2日
試験登録日
最初に提出
2015年8月4日
QC基準を満たした最初の提出物
2015年8月4日
最初の投稿 (見積もり)
2015年8月6日
学習記録の更新
投稿された最後の更新 (実際)
2021年1月5日
QC基準を満たした最後の更新が送信されました
2020年12月9日
最終確認日
2019年10月1日
詳しくは
本研究に関する用語
その他の研究ID番号
- CLJN452X2201
- 2015-001590-41 (EudraCT番号)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
はい
IPD プランの説明
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
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
はい
米国FDA規制機器製品の研究
いいえ
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。