E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Agitation and Aggression in Moderate to Severe Alzheimer’s Disease |
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E.1.1.1 | Medical condition in easily understood language |
Agitation and Aggression in Patients With Alzheimer’s Disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 efficacy of ELND005 treatment compared with placebo in reducing the severity of agitation and aggression at 12 weeks;
To evaluate the safety and tolerability of the ELND005 dosing regimen in Moderate to Severe AD patients |
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E.2.2 | Secondary objectives of the trial |
To evaluate additional efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) endpoints.
To evaluate the efficacy of ELND005 on the patient’s dependence status and on caregiver distress. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Has a diagnosis of Probable AD according to the National Institute on Aging-Alzheimer’s Association (NIA-AA) guidelines (McKhann et al 2011).
-Has an MMSE score of 5 to 24 (inclusive) at the Screening Visit.
-Has clinically significant agitation/aggression defined as Neuropsychiatric Inventory (NPI)-agitation/aggression subscore of ≥4 at both the Screening and Baseline Visits with a severity score of ≥2 and frequency score of ≥2.
-Has had either no response or suboptimal response to standard nonpharmacological interventions. |
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E.4 | Principal exclusion criteria |
-The agitation/aggression is attributable to concomitant medications, environmental conditions, or active medical or psychiatric condition.
-Has a current diagnosis of major depressive disorder according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition Text Revision (DSM IV TR).
-Has persistent and distressing psychotic symptoms (delusion and/or hallucinations) that require psychiatric hospitalization.
-Treated with injectable depot preparations of an antipsychotic within 3 months of the Screening Visit.
-Has brain abnormalities from brain imaging performed at the Screening Visit, or from an MRI or CT scan taken within 1 year prior to the Screening Visit, that can be attributed to diseases or processes other than AD. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The difference in change from Baseline to Week 12 in NPI-C combined agitation and aggression subscores between the ELND005 and placebo treatment groups |
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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) |
Change from Baseline in:
- mADCS-CGIC agitation domain scores
- NPI-C subitems of agitation, aggression, apathy, depression/dysphoria, anxiety
-NPI subitems of aberrant motor behavior, nighttime behavior, disinhibition, delusions, and hallucination
- Total NPI score
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | 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 | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Canada |
France |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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A study patient will be considered to have completed Study AG201 at the end of 12 weeks of treatment (ie, Week 12 or End of Study [EOS]).
This definition is based on the timepoint for primary endpoint assessment. A safety follow-up phase of 6 weeks will occur following the Week 12 or End of Study [EOS] visit. |
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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 | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 14 |