Masitinib in Combination With Riluzole for the Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS)

• ClinicalTrials.gov Identifier: NCT02588677
• Recruitment Status: Completed
• First Posted: October 28, 2015
• Last Update Posted: December 17, 2018
• Sponsor: AB Science
• Information provided by (Responsible Party): AB Science

Tracking Information

• First Submitted Date: October 20, 2015
• First Posted Date: October 28, 2015
• Last Update Posted Date: December 17, 2018
• Study Start Date: April 2013
• Actual Primary Completion Date: December 5, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 4, 2018)

Change in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised [ Time Frame: From baseline to week 48 ]

The amyotrophic lateral sclerosis functional rating scale (ALSFRS), which is a Validated instrument that assesses the functional status and the disease progression in patients with amyotrophic lateral sclerosis (ALS)

• Original Primary Outcome Measures (submitted: October 27, 2015): Change from baseline to week 48 in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised [ Time Frame: from baseline to week 48 ]

Current Secondary Outcome Measures (submitted: November 27, 2018)

• Change of Forced Vital Capacity (FVC) [ Time Frame: From baseline to week 48 ]
  Forced vital capacity (FVC) measures the volume of air expelled from the lungs during a quick, forceful breath.
• Progression Free Survival [ Time Frame: Time from the randomization date until the earliest date for a decline of more than 9-points in ALSFRS-R score, asssesd over a maximum of 60 months ]
  Progression Free Survival is defined as the time from the randomization date until the earliest date for a decline of more than 9-points in ALSFRS-R score
• Overall Survival [ Time Frame: Time from the randomization date until death, asssesd over a maximum of 60 months ]
  Overall survival is defined as time in months from the randomization date to the date of death due to any cause.

Original Secondary Outcome Measures (submitted: October 27, 2015)

• Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised [ Time Frame: up to 48 weeks ]
• Overall survival (OS) [ Time Frame: up to 48 weeks ]
• Forced vital capacity (FVC) [ Time Frame: Up to 48 weeks ]
• Quality of life [ Time Frame: Up to 48 weeks ]
• Safety profile [ Time Frame: Up to 48 weeks ]

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

Descriptive Information

• Brief Title: Masitinib in Combination With Riluzole for the Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS)
• Official Title: Multicenter, Randomised, Double-blind, Placebo-controlled, Parallel Group, Phase 2/3 Study to Compare the Efficacy and Safety of Masitinib
• Brief Summary: The objective is to compare the efficacy and safety of masitinib in combination with riluzole in the treatment of patients suffering from Amyotrophic Lateral Sclerosis (ALS).

Detailed Description

Masitinib is novel tyrosine kinase inhibitor that targets microglia and mast cells through inhibiting a limited number of kinases. Masitinib blocks microglia proliferation and activation, and mast cell-mediated degranulation, the release of cytotoxic substances that might further damage the motor nerves.

There are two distinct populations of ALS patients: population of "Normal progressors" and population of "Faster progressors". Targeted population for primary analysis is population of "Normal progressors".

"Normal progressors" are ALS patients whose progression of ALSFRS-R score before randomization is less than 1.1 point per month.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis (ALS)

Intervention

• Drug: Masitinib (4.5)
  4.5 mg/kg/day
  Other Name: AB1010
• Drug: Riluzole
  Other Name: Rilutek
• Drug: Placebo
  Other Name: Placebo Oral Tablet
• Drug: Masitinib (3.0)
  3 mg/kg/day
  Other Name: AB1010

Study Arms

• Experimental: Masitinib (3.0) & Riluzole
  masitinib 3 mg/kg/day + riluzole
  Interventions:

  • Drug: Riluzole
  • Drug: Masitinib (3.0)
• Experimental: Masitinib (4.5) & Riluzole
  masitinib 4.5 mg/kg/day (2) + riluzole
  Interventions:

  • Drug: Masitinib (4.5)
  • Drug: Riluzole
• Placebo Comparator: Placebo & Riluzole
  Matched placebo
  Interventions:

  • Drug: Riluzole
  • Drug: Placebo

• Publications *: Mora JS, Bradley WG, Chaverri D, Hernandez-Barral M, Mascias J, Gamez J, Gargiulo-Monachelli GM, Moussy A, Mansfield CD, Hermine O, Ludolph AC. Long-term survival analysis of masitinib in amyotrophic lateral sclerosis. Ther Adv Neurol Disord. 2021 Jul 19;14:17562864211030365. doi: 10.1177/17562864211030365. eCollection 2021.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 20, 2017): 394
• Original Estimated Enrollment (submitted: October 27, 2015): 381
• Actual Study Completion Date: March 2018
• Actual Primary Completion Date: December 5, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Main inclusion criteria:

1. Familial or sporadic ALS
2. Patient diagnosed with probable of definite ALS
3. Patient treated with a stable dose of riluzole (100 mg/day) for at least 30 days prior to screening

Exclusion Criteria:

1. Patient who underwent tracheostomy and/or gastrostomy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT02588677
• Other Study ID Numbers: AB10015
• Has Data Monitoring Committee: Yes

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: Not Provided
• Current Responsible Party: AB Science
• Original Responsible Party: Same as current
• Current Study Sponsor: AB Science
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jesus S Mora, MD; Unidad de ELA, Hospital San Rafael, c/ Serrano, 199, 28016 Madrid, Spain

• PRS Account: AB Science
• Verification Date: December 2018