E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prodromal Alzheimer's disease. |
Alzheimer prodromico. |
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E.1.1.1 | Medical condition in easily understood language |
Early Alzheimer's disease. |
Alzheimer precoce. |
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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 | HLT |
E.1.2 | Classification code | 10001897 |
E.1.2 | Term | Alzheimer's disease (incl subtypes) |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The two primary objectives are as follows: 1. To evaluate the safety and tolerability of MK-8931 in the long term treatment of prodromal Alzheimer’s Disease (AD). 2. To compare the efficacy of MK-8931 administered to subjects for 30 months to that of subjects administered placebo for 24 months followed by MK-8931 for 6 months using the change from baseline score CDR-SB score at Week 130. |
I due obiettivi primari sono i seguenti: 1. Valutare la sicurezza e la tollerabilità di MK-8931 nel trattamento a lungo termine della Malattia di Alzheimer prodromico (AD). 2. Confrontare l’efficacia di MK-8931 somministrato per 30 mesi con l’efficacia di placebo somministrato per 24 mesi seguito da MK-8931 per 6 mesi, in base alla variazione del punteggio basale del CDR-SB (Clinical Dementia Rating scale - Sum of Boxes [Somma degli item per la valutazione clinica della demenza di Alzheimer]) alla Settimana 130. |
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E.2.2 | Secondary objectives of the trial |
There are no secondary objectives for this long term safety trial. |
Non sono previsti ipotesi o obiettivi secondari per questa estensione a lungo termine. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible for participation in this trial, the subject must: 1. Have tolerated study medication and completed the initial 104-week trial. Subjects who did not complete the initial 104-weeks of treatment but continued with and completed scheduled visits may be permitted to continue in the long term extension at the discretion of the Sponsor. Subjects who repeatedly deviate from protocol requirements will not be permitted to continue in this extension. In addition, subjects who are less than 75% compliant with trial medication during the initial 104-week trial will not be permitted to continue in the long term extension, except in special circumstances, which require Sponsor approval (or, where required locally, approval of the investigator rather than the Sponsor). 2. Have a trial partner who is reliable and competent. The trial partner must have a close relationship with the subject, have face to face contact at least 3 days/week for a minimum of 6 waking hours/week (or more, based on local requirements), be willing to accompany the subject to all trial visits, and be willing to monitor compliance of the administration of the trial medication. The trial partner should understand the nature of the trial and adhere to trial requirements (e.g. dose, visit scheduled and evaluations). It is recommended that the trial partner accompany the subject to all trial visits. 3. Sign (or legal representative signature) the informed consent in accordance with local requirements, after the scope and nature of the trial have been explained. |
Per essere idoneo alla partecipazione a questo studio clinico, il soggetto deve: 1. Aver tollerato il farmaco in studio e portato a termine lo studio iniziale di 104 settimane. I soggetti che non abbiano portato a termine le 104 settimane iniziali di trattamento ma che abbiano proseguito e completato le visite previste potranno continuare la partecipazione a questa estensione a lungo termine a discrezione dello Sponsor. I soggetti che abbiano ripetutamente manifestato eventi contrari ai requisiti del protocollo non potranno avere accesso a questa estensione. Inoltre, i soggetti che mostrino una compliance al farmaco in studio inferiore al 75% nel corso dello studio iniziale di 104 settimane non potranno proseguire nell’estensione a lungo termine, salvo in speciali circostanze, che richiedono l’approvazione dello Sponsor (o, laddove richiesto dalle normative locali, l’approvazione dello sperimentatore anziché dello Sponsor). 2. Avere un partner dello studio (caregiver/accompagnatore) affidabile e competente. Il partner dello studio deve avere uno stretto rapporto con il soggetto, un contatto diretto di almeno 3 giorni a settimana per un minimo di 6 ore di veglia a settimana (o tempo superiore, in base ai requisiti locali), e deve essere disposto ad accompagnare il soggetto a tutte le visite dello studio nonché a monitorare la compliance della somministrazione del farmaco sperimentale. Il partner dello studio deve comprendere la natura dello studio e aderire ai requisiti dello stesso (ad es. dose, visita pianificata e valutazioni). Si raccomanda che il caregiver accompagni il soggetto a tutte le visite previste nell’ambito dello studio. 3. Firmare (o firma del rappresentante legale) il consenso informato in conformità ai requisiti locali, dopo aver ricevuto una spiegazione dell’ambito e della natura dello studio. |
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E.4 | Principal exclusion criteria |
