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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04623242
Registration number
NCT04623242
Ethics application status
Date submitted
14/10/2020
Date registered
10/11/2020
Date last updated
22/09/2022
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 Randomized, Double-Blind, Placebo-Controlled, Cognitive Endpoint, Multi-Center Study of Potential Disease Modifying Therapies in Individuals at Risk for and With 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-sola)
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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
Treatment: Drugs - Solanezumab
Treatment: Drugs - Matching Placebo (Gantenerumab)
Treatment: Drugs - Matching Placebo (Solanezumab)
Experimental: Gantenerumab -
Experimental: Solanezumab -
Placebo Comparator: Matching placebo (Gantenerumab) -
Placebo Comparator: Matching Placebo (Solanezumab) -
Treatment: Drugs: Gantenerumab
Subcutaneously every 4 weeks at escalating doses
Treatment: Drugs: Solanezumab
Intravenous infusion every 4 weeks at escalating doses
Treatment: Drugs: Matching Placebo (Gantenerumab)
Subcutaneous injection of placebo every 4 weeks
Treatment: Drugs: Matching Placebo (Solanezumab)
Intravenous infusion of placebo every 4 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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Assess Cognitive Efficacy in Individuals With Mutations Causing Dominantly Inherited AD as Measured by the DIAN-Multivariate Cognitive Endpoint (DIAN-MCE);
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Assessment method [1]
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Multivariate Disease Progression Model adjusted for Estimated Years to Onset (EYO)and includes all timepoints up to treatment discontinuation. The treatment effect is reported relative to the mutation positive placebo arm.
Multivariate Cognitive Endpoint comprising: (i) Wechsler Memory Scale-Revised Logical Memory Delayed Recall Test (MEMUNITS), (ii) Wechsler Adult Intelligence Scale Digit Symbol Substitution Test (WAIS), (iii) Mini-Mental State Examination (MMSE), and (iv) International Shopping List Task (ISLT). Measurements for each test were normalized using the mean (SD) at DIAN-TU-001 baseline for mutation negative subjects. Higher scores indicate more favourable cognitive performance.
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Timepoint [1]
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Baseline through Week 260
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Secondary outcome [1]
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Gantenerumab: Rate of Change Over Time- Clinical Dementia Rating Sum of Boxes (CDR-SB)
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Assessment method [1]
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CDR-SB score is considered a more detailed quantitative general index of cognition and function, and provides more information than the global CDR score in patients with mild dementia
Scores range from 0-18 with lower scores showing more favorable cognitive function.
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Timepoint [1]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [2]
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Gantenerumab: Rate of Change Over Time- Functional Assessment Scale (FAS)
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Assessment method [2]
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The Functional Assessment Scale is to be administered and completed by the study partner about subjects for whom they care. This scale measures instrumental activities of daily living such as preparing balanced meals and managing personal finances. The intent of the FAS is to assess change in an individual's functional activities, relative to previously attained abilities, that are caused by cognitive dysfunction. If the study partner indicates that the subject no longer performs a particular task, it is reasonable to probe further and ask if they think the subject could still do the task. This will help tease out the relevant cognitive impairment
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Timepoint [2]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [3]
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Gantenerumab: Imaging Measures Composite [11C] PiB Partial Volume Corrected Regional Spread Function Standardized Uptake Value Ratio - Composite
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Assessment method [3]
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In vivo quantification of ß-amyloid deposition using positron emission tomography. This measure is a composite of brain regions. Higher scores indicate worse disease stage.
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Timepoint [3]
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Baseline, Weeks 52, 104 and 208
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Secondary outcome [4]
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Solanezumab: Clinical Measures- Clinical Dementia Rating (CDR)
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Assessment method [4]
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Clinical Dementia Rating - Global Score - Number of Subjects with an Increase from Baseline by Visit
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Timepoint [4]
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Baseline and Weeks 52, 104, 156, and 208
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Secondary outcome [5]
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Solanezumab: Clinical Measures- CDR Sum of Boxes (CDR-SB)
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Assessment method [5]
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CDR-SB score is considered a more detailed quantitative general index and provides more information than the global CDR score in patients with mild dementia
Scores range from 0-18 with lower scores showing more favorable cognitive function.
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Timepoint [5]
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Baseline and Weeks 52, 104, 156, and 208
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Secondary outcome [6]
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Solanezumab: Clinical Measures- Geriatric Depression Scale (GDS)
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Assessment method [6]
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The Geriatric Depression Scale (GDS) is a self-report measure of depression in older adults. Users respond in a "Yes/No" format. Of the 15 items, 10 indicate the presence of depression when answered positively while the other 5 are indicative of depression when answered negatively.
Scores range from 0-15 for completed questionnaires. A score of 88 is recorded for participants unable to complete the test.
Lower scores show more favorable outcome.
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Timepoint [6]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [7]
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Solanezumab: Clinical Measures- Neuropsychiatric Inventory Questionnaire (NPI-Q)
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Assessment method [7]
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The questionnaire is to be administered and completed by the study partner about patients for whom they care. Each of the 12 NPI-Q domains contains a survey question that reflects cardinal symptoms of that domain. Initial responses to each domain question are "Yes"(present) or "No" (absent). If the response to the domain question is "No", the study partner goes to the next question. If "Yes", the study partner then rates both the Severity of the symptoms present within the last month on a 3-point scale and the associated impact of the symptom manifestations on them (i.e. Caregiver Distress) using a 5-point scale. The NPI-Q provides symptom 'Severity' and 'Distress' ratings for each symptom reported, and total 'Severity' and 'Distress' scores reflecting the sum of individual domain scores.
Scores range from 0-36 with lower scores indicating more favorable cognitive function.
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Timepoint [7]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [8]
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Solanezumab: Clinical Measures- Functional Assessment Scale (FAS)
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Assessment method [8]
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The Functional Assessment Scale is to be administered and completed by the study partner about subjects for whom they care. This scale measures instrumental activities of daily living such as preparing balanced meals and managing personal finances. The intent of the FAS is to assess change in an individual's functional activities, relative to previously attained abilities, that are caused by cognitive dysfunction. If the study partner indicates that the subject no longer performs a particular task, it is reasonable to probe further and ask if they think the subject could still do the task. This will help tease out the relevant cognitive impairment
Scores range from 0-30 with lower scores indicate more favorable cognitive performance
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Timepoint [8]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [9]
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Solanezumab: Clinical Measures- Mini-Mental Status State Examination (MMSE)
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Assessment method [9]
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MMSE is a brief, quantitative measure of cognitive status in adults used to screen for cognitive impairment, to estimate the severity of cognitive impairment at a given point in time, to follow the course of cognitive changes in an individual over time, and to document an individual's response to treatment.
Scores range from 0-30 and higher scores indicate more favorable cognitive function.
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Timepoint [9]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [10]
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Solanezumab: Cognitive Measures- International Shopping List Task 30-Minute Delayed Recall
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Assessment method [10]
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Classic list-learning test that measures verbal learning & memory.
Scores range from 0-12 with higher scores indicating more favorable cognitive performance.
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Timepoint [10]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [11]
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Solanezumab: Cognitive Measures- Groton Maze Learning Test 30 Minute Delayed Recall
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Assessment method [11]
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The Groton Maze Learning Test 30 minute delayed recall measures episodic memory. The primary outcome is the number of errors made during recall of the previously memorized pathway from the Groton Maze Learning Test. The minimum score is 0 errors and the max is 999. Lower scores indicate better cognitive performance.
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Timepoint [11]
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Baseline, Week 52, 104, 156, 208 and 260
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Secondary outcome [12]
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Solanezumab: Cognitive Measures- Groton Maze Learning Test Delayed Reversed Recall
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Assessment method [12]
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The Groton Maze Learning Test measures executive function using a maze learning paradigm. A 10 x 10 grid of tiles is presented to the participant on the screen. A 28-step pathway is hidden among these tiles. A blue tile indicates the start and a tile with red circles indicates the finish. The participant must move one step at a time from the start toward the end by touching a tile next to their current location. If the correct move is made a green checkmark appears and if the move is incorrect a red cross is revealed. Once completed, they are returned to the start location to repeat the test and must try to remember the pathway they have just completed. "Delayed Reverse Recall" measures spatial working memory.
The outcome is the number of errors made with the range of 0-999. Lower scores indicate better cognitive performance.
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Timepoint [12]
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Baseline, Week 52, 104, 156, 208 and 260
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Secondary outcome [13]
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Solanezumab: Cognitive Measures- Trailmaking Test Part A
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Assessment method [13]
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Trail Making test taps attention, processing speed, and executive function. Part A consists of 25 circles numbered 1 through 25 distributed over a white sheet of standard document-sized paper. The subject is instructed to connect the circles with a drawn line as quickly as possible in ascending numerical order without lifting their pen.
The subject's performance is judged in terms of the time, in seconds, required to complete each trail (Max time 150 seconds). Lower scores indicate more favorable cognitive function.
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Timepoint [13]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [14]
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Solanezumab: Cognitive Measures- Trailmaking Test Part B
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Assessment method [14]
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This test taps attention, processing speed, and executive function and depends on visuo-motor and perceptual-scanning skills and also requires considerable cognitive flexibility in shifting from number to letter sets under time pressure. Part B consists of 25 circles, but these circles contain either numbers (1 through 13) or letters (A through L). The subject must connect the circles while alternating between numbers and letters in an ascending order (e.g., A to 1; 1 to B; B to 2; 2 to C).
The subject's performance is judged in terms of the time, in seconds, required to complete each Trail (Max of 300 seconds). Lower scores indicate more favorable cognitive function.
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Timepoint [14]
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Baseline, Weeks 52, 104, 156, 208 and 260
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Secondary outcome [15]
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Solanezumab: Cognitive Measures- WAIS-R Digit-Symbol Substitution Test
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Assessment method [15]
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This test engages multiple cognitive abilities, including attention, psychomotor speed, complex scanning, visual tracking, and immediate memory.
Scores range from 0-93 with higher scores indicate more favorable cognitive function.
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Timepoint [15]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [16]
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Solanezumab: Cognitive Measures- WMS-R Digit Span Backward
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Assessment method [16]
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Widely used measure of working memory (or attention) in which the subject is read number sequences of increasing length and then asked to repeat each sequence backward. The primary measure of performance is the number of digit sequences correctly reversed.
The unit of measure is number of digit sequences correctly recalled and ranges from 0-12. Higher scores indicate more favorable cognitive function.
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Timepoint [16]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [17]
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Solanezumab: Cognitive Measures- WMS-R Digit Span Forward
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Assessment method [17]
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This is a widely-used test of working memory in which the subject is read number sequences of increasing length and asked to repeat them. The total score is the number of sequences correctly repeated.
The unit of measure is number of digit sequences correctly recalled and ranges from 0-12. Higher scores indicate more favorable cognitive function.
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Timepoint [17]
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Baseline, Weeks 52, 104, 156, 208 and 260
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Secondary outcome [18]
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Solanezumab: Cognitive Measures- Raven's Progressive Matrices (Set A)
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Assessment method [18]
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This is a measure of fluid intelligence. This test is used to get an estimate of the subjects IQ at baseline. Subjects are asked to complete a visual pattern by circling one of six response choices.
Scores range from 0-12 with higher scores indicating more favorable cognitive performance.
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Timepoint [18]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [19]
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Solanezumab: Cognitive Measures- Category Fluency (Animals)
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Assessment method [19]
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Category Fluency is a widely used measure of semantic memory (verbal fluency, language). The subject is asked to name different exemplars of a given semantic category (animals), and the number of unique exemplars named is scored.
Higher scores indicate more favorable cognitive function.
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Timepoint [19]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [20]
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Solanezumab: Cognitive Measures- Category Fluency (Vegetables)
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Assessment method [20]
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Category Fluency is a widely used measure of semantic memory (verbal fluency, language). The subject is asked to name different exemplars of a given semantic category (vegetables), and the number of unique exemplars named is scored.
Higher scores indicate more favorable cognitive function.
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Timepoint [20]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [21]
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Solanezumab: Cognitive Measures- WMS-R Logical Memory Delayed Recall Test
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Assessment method [21]
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Measure of delayed recall (episodic memory) of a story read to the subject at the beginning of the testing session and subject is asked to relay the story 20 minutes later.
Scores range from 0-25 with higher scores indicating more favorable cognitive performance.
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Timepoint [21]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [22]
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Solanezumab: Cognitive Measures- WMS-R Logical Memory Immediate Recall Test
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Assessment method [22]
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This test assesses the ability to recall a short story. The subject is read a short story and immediately after hearing the story, the subject is asked to retell the story from memory.
Scores range from 0-25 with higher scores indicating more favorable cognitive performance.
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Timepoint [22]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [23]
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Solanezumab: Cognitive Measures- Composite Including: Alternative Multivariate Composite: (1) Digit Span Backwards; (2) Logical Memory (Immediate); (3) Trailmaking B; (4) Category Fluency (Animals)
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Assessment method [23]
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Multivariate Disease Progression Model adjusted for estimated years from symptom onset (EYO) and includes all time points up to treatment discontinuation. The treatment effect for Solanezumab is reported relative to the mutation positive placebo arm.
This alternative multivariate endpoint includes four tests: Logical Memory Immediate Recall, Digit Span Backward Recall, Category Fluency (Animals), Trailmaking Test Part B. Measurements for each test will be normalized using the mean (SD) at DIAN-TU-001 baseline among mutation negative subjects before being analyzed. For the Trailmaking Test B, the scores will be multiplied by -1 as higher scores indicate worse performance; whereas for the other three, lower scores indicate worse performance. Therefore, on the standardized endpoints, lower scores indicate worse performance.
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Timepoint [23]
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Baseline through Week 260
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Secondary outcome [24]
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Solanezumab: Imaging Measures- Brain Amyloid Load as Measured by [11C]PiB-PET Non-partial Volume Corrected
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Assessment method [24]
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PiB Standardized Uptake Value Ratio ([11C]PiB SUVR) is the most common quantitative method used to make regional comparisons within a subject as well as between subjects and computed as the degree of radiotracer uptake in a target region of interest (regions dervived via automated segmentation using FreeSurfer) with respect to a reference region. In amyloid and tau imaging, SUVR is typically generated using some portion or the entire cerebellum as a reference because cerebellum is not affected until late in the progression of AD.
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Timepoint [24]
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Baseline and Weeks 52, 104 and 208
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Secondary outcome [25]
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Solanezumab: Imaging Measures- Brain Amyloid Load as Measured by Florbetapir PET
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Assessment method [25]
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Florbetapir Standardized Uptake Value Ratio ([18F]AV-45 SUVR) is the most common quantitative method used to make regional comparisons within a subject as well as between subjects and computed as the degree of radiotracer uptake in a target region of interest (regions derivved via automated segmentation using FreeSurfer) with respect to a reference region. In amyloid and tau imaging, SUVR is typically generated using some portion or the entire cerebellum as a reference because cerebellum is not affected until late in the progression of AD.
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Timepoint [25]
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Weeks104 and 208
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Secondary outcome [26]
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Solanezumab: Imaging Measures- Brain Glucose Metabolism as Measured by Fluorodeoxyglucose (FDG)-PET Non-partial Volume Corrected
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Assessment method [26]
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FDG Standardized Uptake Value Ratio ([18F]FDG SUVR) is the most common quantitative method used to make regional comparisons within a subject as well as between subjects and computed as the degree of radiotracer uptake in a target region of interest (regions derivved via automated segmentation using FreeSurfer) with respect to a reference region. In amyloid and tau imaging, SUVR is typically generated using some portion or the entire cerebellum as a reference because cerebellum is not affected until late in the progression of AD.
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Timepoint [26]
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Baseline and Weeks 52, 104 and 208
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Secondary outcome [27]
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Solanezumab: Imaging Measures- Brain Atrophy as Measured by Cortical Thickness of Regions of Interest - Precuneus Region
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Assessment method [27]
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Brain atrophy was defined by structural magnetic resonance imaging (MRI) A Magnetization Prepared - RApid Gradient Echo) (MPRAGE) sequence was processed using the Freesurfer software suite. This package provides volumes and thickness values for cortical regions and volumes for subcortical regions. For the clinical trial we examined cortical thickness values in prespecified regions of interest known to show atrophy in autosomal dominant Alzheimer Disease. Higher measurements are more favorable.
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Timepoint [27]
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Baseline and Weeks 52, 104, 156 and 208
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Secondary outcome [28]
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Solanezumab: Imaging Measures- Volumetric MRI Combined Total Volume Corrected for Head Size - Hippocampus Volume
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Assessment method [28]
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Brain atrophy was defined by structural magnetic resonance imaging (MRI) A Magnetization Prepared - RApid Gradient Echo) (MPRAGE) sequence was processed using the Freesurfer software suite. This package provides volumes and thickness values for cortical regions and volumes for subcortical regions. For the clinical trial we examined volume values in prespecified regions of interest known to show atrophy in autosomal dominant Alzheimer Disease.
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Timepoint [28]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [29]
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Solanezumab: Imaging Measures- Brain Tau Load as Measured by Flortaucipir PET Non-partial Volume Corrected
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Assessment method [29]
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This variable represents how much neurofibrillary tau pathology is present in brain as assessed using positron emission tomography (PET). Scans were conducted using [F18] Flortaucipir, a commonly used tracer in the field.
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Timepoint [29]
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Baseline and Weeks 52, 104 and 208
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Secondary outcome [30]
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Solanezumab: Imaging Measures- Brain Atrophy as Measured by Whole Brain Volume Corrected for Head Size
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Assessment method [30]
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Brain atrophy was defined by structural magnetic resonance imaging (MRI) A Magnetization Prepared - RApid Gradient Echo) (MPRAGE) sequence was processed using the Freesurfer software suite. This package provides volumes and thickness values for cortical regions and volumes for subcortical regions. A whole brain volume measure was generated to represent global atrophy across the cortical and subcortical regions.
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Timepoint [30]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [31]
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Solanezumab: Imaging Measures- Brain Atrophy as Measured by Ventricular Volume (Volumetric MRI) Corrected for Head Size
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Assessment method [31]
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Rather than looking at how tissue in the brain changes, it is also possible to quantify how the ventricles, fluid filled spaces in the brain, change. Increasing ventricular volume represents greater amounts of cerebral spinal fluid which suggests atrophy of the brain. Magnetization Prepared - RApid Gradient Echo) (MPRAGE) sequences were processed using the Freesurfer software suite. Total ventricular volume was calculated from the ventricular volumes generated by this program.
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Timepoint [31]
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Baseline and Weeks 52, 104, 156, 208 and 260
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Secondary outcome [32]
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Solanezumab: Fluid Biomarker Measures- CSF Aß 40 Free Change From Baseline
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Assessment method [32]
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Measured concentration of the drug bound and free soluble Aß1-40 peptide in cerebrospinal fluid using enzyme-linked immunosorbent assay (ELISA)
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Timepoint [32]
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Baseline and Weeks 52, 104 and 208
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Secondary outcome [33]
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Solanezumab: Fluid Biomarker Measures- CSF Aß 42 Free
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Assessment method [33]
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Measured concentration of the total soluble Aß 1-42 peptide in cerebrospinal fluid using ELISA
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Timepoint [33]
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Baseline and Weeks 52, 104 and 208
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Secondary outcome [34]
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Solanezumab: Fluid Biomarker Measures- CSF Tau
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Assessment method [34]
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Measured concentration of the soluble Tau peptide in cerebrospinal fluid
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Timepoint [34]
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Baseline and Weeks 52, 104 and 208
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Secondary outcome [35]
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Solanezumab: Fluid Biomarker Measures- CSF pTau 181
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Assessment method [35]
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Measured concentration of phosphorylated tau at threonine-181 in cerebrospinal fluid
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Timepoint [35]
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Baseline and Weeks 52, 104 and 208
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Secondary outcome [36]
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Solanezumab: Change From Baseline Fluid Biomarker Measures- CSF Neurofilament Light Chain (NfL)
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Assessment method [36]
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Measured concentration of neurofilament light chain in cerebrospinal fluid using SIMO
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Timepoint [36]
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Baseline and Weeks 52, 104 and 208
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Secondary outcome [37]
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Solanezumab: Fluid Biomarker Measures- Plasma Neurofilament Light Chain (NfL)
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Assessment method [37]
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Measured concentration of neurofilamnet light chain in plasma using Single Molecule Array (SIMOA)
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Timepoint [37]
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Baseline and Weeks 52, 104 and 208
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Secondary outcome [38]
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Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA)
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Assessment method [38]
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Measurement of the presence or absence of anti-drug antibodies in serum
Note: Mutation Negative Placebo subjects are not displayed as anti-drug antibody testing was not to be evaluated for these subjects.
Note: Treatment Emergent Anti-Drug Antibody Positive subjects are defined as those with either (a) a baseline status of ADA Not Present and at least one post-baseline ADA present with a titer >= 1:20 or (b) both a baseline and post-baseline status of ADA Present with the post-baseline titer being 2 dilutions (4-fold) greater than the baseline titer.
Note: Treatment Emergent Anti-Drug Antibody Inconclusive subjects are defined as those for whom >=20% of the subject's post-baseline ADA results are ADA Inconclusive and all remaining post-baseline samples are ADA Not Present.
Note: Treatment Emergent Anti-Drug Antibody Negative subjects are defined as those who are evaluable for TE ADA but are neither TE ADA Positive nor TE ADA Inconclusive.
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Timepoint [38]
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Baseline and Weeks 52, 104 and 208
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Secondary outcome [39]
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Solanezumab: Fluid Biomarker Measures- Total Plasma Aß 1-40
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Assessment method [39]
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Measured concentration of the total soluble Aß 1-40 peptide in cerebrospinal fluid using ELISA
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Timepoint [39]
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Baseline and Weeks 52, 104 and 208
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Secondary outcome [40]
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Solanezumab: Fluid Biomarker Measures- Total Plasma Aß 42
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Assessment method [40]
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Measured concentration of the total soluble Aß 1-42 peptide in cerebrospinal fluid using ELISA
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Timepoint [40]
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Baseline and Weeks 52, 104 and 208
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Secondary outcome [41]
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Solanezumab: Fluid Biomarker Measures- CSF Aß 42 Total
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Assessment method [41]
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Measured concentration of the total soluble Aß1-42 peptide in cerebrospinal fluid using enzyme-linked immunosorbent assay (ELISA)
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Timepoint [41]
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Baseline and Weeks 52, 104 and 208
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Secondary outcome [42]
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Solanezumab: Fluid Biomarker Measures- CSF Aß 40 Total
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Assessment method [42]
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Measured concentration of the total soluble Aß1-40 peptide in cerebrospinal fluid using enzyme-linked immunosorbent assay (ELISA)
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Timepoint [42]
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Baseline and Weeks 52, 104 and 208
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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 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.
- 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.
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Minimum age
18
Years
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Maximum age
80
Years
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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
Randomised controlled trial
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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
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2/Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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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
1/12/2012
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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
6/03/2020
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Sample size
Target
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Accrual to date
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Final
194
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Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
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Recruitment hospital [1]
0
0
Neuroscience Research Australia - Randwick
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Recruitment hospital [2]
0
0
Mental Health Research Institute - Melbourne
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Recruitment hospital [3]
0
0
The McCuster Foundation of Alzheimer's Disease Research - Nedlands
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Recruitment postcode(s) [1]
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0
2031 - Randwick
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Recruitment postcode(s) [2]
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0
3010 - Melbourne
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Recruitment postcode(s) [3]
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0
6009 - Nedlands
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Recruitment outside Australia
Country [1]
0
0
United States of America
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State/province [1]
0
0
Alabama
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Country [2]
0
0
United States of America
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0
0
California
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0
0
United States of America
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0
0
Connecticut
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0
0
United States of America
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0
0
Georgia
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Country [5]
0
0
United States of America
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0
0
Indiana
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Country [6]
0
0
United States of America
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State/province [6]
0
0
Missouri
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Country [7]
0
0
United States of America
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State/province [7]
0
0
New York
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Country [8]
0
0
United States of America
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State/province [8]
0
0
Pennsylvania
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Country [9]
0
0
United States of America
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State/province [9]
0
0
Rhode Island
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Country [10]
0
0
United States of America
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State/province [10]
0
0
Washington
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Country [11]
0
0
Canada
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State/province [11]
0
0
British Columbia
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Country [12]
0
0
Canada
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State/province [12]
0
0
Ontario
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Country [13]
0
0
Canada
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State/province [13]
0
0
Quebec
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Country [14]
0
0
France
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State/province [14]
0
0
Haute Garonne
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Country [15]
0
0
France
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State/province [15]
0
0
Nord
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Country [16]
0
0
France
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State/province [16]
0
0
Paris
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Country [17]
0
0
France
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State/province [17]
0
0
Rhone
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Country [18]
0
0
France
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State/province [18]
0
0
Seine Maritime
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Country [19]
0
0
Ireland
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State/province [19]
0
0
Dublin
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Country [20]
0
0
Puerto Rico
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State/province [20]
0
0
San Juan
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Country [21]
0
0
Spain
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State/province [21]
0
0
Barcelona
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Country [22]
0
0
United Kingdom
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State/province [22]
0
0
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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Country
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Other collaborator category [1]
0
0
Commercial sector/Industry
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Name [1]
0
0
Eli Lilly and Company
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Address [1]
0
0
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0
0
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Other collaborator category [2]
0
0
Commercial sector/Industry
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Name [2]
0
0
Hoffmann-La Roche
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Address [2]
0
0
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Country [2]
0
0
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Other collaborator category [3]
0
0
Other
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Name [3]
0
0
Alzheimer's Association
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Address [3]
0
0
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Country [3]
0
0
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Other collaborator category [4]
0
0
Government body
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Name [4]
0
0
National Institute on Aging (NIA)
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Address [4]
0
0
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Country [4]
0
0
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Other collaborator category [5]
0
0
Commercial sector/Industry
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Name [5]
0
0
Avid Radiopharmaceuticals
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Address [5]
0
0
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0
0
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Other collaborator category [6]
0
0
Other
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Name [6]
0
0
Accelerating Medicines Partnership (AMP)
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Address [6]
0
0
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Country [6]
0
0
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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 and cognitive
efficacy of investigational products in subjects who are known to have an Alzheimer's
disease-causing mutation by determining if treatment with the study drug slows the rate of
progression of cognitive impairment and improves disease-related biomarkers.
This is an analysis study for an MPRP: DIAN-TU-001 Master NCT01760005
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04623242
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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.
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Public notes
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Contacts
Principal investigator
Name
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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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Fax
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Contact person for public queries
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04623242
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