Table 2 A summary list of AD drugs and therapies tested in clinical trials
From: Advances in developing novel therapeutic strategies for Alzheimer’s disease
AD drugs tested in clinical trials | |||||
|---|---|---|---|---|---|
Drug | Phase | Subject | NCT | Summary | Reference |
1.Therapies Targeted at Amyloid | |||||
1.1 Reducing Aβ Generation | |||||
MK-8931 (BACE inh.) | III | Prodromal AD | NCT01953601 | lack of efficacy | 14-16 |
LY450139 | III | Mild to moderate AD | NCT00762411; NCT00594568 | lack of efficacy | 15,18, 19, |
(γ-secretase inh.) | NCT01035138 | 34, 36, 37 | |||
Avagacestat | II | Prodromal AD | NCT00890890 | no efficacy | 35 |
NIC5-15 | II | Probable AD | NCT01928420 | completed | 15,40 |
R-flurbiprofen | III | Probable AD | NCT00105547; NCT00322036 | lack of efficacy | 42 |
EVP-0962 | II | Healthy, MCI or early AD | NCT01661673 | terminated | 15 |
1.2 Accelerating Aβ Clearance | |||||
AN-1792 | II | Mild-to-moderate AD | NCT00021723 | severe meningoencephalitis | 44 |
Affitope AD02 | II | Early AD | NCT02008513; NCT01117818 | no efficacy | 46 |
CAD106 | II/III | Mild AD | NCT02565511 | ongoing | 15, 47 |
Bapineuzumab | III | Mild-to-moderate AD | NCT00667810; NCT00575055 NCT00574132 | no efficacy | 43, 48 |
Solanezumab | III | Mild-to-moderate AD probable AD | NCT00905372; NCT00904683 NCT01900665 | no efficacy | 43, 49 |
BAN2401 | II | MCI due to AD and mild AD | NCT01767311 | positive results | 50 |
Crenezumab | III | Probable AD or prodromal AD | NCT03114657; NCT02670083 | ongoing | |
Gantenerumab | III | Probable AD or prodromal AD | NCT03443973; NCT03444870 | ongoing | |
Aducanumab | I | Prodromal or Mild AD | NCT01677572 | positive results but ARIA | 51 |
III | MCI due to AD or mild AD | NCT02484547; NCT02477800 | ongoing | ||
1.3 Other Anti-amyloidogenic Compounds with Diverse Mechanisms of Action | |||||
ALZT-OP1 | III | Early AD | NCT02547818 | ongoing | 43 |
GV-971 | III | Mild-to-moderate AD | NCT02293915 | completed | 43 |
Posiphen | I | MCI or probably AD | NCT02925650 | ongoing | 52 |
ELND005 | II/III | Mild-to-severe AD | ongoing | 53 | |
ALZ801 | III | Mild AD (ApoE4 carriers) | ongoing | 43 | |
2. Therapies Targeted at Tau | |||||
2.1 Tau Stabilizers and Aggregation Inhibitors | |||||
TPI 287 | I | Probable AD | NCT01966666 | ongoing | |
Rember™ | II | Mild or moderate AD | NCT00684944; NCT00515333 | no efficacy | 62, 63 |
TRx0237 | III | Mild-to-moderate AD/BvFTD | NCT01689233; NCT01689246 NCT02245568 | no efficacy | 64 |
TauRx | II/III | Mild or moderate AD | NCT03539380 | ongoing | |
2.2 Therapies Targeted at Tau Post-translational Modifications | |||||
Lithium and Valproate | II | AD | NCT00088387 | no efficacy | 67, 68 |
NP-12 | IIb | Mild-to-moderate AD | NCT01350362 | no efficacy | 69-71 |
2.3 Anti-tau Immunotherapy | |||||
AADvac1 | II | Mild-to-moderate AD | NCT02579252 | ongoing | 94 |
ACI-35 | I | Mild-to-moderate AD | ISRCTN13033912 | completed | 61 |
ABBV-8E12 | II | PSP; MCI or probable AD | NCT03391765; NCT02880956 | ongoing | |
RO7105705 | I | Healthy | NCT02820896 | ongoing | |
3. Therapies Targeted at ApoE | |||||
Bexarotene | II | Probable AD | NCT01782742 | no efficacy | 142 |
4. Neuroprotective Therapies | |||||
4.1 Neurotrophins and Their Receptor-based Therapies | |||||
NGF | I | Probable early AD | NCT00017940 | positive results | 170 |
AAV2-NGF | II | Mild-to-moderate AD | NCT00876863 | no efficacy | 173 |
LM11A-31 (p75 inh.) | I/II | Mild-to-moderate AD | NCT03069014 | ongoing | |
4.2 Therapies Targeted at Neuroinflammation and Oxidative Stress | |||||
Dimebon | III | AD | NCT00912288 | no efficacy | 209 |
valacyclovir | II | Probable AD | NCT03282916 | ongoing | |
5. Symptomatic Cognitive Enhancers | |||||
Idalopirdine | II | Probable AD | NCT01019421 | positive results | 233 |
(5-HT6 antag.) | III | Mild-to-moderate AD | NCT01955161; NCT02006641 NCT02006654 | no efficacy | 234 |
GSK239512 (H3R antag.) | II | Probable AD | NCT01009255 | no efficacy | 235 |
ABT288 (H3R antag.) | II | Mild-to-moderate AD | NCT01018875 | no efficacy | 236 |
Rasagiline (MAOB inh.) | II | Probable AD | NCT02359552 | ongoing | 237 |
Ladostigil (combined) | II | MCI or Mild-to-moderate AD | NCT01429623; NCT01354691 | no efficacy | 238-241 |
AZD0530 | Ib | Mild-to-moderate AD | NCT01864655 | safety and tolerance | 252 |
(Fyn kinase inh.) | II | Mild AD | NCT02167256 | ongoing | |
Cilostazol | II | MCI | NCT02491268 | positive results | 255-257 |
(PDE3 inh.) | IV | Mild-to-moderate AD | NCT01409564 | ongoing | |
HT-0712 (PDE4 inh.) | II | Age-associated memory impairment | NCT02013310 | completed | 253, 254 |
Roflumilast (PDE4 inh.) | I | Scopolamine-induced CI | NCT02051335 | no efficacy | 253, 254 |
II | Healthy | NCT01433666 | positive results | 253, 254 | |
Age-associated memory impairment | ISRCTN96013814 | completed | 253, 254 | ||
BPN14770 (PDE4 inh.) | I | Healthy | NCT02648672; NCT02840279 | positive results | 253, 254 |
BI 409306 (PDE9 inh.) | I | Healthy | NCT01343706 | safety and tolerance | 253 |
II | MCI due to AD and mild AD | NCT02337907 | ongoing | 253, 254 | |
PF044467943 | I | Mild-to-moderate AD | NCT00988598 | safety and tolerance | 253 |
(PDE9 inh.) | II | Mild-to-moderate AD | no efficacy | 253 | |
6. Therapies and Interventions for AD Prevention | |||||
PROSPER (statin) | II | High risk (with AD parents) | NCT00939822 | no efficacy | 265 |
ACCORD-MIND | III | DM2 | NCT00182910 | no efficacy | 268 |
SNIFF (i.n. insulin) | II; II/III | MCI or AD or probable AD | NCT00438568; NCT01767909 | ongoing | 271-273 |
Metformin | IV | Age >60 years with IGT | NCT02432287 | completed | 274 |
Pioglitazone | II | Mild-to-moderate AD | NCT00982202 | safety and tolerance | 275 |
MIND (diet) | BMI≥25 non-demented | NCT02817074 | ongoing | 277, 278 | |
FABS (fitness) | Non-demented | ACTRN12605000136606 | positive results | 280 | |
ACTIVE (cog. training) | II/III | MCI | NCT00298558 | positive results | 282 |
Vit. E + Memantine | III | Mild to moderate AD | NCT00235716 | positive results | 284, 285 |
Ginkgo biloba | III | Non-demented and MCI | NCT00010803 | no efficacy | 286, 287 |
EGb 761® | IV | Subjects with memory complaints | NCT00276510 | no efficacy | 288 |
MIDAS | Age-associated memory impairment | NCT00278135 | positive results | 290 | |
FINGER | High risk | NCT01041989 | positive results | 291 | |
MIND-ADMINI | Prodromal AD | NCT03249688 | ongoing | ||