Table 2.
Characteristics of selected RCTs for prevention of Alzheimer’s disease (AD), based on compounds targeting beta-amyloid
| RCT | ADCS-A4 [82] | API [82] | DIAN [82] | Zinfandel-Takeda prevention study [68, 83] |
|---|---|---|---|---|
| Sample size | 1500 older adults with no cognitive impairment | 300 members of Colombian families (Antioquia) with early-onset AD. Subjects with no cognitive impairment. A small number of individuals from USA (collaboration with the DIAN network) will also be included | 240 members of families with early-onset AD. Subjects can be asymptomatic or have very mild memory and cognitive problems including mild dementia | 5000 elderly subjects with no cognitive impairment |
| Main inclusion criteria | Evidence of brain amyloid accumulation (PET). Subjects with no evidence of amyloid burden will also be included | Carriers of a mutated PSEN1 gene. Non-carriers will also be included, to ensure double-blinding of the genetic status | Carriers (n = 120) of mutation in PSEN1, PSEN2 or APP. Non-carriers (n = 120) will also be included, to ensure double-blinding of the genetic status | Subjects at risk of developing MCI due to AD within 5 years. The risk stratification is based on an algorithm including age and TOMM40 and APOE genotype. Subjects with high and low risk will be included |
| Age at enrolment | ≥70 years | ≥30 years | 18–80 years | 68–83 years |
| Study design | Randomized, double blind, placebo-controlled trial | Randomized, double-blind, placebo-controlled trial | Phase II/III randomized, double-blind, placebo-controlled trial | Phase III randomized, double-blind, placebo-controlled trial |
| Intervention | Anti-amyloid monoclonal antibody: solanezumab (Eli Lilly) | Anti-amyloid monoclonal antibody: crenezumab (Genentech) | Two anti-amyloid therapies: the anti-amyloid monoclonal antibodies gantenerumab (Hoffmann-La Roche) and solanezumab | Pioglitazone, an oral medication already approved for the treatment of type 2 diabetes (Zinfandel-Takeda) |
| Duration | 3 years + 2-year extension | 5 years, (interim analysis at 2 years) | 2 years + 3-year extension | 5 years |
| Outcomes | Primary: cognitive function Secondary: change in AD biomarkers |
Primary: cognitive function Secondary: change in AD biomarkers, including brain amyloid load and brain atrophy |
Initial phase (2 years): change in AD biomarkers, including brain and CSF amyloid, to identify the most promising drug candidate Follow-up phase (3 years): cognitive function |
Primary: cognitive function (i.e. time to onset of MCI due to AD) Secondary: qualification (predictive values) of the algorithm based on age and TOMM40 and APOE genotype |
| Status | Start in 2013 | Start in 2013 | Start in 2013 | Start in 2013 |
ADCS-A4, Anti-Amyloid Treatment of Asymptomatic Alzheimer’s disease; API, Alzheimer’s Prevention Initiative; DIAN, Dominantly Inherited Alzheimer Network; MCI, mild cognitive impairment; CSF, cerebrospinal fluid; APOE: apolipoprotein E; APP, amyloid precursor protein; PET, positron emission tomography; PSEN1, presenilin 1; PSEN2, presenilin 1; TOMM40, translocase of outer mitochondrial membrane 40 homolog.