Alzheimers DiseasePhase 2/3DIAN-TUNCT06424236
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
A Phase 2/3 study testing Gantenerumab in people with Alzheimers Disease and Dementia, run by Washington University School of Medicine at 17 sites in 6 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimers Disease, Dementia, Alzheimers Disease, Familial
- What is being tested?
- Gantenerumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 17 sitesin 6 countries
- Study dates
- 3 Jun 2020to 13 Nov 2023
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
17 sites in 6 countries.
17 sites in 6 countries
United States8 sites
Emory University
Atlanta, Georgia, 30329
University of Alabama in Birmingham
Birmingham, Alabama, 35294
Indiana University School of Medicine
Indianapolis, Indiana, 46202
University of California San Diego Medical Center
La Jolla, California, 92037
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Butler Hospital
Providence, Rhode Island, 02096
University of Washington
Seattle, Washington, 98195
Washington University in St. Louis
St Louis, Missouri, 63110
Australia3 sites
Mental Health Research Institute
Melbourne, Victoria, 3010
The McCuster Foundation of Alzheimer's Disease Research
Nedlands, Western Australia, 6009
Neuroscience Research Australia
Randwick, New South Wales, 2031
France3 sites
Groupe Hospitalier Pitie-Salpetriere
Paris, Paris, 69677
CHU de Rouen - Hôpital Charles Nicolle
Rouen, Seine Maritime, 76031
CHU de Toulouse - Hôpital Purpan
Toulouse, Haute Garonne, 31059
Puerto Rico1 site
University of Puerto Rico, School of Medicine
San Juan, 00936
United Kingdom1 site
The National Hospital for Neurology and Neurosurgery
London, Greater London, WC1B 3BG
About this study
Official title: A Phase II/III Multicenter Randomized, Double-Blind, Placebo-Controlled Platform Trial of Potential Disease Modifying Therapies Utilizing Biomarker, Cognitive, and Clinical Endpoints in Dominantly Inherited Alzheimer's Disease
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.
Read the detailed description
Alzheimer's disease (AD) is defined by the presence of abnormal accumulations of amyloid protein (plaques) and tau protein (tangles) in the brain. The double-blind arm of DIAN-TU-001 Master protocol (NCT01760005) tested whether gantenerumab provided a clinical benefit by slowing the onset or the worsening of the disease. A clinical benefit was not observed in the double-blind part of the DIAN-TU-001 study. However, gantenerumab was associated with improvements in measures of amyloid and tau and an improvement in an overall measure of neurodegeneration (when nerve cells in the brain lose function over time). It is not known whether these changes may provide future clinical benefits. Based on this information, an exploratory Open Label Extension (OLE) will further study the effect of gantenerumab on these Alzheimer-related proteins and their relationship to disease progression.
After this final evaluation of study treatment with gantenerumab used in the gantenerumab / solanezumab double-blind arm of the Master protocol (NCT01760005), eligible participants from the placebo, solanezumab, and gantenerumab treatment groups in double-blind period were invited to participate in an OLE period to receive active gantenerumab study treatment as part of the DIAN-TU-001 Master protocol. The OLE period of the study planned to provide study treatment with gantenerumab for up to 3 years (36 months).
This study collected brain scans, blood, and spinal fluid tests (also called biomarkers), as well as safety, clinical and cognitive testing. The goal is to determine if gantenerumab has favorable effects on these tests to determine if and how much treatment may prevent or delay the symptoms of AD.
Update:
Based on the results of the completed studies of gantenerumab in sporadic AD in late 2022, it was decided to determine if dominantly inherited Alzheimer's disease (DIAD) participants in the DIAN-TU-001 OLE study were substantially clinically benefiting from gantenerumab high-dose treatment before the trial reached completion as the Gant program was being stopped.
An interim efficacy analysis of the DIAN-TU-001 OLE was performed to:
- determine if gantenerumab OLE treatment and/or long-term treatment results in clinical benefit and determine the extent of amyloid removal compared to the double-blind period.
- determine the potential effects of gantenerumab on clinical and cognitive measures to support decision-making regarding next steps for the DIAN-TU-001 OLE.
- Conditions
- Alzheimers Disease, Dementia, Alzheimers Disease, Familial
- Being tested
- Gantenerumab
- 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
- Medical subject headings
- Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GantenerumabDrug
Also called RO4909832
Open-label administered Subcutaneously every 4 weeks, at escalating doses; at target, dosing was every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Gantenerumab Open Label Extension | Experimental | Gantenerumab: Subcutaneously every 4 weeks, at escalating doses; at target, dosing was every 2 weeks Receives: Drug: Gantenerumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The efficacy of gantenerumab in reducing disease progression was assessed by CDR - sum of boxes. The CDR-SB score is considered a more detailed quantitative general index of cognition and function than the global CDR score. The CDR - sum of boxes is the sum score of 6 domains of cognitive function (memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care), with the score of each domain ranging from 0 (no impairment) to 3 (severe impairment). The total score ranges from 0 (no impairment) to 18 (severe impairment). Higher score indicates worse performance. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Measured: Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Clinical Dementia Rating - Global Score at Weeks 52, 104 and 156
The efficacy of gantenerumab in reducing disease progression was assessed by CDR - global score. The score ranges from 0 (minimum) to 3 (maximum). Higher score indicates worse performance. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Measured: Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Functional Assessment Scale (FAS) at Weeks 52, 104 and 156
The efficacy of gantenerumab in reducing disease progression was assessed by FAS. This scale measured instrumental activities of daily living such as preparing balanced meals and managing personal finances. The intent of the FAS was to assess change in an individual's functional activities, relative to previously attained abilities, that were caused by cognitive dysfunction. The score ranges from 0 (minimum) to 30 (maximum). Higher score indicates worse performance. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Measured: 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
The efficacy of gantenerumab in reducing disease progression was assessed by MMSE. The MMSE is a brief, quantitative measure of cognitive status in adults used to screen for cognitive impairment. The score ranges from 0 (minimum) to 30 (maximum). Lower score indicates worse performance. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Measured: 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
The efficacy of gantenerumab in reducing disease progression was assessed by Tau PET SUVR. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Measured: Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Phosphorylated Tau (pTau)-181 in Cerebrospinal Fluid (CSF) at Weeks 52, 104 and 156
The efficacy of gantenerumab in reducing disease progression was assessed by CSF pTau-181. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Measured: Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Neurofilament Light Chain (NfL) in Cerebrospinal Fluid at Weeks 52, 104 and 156
The efficacy of gantenerumab in reducing disease progression was assessed by CSF NfL. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Measured: Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Amyloid Beta1-42/40 Ratio in Cerebrospinal Fluid at Weeks 52, 104 and 156
The efficacy of gantenerumab in reducing disease progression was assessed by CSF Amyloid Beta1-42/40. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Measured: Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in DIAN-TU Open Label Extension Cognitive Composite Score at Weeks 52, 104 and 156
The efficacy of gantenerumab in reducing disease progression was assessed by DIAN-TU OLE Cognitive Composite. The cognitive composite was calculated based on the below 4 components,
- The wechsler adult intelligence scale-revised digit span (backward recall). Score ranges from 0 (minimum) to 7 (maximum).
- The category fluency (animals) value. Score ranges from 0 to unlimited.
- The wechsler adult intelligence scale digit symbol substitution test. Score ranges from 0 (minimum) to 93 (maximum).
- The MMSE. Score ranges from 0 (minimum) to 30 (maximum).
Lower scores of each component indicate worse performance. The cognitive composite is a normalized z score and has score range - 4.11 to unlimited as one of the components has score range 0 to unlimited. Lower score indicates worse performance. Baseline was defined as last non-missing measurement prior to OLE study drug administration.
Measured: Baseline (Day 1) and Weeks 52, 104 and 156
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2024
- Study start3 Jun 2020
- Primary completion6 Oct 2023
- Study completion13 Nov 2023
Why it stopped: DIAN-TU announced the discontinuation of the DIAN-TU-001 OLE based on the status of the drug program and findings from an interim efficacy analysis and.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Alzheimers DiseaseStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche, Alzheimer's Association, National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Randall J Bateman, MD, Study director, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06424236
- Sponsor's protocol ID
- DIAN-TU-001 (Gant OLE)
- Other IDs
- The Alzheimer's Association, U01AG042791, 2013-000307-17, R01AG046179, REec-2014-0817, The Alzheimer's Association, GHR Foundation, Alzheimer's Association
- Acronym
- DIAN-TU
- Status last verified
- Jan 2025
- First submitted
- 16 Apr 2024
- Last updated
- 4 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Access to DIAN-TU trial data will follow the DIAN-TU data access policy, which complies with the guidelines established by the Collaboration for Alzheimer's Prevention \[CAP REF\].
Publications
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.
PubMed 22784036Farlow 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.
PubMed 22672770Bateman 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.
PubMed 27583651Mills 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.
PubMed 24016464Wang 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.
PubMed 29761523Weninger 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.
PubMed 27157073Grill 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.
PubMed 26203303McDade E, Bateman RJ. Stop Alzheimer's before it starts. Nature. 2017 Jul 12;547(7662):153-155. doi: 10.1038/547153a. No abstract available.
PubMed 28703214McDade 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.
PubMed 30217935Ryman 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.
PubMed 24928124Weng 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.
PubMed 29250611Bateman, 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.
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.
PubMed 40120616Bateman 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.
PubMed 39974075
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II/III Multicenter Randomized, Double-Blind, Placebo-Controlled Platform Trial of Potential Disease Modifying Therapies Utilizing Biomarker, Cognitive, and Clinical Endpoints in Dominantly Inherited Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT06424236
- Acronym / sponsor ID
- DIAN-TU / DIAN-TU-001 (Gant OLE)
- 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
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: DIAN-TU announced the discontinuation of the DIAN-TU-001 OLE based on the status of the drug program and findings from an interim efficacy analysis and.
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche, Alzheimer's Association, National Institute on Aging (NIA)
- Study start
- 3 Jun 2020 (actual)
- Primary completion
- 6 Oct 2023 (actual)
- Study completion
- 13 Nov 2023 (actual)
- First posted
- 22 May 2024 (actual)
- Results
- Posted 4 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Alzheimer's disease (AD) is defined by the presence of abnormal accumulations of amyloid protein (plaques) and tau protein (tangles) in the brain. The double-blind arm of DIAN-TU-001 Master protocol (NCT01760005) tested whether gantenerumab provided a clinical benefit by slowing the onset or the worsening of the disease. A clinical benefit was not observed in the double-blind part of the DIAN-TU-001 study. However, gantenerumab was associated with improvements in measures of amyloid and tau and an improvement in an overall measure of neurodegeneration (when nerve cells in the brain lose function over time). It is not known whether these changes may provide future clinical benefits. Based on this information, an exploratory Open Label Extension (OLE) will further study the effect of gantenerumab on these Alzheimer-related proteins and their relationship to disease progression.
After this final evaluation of study treatment with gantenerumab used in the gantenerumab / solanezumab double-blind arm of the Master protocol (NCT01760005), eligible participants from the placebo, solanezumab, and gantenerumab treatment groups in double-blind period were invited to participate in an OLE period to receive active gantenerumab study treatment as part of the DIAN-TU-001 Master protocol. The OLE period of the study planned to provide study treatment with gantenerumab for up to 3 years (36 months).
This study collected brain scans, blood, and spinal fluid tests (also called biomarkers), as well as safety, clinical and cognitive testing. The goal is to determine if gantenerumab has favorable effects on these tests to determine if and how much treatment may prevent or delay the symptoms of AD.
Update:
Based on the results of the completed studies of gantenerumab in sporadic AD in late 2022, it was decided to determine if dominantly inherited Alzheimer's disease (DIAD) participants in the DIAN-TU-001 OLE study were substantially clinically benefiting from gantenerumab high-dose treatment before the trial reached completion as the Gant program was being stopped.
An interim efficacy analysis of the DIAN-TU-001 OLE was performed to:
- determine if gantenerumab OLE treatment and/or long-term treatment results in clinical benefit and determine the extent of amyloid removal compared to the double-blind period.
- determine the potential effects of gantenerumab on clinical and cognitive measures to support decision-making regarding next steps for the DIAN-TU-001 OLE.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gantenerumab Open Label Extension | Experimental | Drug: GantenerumabGantenerumab: Subcutaneously every 4 weeks, at escalating doses; at target, dosing was every 2 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GantenerumabAlso: RO4909832Open-label administered Subcutaneously every 4 weeks, at escalating doses; at target, dosing was every 2 weeks | Drug | Gantenerumab Open Label Extension |
Primary outcome
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
Time frame: Baseline (Day 1) and 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.
9 secondary outcomes
Change From Baseline in Clinical Dementia Rating (CDR) - Sum of Boxes Score at Weeks 52, 104 and 156
Time frame: Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Clinical Dementia Rating - Global Score at Weeks 52, 104 and 156
Time frame: Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Functional Assessment Scale (FAS) at Weeks 52, 104 and 156
Time frame: 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
Time frame: 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
Time frame: Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Phosphorylated Tau (pTau)-181 in Cerebrospinal Fluid (CSF) at Weeks 52, 104 and 156
Time frame: Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Neurofilament Light Chain (NfL) in Cerebrospinal Fluid at Weeks 52, 104 and 156
Time frame: Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Amyloid Beta1-42/40 Ratio in Cerebrospinal Fluid at Weeks 52, 104 and 156
Time frame: Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in DIAN-TU Open Label Extension Cognitive Composite Score at Weeks 52, 104 and 156
Time frame: Baseline (Day 1) and Weeks 52, 104 and 156
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22784036Bateman 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.
- Background: PubMed 22672770Farlow 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.
- Background: PubMed 27583651Bateman 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.
- Background: PubMed 24016464Mills 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.
- Background: PubMed 29761523Wang 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.
- Background: PubMed 27157073Weninger 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.
- Background: PubMed 26203303Grill 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.
- Background: PubMed 28703214McDade E, Bateman RJ. Stop Alzheimer's before it starts. Nature. 2017 Jul 12;547(7662):153-155. doi: 10.1038/547153a. No abstract available.
- Background: PubMed 30217935McDade 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.
- Background: PubMed 24928124Ryman 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.
- Background: PubMed 29250611Weng 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.
- Results publicationBateman, 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.
- Expanded registryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Access to DIAN-TU trial data will follow the DIAN-TU data access policy, which complies with the guidelines established by the Collaboration for Alzheimer's Prevention [CAP REF].
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Randall J Bateman, MD study director
Washington University School of Medicine
17 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Gantenerumab in people with Alzheimers Disease and Dementia, run by Washington University School of Medicine at 17 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Australia, France, Puerto Rico, Spain and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Baseline (Day 1) and Weeks 52, 104 and 156). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06424236, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.