Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Open-Label Extension Study
无症状阿尔茨海默病 (A4) 开放标签扩展研究中的抗淀粉样蛋白治疗
基本信息
- 批准号:10358480
- 负责人:
- 金额:$ 694.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-05-15 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAgeAlzheimer disease preventionAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAlzheimer’s disease biomarkerAmyloidAmyloid beta-ProteinApplications GrantsAtrophicAttenuatedAustraliaBiological SciencesBlindedBrainCanadaClinicalClinical TrialsCognitionCognitiveCompanionsDataDedicationsDetectionDiseaseDoseDouble-Blind MethodEducationEligibility DeterminationEnrollmentEvaluationFoundationsFunctional disorderFundingGenderGoalsImmunotherapyImpaired cognitionIndividualInterventionJapanLearningLong-Term EffectsLongterm Follow-upMagnetic Resonance ImagingMedicineMinorityModificationMonoclonal AntibodiesNerve DegenerationObservational StudyParticipantPerformancePharmaceutical PreparationsPharmacodynamicsPhasePlacebosPopulationPositioning AttributePositron-Emission TomographyPrevention therapyPrevention trialPrior TherapyPrivatizationProcessProtocols documentationRandomizedReportingRiskSecondary PreventionSenile PlaquesSiteTestingUnited StatesUnited States National Institutes of Healthabeta accumulationactive methodasymptomatic Alzheimer&aposs diseasebaseblindcognitive functioncohortcomparison groupdata sharingdesignefficacy evaluationeligible participantfunctional declinefunctional outcomeshigh riskimaging biomarkerinclusion criteriameetingsopen labelplacebo controlled trialpre-clinicalpreventprimary outcomepublic-private partnershipresponsescreeningtau Proteinstreatment effect
项目摘要
SUMMARY: This is an application for NIH support to enable an Open Label Extension (OLE) of the Anti-
Amyloid Treatment in Asymptomatic Alzheimer’s disease (A4) Study. The A4 Study was launched in 2014 as
the first of its kind secondary prevention trial in clinically normal (CN) older individuals with evidence of
elevated amyloid-beta (Aβ) accumulation on screening PET scan. A4 eligible participants are in the preclinical
(asymptomatic) stages of AD and at high risk for cognitive decline. The overall goal of the A4 study is to test
the hypothesis that immunotherapy targeting Aβ (solanezumab) can prevent the cognitive decline associated
with early AD pathology, if initiated early enough. The A4 Study screened over 6700 participants (age 65-85,
14% minority) and exceeded our enrollment target with 1169 participants randomized. Our initial prediction of
30% “amyloid positivity” was proven correct with 29.5% of the participants with screening PET meeting
“elevated amyloid” criteria. We also launched the companion Longitudinal Evaluation of Amyloid Risk and
Neurodegeneration (LEARN) observational study in “amyloid negative” CN (n=541) in 2015. Based on the sola
trial results in AD dementia, we quadrupled the dose and extended the double-blind (DB) protocol to 4.5 years.
The first A4 participant will complete the DB protocol in early 2019, with the last participant completing in mid-
2022. Maintaining the blind of the initial treatment assignment, the A4 OLE will enable us to continue to assess
these participants after they complete the DB, and to investigate the long-term effects of sola exposure on
cognitive and functional decline in preclinical AD. In addition, we will explore the “critical window” for optimal
response to anti-Aβ therapy utilizing amyloid PET, MRI, and tau PET (in a subset) acquired at start of OLE.
The A4 Study is a public-private-philanthropic partnership with funding from NIA, Lilly, Alzheimer’s Association,
Fidelity Biosciences, GHR Foundation, and the Accelerating Medicines Partnership (AMP). Here we seek
partial funding from the NIH for the A4 OLE with Lilly providing the remainder of funding and in-kind support.
This funding will allow us to offer all of the very dedicated A4 participants access to study drug in the OLE, and
continue to collect extremely valuable longitudinal data on the largest available cohort of CN characterized by
amyloid status, until the primary efficacy analyses are completed in late 2022. We have already begun to share
the data and biosamples from the A4 screening data, and the A4/LEARN longitudinal data will be made
publicly available within one year of completion of the primary efficacy analyses of the A4 Study. The A4 Study
is well positioned to rigorously test the amyloid hypothesis with a higher dose of solanezumab and at the
appropriate stage of disease, in a population estimated to be up to 15 years earlier in the Aβ accumulation
process than the previous AD dementia trials. The additional longitudinal data from the A4 Study, in
combination with similar data acquired in LEARN, has the potential to fundamentally alter the detection and
treatment of AD, and move us closer to the NAPA goal of finding a successful prevention therapy by 2025.
