Table 3. Change in Exploratory Outcomes From Baseline to End of Study in mITT Analysisa.
| Characteristic | Study Cohort by Treatment Arm, Median (Range) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| AD Trial | 4RT Trial | ||||||||||
| Placebo (n = 8) | TPI-287 | Placebo (n = 12) | TPI-287 | ||||||||
| 2.0 mg/m2 (n = 8) | 6.3 mg/m2 (n = 7) | 20.0 mg/m2 (n = 3) | All (n = 18) | PSP, 2.0 mg/m2 (n = 8) | CBS, 2.0 mg/m2 (n = 7) | CBS, 6.3 mg/m2 (n = 7) | CBS, 20.0 mg/m2 (n = 8) | All (n = 30) | |||
| Clinical | |||||||||||
| MMSE scoreb | −3.0 (−4 to 1) | 0 (−4 to 4) | 0 (−4 to 4) | 0 (−3 to 1) | 0 (−4 to 4)c | 0.5 (−3 to 4) | −0.5 (−9 to 6) | −1.0 (−4 to 2) | 1.0 (−3 to 4) | 0 (−3 to 4)d | 0 (−9 to 6)d |
| ADAS-Cog scoree | 1.5 (−6 to 8) | −3.5 (−12 to 6) | −3.0 (−9 to 9) | 3.5 (0 to 7)d | −2.0 (−12 to 9)d | NA | NA | NA | NA | NA | NA |
| PSPRS scoref | NA | NA | NA | NA | NA | 1.0 (−11 to 8) | 1.0 (−9 to 14) | 1.0 (−17 to 9) | −3.0 (1 to 8) | 2.5 (−10 to 15) | 1.0 (−17 to 15) |
| ADCS-ADL scoreg | −0.5 (−12 to 7) | 2.0 (−25 to 12) | −6.0 (−15 to 3) | −3.0 (−11 to −1) | −4.0 (−25 to 12) | NA | NA | NA | NA | NA | NA |
| SEADL scoreh | NA | NA | NA | NA | NA | 0 (−20 to 30) | 5.0 (−20 to 40) | −10 (−30 to 10) | 0 (−20 to 10) | 5.0 (−20 to 20) | 0 (−30 to 40) |
| GDS scorei | −0.5 (−6 to 2) | 0 (−2 to 1) | −0 (−4 to 1) | 0 (0 to 1) | 0 (−4 to 1) | −1.0 (−4 to 1) | 1.5 (−8 to 6) | 1.0 (−3 to 2) | −1.0 (−3 to 6) | 1.5 (−1 to 6) | 1 (−8 to 6)j |
| CDR plus NACC FTLD-SB scorek | NA | NA | NA | NA | NA | −0.75 (−3 to 3) | 0.5 (−1 to 2.5) | 0 (−3 to 0.5) | 0 (1 to 3.5) | 1.25 (−2.5 to 5) | 0.5 (−3 to 5)j |
| PF scorel | NA | NA | NA | NA | NA | 0 (−10 to 9) | −0.5 (−4 to 8) | −1.0 (−6 to 6) | −5.0 (−10 to 3) | 2.5 (−4 to 6) | −1.0 (−10 to 8) |
| CSF levels | |||||||||||
| Aβ42, pg/mL | −3.5 (−22 to 5) | −8.0 (−23 to 61)d | −2.0 (−50 to 17)d | −4.0 (−22 to 1) | −6.0 (−50 to 61)m | −33.0 (−77 to 42) | −36.0 (−66 to 17) | −18.0 (−76 to 121) | −1.0 (−50 to 72) | −4.0 (−40 to 59) | −11.5 (−76 to 121) |
| t-tau, pg/mL | 1.5 (−24 to 10) | 1.0 (−15 to 14)d | −5.0 (−25 to 11)d | −6.0 (−24 to 26) | −3.0 (−25 to 26)m | −4.0 (−9 to 5) | 2.0 (−6 to 12) | −2.0 (−18 to 9) | −1.0 (−14 to 25) | 1.0 (−14 to 5) | 1.0 (−18 to 25) |
| p-tau, pg/mL | 6.5 (−35 to 29) | −5.0 (−18 to 17)d | −4.0 (−26 to 15)d | 0 (−21 to 26) | −3.0 (−26 to 26)m | 1.0 (−9 to 12) | 0.5 (−8 to 7) | −4.0 (−12 to 3) | 2.0 (−15 to 7) | −0.5 (−7 to 5) | 0 (−15 to 7) |
| NfL, pg/mL | −0.5 (−141 to 256) | −5.0 (−159 to 370)d | 81.5 (−474 to 310)d | −21.0 (−132 to 72) | 10.5 (−474 to 370)m | 92.0 (−575 to 1856) | 148.0 (−464 to 1267) | −161.0 (−578 to 105) | −143.0 (−2162 to 265) | −36.0 (−2114 to 2304) | 67.0 (−2162 to 2304) |
| YKL-40, ng/mL | −30.5 (−37 to 20) | −3.0 (−94 to 18)d | 0.5 (−44 to 26)d | 17.0 (−42 to 30) | 0.5 (−94 to 30)m | 4.0 (−30 to 134) | −19.0 (−34 to 76) | −23.0 (−49 to 29) | −4.0 (−23 to 46) | −14.0 (−26 to 7) | −15.0 (−49 to 76)n |
Abbreviations: Aβ42, β-amyloid 1-42; AD, Alzheimer disease; ADAS-Cog, Alzheimer Disease Assessment Scale–Cognitive; ADCS-ADL, Alzheimer Disease Cooperative Study Activities of Daily Living; CBS, corticobasal syndrome; CDR plus NACC FTLD-SB, Clinical Dementia Rating Scale sum of boxes with frontotemporal dementia measures; CSF, cerebrospinal fluid; GDS, Geriatric Depression Screen; mITT, modified intention to treat; MMSE, Mini-Mental State Examination; NA, not applicable; NfL, neurofilament light chain; PF, phonemic fluency; PSP, progressive supranuclear palsy; PSPRS, Progressive Supranuclear Palsy Rating Scale; p-tau, phosphorylated tau; 4RT, 4-Repeat Tauopathy; SEADL, Schwab and England Activities of Daily Living; t-tau, total tau; YKL-40, chitinase-3–like protein 1.
Data are from mITT analysis of individuals who received 2 or more infusions and had end-of-study assessment data.
Scores range from −9 to 6, with positive scores indicating a worsening from baseline and negative scores indicating an improvement from baseline.
P = .04, treatment group compared with placebo.
One participant was missing data.
Scores range from −12 to 9, with positive scores indicating a worsening from baseline and negative scores an improvement from baseline.
Scores range from −17 to 15, with negative scores indicating improvement in disability and positive scores indicating worsening disability from baseline.
Scores range from −25 to 12, with negative scores indicating a worsening in activity of daily living function from baseline and positive scores indicating an improvement.
Scores range from −30 to 40, with negative scores indicating a worsening in activity of daily living function from baseline and positive scores indicating an improvement.
Scores range from −8 to 6, with negative scores indicating an improvement in depressive symptoms since baseline and positive scores indicating a worsening.
P = .03, treatment group compared with placebo.
Scores range from −3 to 5, with negative scores indicating an improvement in dementia rating since baseline and positive scores indicating worsening dementia.
Scores range from −10 to 9, with negative scores indicating worse phonemic fluency since baseline and positive scores indicating improved phonemic fluency.
Two participants were missing data.
P = .045, treatment group compared with placebo.