DIAN-TU Amyloid Removal Trial (ART) in Dominantly Inherited Alzheimer's Disease

NCT ID: NCT06384573

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-10

Study Completion Date

2030-06-30

Brief Summary

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This is an open label study to treat dominantly inherited Alzheimer's disease (DIAD) mutation carrier participants from the DIAN-TU-001 gantenerumab Open Label Extension (OLE) period with lecanemab to determine the effects of amyloid removal on age of onset and clinical progression compared to external controls, if amyloid plaque as measured by amyloid PET can be fully removed in DIAD, and the effects of amyloid removal on biomarkers of disease progression.

Detailed Description

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The Dominantly Inherited Alzheimer Network (DIAN) and the DIAN Trials Unit (DIAN-TU) have established a global network that has increased understanding of Alzheimer's disease (AD) and identified a reliable cohort of individuals available for clinical trials. Over the past 12 years, the DIAN-TU has conducted a trial with the monoclonal antibody gantenerumab (DIAN-TU-001), providing the longest treatment period for individuals with amyloid removing immunotherapies (trial launched in December 2012, double-blind readout in 2019, currently completing the open-label extension \[OLE\] in 2024). Notably, efficacy and safety outcomes of the DIAN-TU and other trials with dominantly inherited AD (DIAD) populations have predicted and were concordant with sporadic AD (sAD) trials in several programs.

The DIAN-TU-001 gantenerumab OLE period has reached the end of participation and there is an urgent need to launch a trial that will allow for the continued amyloid removal treatment and monitoring of these uniquely informative individuals. The range of exposure duration in these individuals to gantenerumab is large: 2 to 10 years. Because there are a substantial number of participants that are approaching the estimated age that AD symptoms develop, it is critical to continue to monitor and treat these individuals to identify whether robust amyloid reduction prior to symptom onset can provide significant delay in disease progression.

In summary, the main reason for conducting this study is to gather key data to answer important outstanding scientific and clinical care questions for dominantly inherited AD and sporadic AD. These include improved insights into efficacy-related questions regarding drug dose and duration, mechanism of action, target population, and target disease stage that results in optimal benefit to patients. An evaluation of the long-term effects of amyloid removal on disease progression in DIAD could provide the first proof of concept that removing amyloid years before symptom onset could have major effects in delaying symptom onset by years, and to provide estimates for the relative effect sizes by years to symptom onset. Additionally, this study could provide the first evidence that patients can be treated with mechanistically different amyloid removing drugs to achieve full amyloid removal. Together these insights could offer guidance as to how clinicians can use lecanemab, a monoclonal antibody passive immunotherapy, in the era of multiple available amyloid removing treatments.

Participants in this trial will be co-enrolled in the DIAN Observational Study (DIAN Obs, NCT00869817). DIAN Obs represents a unique translational study in AD research that has provided transformational, data-driven models of the sequence of biomarkers abnormalities in preclinical DIAD. DIAN Obs is the largest longitudinal, multi-national study tracking DIAD families using a uniform protocol. To maximize the efficiency and utility of the DIAN Obs, the study introduced several efficiencies including 1) harmonizing protocols with the DIAN-TU, 2) applying International Conference on Harmonization Good Clinical Practice (ICH GCP) standards and a global unique identifier (GUID) at all performance sites to facilitate data sharing between all DIAN studies. Annual assessments will be performed for this population to collect clinical and cognitive data, amyloid and tau PET imaging, and cerebrospinal fluid (CSF) and plasma biomarkers for primary and secondary outcomes.

Conditions

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Alzheimer's Disease Dementia Alzheimer's Disease, Familial

Keywords

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Alzheimer's Alzheimer's Disease Dementia Mutation Genetic Mutation Dominantly Inherited Alzheimer's Disease Dominantly Inherited Alzheimer Network Autosomal Dominant Alzheimer's Disease Early Onset Alzheimer's Disease DIAN DIAN-TU DIAD

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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lecanemab

Starting at Week 0, participants will receive open-label lecanemab administered intravenously approximately every 2 weeks for a minimum of 5 years utilizing a common close design.