摘要:这是NIH支持的一项申请,以启用Anti-的开放标签扩展(OLE)
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Paul S. Aisen其他文献
Poster Number: EI 19 - Association of Subjective Cognitive Complaints and Objective Cognitive Impairment in Late Life Depression
- DOI:
10.1016/j.jagp.2018.01.110 - 发表时间:
2018-03-01 - 期刊:
- 影响因子:
- 作者:
Ruth Morin;David D. Bickford;Yiu Ho Au;Kelly B. Scherer;Daniel C. Catalinotto;Philip Insel;Duygu Tosun;Michelle Zmuda;Arthur W. Toga;Paul S. Aisen;Rema Raman;Andrew Saykin;Michael Weiner;Meryl A. Butters;Craig Nelson;Scott Mackin - 通讯作者:
Scott Mackin
NAP ameliorates Alzheimer’s pathology in ad model mouse
- DOI:
10.1016/j.npep.2006.09.022 - 发表时间:
2006-12-01 - 期刊:
- 影响因子:
- 作者:
Y. Matsuoka;Illana Gozes;Paul S. Aisen - 通讯作者:
Paul S. Aisen
The Development of Anti-Amyloid Therapy for Alzheimer’s Disease
- DOI:
10.2165/00023210-200519120-00002 - 发表时间:
2005-01-01 - 期刊:
- 影响因子:7.400
- 作者:
Paul S. Aisen - 通讯作者:
Paul S. Aisen
Randomised controlled trials for the prevention of cognitive decline or dementia: A systematic review
- DOI:
10.1016/j.arr.2022.101777 - 发表时间:
2022-12-01 - 期刊:
- 影响因子:12.400
- 作者:
Nicola Coley;Caroline Giulioli;Paul S. Aisen;Bruno Vellas;Sandrine Andrieu - 通讯作者:
Sandrine Andrieu
Paul S. Aisen的其他文献
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{{ truncateString('Paul S. Aisen', 18)}}的其他基金
Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Open-Label Extension Study
无症状阿尔茨海默病 (A4) 开放标签扩展研究中的抗淀粉样蛋白治疗
- 批准号:
10554282 - 财政年份:2019
- 资助金额:
$ 694.33万 - 项目类别:
Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Open-Label Extension Study
无症状阿尔茨海默病 (A4) 开放标签扩展研究中的抗淀粉样蛋白治疗
- 批准号:
9930020 - 财政年份:2019
- 资助金额:
$ 694.33万 - 项目类别:
Combination anti-amyloid therapy for preclinical Alzheimer's disease
临床前阿尔茨海默病的抗淀粉样蛋白联合治疗
- 批准号:
9786200 - 财政年份:2018
- 资助金额:
$ 694.33万 - 项目类别:
Combination anti-amyloid therapy for preclinical Alzheimer's disease
临床前阿尔茨海默病的抗淀粉样蛋白联合治疗
- 批准号:
10452475 - 财政年份:2018
- 资助金额:
$ 694.33万 - 项目类别:
Combination anti-amyloid therapy for preclinical Alzheimer's disease
临床前阿尔茨海默病的抗淀粉样蛋白联合治疗
- 批准号:
10666411 - 财政年份:2018
- 资助金额:
$ 694.33万 - 项目类别:
Alzheimer's Clinical Trials Consortium (ACTC)
阿尔茨海默病临床试验联盟 (ACTC)
- 批准号:
10435786 - 财政年份:2017
- 资助金额:
$ 694.33万 - 项目类别:
Alzheimers Clinical Trials Consortium (ACTC)
阿尔茨海默病临床试验联盟 (ACTC)
- 批准号:
9753042 - 财政年份:2017
- 资助金额:
$ 694.33万 - 项目类别:
Trial-Ready Cohort for Preclinical/Prodromal Alzheimer's Disease
临床前/前驱阿尔茨海默病的试验就绪队列
- 批准号:
9885998 - 财政年份:2017
- 资助金额:
$ 694.33万 - 项目类别:
Alzheimer's Clinical Trials Consortium (ACTC)
阿尔茨海默病临床试验联盟 (ACTC)
- 批准号:
10719531 - 财政年份:2017
- 资助金额:
$ 694.33万 - 项目类别:
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