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

Primary Purpose

Amyotrophic Lateral Sclerosis

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Masitinib (6.0)
Riluzole
Placebo
Masitinib (4.5)
Sponsored by
AB Science
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring Amyotrophic Lateral Sclerosis, ALS, Tyrosine kinase inhibitor, Lou Gehrig's disease, Charcot's disease, Motor Neuron disease, MND

Eligibility Criteria

18 Years - 81 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at BirminghamRecruiting
  • University of Southern CaliforniaRecruiting
  • University of KentuckyRecruiting
  • Johns Hopkins Medicine Brain Science InstituteRecruiting
  • Lahey Hospital and Medical CenterRecruiting
  • University of Virginia Health SystemRecruiting
  • University Hospital Leuven (UZ Leuven)Recruiting
  • Bispebjerg HospitalRecruiting
  • CHU de AngersRecruiting
  • Groupe Hospitalier Pellegrin TripodeRecruiting
  • Hôpital neurologique Pierre WertheimerRecruiting
  • CHU Gabriel MontpiedRecruiting
  • CHU de Lille - Hopital Roger SalengroRecruiting
  • CHU de Limoges - Hôpital DupuytrenRecruiting
  • CHU de Marseille - Hôpital de la TimoneRecruiting
  • CHRU de Montpellier - Gui de ChauliacRecruiting
  • CHU de Nancy - Hopital CentralRecruiting
  • CHU Hôpital Pasteur NiceRecruiting
  • CHRU de Tours - Hopital BretonneauRecruiting
  • Department of Neurology, University of Ulm
  • Athens Naval HospitalRecruiting
  • Eginition HospitalRecruiting
  • University General Hospital of LarissaRecruiting
  • General University Hospital of PatrasRecruiting
  • Hadassah University HospitalRecruiting
  • Tel-Aviv Medical Center Hôpital Sourasky (ICHILOV)Recruiting
  • Ospedale Civile Sant'Agostino - EstenseRecruiting
  • ASST degli Spedali Civili di BresciaRecruiting
  • Centro Clinico NeMO Fondazione Serena OnlusRecruiting
  • Clinico Nemo Center (Centro Clinico NeMO Milano)Recruiting
  • IRCCS Istituto Auxologico ItalianoRecruiting
  • Istituti Clinici Scientifici Maugeri IRCCSRecruiting
  • San Raffaele Hospital (Ospedale San Raffaele)Recruiting
  • University Hospital Maggiore della CaritaRecruiting
  • Azienda Ospedale-Università PadovaRecruiting
  • IRCCS Mondino FoundationRecruiting
  • University Hospital in Turin (Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino)Recruiting
  • Oslo University Hospital HF UllevålRecruiting
  • Centrum Medyczne NeuromedRecruiting
  • Hospital de Santa MariaRecruiting
  • Moscow city clinical Hospital after V.M. BuyanovRecruiting
  • Scientific Practical Medical Center "Innovation and Health"Recruiting
  • Clinical Centre of SerbiaRecruiting
  • Klinicni center LjubljanaRecruiting
  • Hospital General Universitario de AlicanteRecruiting
  • Hospital Universitari de BellvitgeRecruiting
  • Hospital Carlos IIIRecruiting
  • Hospital San RafaelRecruiting
  • Clinical Hospital Santiago de CompostelaRecruiting
  • Hospital Universitario y Politecnico La FeRecruiting
  • Centralsjukhuset Karlstad (Central Hospital Karlstad)Recruiting
  • Skåne University HospitalRecruiting
  • Norrlands universitetssjukhusRecruiting
  • The State Institution of Neurology, Psychiatry and Narcology of NAMS of UkraineRecruiting
  • Medical Center of LLC Medical Center Dopomoga PlusRecruiting
  • Communal Non-Profit Enterprise of Lviv Regional Council, Lviv Regional Clinical Hospital, Neurological DepartmentRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Masitinib (4.5) & Riluzole

Masitinib (6.0) & Riluzole

Placebo & Riluzole

Arm Description

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

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.

Participants receive a matched dose placebo, given orally twice daily, in combination with riluzole at 50 mg b.i.d.

Outcomes

Primary Outcome Measures

ALSFRS-R
Change in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised.

