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

• ClinicalTrials.gov Identifier: NCT03127267
• Recruitment Status: Recruiting
• First Posted: April 25, 2017
• Last Update Posted: November 12, 2020
• Sponsor: AB Science
• Information provided by (Responsible Party): AB Science

Tracking Information

• First Submitted Date: April 13, 2017
• First Posted Date: April 25, 2017
• Last Update Posted Date: November 12, 2020
• Actual Study Start Date: October 1, 2020
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 7, 2018)

ALSFRS-R [ Time Frame: 48 weeks ]

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

Original Primary Outcome Measures (submitted: April 20, 2017)

Absolute change from baseline to week 48 in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised. [ Time Frame: Week 48 ]

Revised-ALS Functional Rating Score

Current Secondary Outcome Measures (submitted: December 7, 2018)

• ALSAQ-40 [ Time Frame: 48 weeks ]
  Change in ALS quality of life patient questionnaire (ALSAQ-40)
• PFS [ Time Frame: 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 [ Time Frame: 48 weeks ]
  Change in Forced Vital Capacity (FVC)
• HHD [ Time Frame: 48 weeks ]
  Change in evaluation of upper- and lower-limb muscle strength using hand-held dynamometry (HHD)

Original Secondary Outcome Measures (submitted: April 20, 2017)

Change in ALSAQ-40 from baseline to week 48 [ Time Frame: Week 48 ]

ALS quality of life patient questionnaire

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
• Official Title: A Prospective, Multicenter, Randomised, Double-blind, Placebo-controlled, Parallel Groups, 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)
• 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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis

Intervention

• Drug: Masitinib (6.0)
  Masitinib (titration to 6.0 mg/kg/day)
  Other Name: AB1010
• Drug: Riluzole
  Riluzole 50 mg tablet, treatment per os
  Other Name: Rilutek
• Drug: Placebo
  treatment per os
  Other Name: Placebo Oral Tablet
• Drug: Masitinib (4.5)
  Masitinib (titration to 4.5 mg/kg/day)
  Other Name: AB1010

Study Arms

• Experimental: Masitinib (4.5) & 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
  Interventions:

  • Drug: Riluzole
  • Drug: Masitinib (4.5)
• Experimental: Masitinib (6.0) & 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.
  Interventions:

  • Drug: Masitinib (6.0)
  • Drug: Riluzole
• Placebo Comparator: Placebo & Riluzole
  Participants receive a matched dose placebo, given orally twice daily, in combination with riluzole at 50 mg b.i.d.
  Interventions:

  • Drug: Riluzole
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 7, 2018): 495
• Original Estimated Enrollment (submitted: April 20, 2017): 406
• Estimated Study Completion Date: December 2022
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 81 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Study Coordinator; +33(0)147200014; clinical@ab-science.com

• Listed Location Countries: Germany, United States
• Removed Location Countries: Canada

Administrative Information

• NCT Number: NCT03127267
• Other Study ID Numbers: AB19001
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: AB Science
• Study Sponsor: AB Science
• Collaborators: Not Provided

Investigators

• Principal Investigator: Albert Ludolph, MD, PhD; Department of Neurology, University of Ulm, Germany

• PRS Account: AB Science
• Verification Date: November 2020