Review Article

Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer’s Disease

Table 1

Ongoing phase I–III randomized controlled trials (RCTs) of tau-directed drugs in clinical development for the treatment of Alzheimer’s disease (AD).

Compound (company) Clinicaltrials.gov identifierMechanism of actionEstimated enrollmentCharacteristicsStatus

TRx0237 (LMTX)
(TauRx Therapeutics Ltd.)
NCT01626391
Tau aggregation inhibitor9 patients already taking medications for probable mild to moderate AD (2012-2013)TRx0237 tablets 250 mg/day (given as 125 mg bid) for 4 weeksPhase II trial (completed)

TRx0237 (LMTX)
(TauRx Therapeutics Ltd.)
NCT01689233
Tau aggregation inhibitor700 patients with probable mild AD (2012–2015)TRx0237 100 mg tablets administered twice dailyPhase III trial (active not recruiting)

TRx0237 (LMTX)
(TauRx Therapeutics Ltd.)
NCT01689246
Tau aggregation inhibitor833 patients with probable mild to moderate AD (2013–2016)TRx0237 125 mg tablets administered twice dailyPhase III trial (active not recruiting)

TRx0237 (LMTX)
(TauRx Therapeutics Ltd.)
NCT01626378
Tau aggregation inhibitor220 patients with behavioral variant of FTD (2013–2016)TRx0237 100 mg tablet administered twice dailyPhase II trial (active not recruiting)

TRx0237 (LMTX)
(TauRx Therapeutics Ltd.)
NCT02245568
Tau aggregation inhibitorSubjects who have completed participation in a Phase II or Phase III trial with TRx0237 continued access to therapy to evaluate the long-term safety of TRx0237 (2014–2017)All subjects will initially be given 200 mg/day of TRx0237 administered twice daily. Thereafter, dosing is flexible (100 mg/day to 300 mg/day)Open label Phase II trial (currently recruiting)

TPI-287
(University of California,
San Francisco)
NCT01966666
Microtubule-stabilizing agent33 patients with mild to moderate AD (2013–2015)The purpose of the study is to determine the highest dose of TPI-287 that is safe and tolerable when administered as an intravenous infusionPhase I trial (currently recruiting)

AADvac1
(Axon Neuroscience SE)
NCT01850238
Active tau-based immunotherapy30 patients with mild to moderate AD (2013–2015)Patients will receive 1 dose of AADvac1 per month over 3 months, for a total of 3 administrationsPhase I trial (completed)

AADvac1 (Axon Neuroscience SE)
NCT02031198 FUNDAMANT
Active tau-based immunotherapyThis follow-up study continues to observe patients who have completed the Phase I trial of AADvac1, for another 18 months (2014–2017)Patients who have received 6 doses in the previous trial will be given 1-2 booster doses of AADvac1 (2 if their antibody titers decline below those achieved in the previous trial).
Patients who have received 3 doses in the previous trial will be given another 3 doses and then vaccinated with booster doses as above
18-month follow-up
Phase I trial (active, not recruiting)

AADvac1
(Axon Neuroscience SE)
NCT02579252 ADAMANT
Active tau-based immunotherapy185 patients with mild AD (2016–2019)Patients will receive 6 doses of AADvac1 in 4-week intervals and then 2 individual booster doses in 6-month intervals, for a total of 8 dosesPhase II trial (currently recruiting)

ACI-35
(AC Immune AG)
Active tau-based immunotherapyPatients with mild to moderate AD (2013–2014)This Phase I trial compared two doses of ACI-35 to investigate its safety, tolerability, and immunogenicityPhase I trial (active, not recruiting)

RG7345 (RO6926496, MAb86)
(Hoffmann-La Roche)
NCT02281786
Passive tau-based immunotherapy48 healthy subjects (January 2015–October 2015)Single, ascending dose, intravenous administrationPhase I trial (active, not recruiting)