BioMed Research International / 2014 / Article / Tab 4

Review Article

Potential Therapeutic Strategies for Alzheimer’s Disease Targeting or Beyond β-Amyloid: Insights from Clinical Trials

Table 4

Terminated trials targeting Aβ hypothesis.

MechanismRCTEnd EnrollmentDurationMain reasons

BACE1 inhibitorRosiglitazone2009.269324 weeksUnimproved cognitive status
LY28867212013.8128AE: 4 cases of liver damage in a phase 2 study in June 2013

GSI/GSMSemagacestat 2011.5164>7 monthsUnimproved cognitive status, but worsening functional ability; AE: skin cancers and infections
Avagacestat2010.620924 weeksAE: gastrointestinal and dermatological abnormalities like diarrhea, nausea, vomiting, rash, and itching skin; nonmelanoma skin cancers; and worsened cognition
tarenflurbil 2008.5168418 monthsInsufficient pharmacodynamics: poor capability to penetrate the BBB

Active immunologyAN17922003.9375AE: 6 patients developed aseptic meningoencephalitis due cytotoxic T cell response in phase 2a trial
ACC-0012014.212624 monthsShowed a serious side effect in phase 2 trial

Passive immunologyBapineuzumab (AAB-001)2012.6133118 monthsShowed no treatment effect on either cognitive or functional outcomes in two phase 3 trials

GSK3 inhibitorTideglusib (NP12)2012.630645 weeksMissed its primary endpoint and some secondary endpoints

RCT: randomized controlled trial; AE: adverse event; BBB: blood brain barrier.
Data sources: http://www.clinicaltrials.gov/; http://www.alzforum.org/.