|
Mechanism | RCT | Status | Estimated end | Dementia stage | Enrollment | Duration | Reported outcomes | Details of drugs/RCTs |
|
↓A production | | | | | | | | |
BACE1 inhibitor | Pioglitazone | Phase 2; completed | 2005.1 | Mild-to-moderate | 25 | 18 months | | Insulin sensitizer, class of PPAR agonists |
CTS-21166 | Phase 1; completed | 2008.2 | Healthy | 56 | | | |
MK8931 | Phase 3; ongoing | 2018.3 | Mild-to-moderate | 1960 | ≈6.5 years | | With enhanced BBB permeability |
E2609 | Phase 1; completed | 2013.9 | MCI/mild AD | 65 | | | |
GSI/GSM | NIC5-15 | Phase 2; ongoing | 2013.12 | | 40 | | | Notch-sparing, insulin-sensitizer |
Begacestat | Phase 1; completed | 2009.10 | Elder healthy | 49 | | Dose-dependent changes in plasma A levels | Selectively inhibits cleavage of APP over Notch [208] |
CHF 5074 | Phase 2; completed | 2012.4 | MCI | 96 | 12 weeks | | NSAID |
EVP-0962 | Phase 2; completed | 2013.10 | MCI/early stage | 52 | 14 days | | |
-secretase activator | Atorvastatin | Phase 3; completed* | 2007.7 | Mild-to-moderate | 600 | 80 weeks | | Tested with AchEI |
Simvastatin | Phase 3; completed | 2007.10 | Mild-to-moderate | 400 | 18 months | | |
Etazolate | Phase 2a; completed | 2009.8 | Mild-to-moderate | 159 | | Safe and well tolerated | ↑-secretase activity, acting as a GABA-A receptor modulator and a PDE-4 inhibitor [209] |
Epigallocatechin-3-gallate (EGCg) | Phase 2/3; ongoing | 2015.6 | Early stage | 50 | 18 months | | Prevents the A aggregation via binding to the unfolded peptide |
↓A aggregation/oligomers | Scyllo-inositol (ELND005/AZD103) | Phase 2; completed | 2010.5 | Mild-to-moderate | 350 | 18 months | Insufficient to support/refute benefits [210] | |
Tramiprosate (3APS) | Phase 3 | unknown | Mild-to-moderate | 950 | | Suggesting disease-modifying effects [211] | |
PBT2 | Phase 2; completed | 2007.12 | Mild AD | 80 | 12 weeks | Well-tolerated, ↓CSF A42, and improved executive function [212] | |
|
↑Aβ clearance | | | | | | | | |
Active immunotherapy | Affitope AD02 | Phase 2; completed | 2013.12 | Early stage | 335 | >1 year | | N-terminal A1-6, a synthetic peptide |
Affitope AD03 | Phase 1; completed | 2011.11 | Mild-to-moderate | 28 | | | i.h. with or without adjuvant aluminum |
UB 311 | Phase 1; completed | 2011.4 | Mild-to-moderate | 19 | | | N-terminal A1-14 |
V 950 | Phase 1; completed | 2012.1 | | 86 | | | formulated on Aluminum-containing adjuvant |
CAD 106 | Phase 2; completed | 2012.12 | Mild AD | 177 | | A favourable safety profile [213] | N-terminal A1-6; i.m. of adjuvanted CAD106; |
Passive immunotherapy | BAN2401 | Phase 2; ongoing | 2016.12 | MCI/mild AD | 800 | 18 months | | mAb against A oligomers |
BIIB037 | Phase 1; ongoing | 2014.11 | Prodromal to mild | 160 | | | Administered via intravenous (IV) infusions in subjects |
Ponezumab | Phase 2; completed | 2011.8 | Mild-to-moderate | 198 | 24 months | | |
Crenezumab | Phase 2/3; ongoing | 2016.5 | Mild-to-moderate | 361 | 24 months | | |
Gammagard (IVIg) | Phase 2, completed | 2010.4 | Mild-to-moderate | 24 | 6 months | Improved cognition | |
Phase 3; completed | 2012.12 | Mild-to-moderate | 390 | 70 weeks | Showed no significant effect | |
Phase 2; ongoing | 2014.10 | MCI | 50 | 24 months | | |
AMBAR | Phase 2/3; ongoing | 2016.12 | Mild-to-moderate | 350 | | | |
Gantenerumab | Phase 3; ongoing | 2019.3 | Mild | 1000 | >5 months | Phase 1 RCT↓brain A; high doses, AE | Mainly targets A plagues |
Solanezumab | Phase 3; ongoing | 2016.12 | Mild | 2100 | | No benefits in primary outcomes | Mainly targets soluble oligomeric A |
AAB-003 | Phase 1; ongoing | 2014.8 | Mild-to-moderate | 104 | 52 weeks | | Previously treated with AAB-003 |
GSK933776 | Phase 1; completed | 2011.5 | | 50 | | | |
SAR228810 | Phase 1; ongoing | 2015.1 | Mild-to-moderate | 48 | 14.5–22 months | | |
|
Anti-tau | | | | | | | | |
↓tau production | Valproate | Phase 3; complete | 2009.12 | Mild-to-moderate | 313 | 2 years | Did not show cognitive benefits and prevention of behavioral defects; associated with reduced brain volumes | |
Lithium | Phase 2; ongoing | 2019.4 | | 80 | | A pilot study was insufficient to support or refute the efficacy [214] | |
↓tau fibrillization/deposition | Nicotinamide | Phase 1/2; ongoing | 2014.7 | Mild-to-moderate | 50 | 24 weeks | | Vitamin B3 |
TRx0237 | Phase 3; ongoing | 2015.12 | Mild/mild-to-moderate | 700/833 | 18 months/15 months | | |
Methylene blue (Rember) | Phase 2; completed | | Mild-to-moderate | 321 | 6 months | Showed uncertain results | |
Davunetide (AL108) | Phase 2; completed | 2008.1 | MCI | 144 | 12 weeks | Showed benefits on memory | |
BMS-241027 | Phase 1; completed | 2013.10 | Mild | 40 | 9 weeks | | |
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