Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients

Официальное название

Phase 3 Study to Compare the Efficacy and Safety of Masitinib in Combination With Riluzole Versus Placebo in Combination With Riluzole in the Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS)

Обзор

The objective is to compare the efficacy and safety of masitinib in combination with riluzole versus matched placebo in combination with riluzole for the treatment of Amyotrophic Lateral Sclerosis (ALS).

Подробное описание

Masitinib is a selective, oral tyrosine kinase inhibitor with neuroprotective capability demonstrated via numerous preclinical studies. Two of masitinib's main cellular targets are the mast cell and microglia cell. It is well-established that mast cells play a prominent role in neuroinflammatory processes. Microglia, resident immune cells of the central nervous system (CNS), also constitute an important source of neuroinflammatory mediators and may have fundamental roles in numerous neurodegenerative disorders. The development of masitinib in ALS is therefore based on the pharmacological action of masitinib in microglia cells and mast cells, thereby slowing microglial-related disease progression, reducing neuro-inflammation, and modulating the neuronal microenvironment in both central and peripheral nervous systems. This is a multicenter, double-blind, randomized, placebo-controlled, parallel-group (two ascending dose titrations of masitinib and matching placebo), comparative study of oral masitinib in the treatment of patients with amyotrophic lateral sclerosis (ALS).

Вмешательства

• Препарат Masitinib (6.0)
  Masitinib (titration to 6.0 mg/kg/day)
• Препарат Riluzole
  Riluzole 50 mg tablet, treatment per os
• Препарат Placebo
  treatment per os
• Препарат Masitinib (4.5)
  Masitinib (titration to 4.5 mg/kg/day)

Первичные конечные точки

• ALSFRS-R [Срок оценки: 48 weeks]

Вторичные конечные точки (5)

• ALSAQ-40 [Срок оценки: 48 weeks]
• PFS [Срок оценки: From day of randomization to disease progression or death, assessed for a maximum of 36 months]
• FVC [Срок оценки: 48 weeks]
• HHD [Срок оценки: 48 weeks]
• Change in the Combined Assessment of Function and Survival (CAFS) score from baseline to week 48 [Срок оценки: 48 weeks]

Критерии участия

Main inclusion criteria include:

• Patients diagnosed with laboratory supported probable, clinically probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria
• Patient with a familial or sporadic ALS
• ALS disease duration from diagnosis no longer than 24 months at the screening visit
• Patient treated with a stable dose of riluzole (100 mg/day) for at least 12 weeks days prior to the baseline visit
• Patient with an ALSFRS-R score progression between onset of the disease and screening of > 0.3 per month, confirmed with an ALSFRS-R score progression of ≥ 1 point during a 12-week run-in period between screening and randomization.
• Patient with a score, at screening, of at least 26 overall, including a score of at least 3 on item #3 and at least 2 on each of the 12 ALSFRS-R individual component items and with a score, at randomization, of at least 2 on each of the 12 ALSFRS-R individual component items

Main exclusion criteria include:

• Patient with dementia or significant neurological, psychiatric, systemic or organic disease, uncontrolled or that may interfere with the conduct of the trial or its results
• Patient with a FVC < 60% predicted normal value for gender, height, and age at screening and baseline
• Pregnant, or nursing female patient

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Франция · 11 центров

• CHU de Angers — Angers
• Groupe Hospitalier Pellegrin Tripode — Bordeaux
• Hôpital neurologique Pierre Wertheimer — Bron
• CHU Gabriel Montpied — Clermont-Ferrand
• CHU de Lille - Hopital Roger Salengro — Lille
• CHU de Limoges - Hôpital Dupuytren — Limoges
• CHU de Marseille - Hôpital de la Timone — Marseille
• CHRU de Montpellier - Gui de Chauliac — Montpellier
• … и ещё 3 центра

Италия · 11 центров

• Ospedale Civile Sant'Agostino - Estense — Baggiovara
• ASST degli Spedali Civili di Brescia — Brescia
• Centro Clinico NeMO Fondazione Serena Onlus — Gussago
• Clinico Nemo Center (Centro Clinico NeMO Milano) — Milan
• IRCCS Istituto Auxologico Italiano — Milan
• Istituti Clinici Scientifici Maugeri IRCCS — Milan
• San Raffaele Hospital (Ospedale San Raffaele) — Milan
• University Hospital Maggiore della Carita — Novara
• … и ещё 3 центра

США · 6 центров

• University of Alabama at Birmingham — Birmingham
• University of Southern California — Los Angeles
• University of Kentucky — Lexington
• Johns Hopkins Medicine Brain Science Institute — Baltimore
• Lahey Hospital and Medical Center — Burlington
• University of Virginia Health System — Charlottesville

Испания · 6 центров

• Hospital General Universitario de Alicante — Alicante
• Hospital Universitari de Bellvitge — Barcelona
• Hospital Carlos III — Madrid
• Hospital San Rafael — Madrid
• Clinical Hospital Santiago de Compostela — Santiago de Compostela
• Hospital Universitario y Politecnico La Fe — Valencia

Греция · 4 центра

• Athens Naval Hospital — Athens
• Eginition Hospital — Athens
• University General Hospital of Larissa — Larissa
• General University Hospital of Patras — Rio

Швеция · 3 центра

• Centralsjukhuset Karlstad (Central Hospital Karlstad) — Karlstad
• Skåne University Hospital — Malmö
• Norrlands universitetssjukhus — Umeå

Украина · 3 центра

• The State Institution of Neurology, Psychiatry and Narcology of NAMS of Ukraine — Kharkiv
• Medical Center of LLC Medical Center Dopomoga Plus — Kyiv
• Communal Non-Profit Enterprise of Lviv Regional Council, Lviv Regional Clinical Hospital, — Lviv

Израиль · 2 центра

• Hadassah University Hospital — Jerusalem
• Tel-Aviv Medical Center Hôpital Sourasky (ICHILOV) — Tel Aviv

Россия · 2 центра

• Moscow city clinical Hospital after V.M. Buyanov — Moscow
• Scientific Practical Medical Center "Innovation and Health" — Novosibirsk

Бельгия · 1 центр

• University Hospital Leuven (UZ Leuven) — Leuven

Дания · 1 центр

• Bispebjerg Hospital — Copenhagen

Германия · 1 центр

• Department of Neurology, University of Ulm — Ulm

Норвегия · 1 центр

• Oslo University Hospital HF Ullevål — Oslo

Польша · 1 центр

• Centrum Medyczne Neuromed — Bydgoszcz

Португалия · 1 центр

• Hospital de Santa Maria — Lisbon

Сербия · 1 центр

• Clinical Centre of Serbia — Belgrade

Словения · 1 центр

• Klinicni center Ljubljana — Ljubljana

Публикации

• Latham BD, Oskin DS, Crouch RD, Vergne MJ, Jackson KD. Cytochromes P450 2C8 and 3A Catalyze the Metabolic Activation of the Tyrosine Kinase Inhibitor Masitinib. Chem Res Toxicol. 2022 Sep 19;35(9):1467-1481. doi: 10.1021/acs.chemrestox.2c00057. Epub 2022 Sep 1. PMID 36048877

Идентификаторы

NCT: NCT03127267 · AB19001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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