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 |
Amyotrophic Lateral Sclerosis |
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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 long-term safety of arimoclomol treatment of ALS. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term efficacy of arimoclomol treatment of ALS. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is able to comprehend and is willing to provide written informed consent and is capable and willing to comply with trial procedures or in the circumstance that the subject is incompetent, informed consent/assent is provided in accordance with local regulation and/or procedures. 2. Subject has completed the ORARIALS-01 trial (i.e., met one of the surrogate survival endpoints of tracheostomy or PAV or has completed the 76 weeks randomised treatment period). 3. Subjects completed ORARIALS-01 while on treatment, where on treatment is defined as having taken the last dose of IMP within 2 weeks of the End of Trial visit. (whether at week 76 or prior)
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E.4 | Principal exclusion criteria |
1. Known or suspected allergy or intolerance to the IMP (arimoclomol or constituents). 2. Exposure to any other investigational treatment, advanced therapy medicinal product(ATMP) or use of any other prohibited concomitant medications. 3. Women who are lactating or pregnant, or men or women unwilling to use a highly effective method of birth control if not surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy, or orhysterectomy for women; vasectomy for men) for female participants until 4 weeks after last dose and for male participants until 3 months after last dose. Pre-menopausal women must have a negative pregnancy test prior to dosing with trial medication. Acceptable methods of birth control are: a. Hormonal methods associated with inhibition of ovulation such as oral, implantable, injectable, or transdermal contraceptives for a minimum of 1 full cycle (based on the subject's usual menstrual cycle period) before IMP administration. b. Total abstinence from sexual intercourse since the last menses before IMP administration. (The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence methods [calendar, symptothermal, post-ovulation methods] are not acceptable methods of contraception). c. Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS). 4. Any of the following medically significant conditions: a. Clinically significant renal or hepatic disease OR clinical laboratory assessment (results ≥ 3 times the upper limit of normal [ULN] for aspartate aminotransferase and/or alanine aminotransferase, bilirubin ≥ 2 times the ULN, or creatinine ≥ 1.5 times the ULN). b. Any new condition or worsening of existing condition which, in the opinion of the investigator would put the subject at undue risk. 5. Any serious adverse event or moderate/severe adverse event from the ORARIALS-01 trial which is ongoing at the time of transitioning to ORARIALS-02 and assessed as probably related to IMP. 6. Subjects who exceed 60 days from the End of Trial Visit date of the ORARIALS-01 trial at the time of enrolment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Incidence and severity of TEAEs over a treatment period of 76 weeks 2. Mean and change from Baseline (of the present trial) to Week 76 (or end of trial Treatment Period 1) in clinical safety laboratory tests and vital signs 3. Incidence of potentially clinically significant abnormalities in clinical safety laboratory tests and vital signs over a treatment period of 76 weeks 4. C-SSRS over a treatment period of 76 weeks |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
76 weeks (or end-of-trial) |
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E.5.2 | Secondary end point(s) |
1. Time to PAV/tracheostomy/death (for subjects entering this trial having completed 76 weeks of randomised treatment in ORARIALS-01) 2. Change in ALSFRS-R from Baseline (of the present trial) to week 76 (End of Trial – Treatment Period 1) 3. Change in SVC from Baseline (of the present trial) to the week 76 (End of Trial – Treatment Period 1) (for subjects who did not meet the survival endpoint in the ORARIALS-01 trial) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
76 weeks (or end-of-trial) |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | No |
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 | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 18 |
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 |
Canada |
United States |
Belgium |
Denmark |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
Sweden |
Switzerland |
United Kingdom |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |