Study to Investigate the Efficacy and Safety of FAB122 (Daily Oral Edaravone) in Patients With Amyotrophic Lateral Sclerosis
- Registration Number
- NCT05178810
- Lead Sponsor
- Ferrer Internacional S.A.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 300
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Age 18 - 80 years (both inclusive), male or female;
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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;
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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
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Speech/swallowing difficulties
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Respiratory symptoms: dyspnea was noticed
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SVC equal to or more than 70% of the predicted normal value for gender, height and age at screening visit;
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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;
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Capable of providing informed consent and complying with trial procedures.
Main
- 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;
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FAB122 FAB122 - Placebo Placebo -
- Primary Outcome Measures
Name Time Method Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score After 48 Weeks. 48 weeks Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), Maximum value is 48 points and represents better outcome. Minimum value is 0 and represents worse outcome.
- Secondary Outcome Measures
Name Time Method Overall Survival: Proportion of Subjects Alive (Survival Rate) After 24, 48 and 72* Weeks; 24, 48 and 72* weeks; 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 24, 48 and 72* weeks Change From Baseline in Slow Vital Capacity (SVC, Liters) at 24, 48 and 72* Weeks; 24, 48 and 72* weeks Change From Baseline in the Overall Mega Score for the Hand-held Dynamometer (HHD) at 24, 48 and 72* Weeks. 24, 48 and 72* weeks HHD is a procedure for quantitative strength testing performed in the upper and lower extremities bilaterally. The overall mega score are derived as z-scores of average muscle HHD assessments, percent changes from Baseline are used to derive individual muscle scores.
Muscle strength is expressed as the percent change from baseline: (post-baselinevalue-baselinevalue)/baselinevalue×100(post-baseline value - baseline value) / baseline value \\times 100(post-baselinevalue-baselinevalue)/baselinevalue×100. If the baseline value is zero, the data is considered missing.
The HDD mega-score averages strength across four muscle locations. It is calculated by averaging the non-missing transformed values. Maximum muscle strength is then standardized using a z-score, based on data from a healthy population.
Z-score of 0 represents the healthy population mean. Negative z-score value means worse outcome.Change From Baseline in the Total Score on the ALS Assessment Questionnaire-40-Item (ALSAQ-40) Form at 24, 48 and 72* Weeks; 24, 48 and 72* weeks ALS Assessment Questionnaire-40-Item. The ALSAQ-40 is specifically used to measure the subjective wellbeing of patients with ALS. There are 40 items/questions in the long form, the ALSAQ-40, with 5 discrete scales: physical mobility (10 items), activities of daily living and independence (10 items), eating and drinking (3 items), communication (7 items), and emotional reactions (10 items). Range is from 0 to 100 scale, where 0 indicates the best quality of life and 100 the worst.
Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. 24, 48 and 72* weeks European Quality of Life 5 levels and 5 dimensions is a generic questionnaire of health-related quality of life.
5 Domains: Mobility, Self-care, Usual activities, Pain/Discomfort and Anxiety/Depression.
Scale range is from 0 to 100, being 0 the worst and 100 the best.Change From Baseline in Visual Analogue Scale (VAS) Score at 24, 48 and 72* Weeks. 24, 48 and 72* weeks The Health-Related Quality of Life (HR-QoL) is a questionnaire using a Visual Analog Scale (VAS) ranging from 0 (bad) to 100 (very good).
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; 72 weeks The ECAS (Edinburgh Cognitive and behavioural ALS Screen) is a brief multidomain assessment originally designed for people with ALS.
Total Score Range: 0 to 136 points. Higher scores indicate better cognitive function.
For ALS-Specific (Assesses cognitive domains most often affected in ALS) Score Range: 0 to 100 points. Higher scores indicate better cognitive function.
And ALS Non-Specific (Evaluates broader cognitive abilities unrelated to ALS pathology) Score Range: 0 to 36 points. Higher scores indicate better cognitive function.Combined Assessment of Function and Survival (CAFS) at 48 and 72 Weeks. 48 weeks and 72 weeks The CAFS (Combined assessment of function and survival) combined information on survival time and ALSFRS-R (ALS Functional Rating Scale-Revised) scores. For this endpoint, each subject's outcome was ranked: the worst subject outcomes received the lowest rank numbers such that a higher CAFS score indicates a better outcome.
CAFS rankings are computed using:
Survival data: Patients who die earlier are ranked lower than those who survive longer.
ALSFRS-R scores: For patients with the same survival duration, ranks are determined by their functional decline (change in ALSFRS-R from baseline).
For this study the range could go from 1 to 302. Better Outcome: Higher CAFS rank, indicating prolonged survival and/or less functional decline.
Worse Outcome: Lower CAFS rank, indicating shorter survival and/or greater functional decline.Survival Probability 72 weeks Results are based on the overall survival over 72 weeks of treatment, the result is the survival probability estimated over 72 weeks.
Survival probability is calculated considering time to death, tracheostomy or initiation of non-invasive ventilation for more than 20 hours a day for more than 10 consecutive days, over 72 weeks.Change From Baseline in ALSFRS-R Score After 24 and 72* Weeks 24 weeks, 72 weeks Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), Maximum value is 48 points and represents better outcome. Minimum value is 0 and represents worse outcome.
The Slope of the Decrease in ALSFRS-R Score Over Time at 24, 48 and 72* Weeks; 24, 48, 72 weeks Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), Maximum value is 48 points and represents better outcome. Minimum value is 0 and represents worse outcome.