The subject must be excluded from participating in the trial if the subject: 1. Is in imminent risk of self harm, based on clinical interview or on the Columbia Suicidality Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator. Subjects who report suicidal ideation with intent, with or without a plan (e.g., suicidal ideation item 4 or 5 on the C-SSRS) in the past one (1) month or suicidal behavior in the past six (6) months should be excluded. Such subjects will be permitted to rescreen for entry into this study once in the Investigator’s opinion, this risk of harm to self or others is no longer present. 2. Has developed a recent or ongoing, uncontrolled, clinically significant medical or psychiatric condition that precludes participation in this protocol in the judgment of the investigator. 3. Based on results from the EOT Visit (Visit 12) in the initial 104-week trial has results of clinical laboratory tests (complete blood count [CBC], blood chemi stries, and urinalysis) that are clinically unacceptable to the investigator. 4. Based on the results from the EOT Visit (Visit 12) has results of a physical examination, and vital signs that are clinically unacceptable to the investigator. 5. Has developed a form of dementia that is not Alzheimer's Disease, including but not limited to, dementia due to HIV infection, head trauma, vascular disease, Parkinson's disease, frontotemporal dementia, or Huntington's disease, as determined by the investigator. 6. Anticipates receiving any of the treatments listed among those forbidden. |
Il soggetto deve essere escluso dalla partecipazione allo studio nei seguenti casi: 1. È a rischio imminente di autolesionismo sulla base del colloquio clinico o della Scala della Columbia University per la valutazione della gravità del rischio di suicidio (Columbia Suicidality Severity Rating Scale, C-SSRS) oppure di causare danni ad altri secondo il parere dello sperimentatore. I soggetti che riportino ideazioni suicidarie con intenzione, con o senza piano (ad es. ideazione suicidaria punto 4 o 5 della scala C-SSRS) nel (1) mese precedente o comportamento suicidario nei precedenti sei (6) mesi saranno esclusi. Tali soggetti potranno essere sottoposti a nuovo screening per l’ingresso in questo studio quando, secondo il parere dello sperimentatore, tale rischio di autolesione o lesione altrui non sia più presente. 2. Sviluppa una condizione medica o psichiatrica recente o in atto, non controllata, clinicamente significativa che precluda la partecipazione a questo protocollo secondo il giudizio dello sperimentatore. 3. In base ai risultati della visita EOT (End of Treatment [fine trattamento]) (Visita 12) nell’ambito dello studio iniziale di 104 settimane, gli esiti dei test di laboratorio clinici (emocromo completo, analisi ematochimiche e analisi delle urine) sono clinicamente inaccettabili a parere dello sperimentatore. 4. In base ai risultati della Visita EOT (Visita 12) gli esiti dell’esame obiettivo e i parametri vitali sono clinicamente inaccettabili a parere dello sperimentatore. 5. Sviluppa una forma di demenza che non è Malattia di Alzheimer, che include, ma non solo, demenza dovuta a infezione da HIV, trauma cranico, patologia vascolare, morbo di Parkinson, demenza fronto-temporale, oppure malattia di Huntington, come determinato dallo sperimentatore. 6. Prevede di ricevere uno qualsiasi dei trattamenti elencati tra quelli proibiti. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change from baseline (CFB) in CDR-SB score at Week 130. |
L’endpoint primario è la differenza tra i trattamenti nella variazione dal basale in base alla variazione del punteggio basale del CDR-SB alla Settimana 130. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and Week 130. |
Basale e alla settimana 130. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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 | 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 | No |
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
| 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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 58 |
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 | Information not present in EudraCT |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Finland |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Netherlands |
New Zealand |
Norway |
Poland |
Spain |
Switzerland |
United Kingdom |
United States |
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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
|
The study is expected to last up to approximately five years or until a) MK-8931 becomes commercially available (locally) or b) when the MK-8931 program is terminated (whichever comes first). |
La durata prevista dello studio di estensione è di circa 5 anni o a) fino a quando MK-8931 diverrà disponibile sul mercato (localmente) b) oppure fino al termine del programma di sviluppo del trattamento MK-8931. Tale periodo potrebbe essere limitato ai sensi delle normative locali. |
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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 | 5 |
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 | 5 |
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 |