E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Early Symptomatic 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 | 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 |
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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 assess the effect of donanemab versus placebo on clinical progression in participants with early symptomatic AD. |
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E.2.2 | Secondary objectives of the trial |
-To assess the effect of donanemab versus placebo on clinical progression in participants with early symptomatic AD -To assess the effect of donanemab versus placebo on brain amyloid deposition; -To assess the effect of donanemab versus placebo on brain tau deposition; -To assess the effect of donanemab versus placebo on brain region volumes; -To evaluate safety and tolerability of donanemab; -To assess peripheral PK and presence of anti-donanemab antibodies
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-60 to 85 years of age inclusive, at the time of signing the informed consent, -Gradual and progressive change in memory function reported by the participant or informant for ≥6 months, -An MMSE score of 20 to 28 (inclusive) at LEAD-IN SCREENING or COMPLETE SCREENING, -Meet flortaucipir F18 scan (central read) criteria, -Meet florbetapir F18 scan (central read) criteria, -Have a study partner who will provide written informed consent to participate, is in frequent contact with the participant (defined as at least 10 hours per week), and will accompany the participant to study visits or be available by telephone at designated times
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E.4 | Principal exclusion criteria |
-Significant neurological disease affecting the central nervous system other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson’s disease, multiple concussions, or epilepsy or recurrent seizures (except febrile childhood seizures), -Current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), psychiatric,immunologic, or hematologic disease and other conditions that, in the investigator’s opinion, could interfere with the analyses in this study; or has a life expectancy of <24months, -History of cancer within the last 5 years, with the exception of non-metastatic basal and/or squamous cell carcinoma of the skin, in situ cervical cancer, nonprogressive prostate cancer, or other cancers with low risk of recurrence or spread, -Participants with any current primary psychiatric diagnosis other than AD if, in the judgment of the investigator, the psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect cognitive assessment, or affect the participant’s ability to complete the study. Participants with history of schizophrenia or other chronic psychosis are excluded, -History of clinically significant multiple or severe drug allergies, significant atopy, or severe posttreatment hypersensitivity reactions (including but not limited to erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis,and/or exfoliative dermatitis),
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to test the hypothesis that IV infusion of donanemab will slow the cognitive and/or functional decline of AD as measured by iADRS score compared with placebo in participants with early symptomatic AD with low-medium tau pathology or the overall population at baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary time point for treatment comparison will be at Week 76. The treatment group contrast in least-squares mean progression and its associated p-value and 95% CI will be calculated for the treatment comparison of donanemab versus placebo using the MMRM model. |
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E.5.2 | Secondary end point(s) |
This will be assessed using DPM, MMRM and NCS analysis for the low-medium tau population, overall population and high-tau population. The secondary efficacy outcomes include ADAS-Cog13, ADCS-iADL, CDR-SB and MMSE. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The safety secondary endpoints are evaluated through week 76 and on an ongoing basis. |
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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 | 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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Cohort 1 only will be sponsor-unblinded at a prespecified timepoint |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 |
Canada |
Japan |
United States |
Czechia |
France |
Germany |
Netherlands |
Poland |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 12 |