Clinical trial NCT03127267: Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Amyotrophic Lateral Sclerosis
ALS
Tyrosine kinase inhibitor
Lou Gehrig's disease
Charcot's disease
Motor Neuron disease
MND
Lead sponsor: AB Science
Sponsor class: INDUSTRY
First posted: 2017-04-25
Enrollment: 495
Sex: ALL
Minimum age (years): 18
Maximum age (years): 81
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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).

Eligibility criteria: 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

Primary outcomes:
measure: ALSFRS-R
timeFrame: 48 weeks
Secondary outcomes:
measure: ALSAQ-40
timeFrame: 48 weeks
measure: PFS
timeFrame: From day of randomization to disease progression or death, assessed for a maximum of 36 months
measure: FVC
timeFrame: 48 weeks
measure: HHD
timeFrame: 48 weeks
measure: Change in the Combined Assessment of Function and Survival (CAFS) score from baseline to week 48
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Medicine Brain Science Institute
state: Maryland
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Leuven
country: Belgium
facility: University Hospital Leuven (UZ Leuven)
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Angers
country: France
facility: CHU de Angers
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin Tripode
city: Bron
country: France
facility: Hôpital neurologique Pierre Wertheimer
city: Clermont Ferrand
country: France
facility: CHU Gabriel Montpied
city: Lille
country: France
facility: CHU de Lille - Hopital Roger Salengro
city: Limoges
country: France
facility: CHU de Limoges - Hôpital Dupuytren
city: Marseille
country: France
facility: CHU de Marseille - Hôpital de la Timone
city: Montpellier
country: France
facility: CHRU de Montpellier - Gui de Chauliac
city: Nancy
country: France
facility: CHU de Nancy - Hopital Central
city: Nice
country: France
facility: CHU Hôpital Pasteur Nice
city: Tours
country: France
facility: CHRU de Tours - Hopital Bretonneau
city: Ulm
country: Germany
facility: Department of Neurology, University of Ulm
city: Athens
country: Greece
facility: Athens Naval Hospital
city: Athens
country: Greece
facility: Eginition Hospital
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Río
country: Greece
facility: General University Hospital of Patras
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Tel Aviv
country: Israel
facility: Tel-Aviv Medical Center Hôpital Sourasky (ICHILOV)
city: Baggiovara
country: Italy
facility: Ospedale Civile Sant'Agostino - Estense
state: Modena
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia
city: Gussago
country: Italy
facility: Centro Clinico NeMO Fondazione Serena Onlus
city: Milano
country: Italy
facility: Clinico Nemo Center (Centro Clinico NeMO Milano)
city: Milano
country: Italy
facility: IRCCS Istituto Auxologico Italiano
city: Milano
country: Italy
facility: Istituti Clinici Scientifici Maugeri IRCCS
city: Milano
country: Italy
facility: San Raffaele Hospital (Ospedale San Raffaele)
city: Novara
country: Italy
facility: University Hospital Maggiore della Carita
city: Padova
country: Italy
facility: Azienda Ospedale-Università Padova
city: Pavia
country: Italy
facility: IRCCS Mondino Foundation
city: Torino
country: Italy
facility: University Hospital in Turin (Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino)
city: Oslo
country: Norway
facility: Oslo University Hospital HF Ullevål
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Neuromed
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria
city: Moscow
country: Russian Federation
facility: Moscow city clinical Hospital after V.M. Buyanov
city: Novosibirsk
country: Russian Federation
facility: Scientific Practical Medical Center "Innovation and Health"
city: Belgrad
country: Serbia
facility: Clinical Centre of Serbia
city: Ljubljana
country: Slovenia
facility: Klinicni center Ljubljana
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Madrid
country: Spain
facility: Hospital Carlos III
city: Madrid
country: Spain
facility: Hospital San Rafael
city: Santiago De Compostela
country: Spain
facility: Clinical Hospital Santiago de Compostela
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Karlstad
country: Sweden
facility: Centralsjukhuset Karlstad (Central Hospital Karlstad)
city: Malmö
country: Sweden
facility: Skåne University Hospital
city: Umeå
country: Sweden
facility: Norrlands universitetssjukhus
city: Kharkiv
country: Ukraine
facility: The State Institution of Neurology, Psychiatry and Narcology of NAMS of Ukraine
city: Kyiv
country: Ukraine
facility: Medical Center of LLC Medical Center Dopomoga Plus
city: Lviv
country: Ukraine
facility: Communal Non-Profit Enterprise of Lviv Regional Council, Lviv Regional Clinical Hospital, Neurological Department
Study officials:
affiliation: Department of Neurology, University of Ulm, Germany
name: Albert Ludolph, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.