E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
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 verify the clinical benefit of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the CDR-SB score as compared with placebo in participants with early Alzheimer's disease. |
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E.2.2 | Secondary objectives of the trial |
Key Secondary Objectives: To assess the effect of monthly doses of aducanumab as compared with placebo on clinical decline as measured by the iADRS. To assess the effect of monthly doses of aducanumab as compared with placebo on clinical decline as measured by ADCS-ADL-MCI. To assess the effect of monthly doses of aducanumab as compared with placebo on clinical decline as measured by ADASCog13. To assess the effect of monthly doses of aducanumab as compared with placebo on clinical decline as measured by the MMSE. To assess the effect of monthly doses of aducanumab as compared with placebo on clinical decline as measured by NPI- 10. |
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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 |
Approximately 400 participants are expected to enroll in each of the following 3 biomarker sub-studies: 1. Measurement of amyloid plaque burden in certain areas of the brain as measured by amyloid PET 2. Measurement of neurofibrillary tangle burden in certain areas of the brain as measured by tau PET 3. Measurement of disease- or treatment-related CSF biomarkers |
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E.3 | Principal inclusion criteria |
Key Inclusion Criteria: - The participant must have confirmed amyloid beta pathology by CSF (historical CSF test results not allowed) or amyloid PET - The participant must have a history of subjective memory decline with gradual onset and slow progression over the 6 months before Screening, confirmed by study partner - The participant must have 1 informant/care partner who, in the Investigator's opinion, has frequent and sufficient contact with the participant (at least 10 hours/week in person or by phone) as to be able to provide accurate information about the participant's cognitive and functional abilities over time - The participant must meet all of the following clinical criteria for MCI due to Alzheimer's disease or mild Alzheimer's disease according to NIA-AA criteria [Albert 2011; McKhann 2011]: a. Have an MMSE score between 22 and 30 inclusive b. Have a CDR memory score >0.5 c. Have a CDR-GS of 0.5 or 1.0 d. Have a RBANS score of 85 or lower indicative of objective cognitive impairment (based upon the DMI score). - The participant must be in good health, apart from a clinical diagnosis of early Alzheimer's disease, as determined by the Investigator based on medical history and screening assessments - The participant must consent to ApoE genotyping - Must consent to apolipoprotein E (ApoE) genotyping. (Note: Participants are not required to be ApoE ε4 carriers) |
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria: - Any uncontrolled medical or neurological/neurodegenerative condition (other than Alzheimer's disease) that, in the opinion of the Investigator, might be a contributing cause of the participant's cognitive impairment - Clinically significant and/or unstable psychiatric illness within 6 months prior to Screening - Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening - History of severe allergic or anaphylactic reactions or of hypersensitivity to any of the inactive ingredients in the drug product - Participation in any study with purported disease-modifying effect in Alzheimer's disease within 12 months prior to Screening unless documentation of receipt of placebo is available - Current use or previous use of medications with a purported disease modifying effect in Alzheimer's disease, outside of investigational studies - Use of any medications that, in the opinion of the Investigator, may contribute to cognitive impairment, put the participant at higher risk for AEs, or impair the participant's ability to perform cognitive testing or complete study procedures - Use of any investigational drug - Prior exposure to aducanumab either commercially or by participation in a previous study with aducanumab. (Participants are eligible if they did not receive active aducanumab.) - A negative PET scan result with any amyloid-targeting ligand within 12 months prior to Screening NOTE: Other protocol defined Inclusion/Exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in CDR-SB score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in iADRS score 2. Change from baseline in ADCS-ADL-MCI score 3. Change from baseline in ADAS-Cog13 score 4. Change from baseline in MMSE score 5. Change from baseline in NPI-10 score 6. Change from baseline in PET Signal 7. Change from baseline in Tau PET Signal 8. Change from baseline in CDR-SB Score 9. Change from baseline in GST Composite Z-Score |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Week 78, Week 106 2. Week 78, Week 106 3. Week 78, Week 106 4. Week 78, Week 106 5. Week 78, Week 106 6. Week 78, Week 104 7. Week 78, Week 104 8. Week 106 9. Week 78, Week 106 |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Verify the Clinical Benefit of the IMP |
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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) | Yes |
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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 61 |
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 |
Brazil |
Canada |
China |
Mexico |
United States |
Switzerland |
United Kingdom |
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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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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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |