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

Phase 3

Recruiting

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: Masitinib (6.0); Drug: Riluzole; Drug: Masitinib (4.5); Drug: Placebo

• Registration Number: NCT03127267
• Lead Sponsor: AB Science

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).

Study Timeline

• Study First Submitted: 2017-04-13
• Study First Submitted QC: 2017-04-20
• Study First Posted: 2017-04-25
• Study Start: 2021-02-02
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-14
• Last Update Posted: 2023-04-18
• Primary Completion: 2023-12
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 495

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Masitinib (4.5) & Riluzole	Masitinib (4.5)	Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control. Masitinib will be administered as an add-on to riluzole at 50 mg b.i.d
Placebo & Riluzole	Placebo	Participants receive a matched dose placebo, given orally twice daily, in combination with riluzole at 50 mg b.i.d.
Masitinib (6.0) & Riluzole	Masitinib (6.0)	Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control. Masitinib will be administered as an add-on to riluzole at 50 mg b.i.d.
Masitinib (4.5) & Riluzole	Riluzole	Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control. Masitinib will be administered as an add-on to riluzole at 50 mg b.i.d
Masitinib (6.0) & Riluzole	Riluzole	Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control. Masitinib will be administered as an add-on to riluzole at 50 mg b.i.d.
Placebo & Riluzole	Riluzole	Participants receive a matched dose placebo, given orally twice daily, in combination with riluzole at 50 mg b.i.d.

Primary Outcome Measures

Name	Time	Method
ALSFRS-R	48 weeks	Change in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised.

Secondary Outcome Measures

Name	Time	Method
ALSAQ-40	48 weeks	Change in ALS quality of life patient questionnaire (ALSAQ-40)
PFS	From day of randomization to disease progression or death, assessed for a maximum of 36 months	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
FVC	48 weeks	Change in Forced Vital Capacity (FVC)
HHD	48 weeks	Change in evaluation of upper- and lower-limb muscle strength using hand-held dynamometry (HHD)
Change in the Combined Assessment of Function and Survival (CAFS) score from baseline to week 48	48 weeks	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.

Trial Locations

Locations (56)

Johns Hopkins Medicine Brain Science Institute; 🇺🇸 Baltimore, Maryland, United States

University Hospital Leuven (UZ Leuven); 🇧🇪 Leuven, Belgium

Communal Non-Profit Enterprise of Lviv Regional Council, Lviv Regional Clinical Hospital, Neurological Department; 🇺🇦 Lviv, Ukraine

Moscow city clinical Hospital after V.M. Buyanov; 🇷🇺 Moscow, Russian Federation

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

General University Hospital of Patras; 🇬🇷 Río, Greece

Bispebjerg Hospital; 🇩🇰 Copenhagen, Denmark

Eginition Hospital; 🇬🇷 Athens, Greece

University General Hospital of Larissa; 🇬🇷 Larissa, Greece

Hadassah University Hospital; 🇮🇱 Jerusalem, Israel

Centro Clinico NeMO Fondazione Serena Onlus; 🇮🇹 Gussago, Italy

Hôpital neurologique Pierre Wertheimer; 🇫🇷 Bron, France

CHU de Limoges - Hôpital Dupuytren; 🇫🇷 Limoges, France

Athens Naval Hospital; 🇬🇷 Athens, Greece

CHU Hôpital Pasteur Nice; 🇫🇷 Nice, France

Department of Neurology, University of Ulm; 🇩🇪 Ulm, Germany

Tel-Aviv Medical Center Hôpital Sourasky (ICHILOV); 🇮🇱 Tel Aviv, Israel

Ospedale Civile Sant'Agostino - Estense; 🇮🇹 Baggiovara, Modena, Italy

IRCCS Istituto Auxologico Italiano; 🇮🇹 Milano, Italy

Hospital de Santa Maria; 🇵🇹 Lisboa, Portugal

Clinical Centre of Serbia; 🇷🇸 Belgrad, Serbia

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, Italy

Klinicni center Ljubljana; 🇸🇮 Ljubljana, Slovenia

Clinical Hospital Santiago de Compostela; 🇪🇸 Santiago De Compostela, Spain

Centralsjukhuset Karlstad (Central Hospital Karlstad); 🇸🇪 Karlstad, Sweden

Skåne University Hospital; 🇸🇪 Malmö, Sweden

Medical Center of LLC Medical Center Dopomoga Plus; 🇺🇦 Kyiv, Ukraine

Norrlands universitetssjukhus; 🇸🇪 Umeå, Sweden

CHU Gabriel Montpied; 🇫🇷 Clermont Ferrand, France

CHU de Lille - Hopital Roger Salengro; 🇫🇷 Lille, France

CHRU de Montpellier - Gui de Chauliac; 🇫🇷 Montpellier, France

CHU de Nancy - Hopital Central; 🇫🇷 Nancy, France

CHRU de Tours - Hopital Bretonneau; 🇫🇷 Tours, France

Hospital Carlos III; 🇪🇸 Madrid, Spain

Hospital General Universitario de Alicante; 🇪🇸 Alicante, Spain

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

CHU de Angers; 🇫🇷 Angers, France

Groupe Hospitalier Pellegrin Tripode; 🇫🇷 Bordeaux, France

CHU de Marseille - Hôpital de la Timone; 🇫🇷 Marseille, France

ASST degli Spedali Civili di Brescia; 🇮🇹 Brescia, Italy

Clinico Nemo Center (Centro Clinico NeMO Milano); 🇮🇹 Milano, Italy

Oslo University Hospital HF Ullevål; 🇳🇴 Oslo, Norway

Istituti Clinici Scientifici Maugeri IRCCS; 🇮🇹 Milano, Italy

San Raffaele Hospital (Ospedale San Raffaele); 🇮🇹 Milano, Italy

Centrum Medyczne Neuromed; 🇵🇱 Bydgoszcz, Poland

Scientific Practical Medical Center "Innovation and Health"; 🇷🇺 Novosibirsk, Russian Federation

Hospital Universitario y Politecnico La Fe; 🇪🇸 Valencia, Spain

The State Institution of Neurology, Psychiatry and Narcology of NAMS of Ukraine; 🇺🇦 Kharkiv, Ukraine

Hospital San Rafael; 🇪🇸 Madrid, Spain

Lahey Hospital and Medical Center; 🇺🇸 Burlington, Massachusetts, United States

University of Virginia Health System; 🇺🇸 Charlottesville, Virginia, United States

Hospital Universitari de Bellvitge; 🇪🇸 Barcelona, Spain