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

NCT06424236 | Terminated Phase 2 Results DMC FDA Drug

• 11 other identifiers: DIAN-TU-001 (Gant OLE)The Alzheimer's AssociationU01AG0427912013-000307-17R01AG046179REec-2014-0817GHR FoundationAlzheimer's AssociationR56AG053267U01AG059798R01AG053267
• Study Type: interventional
• Target: 73
• Locations: 6 countries
• Sites: 17

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)

• Change From Baseline in Composite [11C] Pittsburgh Compound B (PiB)-Positron Emission Tomography (PET) Composite Standardized Uptake Value Ratio (C-SUVR) at Weeks 52, 104 and 156

  The composite PiB partial volume corrected C-SUVR was used as the biomarker endpoint for amyloid deposition using PET. The C-SUVR of precuneus, caudate, gyrus rectus, occipital cortex, parietal cortex, prefrontal cortex, and temporal cortex of brain regions was analyzed. Higher ratio indicate worse disease stage. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.

  Baseline (Day 1) and Weeks 52, 104 and 156

Secondary Outcomes (9)

• Change From Baseline in Clinical Dementia Rating (CDR) - Sum of Boxes Score at Weeks 52, 104 and 156

  Baseline (Day 1) and Weeks 52, 104 and 156

• Change From Baseline in Clinical Dementia Rating - Global Score at Weeks 52, 104 and 156

  Baseline (Day 1) and Weeks 52, 104 and 156

• Change From Baseline in Functional Assessment Scale (FAS) at Weeks 52, 104 and 156

  Baseline (Day 1) and Weeks 52, 104 and 156

• Change From Baseline in Mini-Mental State Examination (MMSE) at Weeks 24, 52, 76, 104, 128 and 156

  Baseline (Day 1) and Weeks 24, 52, 76, 104, 128 and 156

• Change From Baseline in Tau Positron Emission Tomography Binding Partial Volume Corrected Standardized Uptake Value Ratio (Tau PET SUVR) at Weeks 52, 104 and 156

  Baseline (Day 1) and Weeks 52, 104 and 156

Study Arms (1)

Gantenerumab Open Label Extension

EXPERIMENTAL

Gantenerumab: Subcutaneously every 4 weeks, at escalating doses; at target, dosing was every 2 weeks

Drug: Gantenerumab

Interventions

Gantenerumab DRUG

Open-label administered Subcutaneously every 4 weeks, at escalating doses; at target, dosing was every 2 weeks

Also known as: RO4909832

Gantenerumab Open Label Extension

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
• Individuals who have participated in the double-blind period
• In the opinion of the investigator and sponsor, treatment is not contraindicated for safety
• Capable of receiving drug and appropriate clinical safety assessment
• 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
• Hoffmann-La Roche: collaborator
• Alzheimer's Association: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (17)

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

Emory University

Atlanta, Georgia, 30329, 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

University of Washington

Seattle, Washington, 98195, United States

Location

Neuroscience Research Australia

Randwick, New South Wales, 2031, Australia

Location

Mental Health Research Institute

Melbourne, Victoria, 3010, Australia

Location

The McCuster Foundation of Alzheimer's Disease Research

Nedlands, Western Australia, 6009, Australia

Location

CHU de Toulouse - Hôpital Purpan

Toulouse, Haute Garonne, 31059, France

Location

Groupe Hospitalier Pitie-Salpetriere

Paris, Paris, 69677, France

Location

CHU de Rouen - Hôpital Charles Nicolle

Rouen, Seine Maritime, 76031, France

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, Randall J., Yan Li, Eric McDade, Jorge J. Llibre Guerra, David Clifford, Alireza Atri, Susan Mills, et al. "Amyloid Reduction and Dementia Progression in Dominantly Inherited Alzheimer's Disease after Long-Term Gantenerumab Treatment: Results from the Dian-Tu Trial." SSRN Scholarly Paper. Rochester, NY, July 26, 2024. https://doi.org/10.2139/ssrn.4906344.

  RESULT

• 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

Related Links

• Expanded registry

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

gantenerumab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Pharma Partner and Sponsor decided to terminate the study early based on the status of the drug program and findings from the interim efficacy analysis. The Interim Analysis will be updated here at a later date.

Results Point of Contact

• Title: Administrative Director
• Organization: Washington University

DIAN-TUDataRequest@wustl.edu

(314) 221-8344

Study Officials

• Randall J Bateman, MD

  Washington University School of Medicine

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Arm is Open-label as noted in the arm description
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2024
• First Posted: May 22, 2024
• Study Start: June 3, 2020
• Primary Completion: October 6, 2023
• Study Completion: November 13, 2023
• Last Updated: February 4, 2025
• Results First Posted: February 4, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

FR (3); ES (1); GB (1); PR (1); US (8); AU (3)