Amyotrophic Lateral Sclerosis
Conditions
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.
Interventions
DRUGFAB122
Daily dose 100 mg
DRUGPlacebo
Daily dose
Sponsors
Julius Clinical
Stichting TRICALS Foundation
Ferrer Internacional S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion 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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Belgium, France, Germany, Ireland, Italy, Netherlands, Poland, Portugal, Spain, Sweden, United Kingdom
Participant flow
Recruitment details
From the 313 randomized participants, 9 patients were excluded from the analysis and 2 were randomized by mistake and not treated. So a total of 302 participants are considered in the analysis.
Participants by arm
| Arm | Count |
|---|---|
| FAB122 FAB122: Daily dose 100 mg | 205 |
| Placebo Placebo: Daily dose | 97 |
| Total | 302 |
Baseline characteristics
| Characteristic | FAB122 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 59.3 years STANDARD_DEVIATION 10.5 | 59.3 years STANDARD_DEVIATION 10.3 | 59.3 years STANDARD_DEVIATION 10 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 18 Participants | 24 Participants | 6 Participants |
| Race (NIH/OMB) White | 185 Participants | 275 Participants | 90 Participants |
| Region of Enrollment Europe | 205 participants | 302 participants | 97 participants |
| Sex: Female, Male Female | 82 Participants | 117 Participants | 35 Participants |
| Sex: Female, Male Male | 123 Participants | 185 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 20 / 205 | 7 / 97 |
| other Total, other adverse events | 180 / 205 | 82 / 97 |
| serious Total, serious adverse events | 62 / 205 | 28 / 97 |
Outcome results
Primary
Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score After 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.
Time frame: 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FAB122 | Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score After 48 Weeks. | -11.2 units on a scale | Standard Deviation 7.9 |
| Placebo | Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score After 48 Weeks. | -10.8 units on a scale | Standard Deviation 8.4 |
Secondary
Change From Baseline ALS Functional Rating Scale - Revised Score - Fine Motor Function
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.
Time frame: 24, 48 and 72 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FAB122 | Change From Baseline ALS Functional Rating Scale - Revised Score - Fine Motor Function | -2.0 units on a scale | Standard Deviation 2.1 |
| Placebo | Change From Baseline ALS Functional Rating Scale - Revised Score - Fine Motor Function | -1.7 units on a scale | Standard Deviation 2 |
| FAB122 48 Weeks | Change From Baseline ALS Functional Rating Scale - Revised Score - Fine Motor Function | -3.8 units on a scale | Standard Deviation 2.9 |
| Placebo 48 Weeks | Change From Baseline ALS Functional Rating Scale - Revised Score - Fine Motor Function | -3.3 units on a scale | Standard Deviation 2.5 |
| FAB122 100mg 72 Weeks | Change From Baseline ALS Functional Rating Scale - Revised Score - Fine Motor Function | -4.7 units on a scale | Standard Deviation 3.1 |
| Placebo 72 Weeks | Change From Baseline ALS Functional Rating Scale - Revised Score - Fine Motor Function | -4.2 units on a scale | Standard Deviation 3.3 |
Secondary
Change From Baseline ALS Functional Rating Scale - Revised Score - Gross Motor Function
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.
Time frame: 24, 48, 72 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FAB122 | Change From Baseline ALS Functional Rating Scale - Revised Score - Gross Motor Function | -2.0 units on a scale | Standard Deviation 1.9 |
| Placebo | Change From Baseline ALS Functional Rating Scale - Revised Score - Gross Motor Function | -1.7 units on a scale | Standard Deviation 1.8 |
| FAB122 48 Weeks | Change From Baseline ALS Functional Rating Scale - Revised Score - Gross Motor Function | -3.4 units on a scale | Standard Deviation 2.7 |
| Placebo 48 Weeks | Change From Baseline ALS Functional Rating Scale - Revised Score - Gross Motor Function | -3.3 units on a scale | Standard Deviation 2.2 |
| FAB122 100mg 72 Weeks | Change From Baseline ALS Functional Rating Scale - Revised Score - Gross Motor Function | -4.5 units on a scale | Standard Deviation 3.1 |
| Placebo 72 Weeks | Change From Baseline ALS Functional Rating Scale - Revised Score - Gross Motor Function | -3.8 units on a scale | Standard Deviation 2.4 |
Secondary
Change From Baseline ALS Functional Rating Scale - Revised Score - Respiratory Function
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 frame: 24, 48, 72 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FAB122 | Change From Baseline ALS Functional Rating Scale - Revised Score - Respiratory Function | -0.9 units on a scale | Standard Deviation 2.2 |
| Placebo | Change From Baseline ALS Functional Rating Scale - Revised Score - Respiratory Function | -0.8 units on a scale | Standard Deviation 2.1 |
| FAB122 48 Weeks | Change From Baseline ALS Functional Rating Scale - Revised Score - Respiratory Function | -1.9 units on a scale | Standard Deviation 3.2 |
| Placebo 48 Weeks | Change From Baseline ALS Functional Rating Scale - Revised Score - Respiratory Function | -2.0 units on a scale | Standard Deviation 3.3 |
| FAB122 100mg 72 Weeks | Change From Baseline ALS Functional Rating Scale - Revised Score - Respiratory Function | -2.8 units on a scale | Standard Deviation 4.2 |
| Placebo 72 Weeks | Change From Baseline ALS Functional Rating Scale - Revised Score - Respiratory Function | -2.0 units on a scale | Standard Deviation 2.8 |
Secondary
Change From Baseline in ALSFRS-R Score After 24 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.
Time frame: 24 weeks, 72 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FAB122 | Change From Baseline in ALSFRS-R Score After 24 and 72* Weeks | -6.0 units on a scale | Standard Deviation 5.4 |
| Placebo | Change From Baseline in ALSFRS-R Score After 24 and 72* Weeks | -5.4 units on a scale | Standard Deviation 5.1 |
| FAB122 48 Weeks | Change From Baseline in ALSFRS-R Score After 24 and 72* Weeks | -15.2 units on a scale | Standard Deviation 10.5 |
| Placebo 48 Weeks | Change From Baseline in ALSFRS-R Score After 24 and 72* Weeks | -12.6 units on a scale | Standard Deviation 8.2 |
Secondary
Change From Baseline in ALSFRS-R Score on Bulbar Function (Question 1-3 of the ALSFRS-R) After 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.
Time frame: 24, 48 and 72 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FAB122 | Change From Baseline in ALSFRS-R Score on Bulbar Function (Question 1-3 of the ALSFRS-R) After 24, 48 and 72* Weeks; | -1.1 units on a scale | Standard Deviation 1.7 |
| Placebo | Change From Baseline in ALSFRS-R Score on Bulbar Function (Question 1-3 of the ALSFRS-R) After 24, 48 and 72* Weeks; | -1.2 units on a scale | Standard Deviation 1.6 |
| FAB122 48 Weeks | Change From Baseline in ALSFRS-R Score on Bulbar Function (Question 1-3 of the ALSFRS-R) After 24, 48 and 72* Weeks; | -2.1 units on a scale | Standard Deviation 2.5 |
| Placebo 48 Weeks | Change From Baseline in ALSFRS-R Score on Bulbar Function (Question 1-3 of the ALSFRS-R) After 24, 48 and 72* Weeks; | -2.2 units on a scale | Standard Deviation 2.8 |
| FAB122 100mg 72 Weeks | Change From Baseline in ALSFRS-R Score on Bulbar Function (Question 1-3 of the ALSFRS-R) After 24, 48 and 72* Weeks; | -3.1 units on a scale | Standard Deviation 3.5 |
| Placebo 72 Weeks | Change From Baseline in ALSFRS-R Score on Bulbar Function (Question 1-3 of the ALSFRS-R) After 24, 48 and 72* Weeks; | -2.7 units on a scale | Standard Deviation 2.9 |
Secondary
Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 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.
