The AlzMatch Pilot Study - Feasibility of Remote Blood Collection of Plasma Biomarkers for Preclinical Alzheimer's Disease Trials.

BACKGROUND

Advances in plasma biomarkers to detect Alzheimer's disease (AD) biology allows researchers to improve the efficiency of participant recruitment into preclinical trials. Recently, protein levels of plasma amyloid-beta and tau proteins have been shown to be predictive of elevated amyloid in brain. Online registries, such as the Alzheimer's Prevention Trials (APT) Webstudy, include and follow participants using remote assessments to facilitate efficient screening and enrollment of large numbers of individuals who may be at higher risk for AD.

OBJECTIVES

The AlzMatch Pilot Study investigated the feasibility of recruiting individuals from an online registry for blood sample collection at community-based phlebotomy centers and plasma biomarker quantification to assess an individual's eligibility for AD preclinical trials.

DESIGN

Pilot feasibility study with co-primary outcomes.

SETTING

This pilot feasibility study included participants from the APT Webstudy, the remote assessment arm of the Trial-ready cohort for Preclinical and Prodromal AD (TRC-PAD) Platform. Novel design included collection of electronic consent, use of community laboratories for plasma collection, mass spectrometry-based biomarker assay, and telephone communication of plasma biomarker screening eligibility.

PARTICIPANTS

Participants invited to the AlzMatch pilot feasibility study were active in the APT Webstudy, 50 years of age or older, resided within 50 miles of both a Quest Diagnostics Patient Services Center (a national diagnostic laboratory with convenient locations for sample collection and processing) and one of six TRC-PAD vanguard clinical trial sites, had no self-reported dementia diagnosis, were able to communicate in English and engaged with the APT Webstudy within the prior 6 months.

MEASUREMENTS

Primary feasibility outcomes were completion of electronic consent (e-consent) for invited participants and collection of usable blood samples. Additional feasibility outcomes included invitation response rate, plasma biomarker eligibility status (based on amyloid beta-42/40 [Aβ42/40] concentration ratio), ApoE proteotype, and trial inclusion criterion), and completion of telephone contact to learn eligibility to screen for a study.

RESULTS

300 APT Webstudy participants were invited to consent to the AlzMatch study. The AlzMatch e-consent rate was 39% (n=117) (95% CI of 33.5%-44.5%) overall, which was higher than the expected rate of 25%. Similar consent rates were observed across participants based on self-defined sex (41% Female (n=75), 37% Male (n=42)) and race and ethnicity (37% from underrepresented groups (URG) (n=36), 40% not from URG (n=79)). Among those that consented (n=117), plasma was successfully collected from 74% (n=87) (95% CI of 66%-82%), with similar rates across sex (76% Female (n=57), 71% Male (n=30)) and race and ethnicity (75% URG (n=27) and 75% not from URG (n=59)). 60% (n=51) of participants with plasma biomarker results were eligible to screen for future preclinical AD trials.

CONCLUSION

Electronic consent of participants through an online registry, blood sample collection at community-based centers, plasma biomarker quantification and reporting, and biomarker assessments for study eligibility were all feasible with similar engagement rates across demographic groups. Although this pilot was a small and selective sample, participants engaged and consented at higher than expected rates. We conclude that collecting blood at community laboratories for biomarker analyses may improve accessibility beyond research, and may facilitate broader access for clinical use of AD plasma biomarkers. Based on our results, an expanded version of the AlzMatch study is underway, which involves expanding invitations to additional APT Webstudy participants and clinical trial sites.

