Efficacy and Safety of Netakimab, A Novel Anti-IL-17 Monoclonal Antibody, in Patients with Moderate to Severe Plaque Psoriasis. Results of A 54-Week Randomized Double-Blind Placebo-Controlled PLANETA Clinical Trial

Altres ajuts: Sponsorship for this study and the Rapid Service Fee were funded by JSC BIOCAD, Ul. Italianskaya 17, St Petersburg, Russia, 191186Introduction: Netakimab (NTK), an original humanized anti-interleukin-17 monoclonal antibody, showed therapeutic efficacy in moderate-to-severe plaque psoriasis in a phase 2 clinical study. Herein we report the results of 54 weeks of a phase 3 PLANETA trial aimed to evaluate the efficacy and safety of two NTK regimens vs. placebo. Methods: Two hundred thirteen patients with moderate-to-severe plaque psoriasis were randomly assigned to receive NTK 120 mg once every 2 weeks (NTK Q2W), NTK 120 mg once every 4 weeks (NTK Q4W) or placebo. During the first 3 weeks, patients received subcutaneous injections of NTK or placebo (according to the allocation) once a week. Patients in the NTK Q2W group then received NTK at weeks 4, 6, 8 and 10. Subjects in the NTK Q4W group received NTK at weeks 6 and 10 and placebo at weeks 4 and 8. Patients in the placebo group received placebo injections at weeks 4, 6, 8 and 10. Treatment was unblinded at week 12. During the open-label phase, patients in both NTK groups continued to receive NTK Q4W. The primary efficacy endpoint was the proportion of patients in each group who achieved a ≥ 75% reduction from baseline in psoriasis area and severity index (PASI 75) at week 12. Results: A total of 77.7%, 83.3% and 0% of patients had a PASI 75 response at week 12 in the NTK Q2W, NTK Q4W and placebo groups, respectively (P < 0.0001, Fisher's exact test, ITT). The effect was maintained throughout the 1-year treatment. NTK showed a good safety profile and low immunogenicity. Conclusion: Treatment with NTK results in high rates of sustained clinical response in patients with moderate-to-severe plaque psoriasis. The study is ongoing; thus, long-term use efficacy and safety data are forthcoming. Clinical Trial Registration: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT03390101)

SOCIAL CONTEXT AS A CATALYST FOR THE EVOLUTION OF REALIZED UTOPIAN MODEL OF URBAN MORPHOSTRUCTURE: THE CASE OF TOGLIATTI, RUSSIA

Proceedings of the XXV ISUF International Conference “Urban Form and Social Context: from Traditions to Newest Demands” (Krasnoyarsk, July 5–9, 2018)The article describes the role of social context in the evolution of a realized urban utopia’s morphostructure. Using the case of Togliatti, which is a typical Russian large single-industry city, the evolution of its morphostructure is investigated - from the utopian model of the industrial center, with its features of Le Corbusier’s “Radiant City”, to the modern pluralistic, polyfunctional city. The problems, which have been revealed in process of the functioning of this realized Soviet city utopia, are considered. Avtozavodskiy District of Togliatti is a large industrial area of the city, and its morphostructure reflects the functional workflow of the “ideal socialist city”, which was proposed by N.A. Milyutin in the 20-30ies of the 20th century. Under the supervision of B.R. Rubanenko, V.A. Shkvarikov, Yu. P. Bocharov in 1967-1968, under optimal geodemographic conditions, a regular urban grid-frame was laid. The functional structure of the grid is represented only by transport, and the main frame functions are redirected to the fabric, which is characterized by self-sufficiency, homogeneity and immanent intolerance to social context. Thus, the city’s layout was a system which, on the one hand, fully answered the ideal concept of a modernist city, built in accordance with the Athenian Charter principles, and on the other hand, contradicted the idea of the city as a concentrated environment. The solution which will help to overcome the critical condition of Togliatti lies in the field of generating new utopias. A team of young architects proposed a utopia, which they called “New Togliatti”. It is based on the concept of a macro frame, which will integrate the structures of both the historically established urban grids and of Avtozavodskiy District. The essence of the new concept was the replacement of redundant conceptuality with contextuality, in accordance with the new paradigm formed by socio-ecological thinking model

Эффективность и безопасность нового моноклонального антитела к ИЛ-17 нетакимаба у пациентов со среднетяжелым и тяжелым бляшечным псориазом. Результаты 54-недельного рандомизированного двойного слепого плацебо-контролируемого клинического исследования PLANETA