Time frame: 24, 48 and 72* weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 4 | 12 units on a scale | Standard Deviation 5.9 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 4 | 41 units on a scale | Standard Deviation 20 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 2 | 34 units on a scale | Standard Deviation 16.6 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 1 | 82 units on a scale | Standard Deviation 40 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 5 | 40 units on a scale | Standard Deviation 19.5 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 1 | 36 units on a scale | Standard Deviation 17.6 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 4 | 49 units on a scale | Standard Deviation 23.9 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 5 | 0 units on a scale | Standard Deviation 0 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 3 | 43 units on a scale | Standard Deviation 21 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 1 | 66 units on a scale | Standard Deviation 32.2 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 2 | 53 units on a scale | Standard Deviation 25.9 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 2 | 35 units on a scale | Standard Deviation 17.1 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 2 | 61 units on a scale | Standard Deviation 29.8 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 3 | 48 units on a scale | Standard Deviation 23.4 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 1 | 29 units on a scale | Standard Deviation 14.1 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 4 | 9 units on a scale | Standard Deviation 4.4 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 5 | 51 units on a scale | Standard Deviation 24.9 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 5 | 2 units on a scale | Standard Deviation 1 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 5 | 31 units on a scale | Standard Deviation 15.1 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 1 | 21 units on a scale | Standard Deviation 10.2 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 4 | 24 units on a scale | Standard Deviation 11.7 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 2 | 35 units on a scale | Standard Deviation 17.1 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 3 | 39 units on a scale | Standard Deviation 19 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 3 | 42 units on a scale | Standard Deviation 20.5 |
| FAB122 | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 3 | 50 units on a scale | Standard Deviation 24.4 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 2 | 26 units on a scale | Standard Deviation 26.8 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 5 | 12 units on a scale | Standard Deviation 12.4 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 4 | 11 units on a scale | Standard Deviation 11.3 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 1 | 33 units on a scale | Standard Deviation 34 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 2 | 13 units on a scale | Standard Deviation 13.4 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 1 | 10 units on a scale | Standard Deviation 10.3 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 5 | 0 units on a scale | Standard Deviation 0 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 2 | 20 units on a scale | Standard Deviation 20.6 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 1 | 17 units on a scale | Standard Deviation 17.5 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 3 | 22 units on a scale | Standard Deviation 22.7 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 3 | 29 units on a scale | Standard Deviation 29.9 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 4 | 7 units on a scale | Standard Deviation 7.2 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 2 | 17 units on a scale | Standard Deviation 17.5 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 4 | 22 units on a scale | Standard Deviation 22.7 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 5 | 20 units on a scale | Standard Deviation 20.6 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 3 | 31 units on a scale | Standard Deviation 32 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 2 | 8 units on a scale | Standard Deviation 8.2 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 5 | 16 units on a scale | Standard Deviation 16.5 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 1 | 39 units on a scale | Standard Deviation 40.2 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 1 | 11 units on a scale | Standard Deviation 11.3 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 5 | 0 units on a scale | Standard Deviation 0 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 4 | 27 units on a scale | Standard Deviation 27.8 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 3 | 26 units on a scale | Standard Deviation 26.8 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 4 | 3 units on a scale | Standard Deviation 3.1 |
| Placebo | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 3 | 19 units on a scale | Standard Deviation 19.6 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 4 | 14 units on a scale | Standard Deviation 6.8 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 5 | 3 units on a scale | Standard Deviation 1.5 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 2 | 25 units on a scale | Standard Deviation 12.2 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 4 | 26 units on a scale | Standard Deviation 12.7 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 2 | 21 units on a scale | Standard Deviation 10.2 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 3 | 29 units on a scale | Standard Deviation 14.1 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 1 | 57 units on a scale | Standard Deviation 27.8 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 1 | 57 units on a scale | Standard Deviation 27.8 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 3 | 30 units on a scale | Standard Deviation 14.6 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 1 | 16 units on a scale | Standard Deviation 7.8 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 4 | 42 units on a scale | Standard Deviation 20.5 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 1 | 10 units on a scale | Standard Deviation 4.9 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 3 | 38 units on a scale | Standard Deviation 18.5 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 2 | 47 units on a scale | Standard Deviation 22.9 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 2 | 22 units on a scale | Standard Deviation 10.7 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 1 | 16 units on a scale | Standard Deviation 7.8 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 4 | 12 units on a scale | Standard Deviation 5.9 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 4 | 49 units on a scale | Standard Deviation 23.9 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 5 | 47 units on a scale | Standard Deviation 22.9 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 3 | 39 units on a scale | Standard Deviation 19 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 2 | 52 units on a scale | Standard Deviation 25.4 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 5 | 5 units on a scale | Standard Deviation 2.4 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 5 | 69 units on a scale | Standard Deviation 33.7 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 3 | 26 units on a scale | Standard Deviation 12.7 |
| FAB122 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 5 | 57 units on a scale | Standard Deviation 27.8 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 1 | 5 units on a scale | Standard Deviation 5.2 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 1 | 29 units on a scale | Standard Deviation 29.9 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 2 | 15 units on a scale | Standard Deviation 15.5 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 3 | 21 units on a scale | Standard Deviation 21.6 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 4 | 4 units on a scale | Standard Deviation 4.1 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 5 | 0 units on a scale | Standard Deviation 0 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 1 | 27 units on a scale | Standard Deviation 27.8 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 2 | 19 units on a scale | Standard Deviation 19.6 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 3 | 19 units on a scale | Standard Deviation 19.6 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 4 | 4 units on a scale | Standard Deviation 4.1 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 5 | 0 units on a scale | Standard Deviation 0 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 1 | 4 units on a scale | Standard Deviation 4.1 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 2 | 4 units on a scale | Standard Deviation 4.1 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 3 | 22 units on a scale | Standard Deviation 22.7 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 4 | 22 units on a scale | Standard Deviation 22.7 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 5 | 17 units on a scale | Standard Deviation 17.5 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 2 | 6 units on a scale | Standard Deviation 6.2 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 3 | 19 units on a scale | Standard Deviation 19.6 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 4 | 15 units on a scale | Standard Deviation 15.5 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 5 | 24 units on a scale | Standard Deviation 24.7 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 1 | 9 units on a scale | Standard Deviation 9.3 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 2 | 6 units on a scale | Standard Deviation 6.2 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 3 | 14 units on a scale | Standard Deviation 14.4 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 4 | 21 units on a scale | Standard Deviation 21.6 |
| Placebo 48 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 5 | 19 units on a scale | Standard Deviation 19.6 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 2 | 4 units on a scale | Standard Deviation 2 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 1 | 1 units on a scale | Standard Deviation 0.5 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 1 | 13 units on a scale | Standard Deviation 6.3 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 4 | 6 units on a scale | Standard Deviation 2.9 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 1 | 12 units on a scale | Standard Deviation 5.9 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 2 | 3 units on a scale | Standard Deviation 1.5 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 4 | 14 units on a scale | Standard Deviation 6.8 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 5 | 0 units on a scale | Standard Deviation 0 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 2 | 12 units on a scale | Standard Deviation 5.9 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 4 | 6 units on a scale | Standard Deviation 2.9 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 5 | 24 units on a scale | Standard Deviation 11.7 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 3 | 6 units on a scale | Standard Deviation 2.9 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 5 | 0 units on a scale | Standard Deviation 0 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 3 | 12 units on a scale | Standard Deviation 5.9 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 3 | 11 units on a scale | Standard Deviation 5.4 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 3 | 5 units on a scale | Standard Deviation 2.4 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 2 | 10 units on a scale | Standard Deviation 4.9 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 5 | 18 units on a scale | Standard Deviation 8.8 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 2 | 3 units on a scale | Standard Deviation 1.5 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 1 | 3 units on a scale | Standard Deviation 1.5 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 4 | 6 units on a scale | Standard Deviation 2.9 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 4 | 13 units on a scale | Standard Deviation 6.3 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 1 | 3 units on a scale | Standard Deviation 1.5 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 3 | 5 units on a scale | Standard Deviation 2.4 |
| FAB122 100mg 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 5 | 15 units on a scale | Standard Deviation 7.3 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 4 | 5 units on a scale | Standard Deviation 5.2 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 2 | 2 units on a scale | Standard Deviation 2.1 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 2 | 2 units on a scale | Standard Deviation 2.1 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 1 | 1 units on a scale | Standard Deviation 1 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 3 | 2 units on a scale | Standard Deviation 2.1 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 5 | 1 units on a scale | Standard Deviation 1 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 4 | 7 units on a scale | Standard Deviation 7.2 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 4 | 5 units on a scale | Standard Deviation 5.2 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 4 | 1 units on a scale | Standard Deviation 1 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 3 | 6 units on a scale | Standard Deviation 6.2 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 5 | 14 units on a scale | Standard Deviation 14.4 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 2 | 8 units on a scale | Standard Deviation 8.2 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 1 | 7 units on a scale | Standard Deviation 7.2 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 1 | 5 units on a scale | Standard Deviation 5.2 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Pain/Discomfort - Level 1 | 8 units on a scale | Standard Deviation 8.2 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 5 | 0 units on a scale | Standard Deviation 0 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 2 | 1 units on a scale | Standard Deviation 1 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 4 | 4 units on a scale | Standard Deviation 4.1 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 5 | 9 units on a scale | Standard Deviation 9.3 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Mobility - Level 3 | 2 units on a scale | Standard Deviation 2.1 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 3 | 6 units on a scale | Standard Deviation 6.2 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Anxiety/Depression - Level 2 | 7 units on a scale | Standard Deviation 7.2 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 5 | 11 units on a scale | Standard Deviation 11.3 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Self-care - Level 1 | 1 units on a scale | Standard Deviation 1 |
| Placebo 72 Weeks | Change From Baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Score 24, 48 and 72* Weeks. | Usual Activities - Level 3 | 5 units on a scale | Standard Deviation 5.2 |
Secondary
Change From Baseline in Slow Vital Capacity (SVC, Liters) at 24, 48 and 72* Weeks;
Time frame: 24, 48 and 72* weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FAB122 | Change From Baseline in Slow Vital Capacity (SVC, Liters) at 24, 48 and 72* Weeks; | -0.4 liters | Standard Deviation 0.5 |
| Placebo | Change From Baseline in Slow Vital Capacity (SVC, Liters) at 24, 48 and 72* Weeks; | -0.5 liters | Standard Deviation 0.7 |
| FAB122 48 Weeks | Change From Baseline in Slow Vital Capacity (SVC, Liters) at 24, 48 and 72* Weeks; | -0.7 liters | Standard Deviation 0.7 |
| Placebo 48 Weeks | Change From Baseline in Slow Vital Capacity (SVC, Liters) at 24, 48 and 72* Weeks; | -0.7 liters | Standard Deviation 0.7 |
| FAB122 100mg 72 Weeks | Change From Baseline in Slow Vital Capacity (SVC, Liters) at 24, 48 and 72* Weeks; | -1 liters | Standard Deviation 1 |
| Placebo 72 Weeks | Change From Baseline in Slow Vital Capacity (SVC, Liters) at 24, 48 and 72* Weeks; | -1 liters | Standard Deviation 0.7 |
Secondary
Change From Baseline in the Overall Mega Score for the Hand-held Dynamometer (HHD) at 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.
Time frame: 24, 48 and 72* weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FAB122 | Change From Baseline in the Overall Mega Score for the Hand-held Dynamometer (HHD) at 24, 48 and 72* Weeks. | -0.4 Z-Score | Standard Deviation 0.7 |
| Placebo | Change From Baseline in the Overall Mega Score for the Hand-held Dynamometer (HHD) at 24, 48 and 72* Weeks. | -0.4 Z-Score | Standard Deviation 0.6 |
| FAB122 48 Weeks | Change From Baseline in the Overall Mega Score for the Hand-held Dynamometer (HHD) at 24, 48 and 72* Weeks. | -0.7 Z-Score | Standard Deviation 1.1 |
| Placebo 48 Weeks | Change From Baseline in the Overall Mega Score for the Hand-held Dynamometer (HHD) at 24, 48 and 72* Weeks. | -0.8 Z-Score | Standard Deviation 0.9 |
| FAB122 100mg 72 Weeks | Change From Baseline in the Overall Mega Score for the Hand-held Dynamometer (HHD) at 24, 48 and 72* Weeks. | -1.2 Z-Score | Standard Deviation 1.2 |
| Placebo 72 Weeks | Change From Baseline in the Overall Mega Score for the Hand-held Dynamometer (HHD) at 24, 48 and 72* Weeks. | -1.4 Z-Score | Standard Deviation 0.8 |
Secondary
Change From Baseline in the Total Score on the ALS Assessment Questionnaire-40-Item (ALSAQ-40) Form at 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.
