Table 4.
Percent changes in cerebrospinal fluid amyloid precursor protein fragment levels and cerebrospinal fluid total tau/phosphorylated tau protein levels from baseline at day 28 across treatment groups
| Safety analysis set | Caucasian | Japanese | ||||
|---|---|---|---|---|---|---|
| Early AD | Preclinical AD | |||||
| Percent change from baseline at day 28 | Placebo | JNJ-54861911 | Placebo | JNJ-54861911 | ||
| 10 mg | 50 mg | 10 mg | 50 mg | |||
| CSF sAPPα (μg/ml), n | 12 | 15 | 15 | 6 | 6 | 6 |
| Mean (SD) | − 2.60 (15.336) | 88.74 (60.035) | 114.28 (50.461) | 11.96 (33.788) | 61.37 (24.755) | 82.49 (42.820) |
| Median (range) | − 6.14 (− 27.1; 23.2) | 69.32 (28.4; 264.2) | 121.38 (11.4; 187.7) | 2.03 (− 21.1; 66.8) | 60.22 (33.7; 104.2) | 86.71 (11.6; 136.2) |
| 95% CI of mean | (− 12.3; 7.1) | (55.5; 122.0) | (86.3; 142.2) | (− 23.50; 47.42) | (35.39; 87.35) | (37.55; 127.42) |
| LS mean | 113.02 | 218.19 | 249.66 | 11.04 | 62.60 | 82.17 |
| Difference of LS means (SE) | – | 1.93 (1.100) | 2.21 (1.101) | – | 51.57 (21.480) | 71.13 (20.649) |
| 95% CI | – | (1.59; 2.34) | (1.82; 2.68) | – | (5.49; 97.64) | (26.84; 115.41) |
| CSF sAPPβ (μg/ml), n | 12 | 15 | 15 | 6 | 6 | 6 |
| Mean (SD) | − 2.05 (13.485) | − 64.34 (10.208) | − 90.70 (2.785) | 12.40 (29.163) | − 66.90 (5.222) | − 91.30 (3.570) |
| Median (range) | − 5.32 (− 21.7; 22.7) | − 67.25 (− 75.4; − 39.6) | − 90.40 (− 96.7; − 85.3) | 3.29 (− 17.5; 59.5) | − 65.78 (− 76.1; −61.1) | − 91.21 (− 96.5; − 86.0) |
| 95% CI of mean | (− 10.6; 6.5) | (− 70.0; − 58.7) | (− 92.2; − 89.2) | (− 18.20; 43.01) | (− 72.38; − 61.42) | (− 95.05; − 87.55) |
| LS mean | 142.68 | 51.70 | 13.51 | 11.98 | − 65.86 | − 91.91 |
| Difference of LS means (SE) | – | 0.36 (1.113) | 0.09 (1.116) | – | − 77.84 (10.543) | − 103.88 (10.196) |
| 95% CI | – | (0.29; 0.45) | (0.08; 0.12) | (− 100.45; − 55.23) | (− 125.75; − 82.02) | |
| CSF total sAPP (μg/ml), n | 12 | 15 | 15 | 6 | 6 | 6 |
| Mean (SD) | − 7.80 (13.442) | − 13.34 (19.260) | − 15.29 (20.330) | 0.06 (16.444) | − 1.55 (27.494) | − 24.85 (21.689) |
| Median (range) | − 5.86 (− 34.4; 19.7) | − 13.34 (− 41.3; 19.6) | − 17.39 (− 44.7; 21.9) | 1.73 (− 27.0; 22.8) | − 10.40 (− 23.3; 51.2) | − 16.94 (− 53.7; − 2.6) |
| 95% CI of mean | (− 16.3; 0.7) | (− 24.0; − 2.7) | (− 26.6; − 4.0) | (− 17.19; 17.32) | (− 30.40; 27.31) | (− 47.61; − 2.08) |
| LS mean | 734.76 | 701.82 | 679.71 | 0.49 | − 2.16 | − 24.65 |
| Difference of LS means (SE) | – | 0.96 (1.087) | 0.93 (1.086) | – | − 2.65 (14.338) | − 25.14 (13.383) |
| 95% CI | – | (0.81; 1.13) | (0.78; 1.09) | – | (− 33.40; 28.10) | (− 53.85; 3.56) |
| CSF total tau (ng/L), n | 13 | 15 | 15 | 6 | 6 | 6 |
| Mean (SD) | − 1.68 (4.130) | 4.18 (7.629) | 8.02 (6.557) | − 17.00 (13.054) | − 4.67 (48.718) | − 38.83 (52.648) |
| Median (range) | − 2.48 (− 9.8; 5.6) | 6.76 (− 11.2; 16.1) | 7.64 (− 4.5; 23.4) | − 20.50 (− 28.0; 7.0) | − 21.00 (− 38.0; 90.0) | − 32.50 (− 110.0; 25⋅0) |
| 95% CI of mean | (− 4.18; 0.81) | (− 0.04; 8.41) | (4.39; 11.65) | (− 30.70; − 3.30) | (− 55.79; 46.46) | (− 94.08; 16.42) |
| CSF P-tau (ng/L), n | 12 | 15 | 14 | 6 | 6 | 6 |
| Mean (SD) | − 1.55 (4.252) | 3.56 (4.797) | 7.36 (3.648) | − 1.67 (2.422) | − 0.67 (5.046) | − 2.17 (6.911) |
| Median (range) | 0.00 (− 8.0; 5.4) | 3.45 (− 4.6; 11.5) | 7.42 (1.6; 16.7) | − 1.00 (− 5.0; 1.0) | − 2.00 (− 5.0; 9.0) | − 0.50 (− 11.0; 5.0) |
| 95% CI of mean | (− 4.26; 1.15) | (0.91; 6.22) | (5.25; 9.47) | (− 4.21; 0.88) | (− 5.96; 4.63) | (− 9.42; 5.09) |
Abbreviations: AD Alzheimer’s disease, Aβ Amyloid-beta, CSF Cerebrospinal fluid, LS Least squares, sAPP Soluble amyloid precursor protein