Déclaration de conflit d'intérêts

SW, OL, SAL, SB and KH are supported by grants from the National Institute on Aging. GJ reports research support from the National Institute on Aging and from contract research with AbbVie, Cassava, Cognition Therapeutics, Eisai, and Novo Nordisk. MR is an employee of and owns stock in Quest Diagnostics. RAR has research support from the National Institute on Aging, the Alzheimer’s Association and is a consultant for Amydis Inc, Bioivt, Lexeo, Keystone Bio, Allyx, DiamiR, Ionis and PrecisionMed. JG reports grants from NIA, Alzheimer’s Association, BrightFocus Foundation, grants from Eli Lilly, Genentech, Biogen, Eiasai, outside the submitted work. JK reports grants from Lilly, outside the submitted work. GAM reports research funding from National Institute on Aging, Eli Lilly and Company (for serving as a clinical trial site principal investigator), and Eisai Inc. (for serving as a clinical trial site principal investigator). AA reports personal fees from Acadia, grants and other from Alzheimer’s Clinical Trials Consortium (ACTC), grants from Alzheimer’s Disease Cooperative Study (ADCS), grants and other from National Institutes of Health (NIH), grants and other from Alzheimer’s Association, other from Alzheimer’s Disease International (ADI), grants and other from Alzheimer’s Therapeutics Research Institute (ATRI), grants from Athira, grants from Alzheon, grants and other from Arizona Department of Health Services (AZ DHS), personal fees from Biohaven (with ADCS), from Biogen, grants, personal fees and other from Eisai, grants from Gates Ventures, personal fees from Harvard Medical School, grants from Foundation for NIH (FNI), grants from Lilly (with ACTC), grants from Indiana University (with ATRI, Alz Assoc, NIH), grants from Johns Hopkins University (with NIH), personal fees from Life Molecular Imaging, personal fees from AriBio, personal fees from ONO, personal fees and other from Lundbeck, personal fees and other from Novo Nordisk, personal fees and other from Prothena, personal fees and other from Merck, personal fees from Qynapse, grants from Vivoryon (with ADCS), other from Oxford University Press, outside the submitted work. MCD has consulted for Roche and his spouse is a full-time employee of Janssen. RST reports grants from Alector, Biogen, Cognition Therapeutics, Eisai, janssen, Lilly, Roche/Genentech, Vaccinex, and Vivoryon, personal fees from Re:Cognition Health, outside the submitted work. CVD reports grants for clinical trials from Biogen, Eli Lilly, Roche, Genentech, Eisai, UCB, Cerevel, Janssen, and Biohaven, and personal fees for consultancies from Roche, Eisai, Cerevel, and Ono, outside the submitted work. VV and KEY are employed by C2N Diagnostics. C2N Diagnostics received support from the NIH (grant No. R44 AG059489), BrightFocus (grant No. CA2016636), The Gerald and Henrietta Rauenhorst Foundation, and the Alzheimer’s Drug Discovery Foundation (grant No. GC-201711-2013978). RAS has received research funding from National Institute on Aging, Eli Lilly (public-private partnership trial funding), Eisai (public-private partnership trial funding) Alzheimer’s Association and GHR Foundation. She has received consulting fees from Abbvie, AC Immune, Acumen, Alector, Alnylam, Bristol-Myers Squibb, Cytox, Genentech, Ionis, Janssen, Oligomerix, Prothena, Roche, Shionogi, and Vaxxinity. MR is an employee of Quest Diagnostics. JC has provided consultation to Acadia, Actinogen, Acumen, AlphaCognition, ALZpath, Aprinoia, AriBio, Artery, Biogen, Biohaven, BioVie, BioXcel, Bristol-Myers Squib, Cassava, Cerecin, Diadem, Eisai, GAP Foundation, GemVax, Janssen, Jocasta, Karuna, Lighthouse, Lilly, Lundbeck, LSP/eqt, Mangrove Therapeutics, Merck, NervGen, New Amsterdam, Novo Nordisk, Oligomerix, ONO, Optoceutics, Otsuka, Oxford Brain Diagnostics, Prothena, ReMYND, Roche, Sage Therapeutics, Signant Health, Simcere, sinaptica, Suven, TrueBinding, Vaxxinity, and Wren pharmaceutical, assessment, and investment companies. JC is supported by NIGMS grant P20GM109025; NIA grant R01AG053798; NIA grant R35AG71476; NIA R25 AG083721-01; Alzheimer’s Disease Drug Discovery Foundation (ADDF); Ted and Maria Quirk Endowment; Joy Chambers-Grundy Endowment. PA has grants from National Institute on Aging and Alzheimer’s Association, Eisai (public-private partnership trial funding) and Lilly (public-private partnership trial funding). He has provided consultation to Roche, Genentech, BMS, Merck, Biogene and Abbvie. RR has research support from the National Institute on Aging, the Alzheimer’s Association, Eisai (public-private partnership funding) and the American Heart Association.