Table 3.
Clinical trials of tau-directed therapeutics.
| Therapeutic | Company/Sponsor | Trial | Stage | Cohort | Treatment Length |
Outcome Measures | Trial End | Result (Ref #) |
|---|---|---|---|---|---|---|---|---|
| GENE EXPRESSION | ||||||||
| BIIB080 | Biogen, IONIS Pharmaceuticals | NCT03186989 | Phase 1/2 | 46 mild AD | 36 weeks | 1°: safe/tol 2°: PK |
May-22* | |
| KINASE INHIBITOR | ||||||||
| Lithium | NINDS, ADDF, Columbia University | NCT00088387 | Phase 2 | 35 AD | 6 weeks | CSF tau | Mar-20 | |
| ISRCTN72046462 | Phase 2 | 71 mild AD | 10 weeks | 1°: CSF ptau, GSK-3β 2°: CSF Aβ/tau, ADAS-Cog, NPI, safe/tol |
Jul-20 | [47] | ||
| NCT00703677 | Phase 1/2 | 17 PSP or CBD | 28 weeks | 1°: safe/tol 2°: CSF tau, BDNF, GSK-3β, PSP-RS, UPDRS, QoL, FAB, GDS |
Jan-20 | |||
| NCT02862210 | Phase 2 | 60 bvFTD | 12 weeks | 1°: agitation/NPI 2°: CGI, NPI, AEs, BDNF |
Mar-21* | |||
| NCT03185208 | Phase 4 | 80 MCI | 2 years | 1°: NPSY, GSK-3β, BDNF, 7 T MRI 2°: 7 T MRI, CSF ptau |
Mar-22* | |||
| Valproate | NINDS | NCT00088387 | Phase 2 | 35 AD | 6 weeks | CSF tau | Mar-20 | |
| NCT00071721 (VALID) | Phase 3 | 313 prob AD | 24 months | 1°: agitation/NPI 2°: ADAS-cog, ADL, CDR, CMAI, CGI |
Dec-20 | [50,51] | ||
| NCT00385710 | Phase 2 | 28 poss or prob PSP | 24 months | 1°: PSP-RS 2°: NPSY |
Jul-20 | [52] | ||
| Tideglusib | Zeltia Group, Neuropharma, Noscira | NCT00948259 | Phase 1/2 | 30 mild to mod AD | 20 weeks | 1°: safe/tol 2°: Cognition and mood |
Nov-20 | [55] |
| NCT01049399 (TAUROS) | Phase 2 | 146 poss or prob PSP | 12 months | 1°: PSP-RS 2°: safety, NPSY, UPDRS, CGI |
Nov-20 | [57,58] | ||
| NCT01350362 (ARGO) | Phase 2 | 306 mild to mod AD | 6 months | 1°: ADAS-cog 2°: safe/tol, ADL, MMSE, fluency, NPI, GDS, CGI, EQ-5D, RUD, urinary incont |
Oct-20 | [56] | ||
| Saracatinib | AstraZeneca | NCT01864655 | Phase 1 | 24 mild AD | 4 weeks | 1°: safe/tol, PK 2°: NPSY, FDG-PET |
Mar-20 | [62] |
| NCT02167256( CONNECT) | Phase 2 | 159 mild AD | 12 months | 1°: safe/tol, PET 2°: ADAS-cog, MMSE, ADL, CDR, MRI, CSF Aβ/tau, ApoE |
Feb-20 | [63] | ||
| Nilotinib | Novartis, Georgetown University | NCT02947893 | Phase 2 | 42 mild to mod AD | 12 months | 1°: safe/tol 2°: PK |
Feb-20* | |
| OGA INHIBITOR | ||||||||
| MK-8719 | Alectos Therapeutics | Phase 1 | 16 healthy ctrls | 1°: safe/tol 2°:PK |
[67] | |||
| ASN120290 | Asceneuron | Phase 1 | 61 healthy ctrls | 10 days | 1°: safe/tol 2°:PK |
[70] | ||
| ACETYLATION INHIBITOR | ||||||||
| Salsalate | UCSF | NCT03277573 (SAL-AD) | Phase 1 | 40 mild to mod AD | 12 months | 1°: safe/tol 2°: PK, MRI, CSF tau, NfL, NPSY, ADL, CDR |
Feb-21* | |
| NCT02422485 | Phase 1 | 10 prob or poss PSP | 6 months | 1°: safe/tol 2°: PSP-RS, CDR, CGI, RBANS, MRI, CSF NfL |
Mar-20 | [72] | ||
| TAU AGGREGATION INHIBITOR | ||||||||
| Rember TM | TauRx Therapeutics Ltd | NCT00515333 | Phase 2 | 323 mild or mod AD | 24 weeks | 1°: ADAS-cog 2°: NPI, CGI, CDR, MMSE,BADLs, SPECT/PET |
Dec-20 | [78,79] |
| NCT00684944 | Extension | 111 mild or mod AD | 12 months | 1°: ADAS-cog, MMSE 2°: CDR, ADFACS |
Dec-20 | |||
| LMTM | TauRx Therapeutics Ltd | NCT01626391 | Phase 1/2 | 9 mild to mod AD | 4 weeks | 1°: safe/tol | Mar-20 | |
| NCT01689246 | Phase 3 | 891 mild to mod AD | 65 weeks | 1°: safe/tol, ADL, ADAS-cog 2°: CGI, MMSE, MRI |
Nov-20 | [80] | ||
