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 |
Medical condition in which an individual's memory, thinking, judgment, and gradually their ability to function is lost. |
|
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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012271 |
E.1.2 | Term | Dementia Alzheimer's type |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
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 assess the hypothesis that solanezumab 400 mg
Q4W will slow the clinical progression of prodromal
AD over 24 months compared to placebo |
|
E.2.2 | Secondary objectives of the trial |
To assess the effect of solanezumab vs. placebo on the clinical
progression of prodromal AD over 24 months
To assess the effect of solanezumab vs. placebo on quality of life and
health outcomes in prodromal AD over 24 months
To assess the effect of solanezumab vs. placebo on biomarkers in
prodromal AD over 24 months
To assess the hypothesis that change from baseline in accumulation of
tau pathology over 12 and 24 months is associated with changes from
baseline in cognition |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Protocol Addendum H8A-MC-LZBE(1)
(18F-AV-1451 tau imaging)
A 24-Month, Phase 3, Multicenter, Placebo-Controlled
Study of Efficacy and Safety of Solanezumab versus
Placebo in Prodromal Alzheimer’s Disease. 28Mar2016. Objectives: To assess the hypothesis that solanezumab will slow
the accumulation of tau pathology over 12 and 24
months compared to placebo; To assess the hypothesis that change from baseline in
accumulation of tau pathology over 12 and 24
months is associated with changes from baseline in
cognition; and To assess the hypothesis that change from baseline in
accumulation of tau pathology over 24 months is
associated with changes from baseline in function.
Protocol Addendum H8A-MC-LZBE(2) (LP)
A 24-Month, Phase 3, Multicenter, Placebo-Controlled
Study of Efficacy and Safety of Solanezumab versus
Placebo in Prodromal Alzheimer’s Disease. 28Mar2016. Objectives: Lumbar punctures (LPs) will be used to collect cerebrospinal fluid (CSF) for assays of
solanezumab, amyloid beta (AB) species, and tau proteins (as described in this addendum); and
for CSF storage. |
|
E.3 | Principal inclusion criteria |
•Has a diagnosis by the study investigator of a clinical syndrome of
cognitive impairment consistent with prodromal AD per International
Working Group (IWG) diagnostic criteria or MCI due to AD per National
Institute on Aging-Alzheimer's Association (NIA-AA) diagnostic criteria.
•Has evidence of amyloid pathology by PET imaging or lumbar puncture CSF
•Scores 17-28 on MoCA at screening.
•Scores <27 on free recall cutoff score from the FCSRT (Picture
version) at screening.
•Scores ≤4 on Modified Hachinski Ischemia Scale (MHIS).
•Scores >0 on the FAQ.
•Has a florbetapir PET scan or CSF result at screening consistent with
the presence of amyloid pathology. |
|
E.4 | Principal exclusion criteria |
•Has had MRI or computerized tomography (CT) of brain within previous
2 years showing pathology that would be inconsistent with a diagnosis
of AD.
•Has known allergy to humanized monoclonal antibodies.
•Has an ongoing clinically significant laboratory abnormality, as
determined by the investigator.
•Has screening MRI with results showing >4 amyloid related imaging
abnormalities H (ARIA-H) micro-hemorrhages or presence of ARIA-E.
•Has any contraindications for MRI studies, including claustrophobia, the
presence of metal (ferromagnetic) implants, or a cardiac pacemaker that
is not compatible with MRI.
•Has received treatment with a stable dose of an achetylcholinesterase
(AChEI)inhibitor or memantine for less than 2 months before
randomization. (If a participant has recently stopped AChEIs and/or
memantine, he or she must have discontinued treatment at least 2
months before randomization.) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Alzheimer´s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) Score |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Alzheimer´s Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCIADL); Mini Mental Status Examination (MMSE); Montreal Cognitive Assessment (MoCA); Functional Activities Questionnaire (FAQ); Neuropsychiatric Inventory (NPI); Clinical Dementia Rating Scale Sum of Boxes (CDR-SB); Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); Free and Cued Selective Reminding Test
(FCSRT); Resource Utilization in Dementia-Lite (RUD-Lite); EuroQol 5-Dimensional Health-Related Quality of Life Scale (EQ-5D); Quality of Life in Alzheimer's Disease Scale (QoL-AD); Concentration of Plasma Amyloid-β Peptide (Aβ) and Plasma Solanezumab; Volumetric Magnetic Resonance Imaging (vMRI); Florbetapir Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVr); Concentration of Cerebrospinal Fluid (CSF) Aβ and CSF Tau Proteins; Pharmacogenomics Markers |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | 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 | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 81 |
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 |
Australia |
Belgium |
Canada |
China |
Finland |
France |
Germany |
Italy |
Japan |
Korea, Democratic People's Republic of |
Netherlands |
Poland |
Spain |
Sweden |
Switzerland |
Taiwan |
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 | 5 |
E.8.9.1 | In the Member State concerned months | 4 |
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 | 4 |