Table 1.
New trials in patients with preclinical AD
| Trial | Participants | Trial duration | Compound and administration | Targeted Aβ species | Primary outcomes | Biomarker measures | Interim analysis |
|---|---|---|---|---|---|---|---|
| ADCS A4 | 1,000 amyloid-positive adults aged 65–85 years (500 per treatment arm) | 168 weeks | Solanezumab IV every 4 weeks | Monomer | ADCS Preclinical Alzheimer Cognitive Composite | Florbetapir PET, MRI, CSF analyses, tau PET | Blinded sample size re-estimation |
| API ADAD | 200 ADAD mutation carriers (100 per treatment arm) and 100 kindred non-carriers (placebo arm) aged 30–60 years without MCI or dementia | 260 weeks | Crenezumab SQ every 2 weeks | Monomeric, oligomeric and fibrillar | API ADAD composite cognitive test score | Florbetapir PET, 18F-FDG-PET, MRI, CSF analyses | After last participant enrolled completes 104 weeks of treatment |
| API APOE4* | Approximately 1,340 APOE*ε4 homozygotes aged 60–75 years without MCI or dementia | 260 weeks | CAD106 IM quarterly, CNP50 (oral pill) daily | Multiple species | API composite cognitive test score, time to diagnosis of MCI or dementia due to AD | Florbetapir PET, 18F-FDG-PET, MRI, CSF analyses, tau PET | TBD |
| DIAN-TU Biomarker | 138 ADAD mutation carriers (52 per active treatment arm, 34 pooled placebo) and 77 kindred non-carriers (placebo arm) −15 years to +10 years from parental age of symptom onset | Up to 104 weeks | Solanezumab IV every 4 weeks, gantenerumab SQ every 4 weeks | Monomer (solanezumab), aggregated (gantenerumab) | CSF Aβ (solanezumab), PiB-PET (gantenerumab) | CSF and plasma analyses, florbetapir PET, PiB-PET, 18F-FDG-PET, MRI, tau PET | Biomarker interim analyses based on adaptive design |
| DIAN-TU Adaptive Prevention Trial | 266 ADAD mutation carriers (133 per treatment arm) and 133 kindred non-carriers (placebo arm) −15 years to +10 years from parental age of symptom onset | 208 weeks | TBD from DIAN-TU Biomarker | TBD from DIAN-TU Biomarker | Cognitive measure or composite TBD | CSF and plasma analyses, florbetapir PET, PiB-PET, 18F-FDG-PET, MRI, tau PET | TBD |
| TOMMORROW | 4,622 APOE/TOMM40 high-risk (2311 per treatment arm) and 600 low-risk (placebo arm) individuals aged 65–83 years without MCI or dementia | 260 weeks‡ | Pioglitazone daily | Not applicable | Time to diagnosis of MCI due to AD | MRI volumetrics in subset | Futility analysis once 50% (205/410) of the anticipated events have occurred |
*
Subject to regulatory authority approval.
‡
Estimate. Exact duration depends on the number of progression events. Abbreviations: Aβ, amyloid-β; AD, Alzheimer disease; ADAD, autosomal dominant AD; ADCS, Alzheimer’s Disease Cooperative Study; API, Alzheimer’s Prevention Initiative; APOE, apolipoprotein E; CSF, cerebrospinal fluid; DIAN-TU, Dominantly Inherited Alzheimer Network Trials Unit; IM, intramuscularly; IV, intravenously; MCI, mild cognitive impairment; PiB, Pittsburgh compound B; SQ, subcutaneously; TBD, to be determined.