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 |
Prodromal Alzheimer's Disease |
|
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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066571 |
E.1.2 | Term | Progression of 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 |
To evaluate the effect of gantenerumab vs. placebo on the change in the Clinical Dementia Rating scale Sum of Boxes (CDR-SOB), a global measure of cognition and functional ability. |
|
E.2.2 | Secondary objectives of the trial |
- Evaluate the effect of gantenerumab vs. placebo on cognition (by the ADAS-Cog, MMSE, CANTAB and the FCSRT-IR), on global measures (based on the CDR global score), on functioning (by the FAQ), on neuropsychiatric functioning (by the NPI-Q) and on onset of dementia.
- Assess the safety and tolerability of gantenerumab assessed by MRI imaging, physical and neurological examinations, vital signs, blood and urine safety tests, ECGs and adverse event monitoring.
- Evaluate the effect of gantenerumab vs. placebo on hippocampal volume, whole brain volume, ventricular enlargement, and possibly other volumetric measures.
- Change in Cerebrospinal Fluid Biomarker Measures. (T-tau, P-tau, and Abeta 1-42 )
- Determine the relationship of plasma and CSF concentrations of gantenerumab on other responses. - To assess incidence of antigantenerumab antibodies, and if relevant, evaluate its effect on the pharmacokinetic, pharmacodynamic, efficacy and safety parameters. |
|
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 |
WN25203-PET, dated 26.06.2010.
Sub-study to protocol WN25203, using positron emission tomography (PET) with an amyloid tracer to assess changes in amyloid load over time in subjects with Prodromal Alzheimer's Disease |
|
E.3 | Principal inclusion criteria |
- Adult patients, 50-85 years of age
- Patients with prodromal Alzheimer's Disease who are not receiving
memantine or cholinesterase inhibitors
- Has a study partner who is able to provide accurate information as to
the patient's cognitive and functional abilities, who agrees to provide
information at clinic visits which require partner input for scale
completion
- Has had sufficient education or work experience to exclude mental
retardation
- Study partner has noticed a recent gradual decrease in patient's
memory (e.g. over the last 12 months), which the patient may or may
not be aware of
- Screening MMSE score of 24 or above
|
|
E.4 | Principal exclusion criteria |
- Other prior or current neurologic or medical disorder which may
currently or during the course of the study impair cognition or
psychiatric functioning
- A history of stroke
- A documented history of transient ischemic attack within the last 12
months
- History of schizophrenia, schizoaffective or bipolar disorder
- Currently meets criteria for major depression
- Within the last 2 years, unstable or clinical significant cardiovascular
disease (e.g. myocardial infarction, angina pectoris) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in the Clinical Dementia Rating scale Sum of Boxes (CDR-SOB), a
global measure of cognition and functional ability |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Change in cognition assessed with Alzheimer Disease Assessment
Scale-Cognition
2. Change in functioning assessed with Functional Activities
Questionnaire
3. Change in Cerebrospinal Fluid Biomarker Measures (T-tau, P-tau, and
Abeta 1-42 )
4. Safety (nature and incidence of adverse events)
5. Pharmacokinetics: gantenerumab levels |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 2 years
2. 2 years
3. 2 years
4. 5 years
5. 2 years |
|
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 | No |
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 |
Biomarkers, Explanatory Biomarkers, Clinical Genotyping, |
|
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 |
|
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 | 3 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 67 |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Italy |
Korea, Republic of |
Mexico |
Netherlands |
Poland |
Portugal |
Russian Federation |
Spain |
Sweden |
Turkey |
United Kingdom |
|
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
|
The end of the study will be considered to be the date of the last visit (including the last scheduled follow-up visit according to study protocol) of the last patient in the study. |
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |