DIAN-TU-001 (gantenerumab and solanezumab arms)
Dominantly Inherited Alzheimer Network Trials Unit trial DIAN-TU-001, gantenerumab and solanezumab drug arms
Phase II/III placebo-controlled trial of gantenerumab or solanezumab in 142 carriers of dominantly inherited Alzheimer disease mutations, with frequent 3T safety MRI (FLAIR, 2D T2*-GRE) centrally read for ARIA-E and ARIA-H, PiB PET, CSF and cognition.
Overview
DIAN-TU-001 is the first platform trial of disease-modifying drugs in dominantly inherited Alzheimer disease (DIAD), run by the Dominantly Inherited Alzheimer Network Trials Unit at Washington University in St. Louis with Roche and Eli Lilly as industry collaborators. This entry covers its first two drug arms, the anti-amyloid antibodies gantenerumab and solanezumab, each with a matching placebo, which ran from 2012 to 2019. Neither drug slowed cognitive decline, but the frequent safety MRI with central reads make the trial a source of amyloid-related imaging abnormalities (ARIA) in a young, genetically defined population.
Composition
The ARIA analysis covers 142 mutation carriers in the PSEN1, PSEN2 or APP gene: 52 on gantenerumab, 50 on solanezumab and 40 on placebo. At entry they were within 15 years before to 10 years after their expected age at symptom onset and had no to mild dementia. Eleven developed ARIA-E (ten on gantenerumab, one on placebo, none on solanezumab), three of them twice. New ARIA-H appeared in 22 participants across the arms.
Acquisition
All MRI was at 3T with MPRAGE, a FLAIR with 5 mm slices for ARIA-E and a 2D T2*-GRE with 4 mm slices for ARIA-H. Safety scans were taken roughly every three months during gantenerumab dose titration, and for solanezumab every three months for two years and then yearly. PiB amyloid PET and CSF were collected at baseline and at weeks 52, 104 and 208.
Annotations
Radiologists at Mayo Clinic read every MRI centrally, blinded to treatment. For ARIA-E they recorded location, focality, parenchymal or sulcal region and the longest diameter, scored with the Barkhof Grand Total Score; for ARIA-H they recorded the type (microhemorrhage or superficial siderosis) and the count over time. These are visual reads, not segmentations.
Known limitations
- ARIA findings are counts, sizes and scores, not voxel masks.
- Treatment-arm data can reveal drug or mutation status, so DIAN-TU reviews requests and publications, and some analyses may be run by its biostatistics core instead of releasing data.
- Small numbers: only ten ARIA-E cases on gantenerumab.
- The master protocol later added other drug arms, which are not covered here.
Cohort
Aggregate numbers from the sources below. Bars are relative to the 142 subjects.
Sex
- Female 72 100%
Covers 72 of 142 subjects.
Condition
subjects, values can overlap
- Alzheimer's disease 142 100%
- Amyloid-related imaging abnormalities 22 15%
License and access
Our reading of the license, not legal advice. Before you use the data, read the original license and confirm that your use is allowed. We take no responsibility for how you use a dataset. Full disclaimer
A research proposal is reviewed and approved
DIAN-TU Data and Biospecimen Sharing, Publication, Authorship and Citation Policies
Qualified researchers get de-identified trial data for research approved by DIAN-TU, with Industry Collaborators able to review requests and manuscripts. Requires IRB or ethics documentation and a Data Use Agreement; no sharing with third parties; data destroyed after analysis; every publication or presentation is reviewed and approved by DIAN-TU first.
Raw imaging data need a justification in the request. Industry Collaborators (the study drug owners) may review requests and manuscripts.
What you can do
- Not stated
- Not stated
- Conditional
- Conditional
What you can share
- No
- Not stated
- Share trained models Not stated
What you must do
- Yes
- Share alike No
- Yes
- Yes
- Yes
- Conditional
- Conditional
- Yes
Limits
- Yes
- No
Citation
Follow the DIAN-TU Authorship and Citation Policy. ARIA reads: Joseph-Mathurin N, et al. Amyloid-Related Imaging Abnormalities in the DIAN-TU-001 Trial of Gantenerumab and Solanezumab: Lessons from a Trial in Dominantly Inherited Alzheimer Disease. Annals of Neurology 92(5):729-744 (2022). doi:10.1002/ana.26511
All numbers
Every number on this page, as stored in stats.csv, with its source.
| Measure | Breakdown | Value | Source |
|---|---|---|---|
| Subjects | total mutation carriers in the analysis: gantenerumab 52, solanezumab 50, placebo 40; the Methods text says 144 were randomized (52 to solanezumab) | 142 | josephmathurin2022 Abstract (Methods); Table 1A |
| Subjects | condition=alzheimers all are DIAD mutation carriers (PSEN1, PSEN2 or APP), CDR 0 to 1 at entry | 142 | josephmathurin2022 Abstract (Methods) |
| Subjects | condition=aria participants with incident ARIA-H: sum of the four disjoint groups (placebo 4, solanezumab 6, gantenerumab without ARIA-E 6, gantenerumab with ARIA-E 6); 11 participants had ARIA-E, and how many of them are not in the ARIA-H count is not stated as a total | 22 | josephmathurin2022 Table 1A |
| Subjects | sex=female sum of the four disjoint groups (placebo 22, solanezumab 29, gantenerumab without ARIA-E 17, gantenerumab with ARIA-E 4) | 72 | josephmathurin2022 Table 1A |
Sources
The keys used in the table above.