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

NCT06384573 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: DIAN-TU-003The Alzheimer's Association
• Study Type: interventional
• Target: 40
• Locations: 3 countries
• Sites: 6

Brief Summary

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.

Conditions

Alzheimer's Disease; Dementia; Alzheimer's Disease, Familial

Keywords

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

Outcome Measures

Primary Outcomes (1)

• The primary endpoint for the final analysis is the time to recurrent progression of Clinical Dementia Rating - Sum of Boxes (CDR-SB).

  Week 0, Week 52, Week 104, Week 156, Week 208, Week 260, Week 312, Week 364

Study Arms (1)

lecanemab

EXPERIMENTAL

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.

Drug: lecanemab

Interventions

lecanemab DRUG

Administered intravenously

Also known as: BAN2401

lecanemab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• History of recurrent ARIA-E (2 or more episodes regardless of location).
• More than 20 ARIA-H MCH.
• More than one area of ARIA-H SS.
• 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.

Sponsors & Collaborators

• Eisai Inc.: collaborator
• Washington University School of Medicine: lead
• Alzheimer's Association: collaborator

Study Sites (6)

University of Alabama in Birmingham

Birmingham, Alabama, 35294, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Neuroscience Research Australia

Randwick, New South Wales, 2031, Australia

Location

The National Hospital for Neurology and Neurosurgery

London, Greater London, WC1B 3BG, United Kingdom

Location

Related Publications (8)

• 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.

  PMID: 34155411 BACKGROUND

• 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.

  PMID: 21211070 BACKGROUND

• 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.

  PMID: 23139856 BACKGROUND

• 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.

  PMID: 24131566 BACKGROUND

• 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.

  PMID: 24016464 BACKGROUND

• 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.

  PMID: 36544184 BACKGROUND

• 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.

  PMID: 36449413 BACKGROUND

• 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.

  PMID: 24928124 BACKGROUND

Related Links

• Expanded registry

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

lecanemab

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Randall J Bateman, MD

  Washington University School of Medicine

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2024
• First Posted: April 25, 2024
• Study Start: June 10, 2024
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (4); AU (1); GB (1)