E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prodromal Alzheimer's Disease |
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E.1.1.1 | Medical condition in easily understood language |
Early Alzheimer's Disease |
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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 |
•To evaluate the safety and tolerability of MK-8931 in the long term treatment of prodromal Alzheimer’s Disease (AD)
•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.
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E.2.2 | Secondary objectives of the trial |
•There are no secondary objectives for this long term safety trial. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•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 safety extension, except in special circumstances, which require Sponsor approval.
•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.
•Sign (or legal representative signature) the informed consent in accordance with local requirements, after the scope and nature of the trial have been explained. |
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E.4 | Principal exclusion criteria |
•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.
•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.
•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 chemistries, and urinalysis) that are clinically unacceptable to the investigator. However, it is recognized that lab results will not be
available at Visit 12/12B if they occur on the same day. Therefore, such
subjects may be enrolled prior to receiving these results; upon their receipt, if the PI feels they are clinically unacceptable the subject should be discontinued.
•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.
•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.
•Anticipates receiving any of the treatments listed as prohibited.
• Has progressed to dementia due to AD per investigator diagnosis in the initial 104-week study. |
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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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and Week 130. It is noted that baseline refers to the baseline from the Initial 104-week trial. |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 8 |
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 | 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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Finland |
France |
Germany |
Hungary |
Ireland |
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
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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). |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |