Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001

NCT01760005 | Active Not Recruiting Phase 2 DMC

• 11 other identifiers: DIAN-TU-001 (Master)The Alzheimer's AssociationU01AG0427912013-000307-17R01AG046179REec-2014-0817GHR FoundationAlzheimer's AssociationR56AG053267U01AG059798R01AG053267
• Study Type: interventional
• Target: 490
• Locations: 15 countries
• Sites: 38

Brief Summary

The purpose of this study is to assess the safety, tolerability, biomarker, cognitive and clinical efficacy of investigational products in participants with an Alzheimer's disease-causing mutation by determining if treatment with the study drug slows the rate of progression of cognitive/clinical impairment or improves disease-related biomarkers.

Conditions

Alzheimers Disease; Dementia; Alzheimers 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; DIAN TU; DIAD

Outcome Measures

Primary Outcomes (1)

• Assess cognitive efficacy in individuals with mutations causing dominantly inherited AD as measured by the change from baseline in the DIAN-Multivariate Cognitive Endpoint (DIAN-MCE)

  The DIAN-Multivariate Cognitive Endpoint (DIAN-MCE) consists of 4 cognitive measures: Wechsler Memory Scale-Revised Logical Memory Delayed Recall Test, Wechsler Adult Intelligence Sale Digit Symbol Substitution Test (WAIS), International Shopping List Task (ISLT), Mini-Mental State Examination (MMSE)

  Baseline and Weeks 52, 104, 156, and 208

Study Arms (8)

Gantenerumab

EXPERIMENTAL

This arm completed and is closed.

Drug: Gantenerumab

Solanezumab

EXPERIMENTAL

This arm completed and is closed.

Drug: Solanezumab

Matching placebo (Gantenerumab)

PLACEBO COMPARATOR

This arm completed and is closed.

Drug: Matching Placebo (Gantenerumab)

Matching Placebo (Solanezumab)

PLACEBO COMPARATOR

This arm completed and is closed.

Drug: Matching Placebo (Solanezumab)

Cognitive Run-in

NO INTERVENTION

This arm is completed and closed.

Gantenerumab Open Label Extension

ACTIVE COMPARATOR

Subcutaneously every 4 weeks at escalating doses. This arm is completed and closed.

Drug: Gantenerumab

E2814 plus lecanemab

EXPERIMENTAL

Symptomatic Population (Cohort 1) At Week 0, participants will receive open-label lecanemab administered intravenously for the full treatment period. At Week 24, participants randomized to E2814 will receive intravenously in a blinded fashion for the remainder of their treatment period. Asymptomatic Population (Cohort 2) At Week 0, participants randomized to E2814 will receive intravenously in a blinded fashion for the full treatment period. At Week 52, all participants will initiate open-label lecanemab administered intravenously for the remainder of their treatment period.

Drug: E2814; Drug: Lecanemab

Matching placebo (E2814) plus lecanemab

EXPERIMENTAL

Symptomatic Population (Cohort 1) At Week 0, participants will receive open-label lecanemab administered intravenously for the full treatment period. At Week 24, participants randomized to E2814 placebo will receive placebo intravenously in a blinded fashion for the remainder of their treatment period. Asymptomatic Population (Cohort 2) At Week 0, participants randomized to E2814 placebo will receive placebo intravenously in a blinded fashion for the full treatment period. At Week 52, all participants will initiate open-label lecanemab administered intravenously for the remainder of their treatment period.

Drug: Lecanemab; Drug: Matching Placebo (E2814)

Interventions

Gantenerumab DRUG

Subcutaneously every 4 weeks at escalating doses

Also known as: RO4909832

Gantenerumab

Solanezumab DRUG

Intravenous infusion every 4 weeks at escalating doses

Also known as: LY2062430

Solanezumab

Matching Placebo (Gantenerumab) DRUG

Subcutaneous injection of placebo every 4 weeks

Matching placebo (Gantenerumab)

Matching Placebo (Solanezumab) DRUG

Intravenous infusion of placebo every 4 weeks

Matching Placebo (Solanezumab)

E2814 DRUG

Administered intravenously in a blinded fashion

E2814 plus lecanemab

Lecanemab DRUG

Administered intravenously

Also known as: BAN2401

E2814 plus lecanemab; Matching placebo (E2814) plus lecanemab

Matching Placebo (E2814) DRUG

Placebo administered intravenously in a blinded fashion.

Matching placebo (E2814) plus lecanemab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 18-80 years of age
• Individuals who know they have an Alzheimer's disease-causing mutation or are unaware of their genetic status and have dominantly inherited Alzheimer's disease (DIAD) mutation in their family.
• Are within -15 to + 10 years of the predicted or actual age of cognitive symptom onset. For Cognitive Run-In (CRI): includes participants who are younger than 15 years prior to the expected age of cognitive symptom onset, in addition to those 15 years younger and no more than 10 years older than expected or actual age of cognitive symptom onset.
• Cognitively normal or with mild cognitive impairment or mild dementia, Clinical Dementia Rating (CDR) of 0-1 (inclusive)
• Fluency in DIAN-TU trial approved language and evidence of adequate premorbid intellectual functioning
• Able to undergo Magnetic Resonance Imaging (MRI), Lumbar Puncture (LP), Positron Emission Tomography (PET), and complete all study related testing and evaluations.
• For women of childbearing potential, if partner is not sterilized, subject must agree to use effective contraceptive measures (hormonal contraception, intra-uterine device, sexual abstinence, barrier method with spermicide).
• Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments.
• Has a Study Partner who in the investigator's judgment is able to provide accurate information as to the subject's cognitive and functional abilities, who agrees to provide information at the study visits which require informant input for scale completion.

You may not qualify if:

• History or presence of brain MRI scans indicative of any other significant abnormality
• Alcohol or drug dependence currently or within the past 1 year
• Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin or body which would preclude MRI scan.
• History or presence of clinically significant cardiovascular disease, hepatic/renal disorders, infectious disease or immune disorder, or metabolic/endocrine disorders
• Anticoagulants except low dose (≤ 325 mg) aspirin.
• Have been exposed to a monoclonal antibody targeting beta amyloid peptide within the past six months.
• History of cancer within the last 5 years, except basal cell carcinoma, non-squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years.
• Positive urine or serum pregnancy test or plans or desires to become pregnant during the course of the trial.
• Subjects unable to complete all study related testing, including implanted metal that cannot be removed for MRI scanning, required anticoagulation and pregnancy.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Eli Lilly and Company: collaborator
• Hoffmann-La Roche: collaborator
• Alzheimer's Association: collaborator
• National Institute on Aging (NIA): collaborator
• Avid Radiopharmaceuticals: collaborator
• Accelerating Medicines Partnership (AMP): collaborator
• Eisai Inc.: collaborator
• Janssen, LP: collaborator

Study Sites (38)

University of Alabama in Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California San Diego Medical Center

La Jolla, California, 92037, United States

Location

USC Keck School of Medicine

Los Angeles, California, 90033, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Emory University

Atlanta, Georgia, 30329, United States

Location

Advocate Lutheran General Hospital

Park Ridge, Illinois, 60068, 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 Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Butler Hospital

Providence, Rhode Island, 02096, United States

Location

Kerwin Medical Center

Dallas, Texas, 75231, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Instituto de Investigaciones Neurologicas Raul Carrea, FLENI

Ciudad Autonoma de Buenos Aire, C1428AQK, Argentina

Location

Neuroscience Research Australia

Randwick, New South Wales, 2031, Australia

Location

Alzheimer's Research Australia

Melbourne, Victoria, 3010, Australia

Location

The McCuster Foundation of Alzheimer's Disease Research

Nedlands, Western Australia, 6009, Australia

Location

Hospital das Clínicas da Faculdade de Medicina da USP

São Paulo, 05403-000, Brazil

Location

UBC Hospital

Vancouver, British Columbia, V6T 2B5, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

McGill Center for Studies in Aging

Verdun, Quebec, H4H 1R3, Canada

Location

CHU de Quebec - Hôpital de l' Enfant Jésus

Québec, G1J 1Z4, Canada

Location

Grupo de Neurociencias Sede de la Universidad de Antioquia

Medellín, Colombia

Location

CHU de Toulouse - Hôpital Purpan

Toulouse, Haute Garonne, 31059, France

Location

Hopital Roger Salengro - CHU Lille

Lille, Nord, 59037, France

Location

Groupe Hospitalier Pitie-Salpetriere

Paris, Paris, 69677, France

Location

Hopital Neurologique Pierre Wertheimer

Bron, Rhone, 69677, France

Location

CHU de Rouen - Hôpital Charles Nicolle

Rouen, Seine Maritime, 76031, France

Location

Universitaetsklinikum Tubingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

LMU-Campus Grosshadern

Munich, Bavaria, 81377, Germany

Location

St Vincent's University Hospital

Dublin, DUBLIN 4, Ireland

Location

IRCCS Centro San Giovanni di Dio Fatebenefratelli

Brescia, 25125, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

Niigata University Medical & Dental Hospital

Niigata, Niigata, 951-8520, Japan

Location

University of Tokyo Hospital

Bunkyō City, Tokyo-To, 113-8655, Japan

Location

Brain Research Center

Amsterdam, 1081 GM, Netherlands

Location

University of Puerto Rico, School of Medicine

San Juan, 00936, Puerto Rico

Location

Hospital Clínic I Provincial de Barcelona

Barcelona, 8036, Spain

Location

The National Hospital for Neurology and Neurosurgery

London, Greater London, WC1B 3BG, United Kingdom

Location

Related Publications (14)

• Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC; Dominantly Inherited Alzheimer Network. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012 Aug 30;367(9):795-804. doi: 10.1056/NEJMoa1202753. Epub 2012 Jul 11.

  PMID: 22784036 BACKGROUND

• Farlow M, Arnold SE, van Dyck CH, Aisen PS, Snider BJ, Porsteinsson AP, Friedrich S, Dean RA, Gonzales C, Sethuraman G, DeMattos RB, Mohs R, Paul SM, Siemers ER. Safety and biomarker effects of solanezumab in patients with Alzheimer's disease. Alzheimers Dement. 2012 Jul;8(4):261-71. doi: 10.1016/j.jalz.2011.09.224. Epub 2012 Jun 5.

  PMID: 22672770 BACKGROUND

• Bateman RJ, Benzinger TL, Berry S, Clifford DB, Duggan C, Fagan AM, Fanning K, Farlow MR, Hassenstab J, McDade EM, Mills S, Paumier K, Quintana M, Salloway SP, Santacruz A, Schneider LS, Wang G, Xiong C; DIAN-TU Pharma Consortium for the Dominantly Inherited Alzheimer Network. The DIAN-TU Next Generation Alzheimer's prevention trial: Adaptive design and disease progression model. Alzheimers Dement. 2017 Jan;13(1):8-19. doi: 10.1016/j.jalz.2016.07.005. Epub 2016 Aug 29.

  PMID: 27583651 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

• Wang G, Berry S, Xiong C, Hassenstab J, Quintana M, McDade EM, Delmar P, Vestrucci M, Sethuraman G, Bateman RJ; Dominantly Inherited Alzheimer Network Trials Unit. A novel cognitive disease progression model for clinical trials in autosomal-dominant Alzheimer's disease. Stat Med. 2018 Sep 20;37(21):3047-3055. doi: 10.1002/sim.7811. Epub 2018 May 14.

  PMID: 29761523 BACKGROUND

• Weninger S, Carrillo MC, Dunn B, Aisen PS, Bateman RJ, Kotz JD, Langbaum JB, Mills SL, Reiman EM, Sperling R, Santacruz AM, Tariot PN, Welsh-Bohmer KA. Collaboration for Alzheimer's Prevention: Principles to guide data and sample sharing in preclinical Alzheimer's disease trials. Alzheimers Dement. 2016 May;12(5):631-2. doi: 10.1016/j.jalz.2016.04.001. No abstract available.

  PMID: 27157073 BACKGROUND

• Grill JD, Bateman RJ, Buckles V, Oliver A, Morris JC, Masters CL, Klunk WE, Ringman JM; Dominantly Inherited Alzheimer's Network. A survey of attitudes toward clinical trials and genetic disclosure in autosomal dominant Alzheimer's disease. Alzheimers Res Ther. 2015 Jul 22;7(1):50. doi: 10.1186/s13195-015-0135-0. eCollection 2015.

  PMID: 26203303 BACKGROUND

• McDade E, Bateman RJ. Stop Alzheimer's before it starts. Nature. 2017 Jul 12;547(7662):153-155. doi: 10.1038/547153a. No abstract available.

  PMID: 28703214 BACKGROUND

• McDade E, Wang G, Gordon BA, Hassenstab J, Benzinger TLS, Buckles V, Fagan AM, Holtzman DM, Cairns NJ, Goate AM, Marcus DS, Morris JC, Paumier K, Xiong C, Allegri R, Berman SB, Klunk W, Noble J, Ringman J, Ghetti B, Farlow M, Sperling RA, Chhatwal J, Salloway S, Graff-Radford NR, Schofield PR, Masters C, Rossor MN, Fox NC, Levin J, Jucker M, Bateman RJ; Dominantly Inherited Alzheimer Network. Longitudinal cognitive and biomarker changes in dominantly inherited Alzheimer disease. Neurology. 2018 Oct 2;91(14):e1295-e1306. doi: 10.1212/WNL.0000000000006277. Epub 2018 Sep 14.

  PMID: 30217935 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

• Weng H, Bateman R, Morris JC, Xiong C. Validity and power of minimization algorithm in longitudinal analysis of clinical trials. Biostat Epidemiol. 2017;1(1):59-77. doi: 10.1080/24709360.2017.1331822. Epub 2017 Jun 13.

  PMID: 29250611 BACKGROUND

• Bateman RJ, Li Y, McDade EM, Llibre-Guerra JJ, Clifford DB, Atri A, Mills SL, Santacruz AM, Wang G, Supnet C, Benzinger TLS, Gordon BA, Ibanez L, Klein G, Baudler M, Doody RS, Delmar P, Kerchner GA, Bittner T, Wojtowicz J, Bonni A, Fontoura P, Hofmann C, Kulic L, Hassenstab J, Aschenbrenner AJ, Perrin RJ, Cruchaga C, Renton AE, Xiong C, Goate AA, Morris JC, Holtzman DM, Snider BJ, Mummery C, Brooks WS, Wallon D, Berman SB, Roberson E, Masters CL, Galasko DR, Jayadev S, Sanchez-Valle R, Pariente J, Kinsella J, van Dyck CH, Gauthier S, Hsiung GR, Masellis M, Dubois B, Honig LS, Jack CR, Daniels A, Aguillon D, Allegri R, Chhatwal J, Day G, Fox NC, Huey E, Ikeuchi T, Jucker M, Lee JH, Levey AI, Levin J, Lopera F, Roh J, Rosa-Neto P, Schofield PR; Dominantly Inherited Alzheimer's Disease-Trials Unit. Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer's disease: an open-label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU trial. Lancet Neurol. 2025 Apr;24(4):316-330. doi: 10.1016/S1474-4422(25)00024-9.

  PMID: 40120616 DERIVED

• Bateman RJ, Li Y, McDade EM, Llibre-Guerra JJ, Clifford DB, Atri A, Mills SL, Santacruz AM, Wang G, Supnet C, Benzinger TLS, Gordon BA, Ibanez L, Klein G, Baudler M, Doody RS, Delmar P, Kerchner GA, Bittner T, Wojtowicz J, Bonni A, Fontoura P, Hofmann C, Kulic L, Hassenstab J, Aschenbrenner AJ, Perrin RJ, Cruchaga C, Renton AE, Xiong C, Goate AA, Morris JC, Holtzman DM, Snider BJ, Mummery C, Brooks WS, Wallon D, Berman SB, Roberson E, Masters CL, Galasko DR, Jayadev S, Sanchez-Valle R, Pariente J, Kinsella J, van Dyck CH, Gauthier S, Robin Hsiung GY, Masellis M, Dubois B, Honig LS, Jack CR, Daniels A, Aguillon D, Allegri R, Chhatwal J, Day G, Fox N, Huey E, Ikeuchi T, Jucker M, Lee JH, Levey AI, Levin J, Lopera F, Roh J, Rosa-Neto P, Schofield PR; Dominantly Inherited Alzheimer's Disease-Trials Unit. Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer's disease: an open label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU Trial. medRxiv [Preprint]. 2025 Jan 29:2024.10.29.24316289. doi: 10.1101/2024.10.29.24316289.

  PMID: 39974075 DERIVED

• Chen CD, McCullough A, Gordon B, Joseph-Mathurin N, Flores S, McKay NS, Hobbs DA, Hornbeck R, Fagan AM, Cruchaga C, Goate AM, Perrin RJ, Wang G, Li Y, Shi X, Xiong C, Pontecorvo MJ, Klein G, Su Y, Klunk WE, Jack C, Koeppe R, Snider BJ, Berman SB, Roberson ED, Brosch J, Surti G, Jimenez-Velazquez IZ, Galasko D, Honig LS, Brooks WS, Clarnette R, Wallon D, Dubois B, Pariente J, Pasquier F, Sanchez-Valle R, Shcherbinin S, Higgins I, Tunali I, Masters CL, van Dyck CH, Masellis M, Hsiung R, Gauthier S, Salloway S, Clifford DB, Mills S, Supnet-Bell C, McDade E, Bateman RJ, Benzinger TLS; DIAN-TU Study Team. Longitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-beta monoclonal antibodies in dominantly inherited Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2023 Jul;50(9):2669-2682. doi: 10.1007/s00259-023-06209-0. Epub 2023 Apr 5.

  PMID: 37017737 DERIVED

Related Links

• Expanded registry

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

gantenerumab; solanezumab; 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 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: One arm is Open-label as noted in the arm descriptions
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Interventional with a non-interventional run-in component (Future interventions to be added)

Study Record Dates

• First Submitted: December 26, 2012
• First Posted: January 3, 2013
• Study Start: December 1, 2012
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

AU (3); AR (1); CO (1); CA (4); NL (1); BR (1); ES (1); IT (2); PR (1); FR (5); JP (2); DE (2); US (12); IE (1); GB (1)