E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neurodegenerative disorders with Tau-pathology; including, but not limited to, Alzheimer's disease, progressive supranuclear palsy, frontotemporal dementia, corticobasal degeneration and mild cognitive impairment.
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E.1.1.1 | Medical condition in easily understood language |
Diseases affecting the brain such as dementia or cognitive impairment; i.e. diseases that typically cause memory problems that the patient and/or relatives have noticed. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053643 |
E.1.2 | Term | Neurodegenerative disorder |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012267 |
E.1.2 | Term | Dementia |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067889 |
E.1.2 | Term | Dementia with Lewy bodies |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10028037 |
E.1.2 | Term | Movement disorders (incl parkinsonism) |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
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 | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009846 |
E.1.2 | Term | Cognitive impairment |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048598 |
E.1.2 | Term | Cognitive disorders |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012285 |
E.1.2 | Term | Dementia due to Pick's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036813 |
E.1.2 | Term | Progressive supranuclear palsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10074616 |
E.1.2 | Term | Prodromal Alzheimer's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
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 | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Study the diagnostic accuracy of Tau PET (18F-RO6958948) and Vizamyl (18F-Flutemetamol) for identifying healthy elderly individuals and patients with subjective or objective mild cognitive symptoms who are at high risk of subsequent development of dementia due to Alzheimer's disease (AD) or other neurodegenerative disorders. |
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E.2.2 | Secondary objectives of the trial |
Study whether Tau pathology (visualized with 18F-RO6958948) or amyloid pathology (visualized using Vizamyl) in non-demented subjects affects functional and structural neuronal connectivity (visualized with MRI; i.e. resting state functional MRI, Arterial Spin Labeling, Diffusion Tensor Imaging, Kurtosis etc). - Study whether CSF biomarkers (especially P-tau, total-tau and oligomeric tau, but also markers of neuroinflammation) are associated with 18F-RO6958948 retention visualized with PET. - Study whether Tau pathology can precede amyloid pathology (visualized using Vizamyl) in preclinical AD, or whether Tau-pathology is always a consequence of amyloid accumulation. - Establish cut offs for pathological PET-scans in a healthy population.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Healthy elderly subjects - No cognitive symptoms reported by study participant - Normal performance on cognitive tests - General cognition and functional performance preserved such that a diagnosis of MCI or dementia cannot be made by physician at the time of the baseline visit - Between 20 and 100 years of age - Fluent in Swedish - Agrees to at least one lumbar puncture, MRI scan of the brain and neuropsychological testing.
Mild cognitive impairment/dementia - Cognitive symptoms reported by patient and/or informant - Between 20 and 100 years of age - General cognition and functional performance sufficiently preserved such that a diagnosis of dementia cannot be made by physician at the time of the baseline visit (MCI) - General cognition and functional performance fulfilling a diagnosis of dementia at the time of the baseline visit (Dementia group) - Fluent in Swedish - Agrees to at least one lumbar puncture, MRI scan of the brain and neuropsychological testing. |
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E.4 | Principal exclusion criteria |
Exclusion Criteria: - Major depression as described in DSM-IV. - History of schizophrenia or other recurrent psychotic disorder - History of alcohol or substance abuse or dependence within the past 5 years - Diseases that will make study participation difficult, such as terminal cancer or significant heart failure. - Certain neurologic diseases, such as Huntington's disease, normal pressure hydrocephalus, brain tumor, subdural hematoma, multiple sclerosis, or persistent neurologic deficits or known structural brain abnormalities. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Detection of specific signal of 18F-RO6958948 or 18F-Flutemetamol in patients with neurodegenerative disease or healthy volunteers.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After dosing and PET-scanning.
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E.5.2 | Secondary end point(s) |
-18F-RO6958948 or 18F-Flutemetamol PET brain:cerebellar uptake ratios measured with a priori VOI analysis in subjects with neurodegenerative disease compared to healthy volunteers. -Associations of 18F-RO6958948 or 18F-Flutemetamol brain uptake ratios measured by VOI analysis with other diagnostic methods, including CSF biomarkers, cognitive tests and MRI findings. -Regional differences in distribution of 18F-RO6958948 or 18F-Flutemetamol brain uptake between different neurodegenerative disease conditions. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After dosing and PET-scanning. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 11 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |