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 |
Alzheimer is defined pathologically by the presence of tau tangles and amyloid senile plaques in the neocortex. To quantify pTAU in vivo, p-tau PET tracers have now been developed, like F18-MK6240. |
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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 |
Evaluate the regional deposition of p-TAU protein aggregates using F18-MK6240 PET/CT, non-invasive in vivo imaging within the brain of patients affected by several neurodegenerative disorders. Patients’ data (MCI, mild AD, non-AD dementia) will be compared to a control group data. Specific aims: To evaluate how: 1)tau PET signal distinguish patients with AD, patients with non-AD syndrome, and controls 2)tau PET signal depends on age, and on genetic risks in non-demented controls 3)To compare tau PET imaging to tau measures in the cerebrospinal fluid (CSF) 4)tau PET imaging can predict progression to dementia in MCI and control participants 5)tau PET signals relate to (functional) MRI data 6)tau PET signals relate to blood-derived biomarkers 7)tau PET signals relate to cognitive performance 8)tau PET signals relate to electroencephalographic (EEG) signals 9)tau PET measures evolve over time, in relation to cognitive performance and the other biomarkers |
Évaluer le dépôt régional d'agrégats de protéines p-TAU à l'aide du PET/CT F18-MK6240, imagerie in vivo non invasive dans le cerveau de patients atteints de plusieurs troubles neurodégénératifs. Les données des patients seront comparées à celles d'un groupe de contrôle. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with MCI due to AD or mild AD : • Age at least 45 years • Able to read and write in French, with a minimum 5 years of formal education • Attended the Memory Clinic of Cliniques Universitaires Saint-Luc • Are able to consent and willing to participate in the study • Are diagnosed either with mild cognitive impairment (MMSE ≥ 24/30) using the Petersen criteria (2004) or with mild AD dementia (MMSE ≥ 20/30) using the McKhann criteria (2011) by a clinical neurologist. • Have a study partner or can identify someone willing in principle to be a study partner • Have either a positive amyloid-PET scan OR an abnormal measure of Aβ-42 in the CSF OR an abnormal ratio between total tau and Aβ-42 in the CSF. Patients with non-AD syndrome • Age at least 20 years • Able to read and write in French, with a minimum 5 years of formal education • Attended the Memory Clinic, the Stroke Clinic (CAA), the Neuromuscular Clinic (ALS), or the Movement Disorder (PSP/CBD/LBD) Clinic of Cliniques Universitaires Saint-Luc • Are able to consent and willing to participate in the study • Are clinically suspected to suffer: - from cerebral amyloid angiopathy (CAA), Fronto-temporal Lobar Degeneration, Progressive Supranuclear Palsy, Corticobasal Degeneration, Lewy body disease, or Amyotrophic Lateral Sclerosis by a clinical neurologist. - from MCI due to AD or mild AD dementia but have either a negative amyloid-PET scan OR a normal measure of Aβ-42 in the CSF • Have a study partner or can identify someone willing in principle to be a study partner
Non-demented controls • Age at least 20 years • Able to read and write in French; minimum 5 years of formal education • Recruited among caregivers of patients attending the Memory Clinics, through advertisement, or among patients attending the Memory Clinics but with normal neuropsychological exam. • Are able to consent and willing to participate in the study • Have normal cognition as defined by an MMSE ≥ 26/30 (25/30 if education lower than high school). • Have an available amyloid-PET scan OR an available CSF measure of Aβ-42 conducted for clinical reasons OR in another research study OR are willing to undertake an amyloid-PET scan for the present study OR are willing to undertake a CSF measure of Aβ-42 for the present study.
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E.4 | Principal exclusion criteria |
• Presence of any neurological, psychiatric or medical conditions associated with a long-term risk of significant cognitive impairment or dementia including but not limited to pre-manifest Huntington’s disease, multiple sclerosis, active alcohol/drug abuse or major psychiatric disorders including current major depressive disorder, schizophrenia, schizoaffective or bipolar disorder. • Any cancer or history of cancer in the preceding 2 years (excluding cutaneous basal or squamous cell cancer resolved by excision and localized prostate cancer in male subjects) • Any current medical conditions that are clinically significant and might make the subject’s participation in an investigational trial unsafe, e.g., uncontrolled or unstable disease of any major organ system; history within the last 3 months of any acute illness of a major organ system requiring emergency care or hospitalization, including re-vascularization procedures; severe renal or hepatic failure; unstable or poorly controlled diabetes mellitus, hypertension, or heart failure; any clinically relevant abnormalities in blood parameters in routine assessments; severe loss of vision, hearing or communicative ability; or any conditions preventing co-operation or completion of the required assessments in the trial, as judged by the investigator. • Any contraindications for MRI or PET scan • Any evidence of intracranial pathology which, in the opinion of the Investigator, may affect cognition, including but not limited to brain tumors (benign or malignant), aneurysm or arteriovenous malformations, territorial stroke (excluding smaller watershed strokes), recent hemorrhage (parenchymal or subdural), or obstructive hydrocephalus. Participants with a MRI scan demonstrating markers of small vessel disease (e.g. white matter changes or lacunar infarcts) judged to be clinically insignificant, or microbleeds are allowed. • Participation in a clinical trial of an investigational product (IMP) in the 30 days preceding the screening visit. Entering a clinical trial of an investigational product (IMP) is allowed during the current study once the baseline examinations have been performed. The follow-up examinations scheduled in the current study will be proposed to the participants who will have entered a clinical trial during their participation in the current study, depending on the examinations that are scheduled in the clinical trial. • Women of child-bearing potential (WOCBP , non-menopausal), younger than 55 years old, following any method of contraception not recommended by the Clinical Trial Facilitation Group (CTFG ). The use of a highly effective contraception measure2 should indeed be maintained during any F18 radio-labelled pharmaceutical exposure, until complete F18 decay (meaning at least a minimum period of 18-24 hours after injection). • Pregnancy, or breastfeeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
F18-MK6240 regional SUVr or spatial extension measure differences between patients and controls |
F18-MK6240 SUVr régional ou l'extension spatiale mesure les différences entre les patients et les témoins |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The inclusion period is scheduled to end on the 30th June 2029. Follow-up is scheduled for a ten-year period (end on 30th June 2039). The minimal follow-up will include a cognitive assessment, a blood-test and a blood pressure measurement. All imaging examinations are optional at follow-up. Examinations will globally be repeated every two years. |
La période d'inclusion devrait se terminer le 30 juin 2029. Le suivi est prévu pour une période de dix ans (fin le 30 juin 2039). Le suivi minimal comprendra une évaluation cognitive, un test sanguin et une mesure de la pression artérielle. Tous les examens d'imagerie sont facultatifs lors du suivi. Les examens seront globalement répétés tous les deux ans. |
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E.5.2 | Secondary end point(s) |
Associations between F18-MK6240 regional SUVr or spatial extension measures and:
Cognitive outcomes - Global cognitive measures (e.g., MMSE, TICS) - Verbal Episodic Memory (e.g., Free and Cued Selective Reminding Test, FCSRT) - Visuospatial/Constructional (e.g., CERAD Figures Copy) - Language (e.g., Picture Naming, Semantic Fluency, Letter Fluency) - Attention/Executive Functioning (e.g., Trail-Making-Test) - Spatial navigational skills; - Face perception and recognition abilities; - Specific semantic memory measures; - Short-term memory binding abilities; - Specific episodic memory processes (e.g., pattern separation, pattern completion); - Implicit learning abilities. CSF biomarker outcomes - Aβ, t-tau, p-tau Amyloid-PET imaging - Global and regional distribution of amyloid deposition Neuroimaging outcomes (MRI) - Regional and whole brain volume - Regional cortical thickness - Resting-state functional connectivity - Diffusion-weighted imaging - Task-related brain activity Blood-derived biomarkers - Amyloid oligomers - Phosphorylated and non-phosphorylated tau species
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Associations entre le SUVr régional F18-MK6240 ou les mesures d'extension spatiale et :
Résultats cognitifs - Mesures cognitives globales (p. ex. MMSE, TICS) - Mémoire épisodique verbale (p. ex. test de rappel sélectif libre et dirigé, FCSRT) - Mémoire visuospatiale/constructionnelle (p. ex. CERAD Figures Copy) - Langage (par exemple, dénomination d'images, fluidité sémantique, fluidité verbale) - Attention/fonctionnement exécutif (p. ex. Trail-Making-Test) - Compétences en matière de navigation spatiale ; - Capacités de perception et de reconnaissance des visages ; - Mesures spécifiques de la mémoire sémantique ; - Capacités de liaison de la mémoire à court terme ; - Processus spécifiques de la mémoire épisodique (par exemple, séparation des formes, achèvement des formes) ; - Capacités d'apprentissage implicite. Résultats des biomarqueurs du LCR - Aβ, t-tau, p-tau Imagerie TEP de l'amyloïde - Distribution globale et régionale des dépôts amyloïdes Résultats de la neuro-imagerie (IRM) - Volume régional et total du cerveau - Épaisseur corticale régionale - Connectivité fonctionnelle à l'état de repos - Imagerie pondérée en diffusion - Activité cérébrale liée à la tâche Biomarqueurs dérivés du sang - Oligomères amyloïdes - Espèces tau phosphorylées et non phosphorylées |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The inclusion period is scheduled to end on the 30th June 2029. Follow-up is scheduled for a ten-year period (end on 30th June 2039). The minimal follow-up will include a cognitive assessment, a blood-test and a blood pressure measurement. All imaging examinations are optional at follow-up. Examinations will globally be repeated every two years. |
La période d'inclusion devrait se terminer le 30 juin 2029. Le suivi est prévu pour une période de dix ans (fin le 30 juin 2039). Le suivi minimal comprendra une évaluation cognitive, un test sanguin et une mesure de la pression artérielle. Tous les examens d'imagerie sont facultatifs lors du suivi. Les examens seront globalement répétés tous les deux ans. |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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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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 | 10 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |