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

Amyotrophic Lateral Sclerosis Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03127267
• Other study ID #: AB19001
• Status: Recruiting
• Phase: Phase 3
• Start date: February 2, 2021
• Est. completion date: December 2023

Study information

• Verified date: April 2023
• Source: AB Science
• Contact: Clinical Study Coordinator
• Phone: +33(0)147200014
• Email: clinical[@]ab-science.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 495
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 81 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

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

Locations

Country	Name	City	State
Belgium	University Hospital Leuven (UZ Leuven)	Leuven
Denmark	Bispebjerg Hospital	Copenhagen
France	CHU de Angers	Angers
France	Groupe Hospitalier Pellegrin Tripode	Bordeaux
France	Hôpital neurologique Pierre Wertheimer	Bron
France	CHU Gabriel Montpied	Clermont Ferrand
France	CHU de Lille - Hopital Roger Salengro	Lille
France	CHU de Limoges - Hôpital Dupuytren	Limoges
France	CHU de Marseille - Hôpital de la Timone	Marseille
France	CHRU de Montpellier - Gui de Chauliac	Montpellier
France	CHU de Nancy - Hopital Central	Nancy
France	CHU Hôpital Pasteur Nice	Nice
France	CHRU de Tours - Hopital Bretonneau	Tours
Germany	Department of Neurology, University of Ulm	Ulm
Greece	Athens Naval Hospital	Athens
Greece	Eginition Hospital	Athens
Greece	University General Hospital of Larissa	Larissa
Greece	General University Hospital of Patras	Río
Israel	Hadassah University Hospital	Jerusalem
Israel	Tel-Aviv Medical Center Hôpital Sourasky (ICHILOV)	Tel Aviv
Italy	Ospedale Civile Sant'Agostino - Estense	Baggiovara	Modena
Italy	ASST degli Spedali Civili di Brescia	Brescia
Italy	Centro Clinico NeMO Fondazione Serena Onlus	Gussago
Italy	Clinico Nemo Center (Centro Clinico NeMO Milano)	Milano
Italy	IRCCS Istituto Auxologico Italiano	Milano
Italy	Istituti Clinici Scientifici Maugeri IRCCS	Milano
Italy	San Raffaele Hospital (Ospedale San Raffaele)	Milano
Italy	University Hospital Maggiore della Carita	Novara
Italy	Azienda Ospedale-Università Padova	Padova
Italy	IRCCS Mondino Foundation	Pavia
Italy	University Hospital in Turin (Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino)	Torino
Norway	Oslo University Hospital HF Ullevål	Oslo
Poland	Centrum Medyczne Neuromed	Bydgoszcz
Portugal	Hospital de Santa Maria	Lisboa
Russian Federation	Moscow city clinical Hospital after V.M. Buyanov	Moscow
Russian Federation	Scientific Practical Medical Center "Innovation and Health"	Novosibirsk
Serbia	Clinical Centre of Serbia	Belgrad
Slovenia	Klinicni center Ljubljana	Ljubljana
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Universitari de Bellvitge	Barcelona
Spain	Hospital Carlos III	Madrid
Spain	Hospital San Rafael	Madrid
Spain	Clinical Hospital Santiago de Compostela	Santiago De Compostela
Spain	Hospital Universitario y Politecnico La Fe	Valencia
Sweden	Centralsjukhuset Karlstad (Central Hospital Karlstad)	Karlstad
Sweden	Skåne University Hospital	Malmö
Sweden	Norrlands universitetssjukhus	Umeå
Ukraine	The State Institution of Neurology, Psychiatry and Narcology of NAMS of Ukraine	Kharkiv
Ukraine	Medical Center of LLC Medical Center Dopomoga Plus	Kyiv
Ukraine	Communal Non-Profit Enterprise of Lviv Regional Council, Lviv Regional Clinical Hospital, Neurological Department	Lviv
United States	Johns Hopkins Medicine Brain Science Institute	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	University of Kentucky	Lexington	Kentucky
United States	University of Southern California	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
AB Science

Countries where clinical trial is conducted

United States,  Belgium,  Denmark,  France,  Germany,  Greece,  Israel,  Italy,  Norway,  Poland,  Portugal,  Russian Federation,  Serbia,  Slovenia,  Spain,  Sweden,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ALSFRS-R	Change in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised.	48 weeks
Secondary	ALSAQ-40	Change in ALS quality of life patient questionnaire (ALSAQ-40)	48 weeks
Secondary	PFS	Progression free survival (PFS) is defined as the time from randomization to progression (decline of more than 9 points in ALSFRS-R score from baseline) or death	From day of randomization to disease progression or death, assessed for a maximum of 36 months
Secondary	FVC	Change in Forced Vital Capacity (FVC)	48 weeks
Secondary	HHD	Change in evaluation of upper- and lower-limb muscle strength using hand-held dynamometry (HHD)	48 weeks
Secondary	Change in the Combined Assessment of Function and Survival (CAFS) score from baseline to week 48	CAFS ranks patients' clinical outcomes based on survival time and change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score. Each patient's outcome is compared to every other patient's outcome, assigned a score, and the summed scores are ranked. The mean rank score for each treatment group can then be calculated. A higher mean CAFS score indicates a better group outcome.	48 weeks