| NCT01689233 | Phase 3 | 800 mild AD | 78 weeks | 1°: safe/tol, ADL, ADAS-cog 2°: CGI, MMSE, NPI, MADRS, MRI |
May-20 | [81] | ||
| NCT01626378 | Phase 3 | 220 bvFTD | 12 months | 1°: ACE-R, FAQ, MRI 2°: UPDRS, FRS, CGI, safe/ tol |
Feb-20 | |||
| NCT02245568 | Extension | 913 AD or bvFTD | 34 months | 1°: safe/tol 2°: EQ-5D, RUD |
May-20 | |||
| NCT03446001 (LUCIDITY) | Phase 3 | 450 early AD | 12 month | 1°: ADAS-cog, ADL, safe/tol 2°: MRI, FDG PET, ADAS-cog, ADL |
Dec-22* | |||
| ACTIVE IMMUNIZATION (VACCINATION) | ||||||||
| AADvac-1 | Axon Neuroscience SE | NCT01850238 | Phase 1 | 30 mild to mod AD | 3 months | 1°: safe/tol 2°: Ab titers |
Mar-20 | [95] |
| NCT02031198 (FUNDAMANT) | Extension | 25 mild to mod AD | 18 months | 1°: long-term safe/tol 2°: Ab titers, ADAS-cog, COWAT |
Dec-20 | [96] | ||
| NCT02579252 (ADAMANT) | Phase 2 | 208 mild AD | 24 months | 1°: safe/tol 2°: CDR, NPSY, ADL, Ab titers |
Jun-20 | |||
| NCT03174886 (AIDA) | Phase 1 | 33 nfv-PPA | 24 months | 1°: safe/tol, Ab titers | Nov-20* | |||
| ACI-35 | AC Immune SA, Janssen | ISRCTN13033912 | Phase 1 | Mild to mod AD | 6 month + 16 month booster | 1°: safe/tol, Ab titers | Jun-20 | |
| PASSIVE IMMUNIZATION (ANTIBODY TRANSFUSION) | ||||||||
| RG7345 | Hoffmann-La Roche | NCT02281786 | Phase 1 | 48 healthy ctrls | 16 weeks | 1°: safe/tol 2°: PK |
Oct-20 | |
| BIIB092 | Biogen, Bristol-Myers Squibb | NCT02294851 (Healthy ctrls) | Phase 1 | 65 healthy ctrls | Single dose | 1°: safe/tol | Apr-20 | [103] |
| NCT02460094 | Phase 1 | 48 poss or prob PSP | 12 weeks | 1°: safe/tol 2°: CSF tau, Ab titers, PK |
Oct-20 | [104] | ||
| NCT02658916 | Extension | 48 poss or prob PSP | 1.5 years+ | 1°: long-term safe/tol 2°: PK, Ab titers, CSF tau |
Feb-20 | |||
| NCT03658135 (TauBasket) | Phase 1 | 22 CBS, nfvPPA, MAPT, and TES | 20 weeks | 1°: safe/tol 2°: PK, CSF tau |
Feb-20 | |||
| NCT03068468 (PASSPORT) | Phase 2 | 490 poss or prob PSP | 48 weeks + 156 week OLE | 1°: PSP-RS, safe/tol 2°: UPDRS, CGI, RBANS, QoL, SEADL, NPSY, MOCA, Ab titers, MRI |
Feb-20 | |||
| NCT03352557 (TANGO) | Phase 2 | 654 MCI or early AD | 76 weeks | 1°: safe/tol 2°: CDR, Ab titers |
Mar-24* | |||
| C2N 8E12 | AbbVie, C2N Diagnostics, LLC | NCT02494024 | Phase 1 | 32 poss or prob PSP | 4 months | 1°: safe/tol 2°: PK, Ab titers |
Aug-20 | [108] |
| NCT03413319 | Extension | 3 poss or prob PSP | 29 months | 1°: safe/tol | Nov-20 | |||
| NCT02985879 (PSP) | Phase 2 | 378 poss or prob PSP | 12 months | 1°: PSP-RS, safe/tol 2°: PK, CGI, MRI, UPDRS, SEADL |
Nov-20 | |||
| NCT03391765 | Extension | 378 poss or prob PSP | 5 years | 1°: PSP-RS 2°: UPDRS, CGI, SEADL |
Nov-20 | |||
| NCT02880956 | Phase 2 | 453 early AD | 96 weeks | 1°: safe/tol, CDR 2°: UPSA, PK, MMSE, ADL, FAQ, RBANS, CGI, ADAS-cog, NPI |
Jul-21* | |||
| NCT03712787 | Extension | 360 early AD | 5.5 years | 1°: safe/tol | Aug-20 6* |
|||
| RO 7,105,705 | AC Immune SA, Genentech, Hoffmann-La Roche | NCT02820896 | Phase 1 | 74 healthy ctrls and mild AD | 19 weeks | 1°: safe/tol, C-SSRS 2°: CDR, Ab titers, PK, MMSE |
Jun-20 | |
| NCT03289143 (TAURIEL) | Phase 2 | 457 prodromal to mild AD | 73 weeks | 1°: CDR, safe/tol 2°: RBANS, ADAS-cog, ADL,PK, Ab titers |
Sep-22* | |||
| LY3303560 | Eli Lilly & Co. | NCT02754830 | Phase 1 | 110 healthy ctrls and mild AD | 85 days | 1°: safe/tol 2°: PK |
Jul-20 | |
| NCT03019536 | Phase 1 | 24 MCI or early AD | 64 weeks | 1°: safe/tol 2°: PK |
Jun-20 | |||
| NCT03518073 | Phase 2 | 285 early AD | 80 weeks | 1°: iADRS 2°: ADAS-cog, ADL, CDR, MMSE, tau PET, MRI, CSSRS, Ab titers |
Oct-21* | |||
| BIIB076 | Biogen, Neurimmune | NCT03056729 | Phase 1 | 56 healthy ctrls and mild AD | 20 weeks | 1°: safe/tol 2°: PK, Ab titers |
Mar-20 | |
| UCB0107 | UCB S.A. | NCT03464227 | Phase 1 | 52 healthy ctrls | 20 weeks | 1°: safe/tol 2°: PK |
Dec-20 | |
| NCT03605082 | Phase 1 | 24 healthy Japanese ctrls | 20 weeks | 1°: safe/tol, PK | Mar-20 | |||
| JNJ-63733657 | Janssen | NCT03375697 | Phase 1 | 72 healthy ctrls and mild AD | 21 weeks | 1°: safe/tol 2°: PK, CSF tau |
Dec-20 | |
| MICROTUBULE STABILIZATION | ||||||||
| Davunetide | Allon Therapeutics Inc., Paladin Labs Inc. | NCT00422981 | Phase 2 | 144 MCI | 12 weeks | 1°: NPSY (12 weeks) 2°: NPSY (16 weeks) |
Jan-20 | [117] |
| NCT01056965 | Phase 1 | 12 PSP, CBS, nfvPPA, and sMAPT | 12 weeks | 1°: safe/tol 2°: PSP-RS, CGI, SEADL, MRI, RBANS, UPDRS, NPI, GDS, CSF Aβ/tau, saccades, CDR, FAQ |
Jul-20 | |||
| NCT01110720 | Phase 2/3 | 313 PSP | 12 months | 1°: PSP-RS, SEADL, safe/tol 2°: CGI, MRI |
Dec-20 | [119] | ||
| Epothilone D | Bristol-Myers Squibb | NCT01492374 | Phase 1 | 40 mild AD | 10 weeks | 1°: safe/tol, CSF tau 2°: CSF tau/NfL, NPSY, PK,MRI |
Oct-20 | |
| TPI 287 | Cortice Biosciences | NCT02133846 | Phase 1 | 44 CBS or PSP | 9 weeks | 1°: safe/tol 2°: PK |
Mar-20 | [123] |
| NCT01966666 | Phase 1 | 33 mild to mod AD | 9 weeks | 1°: safe/tol 2°: PK |
Nov-20 | [123] | ||
= estimated data of completion at time of publication. Abbreviations: antibody (Ab), beta amyloid (Aβ), Addenbrooke's Cognitive Examination - Revised (ACE-R), Alzheimer's Disease Assessment Scale-cognitive Subtest (ADAS-cog), Alzheimer's Disease Functional Assessment and Change Scale (ADFACS), Alzheimer's Disease Cooperative Study Activities of Daily Living (ADL), adverse events (AE), apolipoprotein E (ApoE), basic activities of daily living (BADLs), brain-derived neurotrophic factor (BDNF), cerebrospinal fluid (CSF), Clinical Global Impression of Change (CGI), Cohen-Mansfield Agitation Inventory (CMAI), Controlled oral word association test (COWAT), Columbia Suicide Severity Rating Scale (C-SSRS), European Quality of Life Instrument (EQ-5D), Frontal Assessment Battery (FAB), Functional Activities Questionnaire (FAQ), Frontotemporal Dementia Rating Scale (FRS). Geriatric Depression Scale (GDS), glycogen synthase kinase-3 beta (GSK-3β), integrated Alzheimer's Disease Rating Scale (iADRS), Montgomery-Asberg Depression Rating Scale (MADRS), Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), magnetic resonance imaging (MRI), neurofilament light chain (NfL), Neuropsychiatric Inventory (NPI), neuropsychological testing (NPSY), pharmacokinetics (PK), Progressive Supranuclear Palsy Rating Scale (PSP-RS), PSP-Quality of Life Scale (QoL), Repeatable Battery for the Assessment of Neuropsychological Disease Severity (RBANS), Resource Utilization in Dementia (RUD), safety and tolerability (safe/tol), Schwab and England Activities of Daily Living (SEADL), Unified Parkinson Disease Rating Scale (UPDRS), University of California's Performance Based Skills Assessment, Brief Version (UPSA).