E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Alzheimer's Disease (AD) |
ziekte van Alzheimer |
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E.1.1.1 | Medical condition in easily understood language |
dementia, Alzheimer's Disease |
dementie, ziekte van Alzheimer |
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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 | 18.1 |
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 | 18.1 |
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 | 18.1 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To validate the previously defined simplified tracer kinetic model to quantify specific binding of [18F]AV-1451 |
Het valideren van het eerder gedefineerde versimpelde tracer kinetisch model, waarmee specifieke binding van [18F]AV-1451 wordt gekwantificeerd |
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E.2.2 | Secondary objectives of the trial |
To assess test-retest variability of quantitative [18F]AV-1451 outcome measures |
Het bepalen van de test-hertest variabiliteit van kwantitatieve [18F]AV-1451 uitkomstmaten. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A healthy control subject must meet all of the following criteria: 1. At least 50 years of age; 2. Have no evidence of cognitive impairment as indicated by a cognitive neurologist; 3. Subjects, who in the opinion of the principal investigator, can tolerate the [18F]AV1451 PET scan procedures.
Probable AD subjects must meet the following inclusion criteria: 1. At least 50 years of age; 2. Have a clinical diagnosis of probable AD (McKhann, 2011) and are part of the Amsterdam Dementia Cohort (Flier et al. 2014); 3. Have a Mini Mental State Examination (MMSE) of 18 or higher; 4. Subjects, who in the opinion of the principal investigator, can tolerate the [18F]AV-1451 PET scan and blood sampling procedures.
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Gezonde controles moeten voldoen aan de volgende criteria: 1. Tenminste 50 jaar oud 2. Geen aanwijzingen voor cognitieve achteruitgang, vastgesteld door een cognitief neuroloog 3. Volgens de Principle Investigator in staat om de [18F]AV-1451 scan procedures en arteriële sampling te kunnen ondergaan
Proefpersonen met 'probable' ziekte van Alzheimer moeten voldoen aan de volgende criteria: 1. Tenminste 50 jaar oud 2. Klinische diagnose van 'probable' ziekte van Alzheimer (McKhann, 2011) en deelname aan het Amsterdams Dementie Cohort (Flier et al. 2014) 3. Een Mini Mental State Examination (MMSE) van 18 of hoger; 4. Volgens de Principle Investigator in staat om de [18F]AV-1451 scan procedures en arteriële sampling te kunnen ondergaan |
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E.4 | Principal exclusion criteria |
A potential subject who meets any of the following criteria will be excluded from participation in this study if he or she:
1. Has contra indications for MRI scanning and therefore can not receive brain MRI 2. Has evidence of structural abnormalities such as major stroke or mass on MRI that is likely to interfere with interpretation of a PET scan; 3. Has a history of severe traumatic brain injury (TBI); 4. Has a hemoglobin test (Hb) result of < 8 in males and < 7 in females; 5. Is a female of childbearing potential who is not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception. Females of childbearing potential must not be pregnant or breastfeeding at screening. 6. Has a relevant history of severe drug allergy or hypersensitivity (relevant severe drug allergies should be determined by the Principal Investigator or Co-Principal Investigator, and any questions about a subject’s eligibility can be directed to Avid Radiopharmaceuticals Inc.); 7. Has current clinically significant cardiovascular disease or clinically significant abnormalities on screening ECG (including but not limited to QTc>450 msec). If QTc is >450 at screening, the principal investigator may consult with Avid for approval to enroll; 8. Has a history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT syndrome) or is taking drugs that are known to cause QT-prolongation; 9. Has donated blood within 6 months prior to the [18F]AV-1451 PET scan day; 10. Has ever participated in an experimental study with a tau or amyloid targeting agent, unless it can be documented that the subject received only placebo during the course of the trial. 11. Has been injected with a previously administered radiopharmaceutical within 6 terminal half-lives OR when total yearly radiation exposure exceeds 10 mSv.
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1. Contra-indicaties voor een MRI-scan, en kan daardoor geen MRI-scan ontvangen 2. Aanwijzingen voor structurele afwijkingen op de MRI, zoals een herseninfarct of ruimte-innemend proces, waardoor interpretatie van de PET-scan bemoeilijkt wordt 3. Voorgeschiedenis van ernstig traumatisch hersenletsel (traumatic brain injury, TBI) 4. Hemoglobine (Hb) van <8 (mannen) of <7 (vrouwen) 5. Potentieel vruchtbare vrouwen, niet chirurgisch gesteriliseerd, die zich niet onthouden van seksuele activiteit of geen gebruik maken van betrouwbare anticonceptie. Potentieel vruchtbare vrouwen mogen niet zwanger zijn of borstvoeding geven. 6. Voorgeschiedenis met ernstige medicijnenallergie of hypersensitiviteit 7. Huidige klinisch significante cardiovasculaire ziekte of klinisch significante afwijkingen op ECG 8. Voorgeschiedenis met risicofactoren voor Torsades de Pointes (hartfalen, hypokaliëmie, positieve familie-anamnese voor Long QT Syndrome) of wanneer er medicijnen worden ingenomen die de QT-tijd kunnen verlengen 9. Binnen 6 maanden voorafgaand aan het onderzoek bloed gedoneerd 10. Eerder deelgenomen aan een experimentele studie met een tau of amyloid targeting agent, behalve als kan worden aangetoond dat patiënt alleen placebo kreeg toegediend 11. Voorgaand radiofarmacon toegediend gekregen binnen 6 halfwaardetijden OF wanneer de totale jaarlijkse stralingsdosis meer dan 10 mSv is |
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E.5 End points |
E.5.1 | Primary end point(s) |
Test-retest variability of [18F]AV-1451 binding |
Test-hertest variabiliteit van [18F]AV-1451 binding |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Continuous PET scan from 0-60 and 80-130 minutes post injection and continuous arterial blood draw 0-60 minutes post injection. Repeat after 1 week. |
Continue PET-scan van 0-60 en 80-130 minuten na injectie en continue ateriële bloedafname 0-60 minuten post-injectie. Herhaling na 1 week. |
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E.5.2 | Secondary end point(s) |
Not applicable |
Niet van toepassing |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline and after 1 week follow up |
Op baseline en na 1 week |
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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 | 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.8.3 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |