E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Amyotrophic Lateral Sclerosis |
La Esclerosis Lateral Amiotrófica |
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E.1.1.1 | Medical condition in easily understood language |
Amyotrophic Lateral Sclerosis |
La Esclerosis Lateral Amiotrófica |
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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 | 20.0 |
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. |
Evaluar la seguridad a largo plazo del arimoclomol en el tratamiento de la ELA. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term efficacy of arimoclomol treatment of ALS. |
Evaluar la eficacia a largo plazo del arimoclomol en el tratamiento de la ELA. |
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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. On treatment with IMP defined as last dose within 2 weeks of the last visit of the blinded ORARIALS-01. 4. Able and willing to travel to the site for the Baseline visit and in the investigator’s opinion is expected to be able to attend the clinic for the visit at Week 4. |
1. Sujeto capaz de comprender las informaciones y dispuesto a proporcionar su consentimiento informado por escrito, así como con capacidad y disposición para cumplir con los procedimientos del estudio. En el caso de incompetencia del sujeto, el consentimiento/asentimiento informado se proporcionará de acuerdo con las regulaciones y/o procedimientos locales. 2. Sujeto que haya completado el estudio ORARIALS-01 (es decir, que haya cumplido uno de los criterios de valoración subrogados de la supervivencia (traqueotomía o PAV) o que haya completado las 76 semanas del período de tratamiento aleatorizado). 3. Sujeto en tratamiento con el medicamento en investigación, lo que se define como última dosis en el plazo de 2 semanas desde la última visita del estudio con diseño ciego ORARIALS-01. 4. Sujeto con capacidad y disposición para trasladarse al centro para la visita basal y que, en opinión del investigador, sea previsiblemente capaz de acudir al centro para la visita de la Semana 4. |
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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 hysterectomy 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, alanine aminotransferase, lactate dehydrogenase, 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. |
1. Conocimiento o sospecha de alergia o intolerancia al medicamento en investigación (arimoclomol o sus excipientes). 2. Exposición a algún otro tratamiento en fase de investigación, medicamento de terapia avanzada (ATMP, advanced therapy medicinal product) o uso concomitante de algún otro medicamento prohibido (véase la sección 6.8). 3. Mujeres embarazadas o en fase de lactancia o varones o mujeres que no estén dispuestos a utilizar un método anticonceptivo de alta efectividad en el caso de que no hayan sido sometidos a esterilización quirúrgica (mujeres: ligadura de trompas bilateral, ovariectomía bilateral o histerectomía; varones: vasectomía), en el caso de las mujeres participantes hasta 4 semanas después de la última dosis y, en el caso de los varones participantes, hasta 3 meses después de la última dosis. Las mujeres premenopáusicas deberán disponer de una prueba de embarazo negativa antes de la administración del medicamento del estudio. Son métodos anticonceptivos aceptables: a. Métodos hormonales resultantes en inhibición de la ovulación, como anticonceptivos orales, implantables, inyectables o transdérmicos, durante un mínimo de 1 ciclo completo (basándose en el período del ciclo menstrual habitual de la sujeto) antes de la administración del medicamento en investigación. b. Abstinencia total de relaciones sexuales desde la última menstruación antes de la administración del medicamento en investigación. (La fiabilidad de la abstinencia sexual se evaluará en relación con la duración del estudio clínico y el estilo de vida preferido y habitual del sujeto. Los métodos de abstinencia periódica [calendario, sintotérmico, post-ovulación] no se consideran métodos anticonceptivos aceptables). c. Dispositivo intrauterino (IUD, intrauterine device) o sistema intrauterino (IUS, intrauterine system). 4. Cualquiera de las siguientes afecciones médicamente importantes: a. Enfermedad renal o hepática clínicamente importante, O resultados clínicos de laboratorio (valores ≥ 3 veces el límite superior de normalidad (ULN, upper limit of normal) en el caso de la aspartato aminotransferasa, alanina aminotransferasa y lactato deshidrogenasa, bilirrubina ≥ 2 veces el ULN o creatinina ≥ 1,5 veces el ULN). b. Toda afección nueva o empeoramiento de una afección existente que, en opinión del investigador, ponga en riesgo al sujeto. 5. Todo acontecimiento adverso grave o acontecimiento adverso moderado/severo del estudio ORARIALS-01 que estuviera aún en curso en el momento del cambio del sujeto al estudio ORARIALS-02 y que se considere probablemente relacionado con el medicamento en investigación |
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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) 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 |
• Incidencia y severidad de los acontecimientos adversos surgidos durante el tratamiento (TEAE, treatment-emergent adverse event) durante un período de tratamiento de 76 semanas • Valor medio y variación entre el momento basal (del presente estudio) y la Semana 76 (o final del estudio) de las pruebas de laboratorio de seguridad y de las constantes vitales • Incidencia de las anomalías con posible significación clínica de las pruebas de laboratorio de seguridad y de las constantes vitales, durante un período de tratamiento de 76 semanas • Escala C-SSRS durante un período de tratamiento de 76 semanas |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
76 weeks (or end-of-trial) |
76 semanas (o Final del estudio) |
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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 the end of the trial 3. Change in SVC from Baseline (of the present trial) to the end of the trial (for subjects who did not meet the survival endpoint in the ORARIALS-01 trial) |
• Tiempo hasta PAV/traqueotomía/muerte (en los sujetos participantes en este estudio que hayan completado 76 semanas de tratamiento aleatorizado en el estudio ORARIALS-01) • Variación de la escala ALSFRS-R entre el momento basal (del presente estudio) y el final del estudio • Variación de la capacidad vital lenta (SVC, slow vital capacity) entre el momento basal (del presente estudio) y el final del estudio (en los sujetos que no hayan cumplido el criterio de valoración de supervivencia en el estudio ORARIALS-01) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
76 weeks (or end-of-trial) |
76 semanas (o Final del estudio) |
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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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 |
Belgium |
Canada |
Denmark |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |