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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT06424236
Registration number
NCT06424236
Ethics application status
Date submitted
16/04/2024
Date registered
22/05/2024
Date last updated
25/03/2025
Titles & IDs
Public title
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
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Scientific 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
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Secondary ID [1]
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The Alzheimer's Association
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Secondary ID [2]
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DIAN-TU-001 (Gant OLE)
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Universal Trial Number (UTN)
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Trial acronym
DIAN-TU
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Alzheimers Disease
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Dementia
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Alzheimers Disease, Familial
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Condition category
Condition code
Neurological
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Alzheimer's disease
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Neurological
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Dementias
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Gantenerumab
Experimental: Gantenerumab Open Label Extension - Gantenerumab: Subcutaneously every 4 weeks, at escalating doses; at target, dosing was every 2 weeks
Treatment: Drugs: Gantenerumab
Open-label administered Subcutaneously every 4 weeks, at escalating doses; at target, dosing was every 2 weeks
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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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
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline (Day 1) and Weeks 52, 104 and 156
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Secondary outcome [1]
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Change From Baseline in Clinical Dementia Rating (CDR) - Sum of Boxes Score at Weeks 52, 104 and 156
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline (Day 1) and Weeks 52, 104 and 156
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Secondary outcome [2]
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Change From Baseline in Clinical Dementia Rating - Global Score at Weeks 52, 104 and 156
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Assessment method [2]
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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.
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Timepoint [2]
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Baseline (Day 1) and Weeks 52, 104 and 156
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Secondary outcome [3]
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Change From Baseline in Functional Assessment Scale (FAS) at Weeks 52, 104 and 156
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Assessment method [3]
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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.
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Timepoint [3]
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Baseline (Day 1) and Weeks 52, 104 and 156
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Secondary outcome [4]
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Change From Baseline in Mini-Mental State Examination (MMSE) at Weeks 24, 52, 76, 104, 128 and 156
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Assessment method [4]
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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.
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Timepoint [4]
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Baseline (Day 1) and Weeks 24, 52, 76, 104, 128 and 156
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Secondary outcome [5]
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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
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Assessment method [5]
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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.
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Timepoint [5]
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Baseline (Day 1) and Weeks 52, 104 and 156
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Secondary outcome [6]
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Change From Baseline in Phosphorylated Tau (pTau)-181 in Cerebrospinal Fluid (CSF) at Weeks 52, 104 and 156
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Assessment method [6]
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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.
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Timepoint [6]
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Baseline (Day 1) and Weeks 52, 104 and 156
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Secondary outcome [7]
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Change From Baseline in Neurofilament Light Chain (NfL) in Cerebrospinal Fluid at Weeks 52, 104 and 156
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Assessment method [7]
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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.
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Timepoint [7]
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Baseline (Day 1) and Weeks 52, 104 and 156
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Secondary outcome [8]
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Change From Baseline in Amyloid Beta1-42/40 Ratio in Cerebrospinal Fluid at Weeks 52, 104 and 156
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Assessment method [8]
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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.
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Timepoint [8]
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Baseline (Day 1) and Weeks 52, 104 and 156
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Secondary outcome [9]
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Change From Baseline in DIAN-TU Open Label Extension Cognitive Composite Score at Weeks 52, 104 and 156
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Assessment method [9]
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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, 1. The wechsler adult intelligence scale-revised digit span (backward recall). Score ranges from 0 (minimum) to 7 (maximum). 2. The category fluency (animals) value. Score ranges from 0 to unlimited. 3. The wechsler adult intelligence scale digit symbol substitution test. Score ranges from 0 (minimum) to 93 (maximum). 4. 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.
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Timepoint [9]
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Baseline (Day 1) and Weeks 52, 104 and 156
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Eligibility
Key inclusion criteria
* 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.
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Minimum age
18
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Maximum age
80
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Sex
Both males and females
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Can healthy volunteers participate?
Yes
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Key exclusion criteria
* 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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Not applicable
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Stopped early
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
3/06/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
13/11/2023
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Sample size
Target
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Accrual to date
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Final
73
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Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
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Recruitment hospital [1]
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Neuroscience Research Australia - Randwick
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Recruitment hospital [2]
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Mental Health Research Institute - Melbourne
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Recruitment hospital [3]
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The McCuster Foundation of Alzheimer's Disease Research - Nedlands
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Recruitment postcode(s) [1]
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2031 - Randwick
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Recruitment postcode(s) [2]
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3010 - Melbourne
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Recruitment postcode(s) [3]
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6009 - Nedlands
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Alabama
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Country [2]
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United States of America
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State/province [2]
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California
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United States of America
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State/province [3]
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Georgia
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United States of America
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State/province [4]
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Indiana
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United States of America
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Missouri
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United States of America
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Pennsylvania
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Country [7]
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United States of America
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State/province [7]
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Rhode Island
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Country [8]
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United States of America
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State/province [8]
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Washington
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Country [9]
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France
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State/province [9]
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Haute Garonne
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Country [10]
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France
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Paris
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France
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Seine Maritime
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Country [12]
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Puerto Rico
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State/province [12]
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San Juan
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Country [13]
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Spain
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State/province [13]
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Barcelona
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Country [14]
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United Kingdom
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State/province [14]
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Greater London
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Funding & Sponsors
Primary sponsor type
Other
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Name
Washington University School of Medicine
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Address
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Other collaborator category [1]
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Commercial sector/industry
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Name [1]
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Hoffmann-La Roche
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Address [1]
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Other collaborator category [2]
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Other
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Name [2]
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Alzheimer's Association
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Address [2]
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Other collaborator category [3]
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Government body
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Name [3]
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National Institute on Aging (NIA)
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/study/NCT06424236
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Trial related presentations / 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. Erratum In: N Engl J Med. 2012 Aug 23;367(8):780. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.
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Public notes
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Contacts
Principal investigator
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Randall J Bateman, MD
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Address
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Washington University School of Medicine
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Contact person for public queries
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
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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When will data be available (start and end dates)?
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Available to whom?
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Available for what types of analyses?
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How or where can data be obtained?
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What supporting documents are/will be available?
No Supporting Document Provided
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Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/36/NCT06424236/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/36/NCT06424236/SAP_001.pdf
Results publications and other study-related documents
Type
Citations or Other Details
Journal
Bateman, Randall J., Yan Li, Eric McDade, Jorge J....
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More Details
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Results are available at
https://clinicaltrials.gov/study/NCT06424236
Download to PDF