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 |
|
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 | 18.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10001897 |
E.1.2 | Term | Alzheimer's disease (incl subtypes) |
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 evaluate the efficacy of gantenerumab compared with placebo
administered to patients by SC injection over 100 weeks as measured by
the following co-primary endpoints (final outcome assessment 4 weeks
after the final dose):
• Cognition, as measured by the ADAS-Cog (13-item)
• Function, as assessed by the ADCS-ADL |
|
E.2.2 | Secondary objectives of the trial |
1. to evaluate the benefits of gantenerumab versus placebo administered
to patients by SC injection over 100 weeks on slowing clinical decline
and disease progression by assessing the following:
• Time to clinically evident decline
• Change from baseline at Week 104 in CDR-SB
• ADAS-Cog responder
• Disease pathology biomarkers
2. Additional secondary endpoints
· Global: Effect on severity of dementia and global measures of cognition
and function
· Cognition: Effect on cognition
· Behavioar: Effect on behavioral and neuropsychological symptoms of
AD
· Other AD symptoms and effects: Effect of gantenerumab on healthrelated
QoL, patient-individualized goal achievement (sites in Englishand
French-speaking countries only), on caregiver emotional well-being,
on the amount of assistance patients with dementia require in
performing daily activities |
|
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 |
WN28745-PET Substudy, version 1, dated 19-Nov-2013
Title: PET IMAGING SUBSTUDY ASSOCIATED WITH: A PHASE III,
RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLELGROUP,
MULTICENTER, EFFICACY, AND SAFETY STUDY OF
GANTENERUMAB IN PATIENTS WITH MILD ALZHEIMER'S DISEASE
The primary objective of the WN28745-PET substudy is to assess changes in amyloid load over time using florbetapir in patients enrolled
in Study WN28745 who are treated with gantenerumab (RO4909832) or placebo. This patient population has probable mild AD (based on NINCDS/ADRDA criteria) or probable major NCD due to AD of mild severity (based on the DSM-5 criteria).The secondary objective of this substudy is to assess the concordance between positivity or negativity on CSF Aβ1−42 testing at entry in Study WN28745 and amyloid PET visual read in the WN28745-PET substudy.
WN28745-Cardiac PET Substudy, Version 1, dated 26.11.2014
Title: CARDIAC PET IMAGING SUBSTUDY ASSOCIATED WITH: A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLELGROUP,
MULTICENTER, EFFICACY AND SAFETY STUDY OF GANTENERUMAB IN PATIENTS WITH MILD ALZHEIMER'S DISEASE
Objectives: The primary objective of this cardiac PET substudy is to assess changes in amyloid load in heart over time using florbetapir F18 in patients enrolled in the main study and the brain only PET substudy who are treated with gantenerumab (RO4909832) or placebo. This patient population has probable mild AD (based on NINCDS/ADRDA criteria) or probable major NCD due to AD of mild severity (based on the DSM-5 criteria). |
|
E.3 | Principal inclusion criteria |
- Adult patients, 50 to 90 years of age, inclusive
- Clinical diagnosis of probable mild Alzheimer disease based on
NINCDS/ADRDA criteria whether or not receiving AD approved
medication
- Availability of a person ('caregiver') who in the investigator's
judgment has frequent and sufficient contact with the patient, and is
able to provide accurate information regarding the patient's cognitive
and functional abilities
- Fluency in the language of the tests used at the study site
- Willingness and ability to complete all aspects of the study
- Adequate visual and auditory acuity, in the investigator's judgment,
sufficient to perform the neuropsychological testing (eye glasses and
hearing aids are permitted)
- If currently receiving approved medications for AD, doses must have
been stable for 3 months prior to screening
- Agreement not to participate in other research studies for the
duration of this trial and its associated substudies |
|
E.4 | Principal exclusion criteria |
- Dementia or NCD due to a condition other than AD, including, but not
limited to, frontotemporal dementia, Parkinson disease, dementia with
Lewy bodies, Huntington disease, or vascular dementia
- History or presence of clinically evident vascular disease potentially
affecting the brain that in the opinion of the investigator has the
potential to affect cognitive function
- History or presence of stroke within the past 2 years or documented
history of transient ischemic attack within the last 12 months
- History or presence of systemic autoimmune disorders potentially
causing progressive neurologic disease with associated cognitive deficits
- History of schizophrenia, schizoaffective disorder, or bipolar disorder
- Alcohol and/or substance use disorder (according to the DSM-5)
within the past 2 years (nicotine use is allowed)
- History or presence of atrial fibrillation
Within the last 2 years, unstable or clinically significant cardiovascular
disease (e.g., myocardial infarction, angina pectoris, cardiac failure New
York Heart Association Class II or higher)
- Uncontrolled hypertension
- Chronic kidney disease
- Impaired hepatic function |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Mean change in Alzheimer's Disease Activity Scale-Cognitive subscale 13 (ADAS-Cog13) scores
Mean change in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- from baseline to Week 104 |
|
E.5.2 | Secondary end point(s) |
- Change in biomarkers (t-tau, p-tau, Abeta 1-42 levels) in cerebral
spinal fluid
- Change in MRI volumetry, assessed on structural MRI
- Change in Clinical Dementia Rating (CDR-SB/CDR-GS)
- Change in neuropsychiatric behaviour: Neuropsychiatric Inventory
(NPI) total and domain scores
- Change in cognition: MMSE total score
- Safety: Incidence of adverse events, serious adverse events and
treatment discontinuations
- Change in Clinical Dementia Rating-Sum of Boxes (CDR-SB)
- ADAS-Cog responder |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
from baseline to Week 104
- from baseline to Week 104
- from baseline to Week 104
- from baseline to Week 104
- from baseline to Week 104
- 152 weeks
- from baseline to Week 104
- from baseline to week 104 |
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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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarkers, exploratory biomarkers, clinical genotyping, imaging. |
|
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 | 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 | 66 |
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 |
Bulgaria |
Canada |
Denmark |
Finland |
France |
Germany |
Guatemala |
Hungary |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
Poland |
Portugal |
Russian Federation |
Spain |
Sweden |
Switzerland |
Turkey |
United Kingdom |
United States |
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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
|
The end of the study is defined as the date when the last patient, last visit (LPLV) occurs
or the date on which the last datapoint required for statistical analysis or safety follow-up is received from the last patient, whichever occurs later. |
|
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 |