Lavine Irena, Seo Suna, Tomaino Juli
Division of Gastroenterology, U.S. Food and Drug Administration, Silver Spring, Maryland.
Gastro Hep Adv. 2022 Nov 8;2(3):294-297. doi: 10.1016/j.gastha.2022.11.006. eCollection 2023.
The Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics VI Workshop, held on July 22, 2021, provided a forum for patients and representatives from academia, industry, patient advocacy groups, and Food and Drug Administration to discuss drug development for celiac disease (CeD). The workshop focused on the approach of histologic assessments in clinical trials, considerations for pediatric drug development, and the use of a gluten challenge (GC) in clinical trials. Given that no histologic scoring system is widely accepted for use in clinical trials at this time, early-phase clinical trials should ideally explore a variety of histologic scales and assess the histologic findings of CeD as individual measures to inform future trials. When planning pediatric drug development in CeD, appropriate use of extrapolation of efficacy data from adequate, well-controlled studies in adults could facilitate timely access to safe and effective therapies for pediatric patients. Identification of a fit-for-purpose pediatric clinical outcome assessment could further advance pediatric drug development. Histologic responses to the GC depend on exposure, dose, and duration; short exposures do not appear to cause long-term consequences. However, the GC should be incorporated into clinical trials in a thoughtful manner to generate interpretable results and ensure patient safety. Ongoing collaboration between all stakeholders will facilitate the development of safe and effective therapeutics for CeD.
2021年7月22日举办的第六届胃肠病学监管终点与治疗进展研讨会为患者以及来自学术界、产业界、患者权益倡导组织和美国食品药品监督管理局的代表提供了一个讨论乳糜泻(CeD)药物研发的平台。该研讨会聚焦于临床试验中的组织学评估方法、儿科药物研发的考量因素以及临床试验中麸质激发试验(GC)的应用。鉴于目前尚无组织学评分系统在临床试验中被广泛接受,早期临床试验理想情况下应探索多种组织学量表,并将CeD的组织学发现作为个体指标进行评估,以为未来试验提供参考。在规划CeD的儿科药物研发时,适当地从成人充分且对照良好的研究中推断疗效数据,有助于儿科患者及时获得安全有效的治疗。确定适合目的的儿科临床结局评估方法可进一步推动儿科药物研发。对GC的组织学反应取决于暴露情况、剂量和持续时间;短时间暴露似乎不会造成长期后果。然而,应谨慎地将GC纳入临床试验,以产生可解释的结果并确保患者安全。所有利益相关者之间持续的合作将有助于开发出针对CeD的安全有效的治疗方法。