E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prodromal Alzheimer's Disease |
|
E.1.1.1 | Medical condition in easily understood language |
Early Alzheimer’s Disease |
|
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 |
|
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 with 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. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Have tolerated study medication and completed the initial 104-week trial.
2. Have a trial partner who is reliable and competent.
3. Sign the informed consent. |
|
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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the change from Baseline in the CDR SB score at Week 130. |
|
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. |
|
E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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) | 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 | 2 |
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 |
|
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
|
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | |
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 |