Secondary Outcome Measures

ALSAQ-40
Change in ALS quality of life patient questionnaire (ALSAQ-40)
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
FVC
Change in Forced Vital Capacity (FVC)
HHD
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
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.

Full Information

First Posted
April 13, 2017
Last Updated
April 14, 2023
Sponsor
AB Science
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1. Study Identification

Unique Protocol Identification Number
NCT03127267
Brief Title
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

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 2, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AB Science

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
Amyotrophic Lateral Sclerosis, ALS, Tyrosine kinase inhibitor, Lou Gehrig's disease, Charcot's disease, Motor Neuron disease, MND

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
495 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Masitinib (4.5) & Riluzole
Arm Type
Experimental
Arm Description
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
Arm Title
Masitinib (6.0) & Riluzole
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo & Riluzole
Arm Type
Placebo Comparator
Arm Description
Participants receive a matched dose placebo, given orally twice daily, in combination with riluzole at 50 mg b.i.d.
Intervention Type
Drug
Intervention Name(s)
Masitinib (6.0)
Other Intervention Name(s)
AB1010
Intervention Description
Masitinib (titration to 6.0 mg/kg/day)
Intervention Type
Drug
Intervention Name(s)
Riluzole
Other Intervention Name(s)
Rilutek
Intervention Description
Riluzole 50 mg tablet, treatment per os
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo Oral Tablet
Intervention Description
treatment per os
Intervention Type
Drug
Intervention Name(s)
Masitinib (4.5)
Other Intervention Name(s)
AB1010
Intervention Description
Masitinib (titration to 4.5 mg/kg/day)
Primary Outcome Measure Information:
Title
ALSFRS-R
Description
Change in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised.
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
ALSAQ-40
Description
Change in ALS quality of life patient questionnaire (ALSAQ-40)
Time Frame
48 weeks
Title
PFS
Description
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
Time Frame
From day of randomization to disease progression or death, assessed for a maximum of 36 months
Title
FVC
Description
Change in Forced Vital Capacity (FVC)
Time Frame
48 weeks
Title
HHD
Description
Change in evaluation of upper- and lower-limb muscle strength using hand-held dynamometry (HHD)
Time Frame
48 weeks
Title
Change in the Combined Assessment of Function and Survival (CAFS) score from baseline to week 48
Description
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.
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
81 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Study Coordinator
Phone
+33(0)147200014
Email
clinical@ab-science.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Albert Ludolph, MD, PhD
Organizational Affiliation
Department of Neurology, University of Ulm, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90007
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40506
Country
United States
Individual Site Status
Recruiting
Facility Name
Johns Hopkins Medicine Brain Science Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Individual Site Status
Recruiting
Facility Name
Lahey Hospital and Medical Center
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Virginia Health System
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Individual Site Status
Recruiting
Facility Name
University Hospital Leuven (UZ Leuven)
City
Leuven
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Bispebjerg Hospital
City
Copenhagen
Country
Denmark
Individual Site Status
Recruiting
Facility Name
CHU de Angers
City
Angers
Country
France
Individual Site Status
Recruiting
Facility Name
Groupe Hospitalier Pellegrin Tripode
City
Bordeaux
Country
France
Individual Site Status
Recruiting
Facility Name
Hôpital neurologique Pierre Wertheimer
City
Bron
Country
France
Individual Site Status
Recruiting
Facility Name
CHU Gabriel Montpied
City
Clermont Ferrand
Country
France
Individual Site Status
Recruiting
Facility Name
CHU de Lille - Hopital Roger Salengro
City
Lille
Country
France
Individual Site Status
Recruiting
Facility Name
CHU de Limoges - Hôpital Dupuytren
City
Limoges
Country
France
Individual Site Status
Recruiting
Facility Name
CHU de Marseille - Hôpital de la Timone
City
Marseille
Country
France
Individual Site Status
Recruiting
Facility Name
CHRU de Montpellier - Gui de Chauliac
City
Montpellier
Country
France
