Prediction of cognitive properties of new drug candidates for neurodegenerative diseases in early clinical development (PHARMA-COG)
Funded by European Commission, IMI Innovative Medicines Initiative
WP5 – Identification of biomarkers sensitive to disease progression: Clinical Studies (European ADNI)
Recently the EU Council of Ministers for Health underlined the importance of generating novel therapeutic agents both for symptomatic and disease modifying treatment of Alzheimer’s disease (AD). However, despite the increased in translational medicine activities attrition rates still remain high and progress in bringing these biomarkers and models to a state of readiness as effective decision making tools is slow as each academic and pharmaceutical company work in isolation.
Bringing together European experts in technologies fully translatable from animal to human, experts in translational medicine, drug discovery and mathematical modelling, PHARMA-COG proposes to accelerate this validation using a ‘MATRIX’ approach i.e. conducting parallel experiments in animals and human using a comprehensive and standardised battery of behavioural, neurophysiological, morphological/functional imaging, and biochemical endpoints to:
- develop models with greater predictive capacity for the clinics
- develop and validate translatable pharmacodynamic markers to support dose selection
- develop challenge models to support early hint of efficacy studies
- identify and validate of markers of disease progression and patient stratification.
The PHARMA-COG consortium consists of 30 public (Univeristies, Research Centres, Hospitals) and private partners (SMEs and EFPIA members), as well as a patients’ Association Alzheimer Europe, coming from 10 different EU Members states. PHARMA-COG will also work closely with the EMEA, as an associated partner of this project, to share project progress and discuss the implications for drug development in Europe.. The combined size and expertise of PHARMA-COG provides a truly unique opportunity to validate the tools required to fundamentally change the drug discovery process in AD and accelarte efficacious drug to patients across Europe.
Workpackage 5 of PharmaCog (Identification of biomarkers sensitive to disease progression: Clinical Studies – European ADNI) is about the development of markers to track the progression of the disease in humans that are homologous to those used in animal models. WP5 uses as core markers those harmonized in the context of the North American ADNI and expands them with specific structural, functional, microstructural, molecular, central, and peripheral markers. WP5 is thus labeled as the “European ADNI”.
The study plan to enrol 150 patients with mild cognitive impairment (MCI) according to the following inclusion criteria:
- Written Informed Consent to participate in a 3 year imaging study
- Male and female aged between 55-90 years
- Memory complaint by subject or study partner that is verified by a study partner. (Memory complains expressed by the subjects or their informant that the examiner considers to be relevant and exceed those expected for a subject of their age. The subject may or may not have symptoms of deficiency in other cognitive areas.)
- Abnormal memory function documented by scoring 1 SD below the education adjusted cut-off on the Logical Memory II subscale, (Delayed Paragraph Recall) from the Wechsler Memory Scale.
- General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer’s disease cannot be made by the site physician at the time of the screening visit.
- Mini-Mental State Exam score between 24 and 30 (inclusive)
- Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5.
- Amnestic Mild Cognitive Impairment (MCI) (pure amnestic or multidomain)
- Geriatric Depression Scale less than 6
- Hachinski Modified Ischemic scale< to 4
- Stability of Permitted Medications for 4 weeks (see following pages for examples of excluded medications)
- At least 6 grades education
- Must speak (language) fluently
- Have a study partner with 10+ hr/wk contact (can be in person and telephone), accompanies to visits
- Willing and able to comply with the requirements of the study, as judged by the investigator
By the end of this 5-year project PHARMA-COG will have a) validated the tools necessary to streamline AD drug discovery and accelerate effective medicine to patients, b) set the standard for European drug discovery providing optimised and validated protocols c) provided the infrastructure to sustain world class drug discovery in Europe and d) disseminate the obtained results from health professionals to patients.