Group Type EXPERIMENTAL

lecanemab

Intervention Type DRUG

Administered intravenously

Interventions

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lecanemab

Administered intravenously

Intervention Type DRUG

Other Intervention Names

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BAN2401

Eligibility Criteria

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Inclusion Criteria

* Previously participated in the DIAN-TU-001 gantenerumab OLE period.
* Willing to participate in ongoing anti-amyloid therapy with informed consent by participant or legally authorized representative.
* People of childbearing potential (POCBP), if partner is not sterilized, must agree to use highly effective contraceptive measures (e.g., hormonal contraception, intra-uterine device, sexual abstinence, vasectomized partner) from Consent (V1) until five (5) halflives after last dose of any study drug. Refer to the study procedures manual for acceptable methods of contraception.
* Co-enrollment in the DIAN Observational Study (DIAN Obs, NCT00869817) and is willing to complete DIAN Obs procedures and assessments.
* Able to undergo safety MRI scans as required.
* Vascular access adequate for study drug administration and safety monitoring.

Exclusion Criteria

* Has any significantly increased risks associated with amyloid-related imaging abnormalities characterized by edema/effusion (ARIA-E), ARIA characterized by microhemorrhage (ARIA-H MCH) or superficial siderosis (ARIA-H SS) and vascular factors reviewed by the medical monitoring team. Risks to be reviewed include:

1. History of recurrent ARIA-E (2 or more episodes regardless of location).
2. More than 20 ARIA-H MCH.
3. More than one area of ARIA-H SS.
4. More than 2 lacunar infarcts or stroke involving a major vascular territory.
* Requiring full anticoagulation or on high dose or dual antiplatelet therapy (daily aspirin 325 mg or less allowed).
* History of macrohemorrhages \>1 cm.
* Intolerance for lecanemab.
* Pregnancy.
* Breastfeeding.
* Uncontrolled medical condition that is life threatening or precludes interpretation of AD.
* Uncontrolled blood pressure including mean arterial pressure exceeding 97 mm Hg.
* Uncontrolled seizure disorder.
* Ongoing auto-immune condition, bleeding diathesis, or neutropenia (platelets lower than 50,000) major depression or psychiatric condition.
* Exposure to other AD investigational agents within the past six months, or five half-lives from Visit 2 (Entry Visit) whichever is longer.
* Active cancer/malignancy that could interfere with study evaluations.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alzheimer's Association

OTHER

Sponsor Role collaborator

Eisai Inc.

INDUSTRY

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Randall J Bateman, MD

Role: STUDY_DIRECTOR

Washington University School of Medicine

Locations

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University of Alabama in Birmingham

Birmingham, Alabama, United States

Site Status

Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status

Washington University in St. Louis

St Louis, Missouri, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Neuroscience Research Australia

Randwick, New South Wales, Australia

Site Status

The National Hospital for Neurology and Neurosurgery

London, Greater London, United Kingdom

Site Status

Countries

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United States Australia United Kingdom

References

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Salloway S, Farlow M, McDade E, Clifford DB, Wang G, Llibre-Guerra JJ, Hitchcock JM, Mills SL, Santacruz AM, Aschenbrenner AJ, Hassenstab J, Benzinger TLS, Gordon BA, Fagan AM, Coalier KA, Cruchaga C, Goate AA, Perrin RJ, Xiong C, Li Y, Morris JC, Snider BJ, Mummery C, Surti GM, Hannequin D, Wallon D, Berman SB, Lah JJ, Jimenez-Velazquez IZ, Roberson ED, van Dyck CH, Honig LS, Sanchez-Valle R, Brooks WS, Gauthier S, Galasko DR, Masters CL, Brosch JR, Hsiung GR, Jayadev S, Formaglio M, Masellis M, Clarnette R, Pariente J, Dubois B, Pasquier F, Jack CR Jr, Koeppe R, Snyder PJ, Aisen PS, Thomas RG, Berry SM, Wendelberger BA, Andersen SW, Holdridge KC, Mintun MA, Yaari R, Sims JR, Baudler M, Delmar P, Doody RS, Fontoura P, Giacobino C, Kerchner GA, Bateman RJ; Dominantly Inherited Alzheimer Network-Trials Unit. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease. Nat Med. 2021 Jul;27(7):1187-1196. doi: 10.1038/s41591-021-01369-8. Epub 2021 Jun 21.