Individual Site Status
Recruiting
Facility Name
CHU de Nancy - Hopital Central
City
Nancy
Country
France
Individual Site Status
Recruiting
Facility Name
CHU Hôpital Pasteur Nice
City
Nice
Country
France
Individual Site Status
Recruiting
Facility Name
CHRU de Tours - Hopital Bretonneau
City
Tours
Country
France
Individual Site Status
Recruiting
Facility Name
Department of Neurology, University of Ulm
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Athens Naval Hospital
City
Athens
Country
Greece
Individual Site Status
Recruiting
Facility Name
Eginition Hospital
City
Athens
Country
Greece
Individual Site Status
Recruiting
Facility Name
University General Hospital of Larissa
City
Larissa
Country
Greece
Individual Site Status
Recruiting
Facility Name
General University Hospital of Patras
City
Río
Country
Greece
Individual Site Status
Recruiting
Facility Name
Hadassah University Hospital
City
Jerusalem
Country
Israel
Individual Site Status
Recruiting
Facility Name
Tel-Aviv Medical Center Hôpital Sourasky (ICHILOV)
City
Tel Aviv
Country
Israel
Individual Site Status
Recruiting
Facility Name
Ospedale Civile Sant'Agostino - Estense
City
Baggiovara
State/Province
Modena
Country
Italy
Individual Site Status
Recruiting
Facility Name
ASST degli Spedali Civili di Brescia
City
Brescia
Country
Italy
Individual Site Status
Recruiting
Facility Name
Centro Clinico NeMO Fondazione Serena Onlus
City
Gussago
Country
Italy
Individual Site Status
Recruiting
Facility Name
Clinico Nemo Center (Centro Clinico NeMO Milano)
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Name
IRCCS Istituto Auxologico Italiano
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Name
Istituti Clinici Scientifici Maugeri IRCCS
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Name
San Raffaele Hospital (Ospedale San Raffaele)
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Name
University Hospital Maggiore della Carita
City
Novara
Country
Italy
Individual Site Status
Recruiting
Facility Name
Azienda Ospedale-Università Padova
City
Padova
Country
Italy
Individual Site Status
Recruiting
Facility Name
IRCCS Mondino Foundation
City
Pavia
Country
Italy
Individual Site Status
Recruiting
Facility Name
University Hospital in Turin (Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino)
City
Torino
Country
Italy
Individual Site Status
Recruiting
Facility Name
Oslo University Hospital HF Ullevål
City
Oslo
Country
Norway
Individual Site Status
Recruiting
Facility Name
Centrum Medyczne Neuromed
City
Bydgoszcz
Country
Poland
Individual Site Status
Recruiting
Facility Name
Hospital de Santa Maria
City
Lisboa
Country
Portugal
Individual Site Status
Recruiting
Facility Name
Moscow city clinical Hospital after V.M. Buyanov
City
Moscow
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Scientific Practical Medical Center "Innovation and Health"
City
Novosibirsk
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Clinical Centre of Serbia
City
Belgrad
Country
Serbia
Individual Site Status
Recruiting
Facility Name
Klinicni center Ljubljana
City
Ljubljana
Country
Slovenia
Individual Site Status
Recruiting
Facility Name
Hospital General Universitario de Alicante
City
Alicante
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitari de Bellvitge
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Carlos III
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital San Rafael
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Name
Clinical Hospital Santiago de Compostela
City
Santiago De Compostela
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario y Politecnico La Fe
City
Valencia
Country
Spain
Individual Site Status
Recruiting
Facility Name
Centralsjukhuset Karlstad (Central Hospital Karlstad)
City
Karlstad
Country
Sweden
Individual Site Status
Recruiting
Facility Name
Skåne University Hospital
City
Malmö
Country
Sweden
Individual Site Status
Recruiting
Facility Name
Norrlands universitetssjukhus
City
Umeå
Country
Sweden
Individual Site Status
Recruiting
Facility Name
The State Institution of Neurology, Psychiatry and Narcology of NAMS of Ukraine
City
Kharkiv
Country
Ukraine
Individual Site Status
Recruiting
Facility Name
Medical Center of LLC Medical Center Dopomoga Plus
City
Kyiv
Country
Ukraine
Individual Site Status
Recruiting
Facility Name
Communal Non-Profit Enterprise of Lviv Regional Council, Lviv Regional Clinical Hospital, Neurological Department
City
Lviv
Country
Ukraine
Individual Site Status
Recruiting

12. IPD Sharing Statement

Citations:
PubMed Identifier
36048877
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.
Results Reference
derived

Learn more about this trial

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

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