Time frame: 24, 48 and 72* weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FAB122 | Change From Baseline in the Total Score on the ALS Assessment Questionnaire-40-Item (ALSAQ-40) Form at 24, 48 and 72* Weeks; | 11.2 units on a scale | Standard Deviation 12.8 |
| Placebo | Change From Baseline in the Total Score on the ALS Assessment Questionnaire-40-Item (ALSAQ-40) Form at 24, 48 and 72* Weeks; | 8.9 units on a scale | Standard Deviation 12.3 |
| FAB122 48 Weeks | Change From Baseline in the Total Score on the ALS Assessment Questionnaire-40-Item (ALSAQ-40) Form at 24, 48 and 72* Weeks; | 22.7 units on a scale | Standard Deviation 16.8 |
| Placebo 48 Weeks | Change From Baseline in the Total Score on the ALS Assessment Questionnaire-40-Item (ALSAQ-40) Form at 24, 48 and 72* Weeks; | 19.9 units on a scale | Standard Deviation 17.5 |
| FAB122 100mg 72 Weeks | Change From Baseline in the Total Score on the ALS Assessment Questionnaire-40-Item (ALSAQ-40) Form at 24, 48 and 72* Weeks; | 27.1 units on a scale | Standard Deviation 18.4 |
| Placebo 72 Weeks | Change From Baseline in the Total Score on the ALS Assessment Questionnaire-40-Item (ALSAQ-40) Form at 24, 48 and 72* Weeks; | 22.5 units on a scale | Standard Deviation 19.5 |
Secondary
Change From Baseline in Visual Analogue Scale (VAS) Score at 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).
Time frame: 24, 48 and 72* weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FAB122 | Change From Baseline in Visual Analogue Scale (VAS) Score at 24, 48 and 72* Weeks. | -10.2 units on a scale | Standard Deviation 19.4 |
| Placebo | Change From Baseline in Visual Analogue Scale (VAS) Score at 24, 48 and 72* Weeks. | -7.2 units on a scale | Standard Deviation 23.6 |
| FAB122 48 Weeks | Change From Baseline in Visual Analogue Scale (VAS) Score at 24, 48 and 72* Weeks. | -15.7 units on a scale | Standard Deviation 20.2 |
| Placebo 48 Weeks | Change From Baseline in Visual Analogue Scale (VAS) Score at 24, 48 and 72* Weeks. | -15.6 units on a scale | Standard Deviation 24.9 |
| FAB122 100mg 72 Weeks | Change From Baseline in Visual Analogue Scale (VAS) Score at 24, 48 and 72* Weeks. | -25.1 units on a scale | Standard Deviation 21.3 |
| Placebo 72 Weeks | Change From Baseline in Visual Analogue Scale (VAS) Score at 24, 48 and 72* Weeks. | -15.1 units on a scale | Standard Deviation 22.3 |
Secondary
Change in Clinical Staging (King's Staging System and MiToS) Over 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.
Time frame: 72 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FAB122 | Change in Clinical Staging (King's Staging System and MiToS) Over 72 Weeks | Decline >= 1 | 22 Participants |
| FAB122 | Change in Clinical Staging (King's Staging System and MiToS) Over 72 Weeks | No decline | 17 Participants |
| Placebo | Change in Clinical Staging (King's Staging System and MiToS) Over 72 Weeks | Decline >= 1 | 12 Participants |
| Placebo | Change in Clinical Staging (King's Staging System and MiToS) Over 72 Weeks | No decline | 12 Participants |
Secondary
Combined Assessment of Function and Survival (CAFS) at 48 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.
Time frame: 48 weeks and 72 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FAB122 | Combined Assessment of Function and Survival (CAFS) at 48 and 72 Weeks. | 48.7 score on a scale | Standard Deviation 29.41 |
| Placebo | Combined Assessment of Function and Survival (CAFS) at 48 and 72 Weeks. | 54.15 score on a scale | Standard Deviation 28.83 |
| FAB122 48 Weeks | Combined Assessment of Function and Survival (CAFS) at 48 and 72 Weeks. | 153.31 score on a scale | Standard Deviation 86.2 |
| Placebo 48 Weeks | Combined Assessment of Function and Survival (CAFS) at 48 and 72 Weeks. | 147.68 score on a scale | Standard Deviation 92.38 |
Secondary
Overall Survival: Proportion of Subjects Alive (Survival Rate) After 24, 48 and 72* Weeks;
Time frame: 24, 48 and 72* weeks;
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FAB122 | Overall Survival: Proportion of Subjects Alive (Survival Rate) After 24, 48 and 72* Weeks; | 0.980 proportion of participants |
| Placebo | Overall Survival: Proportion of Subjects Alive (Survival Rate) After 24, 48 and 72* Weeks; | 0.990 proportion of participants |
| FAB122 48 Weeks | Overall Survival: Proportion of Subjects Alive (Survival Rate) After 24, 48 and 72* Weeks; | 0.933 proportion of participants |
| Placebo 48 Weeks | Overall Survival: Proportion of Subjects Alive (Survival Rate) After 24, 48 and 72* Weeks; | 0.933 proportion of participants |
| FAB122 100mg 72 Weeks | Overall Survival: Proportion of Subjects Alive (Survival Rate) After 24, 48 and 72* Weeks; | 0.791 proportion of participants |
| Placebo 72 Weeks | Overall Survival: Proportion of Subjects Alive (Survival Rate) After 24, 48 and 72* Weeks; | 0.870 proportion of participants |
Secondary
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
Time frame: 24, 48 and 72* weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FAB122 | 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 | 0.970 proportion of participants |
| Placebo | 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 | 0.990 proportion of participants |
| FAB122 48 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 | 0.903 proportion of participants |
| Placebo 48 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 | 0.890 proportion of participants |
| FAB122 100mg 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 | 0.728 proportion of participants |
| Placebo 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 | 0.870 proportion of participants |
Secondary
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;
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.
Time frame: 72 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FAB122 | 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; | ALS Specific - Change <8 | 154 Participants |
| FAB122 | 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; | ALS Specific - Change >=8 | 25 Participants |
| FAB122 | 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; | ALS non-Specific - Change <4 | 153 Participants |
| FAB122 | 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; | ALS non-Specific - Change >=4 | 26 Participants |
| FAB122 | 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; | ECAS Total Score - Change <9 | 152 Participants |
| FAB122 | 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; | ECAS Total Score - Change >=9 | 27 Participants |
| Placebo | 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; | ALS Specific - Change >=8 | 19 Participants |
| Placebo | 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; | ALS non-Specific - Change >=4 | 21 Participants |
| Placebo | 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; | ECAS Total Score - Change >=9 | 18 Participants |
| Placebo | 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; | ALS Specific - Change <8 | 69 Participants |
| Placebo | 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; | ALS non-Specific - Change <4 | 67 Participants |
| Placebo | 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; | ECAS Total Score - Change <9 | 70 Participants |
| FAB122 48 Weeks | 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; | ECAS Total Score - Change >=9 | 26 Participants |
| FAB122 48 Weeks | 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; | ECAS Total Score - Change <9 | 121 Participants |
| FAB122 48 Weeks | 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; | ALS non-Specific - Change >=4 | 35 Participants |
| FAB122 48 Weeks | 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; | ALS non-Specific - Change <4 | 112 Participants |
| FAB122 48 Weeks | 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; | ALS Specific - Change <8 | 128 Participants |
| FAB122 48 Weeks | 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; | ALS Specific - Change >=8 | 19 Participants |
| Placebo 48 Weeks | 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; | ALS non-Specific - Change >=4 | 16 Participants |
| Placebo 48 Weeks | 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; | ALS Specific - Change >=8 | 17 Participants |
| Placebo 48 Weeks | 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; | ALS non-Specific - Change <4 | 46 Participants |
| Placebo 48 Weeks | 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; | ECAS Total Score - Change >=9 | 18 Participants |
| Placebo 48 Weeks | 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; | ECAS Total Score - Change <9 | 44 Participants |
| Placebo 48 Weeks | 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; | ALS Specific - Change <8 | 45 Participants |
| FAB122 100mg 72 Weeks | 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; | ALS Specific - Change <8 | 31 Participants |
| FAB122 100mg 72 Weeks | 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; | ECAS Total Score - Change <9 | 29 Participants |
| FAB122 100mg 72 Weeks | 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; | ALS Specific - Change >=8 | 4 Participants |
| FAB122 100mg 72 Weeks | 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; | ALS non-Specific - Change <4 | 29 Participants |
| FAB122 100mg 72 Weeks | 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; | ALS non-Specific - Change >=4 | 6 Participants |
| FAB122 100mg 72 Weeks | 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; | ECAS Total Score - Change >=9 | 6 Participants |
| Placebo 72 Weeks | 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; | ALS non-Specific - Change >=4 | 7 Participants |
| Placebo 72 Weeks | 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; | ALS non-Specific - Change <4 | 15 Participants |
| Placebo 72 Weeks | 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; | ECAS Total Score - Change <9 | 19 Participants |
| Placebo 72 Weeks | 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; | ECAS Total Score - Change >=9 | 3 Participants |
| Placebo 72 Weeks | 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; | ALS Specific - Change >=8 | 4 Participants |
| Placebo 72 Weeks | 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; | ALS Specific - Change <8 | 18 Participants |
Secondary
Survival Probability
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.
Time frame: 72 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FAB122 | Survival Probability | 0.728 Survival probability |
| Placebo | Survival Probability | 0.870 Survival probability |
Secondary
The Slope of the Decrease in ALSFRS-R Score Over Time at 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. For this outcome, measures on the ALSFRS-R were used to determine the slope of the decrease.
Time frame: 24, 48, 72 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FAB122 | The Slope of the Decrease in ALSFRS-R Score Over Time at 24, 48 and 72* Weeks; | -0.2981 units on a scale/week | Standard Error 0.0182 |
| Placebo | The Slope of the Decrease in ALSFRS-R Score Over Time at 24, 48 and 72* Weeks; | -0.2445 units on a scale/week | Standard Error 0.265 |
| FAB122 48 Weeks | The Slope of the Decrease in ALSFRS-R Score Over Time at 24, 48 and 72* Weeks; | -0.2874 units on a scale/week | Standard Error 0.0143 |
| Placebo 48 Weeks | The Slope of the Decrease in ALSFRS-R Score Over Time at 24, 48 and 72* Weeks; | -0.2767 units on a scale/week | Standard Error 0.0206 |
| FAB122 100mg 72 Weeks | The Slope of the Decrease in ALSFRS-R Score Over Time at 24, 48 and 72* Weeks; | -0.3003 units on a scale/week | Standard Error 0.0223 |
| Placebo 72 Weeks | The Slope of the Decrease in ALSFRS-R Score Over Time at 24, 48 and 72* Weeks; | -0.2531 units on a scale/week | Standard Error 0.0313 |
Secondary
Time to a 3, 6, 9 and 12 Points Change or Death From Baseline in ALSFRS-R Score Over 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, the time a 3, 6, 9 and 12 points change or death from baseline in ALSFRS-R.
Time frame: 72 weeks (+/-1 week visit window)
Population: The first 100 patients in the study were planned to complete a 72 weeks follow up. This analysis is done over this population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FAB122 | Time to a 3, 6, 9 and 12 Points Change or Death From Baseline in ALSFRS-R Score Over 72* Weeks; | Time to 3 points change or death from baseline in ALSFRS-R score | 85 days |
| FAB122 | Time to a 3, 6, 9 and 12 Points Change or Death From Baseline in ALSFRS-R Score Over 72* Weeks; | Time to 6 points change or death from baseline in ALSFRS-R score | 194 days |
| FAB122 | Time to a 3, 6, 9 and 12 Points Change or Death From Baseline in ALSFRS-R Score Over 72* Weeks; | Time to 9 points change or death from baseline in ALSFRS-R score | 308 days |
| FAB122 | Time to a 3, 6, 9 and 12 Points Change or Death From Baseline in ALSFRS-R Score Over 72* Weeks; | Time to 12 points change or death from baseline in ALSFRS-R score | 351 days |
| Placebo | Time to a 3, 6, 9 and 12 Points Change or Death From Baseline in ALSFRS-R Score Over 72* Weeks; | Time to 12 points change or death from baseline in ALSFRS-R score | 438 days |
| Placebo | Time to a 3, 6, 9 and 12 Points Change or Death From Baseline in ALSFRS-R Score Over 72* Weeks; | Time to 3 points change or death from baseline in ALSFRS-R score | 114 days |
| Placebo | Time to a 3, 6, 9 and 12 Points Change or Death From Baseline in ALSFRS-R Score Over 72* Weeks; | Time to 9 points change or death from baseline in ALSFRS-R score | 334 days |
| Placebo | Time to a 3, 6, 9 and 12 Points Change or Death From Baseline in ALSFRS-R Score Over 72* Weeks; | Time to 6 points change or death from baseline in ALSFRS-R score | 226 days |