Table 3.
Mean Difference in Change in Outcome Measures from Baseline to 52 Week (Observed Cases)
| Mean 52 wk change (95%CI) | Mean difference (95%CI) |
p value | |||
|---|---|---|---|---|---|
| Davunetide | Placebo | Total | |||
| Clinical | |||||
| n = 118 | n = 123 | n = 241 | |||
| PSPRSa | 11.3 (9.8,12.8) | 10.9 (9.1,13.0) | 11.1 (9.9,12.3) | 0.49 (−1.5, 2.5) | 0.72 |
| SEADLa | −0.16 (−0.19,0.13) | −0.17 (−0.20,−0.14) | −0.17 (−0.19,−0.15) | 0.01 (−0.02,0.04) | 0.76 |
| CGICb | 5.0 (4.8,5.2) | 5.0 (4.8,5.2) | 5.0 (4.9,5.1) | 0.0 (−0.14,0.34) | 0.99 |
| CGIdsc | 0.91 (0.78,1.0) | 0.87 (0.70,1.0) | 0.89 (0.78,1.0) | 0.03 (−0.19,0.25) | 0.73 |
| GDSc | 0.32 (−0.67,1.3) | 0.77 (−0.11,1.6) | 0.55 (−0.11,1.2) | −0.45 (−1.8,0.91) | 0.52 |
| Neuropsychological | n = 106 | n = 111 | n = 217 | ||
| RBANS(Total Scaled)c | −5.6 (−7.3,−3.9) | −6.4 (−7.9,−4.9) | 6.4 (5.3,7.5) | 0.74 (−1.7,3.1) | 0.55 |
| RBANS(Total Raw) | −20.1 (−24.3,−15.8) | −23.8 (−33.8,−13.9) | −22.0 (−24.8,−19.3) | 3.8 (−2.8,10.3) | 0.35 |
| Phonemic Fluency(words/min)c | −2.0 (−1.2,−2.8) | −2.3 (−3.1,−1.5) | −2.1 (−2.7,−1.5) | 0.32 (−0.64,2.0) | 0.63 |
| Letter number seq.c | −1.0 (−1.45,−0.55) | −1.1 (−1.6,−0.62) | −1.1 (−1.4,−0.72) | 0.11 (−0.58,0.80) | 0.73 |
| Color Trails 2c | 36.0 (25.8,46.3) | 31.5 (21.6,41.4) | 33.8 (26.6,40.9) | 4.5 (−10.3,19.3) | 0.56 |
| MRI | |||||
| Absolute volume change | n = 111 | n = 108 | n = 219 | ||
| Ventricular vol.(× 104 mm3)b | 0.43 (0.36,0.50) | 0.42 (0.30,0.44) | 0.43 (0.31,0.41) | 0.01 (−10.6,10.6) | 0.97 |
| Whole brain vol.(× 104 mm3)c | −1.0 (−1.3,−0.79) | −1.2 (−1.4,−0.92) | −1.1 (−1.27,−0.93) | 0.15 (−0.09,0.37) | 0.31 |
| Midbrain volume(× 104 mm3)c | −0.02 (−0.03,−0.02) | −0.02 (−0.03,−0.02) | −0.02 (−0.03,−0.02) | −0.00 (−0.003,0.003) | 0.61 |
| SCP volume(× 104 mm3)c | −0.003(−0.003,−0.002) | −0.003 (−0.004,−0.002) | −0.003 (−0.003,−0.002) | 0.0005 (−0.0002,0.001) | 0.38 |
| Percent volume change | |||||
| Ventricular volume | 9.2% (7.8%, 11%) | 9.6% (7.7%, 10%) | 9.4% (8.6%, 10%) | 0.38% (−1.0%, 1.7%) | 0.64 |
| Whole brain volume | −0.79% (−0.61%,−0.98%) | −0.78% (−1.1%,−0.74%) | −0.86% (−0.86%,−0.85%) | −0.13% (−0.4%,0.2%) | 0.25 |
| Midbrain volume | −3.6% (−4.0%,−3.0%) | −3.4% (−3.9%,−2.9%) | −3.5% (−3.9%,−3.1%) | 0.1% (−0.6%, 0.8%) | 0.76 |
| SCP volume | −6.6% (−9.6%,−6%) | −7.9% (−0.27%,−11%) | −7.3% (−8.5%,−6.0%) | −1.3% (−3.8%, 1.2%) | 0.36 |
| CSF | |||||
| n = 10 | n = 12 | n = 22 | |||
| Aβ 1-42(pg/ml)c | 6.2 (−63.3,75.7) | 37.7 (−17.3,92.8) | 23.6 (−19.3,66.4) | −31.5 (−93.6,57.2) | 0.89 |
| NfL(pg/ml)c | 494 (−197,1186) | 922 (349,1496) | 755 (309,1201) | −498 (−587,−410) | 0.43 |
| Total tau(pg/ml)c | −4.6 (−20.1,10.9) | 9.7 (−1.5,21.0) | 2.9 (−6.7,12.5) | −14.3 (−33.4,4.8) | 0.42 |
| pTau(pg/ml)c | −1.2 (−5.1,2.7) | −0.18 (−6.2,5.9) | −0.67 (−2.3,3.0) | −1.0 (−8.2,6.2) | 0.38 |
| Plasma | |||||
| n=11 | n=12 | n=23 | |||
| pNFH (pg/ml) c | −80 (−0.380, 220) | −160 (−650,330) | −120 (−410, 170) | 80 (−490,650) | 0.93 |
| Ocular motor | |||||
| Horizontal Saccade Latency | n=13 | n=6 | n=19 | ||
| Absolute Change (msec) c | 51.1 (20.6, 81.7) | 20.9 (−3.5,45.3) | 41.6 (18.8, 64.4) | 30.2 (−8.8, 69.3) | 0.24 |
| Percent Change | 21.5% (9.7%, 33.4%) | 8.7% (−3.3%, 20.7%) | 17.5% (8.3%, 26.7%) | 12.8% (−4.1%, 29.7%) | 0.32 |
| Vertical First Saccade Gain | n=7 | n=5 | n=12 | ||
| Absolute Change(degrees) c | −0.86 (−1.4, −0.27) | −0.60 (−1.3,0.06) | −0.74 (−1.2, −0.31) | −0.26 (−1.1, 0.63) | 0.74 |
| Percent Change | −48.3% (−68.1%, −28.5%) | −43.7% (−59.5%, −27.8%) | −46.4% (−59.2%, −33.5%) | −4.6% (−30.0%, 20.7%) | 0.99 |
N and P values are from participants with complete 52 week data.
a
Primary endpoints;
b
Secondary endpoints;
c
Exploratory endpoints. Abbreviations: PSPRS: Progressive Supranuclear Palsy Rating Scale; SEADL: Schwaab and England Activities of Daily Living Scale; GDS: Geriatric Depression Scale; CGIds: Clinical Global Impression of Disease Severity; RBANS: Repeatable Battery for the Assessment of Neuropsychological Disease Severity; SCP = superior cerebellar peduncle; NfL = Neurofilament Light Chain; pTau= phosphorylated tau (residue 181).