Background. Netakimab (NTK), an original humanized anti-interleukin-17 monoclonal antibody, showed therapeutic efficacy in moderate to severe plaque psoriasis in a phase 2 clinical study. Herein we report the results of 54 weeks of a phase 3 trial. Aim. To evaluate the efficacy and safety of two NTK regimens vs. placebo in moderate to severe plaque psoriasis. Methods. PLANETA is the ongoing randomized double-blind placebo-controlled clinical trial. 213 patients with moderate to severe plaque psoriasis were randomly assigned to receive NTK 120 mg once every 2 weeks (NTK Q2W), NTK 120 mg once every 4 weeks (NTK Q4W) or placebo. During the first 3 weeks, patients received subcutaneous injections of NTK or placebo (according to the allocation) once a week. Patients in the NTK Q2W group then received NTK at weeks 4, 6, 8, and 10. Subjects in the NTK Q4W group received NTK at weeks 6 and 10 and placebo at weeks 4 and 8. Patients in the placebo group received placebo injections at weeks 4, 6, 8, and 10. Treatment was unblinded at week 12. During the open-label phase, patients in both NTK groups continued to receive NTK Q4W. The primary efficacy endpoint was the proportion of patients in each group who achieved a 75% or greater reduction from baseline in psoriasis area and severity index (PASI 75) at week 12. Results. A total of 77.7%, 83.3%, and 0% of patients had a PASI 75 response at week 12 in the NTK Q2W, NTK Q4W, and placebo groups, respectively (P 0.0001, Fishers exact test, ITT). The effect was maintained throughout the 1-year treatment. NTK showed a good safety profile and low immunogenicity. Conclusion. Treatment with NTK results in high rates of sustained clinical response in patients with moderate to severe plaque psoriasis. The study is ongoing; thus, long-term use efficacy and safety data are forthcoming.Обоснование. Нетакимаб это оригинальное гуманизированное моноклональное антитело к интерлейкину-17, продемонстрировавшее терапевтическую эффективность при среднетяжелом и тяжелом вульгарном псориазе в клиническом исследовании 2-й фазы. В данной статье представлены результаты 54 недель исследования 3-й фазы. Цель исследования. Оценка эффективности и безопасности двух режимов применения нетакимаба по сравнению с плацебо у пациентов со среднетяжелым и тяжелым бляшечным псориазом. Методы. PLANETA продолжающееся рандомизированное двойное слепое плацебо-контролируемое клиническое исследование 3-й фазы. 213 пациентов со среднетяжелым и тяжелым бляшечным псориазом были рандомизированы в три группы терапии: введение нетакимаба в дозе 120 мг 1 раз в 2 недели (Q2W), введение нетакимаба в дозе 120 мг 1 раз в 4 недели (Q4W) или плацебо. В течение первых 3 недель пациенты получали подкожные инъекции анализируемого препарата или плацебо (в соответствии с распределением) 1 раз в неделю. После этого пациенты в группе нетакимаба Q2W получили инъекции препарата на неделях 4, 6, 8 и 10. Участники в группе нетакимаб Q4W получили инъекции препарата на неделях 6 и 10 и инъекции плацебо на неделях 4 и 8. Пациенты в группе плацебо получили инъекции плацебо на неделях 4, 6, 8 и 10. На неделе 12 было произведено расслепление терапии. В открытой фазе пациенты, получавшие нетакимаб, продолжили его получать 1 раз в 4 недели. Первичной конечной точкой эффективности была доля пациентов в каждой группе, достигших снижения индекса распространенности и тяжести псориаза как минимум на 75% от исходного уровня (PASI 75) на неделе 12. Результаты. В общей сложности ответ PASI 75 на неделе 12 наблюдался у 77,7%, 83,3% и 0% пациентов в группах нетакимаба Q2W и Q4W и плацебо соответственно (Р 0,0001, точный критерий Фишера, ITT). Эффект сохранялся на протяжении 1 года лечения. Анализируемый препарат обладал хорошим профилем безопасности и низкой иммуногенностью. Заключение. Терапия нетакимабом обеспечивает высокую частоту устойчивого клинического ответа у пациентов со среднетяжелым и тяжелым бляшечным псориазом. Исследование продолжается, позже будут представлены данные по эффективности и безопасности длительного применения данного лекарственного препарата