Reference Type BACKGROUND
PMID: 34155411 (View on PubMed)

Bateman RJ, Aisen PS, De Strooper B, Fox NC, Lemere CA, Ringman JM, Salloway S, Sperling RA, Windisch M, Xiong C. Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease. Alzheimers Res Ther. 2011 Jan 6;3(1):1. doi: 10.1186/alzrt59.

Reference Type BACKGROUND
PMID: 21211070 (View on PubMed)

Morris JC, Aisen PS, Bateman RJ, Benzinger TL, Cairns NJ, Fagan AM, Ghetti B, Goate AM, Holtzman DM, Klunk WE, McDade E, Marcus DS, Martins RN, Masters CL, Mayeux R, Oliver A, Quaid K, Ringman JM, Rossor MN, Salloway S, Schofield PR, Selsor NJ, Sperling RA, Weiner MW, Xiong C, Moulder KL, Buckles VD. Developing an international network for Alzheimer research: The Dominantly Inherited Alzheimer Network. Clin Investig (Lond). 2012 Oct 1;2(10):975-984. doi: 10.4155/cli.12.93.

Reference Type BACKGROUND
PMID: 23139856 (View on PubMed)

Moulder KL, Snider BJ, Mills SL, Buckles VD, Santacruz AM, Bateman RJ, Morris JC. Dominantly Inherited Alzheimer Network: facilitating research and clinical trials. Alzheimers Res Ther. 2013 Oct 17;5(5):48. doi: 10.1186/alzrt213. eCollection 2013.

Reference Type BACKGROUND
PMID: 24131566 (View on PubMed)

Mills SM, Mallmann J, Santacruz AM, Fuqua A, Carril M, Aisen PS, Althage MC, Belyew S, Benzinger TL, Brooks WS, Buckles VD, Cairns NJ, Clifford D, Danek A, Fagan AM, Farlow M, Fox N, Ghetti B, Goate AM, Heinrichs D, Hornbeck R, Jack C, Jucker M, Klunk WE, Marcus DS, Martins RN, Masters CM, Mayeux R, McDade E, Morris JC, Oliver A, Ringman JM, Rossor MN, Salloway S, Schofield PR, Snider J, Snyder P, Sperling RA, Stewart C, Thomas RG, Xiong C, Bateman RJ. Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial. Rev Neurol (Paris). 2013 Oct;169(10):737-43. doi: 10.1016/j.neurol.2013.07.017. Epub 2013 Sep 6.

Reference Type BACKGROUND
PMID: 24016464 (View on PubMed)

McDade E, Cummings JL, Dhadda S, Swanson CJ, Reyderman L, Kanekiyo M, Koyama A, Irizarry M, Kramer LD, Bateman RJ. Lecanemab in patients with early Alzheimer's disease: detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study. Alzheimers Res Ther. 2022 Dec 21;14(1):191. doi: 10.1186/s13195-022-01124-2.

Reference Type BACKGROUND
PMID: 36544184 (View on PubMed)

van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer LD, Iwatsubo T. Lecanemab in Early Alzheimer's Disease. N Engl J Med. 2023 Jan 5;388(1):9-21. doi: 10.1056/NEJMoa2212948. Epub 2022 Nov 29.

Reference Type BACKGROUND
PMID: 36449413 (View on PubMed)

Ryman DC, Acosta-Baena N, Aisen PS, Bird T, Danek A, Fox NC, Goate A, Frommelt P, Ghetti B, Langbaum JB, Lopera F, Martins R, Masters CL, Mayeux RP, McDade E, Moreno S, Reiman EM, Ringman JM, Salloway S, Schofield PR, Sperling R, Tariot PN, Xiong C, Morris JC, Bateman RJ; Dominantly Inherited Alzheimer Network. Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology. 2014 Jul 15;83(3):253-60. doi: 10.1212/WNL.0000000000000596. Epub 2014 Jun 13.

Reference Type BACKGROUND
PMID: 24928124 (View on PubMed)

Related Links

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http://www.dianexr.org/

Expanded registry

Other Identifiers

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The Alzheimer's Association

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

DIAN-TU-003

Identifier Type: -

Identifier Source: org_study_id