E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Amyotrophic Lateral Sclerosis (ALS) |
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E.1.1.1 | Medical condition in easily understood language |
ALS is a progressive and irreversible damage or degeneration of the nerve cells responsible for the movement of muscles. |
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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 evaluate the long-term safety of FAB122 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 overall survival; 2. To evaluate the effect of treatment with FAB122 on disease progression in patients with ALS; 3. To evaluate the effect of treatment with FAB122 on cognitive functioning; 4. To evaluate the effect of treatment with FAB122 on quality of life (QoL).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients who meet all of the following criteria, will be eligible for the study: 1. who completed the full study period in the main ADORE study (FAB122-CT-2001; (EudraCT number 2020-003376-40); 2. whom the investigator has no concern and judges tolerable for receiving treatment with FAB122 from a risk and benefit point of view; 3. a female subject should not be able to become pregnant up to 30 days after the last dose of FAB122 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 baseline and is non-lactating. A female subject who is of reproductive potential agrees to use (or have their partner use) 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. 4. a male patient must: - agree he will not donate sperm during the period he will be using FAB122 AND use a condom during sexual intercourse with pregnant or non-pregnant women of childbearing potential (WOCBP) partner even if he is vasectomized and until 104 days after the last dose. - 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: 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; 5. providing informed consent.
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria, will not be eligible for the study: 1. Patient who has a medical condition (e.g. cardiac, pulmonary, gastrointestinal, musculoskeletal, or psychiatric illness) or personal circumstances which, in the opinion of the investigator, will make initiation or continuation of treatment with FAB122 not tolerable for them from a risk and benefit point of view. 2. Patient who discontinued study drug prematurely in the double-blind phase of the study (ADORE Study) for safety reasons. 3. Patient who has received any other investigational drug within the period between last visit of the main study and first visit of the extension study (i.e. another trial, managed access program, open label extension or early access program) 4. - History of known hypersensitivity to edaravone or to any of the excipients. For patients who do not take FAB122 but are only followed up by phone, only inclusion criteria #1 and #5 will apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Nature, frequency and severity of Treatment Emergent Adverse Events. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
As per requirement throughout whole study duration |
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E.5.2 | Secondary end point(s) |
1. Mortality-adjusted change from baseline in ALSFRS-R total score until the end of the study; 2. Overall survival, defined as time to death from any cause or respiratory insufficiency (insufficiency defined as tracheostomy or the use of non-invasive ventilation for ≥20 h per day for ≥10 consecutive days); 3. Change from baseline in SVC until the end of the study 4. Mean change in norm-standardized ECAS total score; 5. Change from baseline in the total score on the ALS Assessment Questionnaire-40-Item (ALSAQ-40) until the end of the study; 6. Change from baseline in EuroQoL – 5 Dimensions – 5 Levels (EQ-5D-5L) until the end of the study; 7. Change from baseline in Health related QoL Visual Analogue Scale (VAS) score until the end of the study; 8. Change from baseline in the prognostic ALS biomarker neurofilament light (NFL); 9. Change from baseline in the ALS biomarkers creatinine and creatinine kinase; 10. Change from baseline in the ALS biomarker Urinary extracellular domain of neurotrophin receptor p75 (Urinary P75ECD); 11. Change from baseline of oxidative stress biomarker 8-hydroxyguanosine (8-OHdG); 12. Cost-Utility analysis of treatment with FAB122.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoints 1, 3, 5, 6, 7 and 12: Every 3 months Endpoint 2: As per requirement throughout whole study duration Endpoint 4: Every 6 months Endpoints 8, 9, 10 and 11: Every 12 months |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open-label extension study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 34 |
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 |
United Kingdom |
Belgium |
France |
Germany |
Ireland |
Italy |
Netherlands |
Poland |
Portugal |
Spain |
Sweden |
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E.8.7 | Trial has a data monitoring committee | No |
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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Marketing Authorization of IMP or prematurely in case the objectives of the main study (ADORE, EudraCT number: 2020-003376-40) are not met. Product commercialization is country dependent, thus study ending will differ between countries. |
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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 | 3 |
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 | 3 |
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 |