For this outcome, measures on the ALSFRS-R were used to determine the slope of the decrease.Change From Baseline in ALSFRS-R Score on Bulbar Function (Question 1-3 of the ALSFRS-R) After 24, 48 and 72* Weeks; 24, 48 and 72 weeks Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), Maximum value is 48 points and represents better outcome. Minimum value is 0 and represents worse outcome.
In this outcome, the Bulbar function (as part of ALSFRS-R) is evaluated, it is related to Speech, Salivation and Swallowing. The maximum score on Bulbar function is 12, and the minimum is 0. Higher score better outcome.Change From Baseline ALS Functional Rating Scale - Revised Score - Fine Motor Function 24, 48 and 72 weeks Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), Maximum value is 48 points and represents better outcome. Minimum value is 0 and represents worse outcome.
In this outcome, the fine motor function (as part of ALSFRS-R) is evaluated, it is related to Handwriting, Eating and Cutting food, Dressing and hygiene. The maximum score on fine motor function is 12, and the minimum is 0. Higher score better outcome.Change From Baseline ALS Functional Rating Scale - Revised Score - Gross Motor Function 24, 48, 72 weeks Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), Maximum value is 48 points and represents better outcome. Minimum value is 0 and represents worse outcome.
In this outcome, the gross motor function (as part of ALSFRS-R) is evaluated, it is related to Climbing stairs, Walking, Rising from a chair. The maximum score on gross motor function is 12, and the minimum is 0. Higher score better outcome.Change From Baseline ALS Functional Rating Scale - Revised Score - Respiratory Function 24, 48, 72 weeks Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), Maximum value is 48 points and represents better outcome. Minimum value is 0 and represents worse outcome.
In this outcome, the respiratory function (as part of ALSFRS-R) is evaluated, it is related to Dyspnea, Orthopnea, Breathing insufficiency. The maximum score on respiratory function is 12, and the minimum is 0. Higher score better outcome.Time to a 3, 6, 9 and 12 Points Change or Death From Baseline in ALSFRS-R Score Over 72* Weeks; 72 weeks (+/-1 week visit window) Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), Maximum value is 48 points and represents better outcome. Minimum value is 0 and represents worse outcome.
For this outcome, the time a 3, 6, 9 and 12 points change or death from baseline in ALSFRS-R.Change in Clinical Staging (King's Staging System and MiToS) Over 72 Weeks 72 weeks The King's staging system is a simple clinical staging system, which defines 4 stages of ALS. The 1st 3 stages are defined by functional involvement of a region: bulbar, upper limbs, and lower limbs. The number of regions involved gives the stage. Stage 4 is reached if swallowing (4A) or respiratory (4B) difficulty is severe enough to require intervention.
The outcome of this measure shows the number of patients which staging decline of 1 point or more or No decline.
Trial Locations
- Locations (38)
UMC Utrecht
🇳🇱Utrecht, Netherlands
CHU Nice
🇫🇷Nice, France
Hôpital de la Salpêtrière
🇫🇷Paris, France
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
University Hospitals Leuven
🇧🇪Leuven, Belgium
CHU de Limoges - Hôpital Dupuytren
🇫🇷Limoges, France
University of Padua - Azienda Ospedaliera di Padova
🇮🇹Padua, Italy
Azienda Ospedaliera Universitaria Cagliari
🇮🇹Cagliari, Italy
Centro Clinico NEMO
🇮🇹Milan, Italy
University of Milan Medical School
🇮🇹Milan, Italy
CHRU de Lille - Hôpital Roger Salengro
🇫🇷Lille, France
Centre Hospitalo-Universitaire La Timone
🇫🇷Marseille, France
CHU de Montpellier
🇫🇷Montpellier, France
CHRU de Tours
🇫🇷Tours, France
Hannover Medical School
🇩🇪Hannover, Germany
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Trinity College Dublin/Beaumont Hospital
🇮🇪Dublin, Ireland
University of Torino - Rita Levi Montalcini Department of Neuroscience
🇮🇹Milan, Italy
Azienda Ospedaliero Universitaria Di Modena
🇮🇹Modena, Italy
Centrum Medyczne Neuromed
🇵🇱Bydgoszcz, Poland
Azienda Ospedaliera Universitaria ( A O U ) dell'Università degli studi della Campania "Luigi Vanvitelli"
🇮🇹Napoli, Italy
Linden Medical Centre
🇵🇱Kraków, Poland
Centro Hospitalar Universitário Lisboa-Norte
🇵🇹Lisboa, Portugal
City Clinic SP. z o. o.
🇵🇱Warsaw, Poland
Hospital Universitario de Basurto
🇪🇸Bilbao, Spain
Hospital Universitario La Paz-Carlos III
🇪🇸Madrid, Spain
Hospital Regional Universitario Málaga
🇪🇸Málaga, Spain
Hospital Clínico Universitario de Santiago de Compostela
🇪🇸Santiago De Compostela, Spain
Hospital Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario y Politécnico La Fe
🇪🇸Valencia, Spain
King's College London
🇬🇧London, United Kingdom
Karolinska Institutet
🇸🇪Estocolmo, Sweden
Manchester MND care centre
🇬🇧Manchester, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
🇬🇧Sheffield, United Kingdom
Hospital San Rafael
🇪🇸Madrid, Spain