Clinical trial NCT05178810: Study to Investigate the Efficacy and Safety of FAB122 (Daily Oral Edaravone) in Patients With Amyotrophic Lateral Sclerosis
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of FAB122 in Patients With Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: Ferrer Internacional S.A.
Sponsor class: INDUSTRY
Collaborators: name: Julius Clinical
name: Stichting TRICALS Foundation
First posted: 2022-01-05
Enrollment: 313
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Multicenter, multinational, double-blind, randomized (2:1), placebo-controlled Phase III study to investigate the efficacy and safety of 100 mg FAB122 once daily as oral formulation in ALS patients.


Eligibility criteria: Main Inclusion Criteria:

* Age 18 - 80 years (both inclusive), male or female;
* Diagnosis of definite, probable, probable laboratory supported or possible ALS as based on the El Escorial and the revised Airlie House diagnostic criteria for ALS;
* Onset of first symptoms\* no longer than 24 months prior to randomization;

  \*Date of onset is the date the patient reported one or more of the following symptoms:
* Muscle weakness in limbs
* Speech/swallowing difficulties
* Respiratory symptoms: dyspnea was noticed
* SVC equal to or more than 70% of the predicted normal value for gender, height and age at screening visit;
* Change in ALSFRS-R score between 0.35 points and 1.5 points per month (both inclusive) in the period from onset of first symptoms to the Screening visit;
* Capable of providing informed consent and complying with trial procedures.

Main Exclusion Criteria:

* Diagnosis of Primary Lateral Sclerosis;
* Diagnosis of Frontotemporal Dementia;
* Diagnosis of other neurodegenerative diseases (e.g. Parkinson disease, Alzheimer disease);
* Diagnosis of polyneuropathy;
* Other causes of neuromuscular weakness;
* Have a significant pulmonary disorder not attributed to ALS and/or require treatment interfering with the evaluation of ALS on respiratory function;
* Use of intravenous (IV) edaravone within 6 months of the screening visit;
* Depend on mechanical ventilation (invasive or non-invasive) or require tracheostomy at Screening;
* Renal impairment as indicated by a creatinine clearance of less than 50 mL/min as calculated by the Cockcroft Gault equation;
* Subject has a history of clinically significant hepatic disease, hepatitis or biliary tract disease, or subject has a positive screening test for HIV, hepatitis B or C;

Primary outcomes:
measure: Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score After 48 Weeks.
timeFrame: 48 weeks
Secondary outcomes:
measure: Combined Assessment of Function and Survival (CAFS) at 48 and 72 Weeks.
timeFrame: 48 weeks and 72 weeks
measure: Survival Probability
timeFrame: 72 weeks
measure: Change From Baseline in ALSFRS-R Score After 24 and 72* Weeks
timeFrame: 24 weeks, 72 weeks
measure: The Slope of the Decrease in ALSFRS-R Score Over Time at 24, 48 and 72* Weeks;
timeFrame: 24, 48, 72 weeks
measure: Change From Baseline in ALSFRS-R Score on Bulbar Function (Question 1-3 of the ALSFRS-R) After 24, 48 and 72* Weeks;
timeFrame: 24, 48 and 72 weeks
measure: Change From Baseline ALS Functional Rating Scale - Revised Score - Fine Motor Function
timeFrame: 24, 48 and 72 weeks
measure: Change From Baseline ALS Functional Rating Scale - Revised Score - Gross Motor Function
timeFrame: 24, 48, 72 weeks
measure: Change From Baseline ALS Functional Rating Scale - Revised Score - Respiratory Function
timeFrame: 24, 48, 72 weeks
measure: Time to a 3, 6, 9 and 12 Points Change or Death From Baseline in ALSFRS-R Score Over 72* Weeks;
timeFrame: 72 weeks (+/-1 week visit window)
measure: Change in Clinical Staging (King's Staging System and MiToS) Over 72 Weeks
timeFrame: 72 weeks
measure: Overall Survival: Proportion of Subjects Alive (Survival Rate) After 24, 48 and 72* Weeks;
timeFrame: 24, 48 and 72* weeks;
measure: Proportion of Subjects Alive and no Tracheostomy, or no Initiation of Non-invasive Ventilation for More Than 20 Hours a Day for More Than 10 Consecutive Days After 24, 48 and 72* Weeks
timeFrame: 24, 48 and 72* weeks
measure: Change From Baseline in Slow Vital Capacity (SVC, Liters) at 24, 48 and 72* Weeks;
timeFrame: 24, 48 and 72* weeks
measure: Change From Baseline in the Overall Mega Score for the Hand-held Dynamometer (HHD) at 24, 48 and 72* Weeks.
timeFrame: 24, 48 and 72* weeks
measure: Change From Baseline in the Total Score on the ALS Assessment Questionnaire-40-Item (ALSAQ-40) Form at 24, 48 and 72* Weeks;
timeFrame: 24, 48 and 72* weeks
measure: Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks.
timeFrame: 24, 48 and 72* weeks
measure: Change From Baseline in Visual Analogue Scale (VAS) Score at 24, 48 and 72* Weeks.
timeFrame: 24, 48 and 72* weeks
measure: Proportion of Subjects With a Change of ≥8, ≥4, and ≥9 for ALS Specific, ALS Non-Specific, and ECAS (Edinburgh Cognitive and Behavioural ALS Screen) Total Score;
timeFrame: 72 weeks
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Lille
country: France
facility: CHRU de Lille - Hôpital Roger Salengro
city: Limoges
country: France
facility: CHU de Limoges - Hôpital Dupuytren
city: Marseille
country: France
facility: Centre Hospitalo-Universitaire La Timone
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nice
country: France
facility: CHU Nice
city: Paris
country: France
facility: Hôpital de la Salpêtrière
city: Tours
country: France
facility: CHRU de Tours
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Hannover
country: Germany
facility: Hannover Medical School
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Dublin
country: Ireland
facility: Trinity College Dublin/Beaumont Hospital
city: Cagliari
country: Italy
facility: Azienda Ospedaliera Universitaria Cagliari
city: Milan
country: Italy
facility: Centro Clinico NEMO
city: Milan
country: Italy
facility: University of Milan Medical School
city: Milan
country: Italy
facility: University of Torino - Rita Levi Montalcini Department of Neuroscience
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria Di Modena
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria ( A O U ) dell'Università degli studi della Campania "Luigi Vanvitelli"
city: Padua
country: Italy
facility: University of Padua - Azienda Ospedaliera di Padova
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Neuromed
city: Kraków
country: Poland
facility: Linden Medical Centre
city: Warsaw
country: Poland
facility: City Clinic SP. z o. o.
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitário Lisboa-Norte
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Bilbao
country: Spain
facility: Hospital Universitario de Basurto
city: Madrid
country: Spain
facility: Hospital San Rafael
city: Madrid
country: Spain
facility: Hospital Universitario La Paz-Carlos III
city: Málaga
country: Spain
facility: Hospital Regional Universitario Málaga
city: Santiago De Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago de Compostela
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Estocolmo
country: Sweden
facility: Karolinska Institutet
city: London
country: United Kingdom
facility: King's College London
city: Manchester
country: United Kingdom
facility: Manchester MND care centre
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
Study officials:
References: