vedomostiregmedРегуляторные исследования и экспертиза лекарственных средствRegulatory Research and Medicine Evaluation3034-30623034-3453Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/1991-2919-2023-499vedomostiregmed-499Research ArticleПРОГРАММЫ КЛИНИЧЕСКИХ ИССЛЕДОВАНИЙCLINICAL TRIAL PROGRAMMESПланирование программы клинических исследований препаратов прямого противовирусного действия для лечения хронического вирусного гепатита СPlanning a clinical trial programme for direct-acting antivirals for chronic viral hepatitis Chttps://orcid.org/0000-0002-5596-0848ГубенкоА. И.GubenkoA. I.

Губенкo Анна Игoревна, канд. мед. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация

Anna I. Gubenko, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

gubenko@expmed.ruhttps://orcid.org/0000-0001-8583-2372ГорячевД. В.GoryachevD. V.

Горячев Дмитрий Владимирович, д-р мед. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация

Dmitry V. Goryachev, Dr. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

Gorachev@expmed.ruhttps://orcid.org/0000-0001-6743-9403МуравьеваА. И.MuravievaA. I.

Муравьева Анна Ивановна

Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация

Anna I. Muravieva

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

https://orcid.org/0000-0002-3553-8340ШукшинаГ. В.ShukshinaG. V.

Шукшина Галина Викторовна

Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация

Galina V. Shukshina

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

shukshinagv@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation202320092023134519530Copyright © Губенко А.И., Горячев Д.В., Муравьева А.И., Шукшина Г.В., 20232023Губенко А.И., Горячев Д.В., Муравьева А.И., Шукшина Г.В.Gubenko A.I., Goryachev D.V., Muravieva A.I., Shukshina G.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.vedomostincesmp.ru/jour/article/view/499Актуальность

Актуальность. Разработка и применение препаратов прямого противовирусного действия существенно повысили эффективность лечения пациентов с инфекцией гепатита С. Однако рекомендации по клинической разработке данной группы препаратов в России и странах Евразийского экономического союза на данный момент отсутствуют.

Цель

Цель. Анализ требований и рекомендаций к планированию клинических исследований эффективности и безопасности противовирусной терапии хронического гепатита С препаратами прямого противовирусного действия на основании нормативной документации регуляторных органов Европейского союза и США.

Обсуждение

Обсуждение. В результате проведенного анализа обоснован выбор целевой популяции пациентов и дизайна клинических исследований эффективности и подтверждающих исследований, а также особенности разработки на клиническом этапе в особых группах пациентов, в том числе с коинфекцией гепатитом С и вирусом иммунодефицита человека, пациентов с трансплантатом печени и наличием предшествующего опыта лечения. Отмечено, что за пациентами, достигшими устойчивого вирусологического ответа, требуется наблюдение в течение одного полного года после завершения терапии для подтверждения длительности эффекта. В исследованиях по подбору дозы рекомендовано сначала изучить достаточный диапазон доз в режиме монотерапии, а затем проводить исследования комбинированного применения препарата. Показана необходимость совершенствования существующих схем лечения и изучения возможности сокращения продолжительности курса лечения.

Выводы

Выводы. Сформулированы основные подходы и определена методология программы клинических исследований с учетом высокой степени корреляции эффективности указанных препаратов с генотипом и подтипом вируса гепатита С, которым инфицирован пациент.

Scientific relevance

Scientific relevance. Direct-acting antivirals have significantly improved the effectiveness of treatment for hepatitis C. However, Russia and the Eurasian Economic Union lack recommendations for the clinical development of medicinal products from this pharmacotherapeutic group.

Aim

Aim. The study aimed to analyse the requirements and recommendations for planning safety and efficacy clinical trials of direct-acting antivirals for chronic viral hepatitis C, outlined in the regulatory documents of the European Union and the United States.

Discussion

Discussion. Upon analysing the requirements and recommendations, the authors explained the reasons behind choosing the target population and the design for the efficacy and confirmatory studies. The article covers the clinical development of direct-acting antivirals in special populations, including patients with hepatitis C and HIV co-infection, a liver transplant, and prior treatment experience. According to the authors, patients who achieved a sustained virological response should be followed up for a full year after the end of treatment in order to confirm the durability of their response. A dose-finding study should first identify a suitable dose range for monotherapy and, subsequently, for combined therapy. Current treatment regimens should be optimised, and studies should be conducted to reduce treatment duration.

Conclusions

Conclusions. The authors outlined the main approaches and a methodology for clinical trial programmes that should take into account the degree of correlation between the efficacy of direct-acting antivirals and the genotype/subtype of hepatitis C virus.

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The authors declare that there are no conflicts of interest present.