Phase 2 study design and analysis approach for BBT-877: an autotaxin inhibitor targeting idiopathic pulmonary fibrosis.

IF 3.4 3区 医学 Q1 RESPIRATORY SYSTEM
Toby Maher, Jin Woo Song, Mordechai Reuven Kramer, Lisa Lancaster, Tamera J Corte, Jeong Yun, KyungJin Kim, Jimin Cho, Luisa Fernanda Sather, Peter M George, Anand Devaraj, Jin Hyuk Jung, Sujin Jung
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引用次数: 0

Abstract

Introduction: Proof-of-concept (POC) studies are vital in determining the feasibility of further drug development, primarily by assessing preliminary efficacy signals with credible endpoints. However, traditional POC studies in idiopathic pulmonary fibrosis (IPF) can suffer from low credibility due to small sample sizes and short durations, leading to non-replicable results in larger phase III trials. To address this, we are conducting a 24-week POC study with 120 patients with IPF, using a statistically supported sample size and incorporating exploratory CT-based imaging biomarkers, to support decision-making in the case of non-significant primary endpoint results. This approach aims to provide data to enable a robust decision-making process for advancing clinical development of BBT-877.

Methods and analysis: In this phase II, double-blind, placebo-controlled study, approximately 120 patients with IPF will be randomised in a 1:1 ratio to receive placebo or 200 mg of BBT-877 two times per day over 24 weeks, with stratification according to background use of an antifibrotic treatment (pirfenidone background therapy, nintedanib background therapy or no background therapy). The primary endpoint is absolute change in forced vital capacity (FVC) (mL) from baseline to week 24. Key secondary endpoints include change from baseline to week 24 in %-predicted FVC, diffusing capacity of the lung for carbon monoxide, 6 min walk test, patient-reported outcomes, pharmacokinetics and safety, and tolerability. Key exploratory endpoints include eLung-based CT evaluation and biomarker-based assessment of pharmacodynamics.

Ethics and dissemination: This study is being conducted following the Declaration of Helsinki principles, Good Clinical Practice guidance, applicable local regulations and local ethics committees. An independent data monitoring committee unblinded to individual subject treatment allocation will evaluate safety and efficacy data on a regular basis throughout the study. The results of this study will be presented at scientific conferences and peer-review publications.

Trial registration number: NCT05483907.

Abstract Image

Abstract Image

针对特发性肺纤维化的自体的士素抑制剂BBT-877的2期研究设计和分析方法。
概念验证(POC)研究对于确定进一步药物开发的可行性至关重要,主要是通过评估具有可信终点的初步疗效信号。然而,特发性肺纤维化(IPF)的传统POC研究由于样本量小、持续时间短,可信度较低,导致在更大规模的III期试验中结果不可复制。为了解决这个问题,我们正在对120名IPF患者进行一项为期24周的POC研究,使用统计支持的样本量,并结合探索性的基于ct的成像生物标志物,以支持在无显著主要终点结果的情况下的决策。该方法旨在提供数据,为推进BBT-877的临床开发提供强有力的决策过程。方法和分析:在这项II期、双盲、安慰剂对照研究中,大约120名IPF患者将按1:1的比例随机分配,接受安慰剂或200 mg BBT-877,每天两次,持续24周,并根据使用抗纤维化治疗的背景(吡非尼酮背景治疗、尼达尼布背景治疗或无背景治疗)进行分层。主要终点是强迫肺活量(FVC) (mL)从基线到第24周的绝对变化。关键的次要终点包括从基线到第24周的变化,预测的FVC,肺一氧化碳弥散能力,6分钟步行测试,患者报告的结果,药代动力学和安全性以及耐受性。关键的探索终点包括基于肺的CT评估和基于生物标志物的药效学评估。伦理与传播:本研究遵循《赫尔辛基宣言》原则、良好临床实践指导、适用的当地法规和当地伦理委员会进行。一个独立的数据监测委员会将在整个研究过程中定期评估安全性和有效性数据。这项研究的结果将在科学会议和同行评审出版物上发表。试验注册号:NCT05483907。
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来源期刊
BMJ Open Respiratory Research
BMJ Open Respiratory Research RESPIRATORY SYSTEM-
CiteScore
6.60
自引率
2.40%
发文量
95
审稿时长
12 weeks
期刊介绍: BMJ Open Respiratory Research is a peer-reviewed, open access journal publishing respiratory and critical care medicine. It is the sister journal to Thorax and co-owned by the British Thoracic Society and BMJ. The journal focuses on robustness of methodology and scientific rigour with less emphasis on novelty or perceived impact. BMJ Open Respiratory Research operates a rapid review process, with continuous publication online, ensuring timely, up-to-date research is available worldwide. The journal publishes review articles and all research study types: Basic science including laboratory based experiments and animal models, Pilot studies or proof of concept, Observational studies, Study protocols, Registries, Clinical trials from phase I to multicentre randomised clinical trials, Systematic reviews and meta-analyses.
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