E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild Cognitive Impairment due to Alzheimer's Disease and Mild Alzheimer's Dementia |
|
E.1.1.1 | Medical condition in easily understood language |
Mild Cognitive Impairment due to Alzheimer's Disease and Mild Alzheimer's Dementia |
|
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 | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
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 |
The primary objective of the study is to assess the safety impact of continuing aducanumab dosing in asymptomatic Amyloid-related Imaging Abnormalities (ARIA) in participants with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) or with mild AD dementia. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to characterize ARIA, from both the imaging and the clinical perspective and to characterize the safety, tolerability, pharmacokinetics (PK), and immunogenicity of aducanumab. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Key Inclusion Criteria:
• Ability of the participant or his/her legally authorized representative to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential
health information in accordance with national and local
participant privacy regulations.
• Must have at least 6 years of education or work
experience to exclude mental deficits other than MCI
due to AD or mild AD dementia.
• Must have evidence of cerebral Aβ accumulation, based on a positive PET scan of the brain. Previously obtained positron emission tomography (PET) scan
(within 12 months of screening) is permissible. Previous PET scan images must be submitted to the central imaging vendor to confirm that study inclusion criteria
are met.
• Must consent to apolipoprotein E (ApoE) genotyping.
• Must meet all of the following clinical criteria for MCI due to AD or mild AD dementia according to NIAAA criteria [Albert 2011; McKhann 2011], and must have
the following: MCI due to AD (a CDR global score of 0.5, and an MMSE score between 24 and 30
(inclusive)), and Mild AD dementia (a CDR global score of 0.5 or 1, and as MMSE score between 20 and 26 (inclusive)).
|
|
E.4 | Principal exclusion criteria |
Key Exclusion Criteria:
• Any uncontrolled medical or
neurological/neurodegenerative condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause of the participant’s cognitive
impairment (e.g., substance abuse, vitamin B12 deficiency, abnormal thyroid function, stroke or other cerebrovascular condition, Lewy body dementia,
frontotemporal dementia, head trauma).
• Clinically significant unstable psychiatric illness
(e.g., uncontrolled major depression, uncontrolled
schizophrenia, uncontrolled bipolar affective disorder)
within 6 months prior to Screening.
• Transient ischemic attack or stroke or any
unexplained loss of consciousness within 1 year prior to Screening.
• Vaccinations within 10 days prior to randomization (Day 1).
• Female participants who are pregnant or currently breastfeeding. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint:
Number of Clinically Impactful
Amyloid-related Imaging
Abnormalities (ARIA)
Clinically impactful ARIA is
defined as symptoms and/or
signs associated with ARIA
that are life threatening,
require hospitalization, and/or
result in persistent or
significant disability as
assessed by the independent
Adjudication Committee. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary endpoint:
Baseline up to Week 54 |
|
E.5.2 | Secondary end point(s) |
1. Number of Participants With
ARIA by Severity as Obtained
on Magnetic Resonance
Imaging (MRI)
2. Time to Onset of ARIA as
Obtained on MRI
3. Time to Resolution of ARIA as
Obtained on MRI
4. Number of Participants With
Symptomatic ARIA by Severity
5. Time to Onset of Symptomatic
ARIA
6. Time to Resolution of
Symptomatic ARIA
7. Number of Participants With
Adverse Events (AEs) and Serious Adverse Events (SAEs)
8.Change From Baseline in the
Montreal Cognitive
Assessment (MoCA) at Week
54
9.Aducanumab Concentration in
Serum
10. Number of Participants With
Antiaducanumab Antibodies in
Serum |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints ;
1-7 will be Baseline up to week 54.
Secondary endpoint 8 ; baseline, week 54
Secondary endpoint 9 and 10; Pre-dose on Day 1 of
Weeks 1, 16, 24, 32, 44,
54, 56, 70, 80, 104
|
|
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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
Please refer to Protocol Section 11.1.2 (0.9% sodium chloride) |
|
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 | 52 |
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 |
Denmark |
Finland |
France |
Germany |
Italy |
Korea, Republic of |
Netherlands |
Poland |
Portugal |
Spain |
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 | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 11 |