TABLE 4.
Safety summary of the phase II and III studies
| Classification of adverse events | Investigation periods | Phase II | Phase III | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MA group | HA group | MB group | HB group | MA group | ||||||||||||
| Number of subjects with events | Number of subjects with events | Number of subjects with events | Number of subjects with events | Number of subjects with events | ||||||||||||
|
Incidence (%) (95%CI) |
Incidence (%) (95%CI) |
Incidence (%) (95%CI) |
Incidence (%) (95%CI) |
Incidence (%) (95%CI) |
||||||||||||
| Number of analyzed subjects | 62 | 62 | 63 | 61 | 369 | |||||||||||
| Adverse events | ||||||||||||||||
| Death | Day 0‐Day 201 | 0 | 0 | 0 | 0 | 0 | ||||||||||
| Serious adverse events | Day 0‐Day 201 | 0 | 0 | 0 | 0 | 2 | 0.5 | (0.1‐1.9) | ||||||||
| Significant adverse events | Day 0‐Day 201 | 0 | 0 | 0 | 0 | 0 | ||||||||||
| Potential immune‐mediated diseases | Day 0‐Day 201 | 0 | 0 | 0 | 0 | 1 | 0.3 | (0.0‐1.5) | ||||||||
| Solicited local adverse events | Day 0‐Day 6, Day 21‐Day 27 | 54 | 87.1 | (76.1‐94.3) | 52 | 83.9 | (72.3‐92.0) | 52 | 82.5 | (70.9‐90.9) | 48 | 78.7 | (66.3‐88.1) | 330 | 89.4 | (85.8‐92.4) |
| Solicited systemic adverse events | Day 0‐Day 6, Day 21‐Day 27 | 43 | 69.4 | (56.3‐80.4) | 46 | 74.2 | (61.5‐84.5) | 45 | 71.4 | (58.7‐82.1) | 35 | 57.4 | (44.1‐70.0) | 247 | 66.9 | (61.9‐71.7) |
| Unsolicited adverse events | Day 0‐Day 42 | 22 | 35.5 | (23.7‐48.7) | 20 | 32.3 | (20.9‐45.3) | 25 | 39.7 | (27.6‐52.8) | 22 | 36.1 | (24.2‐49.4) | 124 | 33.6 | (28.8‐38.7) |
| Day 43‐Day 201 | 0 | 0 | 0 | 0 | 1 | 0.3 | (0.0‐1.5) | |||||||||
| Day 0‐Day 201 | 22 | 35.5 | (23.7‐48.7) | 20 | 32.3 | (20.9‐45.3) | 25 | 39.7 | (27.6‐52.8) | 22 | 36.1 | (24.2‐49.4) | 125 | 33.9 | (29.1‐39.0) | |
| Adverse drug reactions | ||||||||||||||||
| Death | Day 0‐Day 201 | 0 | 0 | 0 | 0 | 0 | ||||||||||
| Serious adverse events | Day 0‐Day 201 | 0 | 0 | 0 | 0 | 0 | ||||||||||
| Significant adverse events | Day 0‐Day 201 | 0 | 0 | 0 | 0 | 0 | ||||||||||
| Potential immune‐mediated diseases | Day 0‐Day 201 | 0 | 0 | 0 | 0 | 0 | ||||||||||
| Solicited local adverse events | Day 0‐Day 6, Day 21‐Day 27 | 54 | 87.1 | (76.1‐94.3) | 52 | 83.9 | (72.3‐92.0) | 52 | 82.5 | (70.9‐90.9) | 48 | 78.7 | (66.3‐88.1) | 330 | 89.4 | (85.8‐92.4) |
| Solicited systemic adverse events | Day 0‐Day 6, Day 21‐Day 27 | 41 | 66.1 | (53.0‐77.7) | 44 | 71.0 | (58.1‐81.8) | 45 | 71.4 | (58.7‐82.1) | 34 | 55.7 | (42.4‐68.5) | 245 | 66.4 | (61.3‐71.2) |
| Unsolicited adverse events | Day 0‐Day 42 | 18 | 29.0 | (18.2‐41.9) | 16 | 25.8 | (15.5‐38.5) | 15 | 23.8 | (14.0‐36.2) | 13 | 21.3 | (11.9‐33.7) | 99 | 26.8 | (22.4‐31.7) |
| Day 43‐Day 201 | 0 | 0 | 0 | 0 | 0 | |||||||||||
| Day 0‐Day 201 | 18 | 29.0 | (18.2‐41.9) | 16 | 25.8 | (15.5‐38.5) | 15 | 23.8 | (14.0‐36.2) | 13 | 21.3 | (11.9‐33.7) | 99 | 26.8 | (22.4‐31.7) | |
Sbjects analyzed: safety analysis set. Study period: Day 0 ‐Day 201. Confidence intervalexact 95% two‐sided confidence interval based on F‐distribution. MA group; 3.75 μg HA + AS03. HA group; 7.5 μg HA + AS03. MB group; 3.75 μg HA + 1/2 AS03. HB group; 7.5 μg HA + 1/2 AS03.