Transcript Alzheimer’s Disease Neuroimaging Initiative STEERING COMMITTEE April 20 2015 Michael W. Weiner The “Big” News • The highly encouraging Biogen phase 1b results, showing reduction of.

Alzheimer’s Disease
Neuroimaging Initiative
STEERING COMMITTEE
April 20 2015
Michael W. Weiner
The “Big” News
• The highly encouraging Biogen phase 1b results,
showing reduction of brain amyloid load and
slowing of cognitive decline, provide POC for antiamyloid treatments
• This encourages
– more clinical trial activity
– more NIH funding
– interest in AD biomarkers detection and monitoring
• Potential problems in enrolling ADNI 3 subjects
THE BIG PICTURE
• Overall, ADNI is doing very well
– We have 15 months left for ADNI2
• Two tau PET studies funded in past year
– DOD Tau PET, includes ADNI subjects
– ADNI competitive supplement for tau PET
– Should allow tau PET on all ADNI and DOD ADNI
subjects and longitudinal studies
• Expect to submit ADNI3 mid October 2015
PLANS FOR ADNI 3
SPECIFIC AIMS
Overall goal: validation of biomarkers for AD
• Longitudinal change of cognition and
biomarkers: measures that capture longitudinal
change with highest statistical power
• Prediction of cognitive decline:
• Clinical trial design: Optimum outcome measures,
predictors, and inclusion/exclusion criteria for
clinical trials
• Discovery: new markers, new targets
ADNI 3 STUDY DESIGN
• About 900 subjects planned
• 40% cognitively normal, 40% MCI, 20% dementia
(from converted MCI)
• Most subjects will be roll-overs, but some new
subjects will be enrolled
• Annual visits: Clinical, cognitive, MRI, amyloid
PET, tau PET, FDG PET?, LP/CSF, genetics,
omics
NEW FEATURES IN ADNI 3
• Use of Brain Health Registry for recruitment,
assessment and longitudinal monitoring
– Includes on-line cognitive testing for screening, F/U
•
•
•
•
•
Tau PET: AVID 1451, and others to be considered
Amyloid PET centaloid project: AVID, Pirimal, ?
Advanced, Connectome, multi-modal MRI
New Platform for CSF analysis, Mass Spec
Systems Biology, Omics, and Data Mining
DISCLOSING RESULTS TO
PATIENTS
• Some clinicans request to disclose results to
patients. Request change in ADNI policy
• Advantages
– Patients have a “right to know”
– Will facilitate recruitment/retention
• Disadvantages
– This action will change the outcome
– Not using “CLIA-approved labs”
– Amyloid PET, CSF results, tau results, genetics?
• Current plan is not to include in grant application
PROBLEM: COMPETITIVE SPACE
• Selection of ADNI 3 Biomarker platform
– Review of all possibilities: consultation with PPSB
• Selection of tau tracer by PET Core
– Currently AVID 1451 is only tracer widely available,
piloted in ADNI2
– All possible tau tracers to be considered
• Selection of on-line cognitive tests
• Compelling data in grant required: goal is to be
funded
– ADNI 3 begins 16 months after grant submission
– ADNI 3 enrollment will compete with many trials
COLLABORATION WITH
INDUSTRY PARTNERS
• ADNI is a grant submitted to NIA, must be
reviewed and funded
• ADNI investigators responsible for scientific
conduct
• UO-1 or UO-19 requires close NIA oversight: For
example, NIA decides on sample release
• Industry supports 30% of funds. The overall goal is
to facilitate industry and academic trials. We greatly
value PPSB input and collaboration
OTHER COLLABORATIONS
• Joint analysis with DIAN
• Joint analysis of ADNI and PPMI data
sponsored by Michael J Fox
• SAGE Challange
GOVERNANCE
• Grant is submitted to NIA from the Northern
California Institute for Research and Education
(NCIRE), Michael Weiner PI
• In the event that the PI cannot function as PI, Bill
Jagust , at UC Berkeley, will become PI and
assume an NCIRE appointment
• After that future decisions will be made by NIA,
NCIRE, ADNI Executive Committee , in
consultation with the PPSB
LONG TERM FUTURE OF ADNI
• If ADNI 3 proceeds, what would happen
after ADNI 3?
• Depending on success of treatments, it may
not be possible to enroll subjects with
preclinical, prodromal or , dementia due to
AD in an observational trial
• Shift to study of younger amyloid negative
subjects at long term risk for developing
amyloid positivity: primary prevention trials
to prevent amyloid /tau formation
• And/or a study of “normal aging”
OPPORTUNITY
• ADNI 3 may be the “last” large
observational study of the natural history of
AD progression
– Availability of treatments will prevent study of
populations without treatment
• High excitement about AD clinical trials
provides compelling rationale for ADNI3 to
inform better trial design
MANY THANKS
•
•
•
•
•
NIA for strong support
Industry Partners, Foundations, and FNIH
Site PIs, study coordinators
ADCS staff
Subjects and their families