E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Amyotrophic Lateral Sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002026 |
E.1.2 | Term | Amyotrophic lateral sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of treatment with 100 mg of FAB122 on disease progression in patients with ALS |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of treatment with FAB122 on survival 2. To evaluate the safety and tolerability of FAB122 3. To evaluate the effect of treatment with FAB122 on quality of life (QoL) 4. To evaluate the effect of treatment with FAB122 on cognitive functioning 5. To evaluate the pharmacokinetics (PK) of FAB122
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There will be an optional PK sub-study, included in the main protocol. The objective is to evaluate the pharmacokinetics (PK) of FAB122. |
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E.3 | Principal inclusion criteria |
1. Age 18 – 80 years (both inclusive), male or female; 2. 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; 3. 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 4. SVC equal to or more than 70% of the predicted normal value for gender, height and age at screening visit; 5. 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; 6. Patients on riluzole should be on stable doses ≥30 days prior to the baseline visit and this dose should be maintained during the entire trial. 7. A female subject should not be able to become pregnant and needs to meet at least one of the following criteria: • female subject who is not of reproductive potential is eligible without requiring the use of contraception. A woman is considered not having childbearing potential when becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause • female who is of reproductive potential and has a negative pregnancy test at screening and at baseline and is non-lactating. A female subject who is of reproductive potential agrees to use (or have their partner use) or practicing adequate birth control methods starting from the time of consent through 30 days after the last dose of study therapy. Longer periods of birth control may be required per local requirements. Acceptable methods of birth control include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), , intrauterine device in place for ≥3 months, intrauterine hormone-releasing system, bilateral tubal occlusion or vasectomised partner. 8. A male patient must: • agree he will not donate sperm during the study and until 104 days after the last dose, AND • use a condom during sexual intercourse with pregnant or non-pregnant women of childbearing potential (WOCBP) partner even if he is vasectomized • in addition WOCBP partner of the male patient must use the following acceptable methods of birth control during the study and until 104 days after the last dose: hormonal contraception (oral, implanted, injected or other hormonal (e.g., patch or contraceptive ring) contraception), intrauterine device in place for ≥3 months, barrier method in conjunction with spermicide OR use of appropriate double barrier contraception as per local regulations or guidelines; 9. Capable of providing informed consent and complying with trial procedures.
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E.4 | Principal exclusion criteria |
1. Diagnosis of Primary Lateral Sclerosis; 2. Diagnosis of Frontotemporal Dementia; 3. Diagnosis of other neurodegenerative diseases (e.g. Parkinson disease, Alzheimer disease); 4. Diagnosis of polyneuropathy; 5. Other causes of neuromuscular weakness; 6. Have a significant pulmonary disorder not attributed to ALS and/or require treatment interfering with the evaluation of ALS on respiratory function; 7. Use of intravenous (IV) edaravone within 6 months of the screening visit; 8. Depend on mechanical ventilation (invasive or non-invasive) or require tracheostomy at Screening; 9. Renal impairment as indicated by a creatinine clearance of less than 50 mL/min as calculated by the Cockcroft Gault equation; 10. 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; 11. Presence of any of the following clinical conditions: a. Unstable cardiac, pulmonary, endocrine, hematologic or active infectious disease b. Unstable psychiatric illness defined as psychosis, untreated major depression within 90 days of the screening visit c. Significant cognitive impairment, clinical dementia or psychiatric illness d. Cancer that is currently under active treatment or is likely to require treatment during the trial that may alter the subject´s function and interfere with assessment of ALS disease progression. 12. Any comorbidity that may interfere with the functions as scored with the ALSFRS-R; 13. History of known sensitivity or intolerability to edaravone, to any related compound, or to any of the excipients; 14. Exposure to any investigational drug within 30 days of the screening visit; 15. Current substance or alcohol dependence.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale – Revised (ALSFRS-R) score after 48 weeks of treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 48 weeks of treatment |
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E.5.2 | Secondary end point(s) |
Key secondary endpoints 1. Combined assessment of function and survival (CAFS) at 48 and 72 weeks of treatment; 2. Survival time, i.e. 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 of treatment
Efficacy 1. Change from baseline in ALSFRS-R score after 12, 24, 60, 72 weeks of treatment; 2. The slope of the decrease in ALSFRS-R score over time at 24, 48, 60 and 72 weeks of treatment; 3. Absolute ALSFRS-R score per assessment time point; 4. Change from baseline in ALSFRS-R score on Bulbar function (question 1-3 of the ALSFRS-R) after 12, 24, 60 and 72 weeks of treatment; 5. Change from baseline in ALSFRS-R score on Fine motor function (question 4-6 of the ALSFRS-R) after 12, 24, 60 and 72 weeks of treatment; 6. Change from baseline in ALSFRS-R score on Gross motor function (question 7-9 of the ALSFRS-R) after 12, 24, 60 and 72 weeks of treatment; 7. Change from baseline in ALSFRS-R score on Respiratory function (question 10-12 of the ALSFRS-R) after 12, 24, 60 and 72 weeks of treatment; 8. Time to a 3, 6, 9 and 12 points change from baseline in ALSFRS-R score; 9. Proportion of subjects with change from baseline in ALSFRS-R score at 24, 48, 60 and 72 weeks of treatment in categories: categories will include change ≥0, change between <0 and ≥-1, change between <-1 and ≥-2 etc.; 10. Staging of disease progression (King’s staging system and MiToS); 11. Overall survival: Proportion of subjects alive (survival rate) after 24, 48, 60 and 72 weeks of treatment; 12. 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, 60 and 72 weeks of treatment; 13. Absolute value and change from baseline in slow vital capacity (SVC, liters) at 24, 48, 60 and 72 weeks of treatment; 14. Absolute value and change from baseline in the overall mega score for the hand-held dynamometer (HHD) at 24, 48, 60 and 72 weeks of treatment.
QoL 1. Absolute values and change from baseline in the total score on the ALS Assessment Questionnaire-40-Item (ALSAQ-40) Form at 24, 48 and 72 weeks of treatment; 2. Absolute values and change from baseline in EuroQoL – 5 Dimensions-5 Levels (EQ-5D-5L) questionnaire score and health related QoL at 24, 48, 60 and 72 weeks of treatment. 3. Visual Analogue Scale (VAS) score at 24, 48, 60 and 72 weeks of treatment.
Cognition 1. 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; 2. Time to a mean change of ≥8, ≥4, and ≥9 for ALS Specific, ALS Non-Specific, and ECAS total score.
Pharmacokinetics (Population) PK parameters of FAB122 and riluzole
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
As indicated in the end points, after 12, 24, 48, 60, and/or 72 weeks of treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Russian Federation |
Belgium |
France |
Germany |
Ireland |
Italy |
Netherlands |
Poland |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |