Table 5.
Adverse reactions within 7 days and overall adverse events within 30 days after the first and the second vaccinations for all schedules in phase 2
|
8 μg day 0 (n=112) |
4 μg days 0 and 14 (n=112) |
4 μg days 0 and 21 (n=112) |
4 μg days 0 and 28 (n=112) |
Total (n=448) |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Vaccination (n=84) | Placebo (n=28) | p value | Vaccination (n=84) | Placebo (n=28) | p value | Vaccination (n=84) | Placebo (n=28) | p value | Vaccination (n=84) | Placebo (n=28) | p value | Vaccination (n=336) | Placebo (n=112) | p value | ||
| All adverse reactions within 0–7 days | ||||||||||||||||
| Any | 33 (39%) | 3 (11%) | 0·0049 | 18 (21%) | 5 (18%) | 0·79 | 15 (18%) | 5 (18%) | >0·99 | 10 (12%) | 6 (21%) | 0·22 | 76 (23%) | 19 (17%) | 0·20 | |
| Grade 1 | 31 (37%) | 3 (11%) | .. | 18 (21%) | 3 (11%) | .. | 13 (15%) | 4 (14%) | .. | 8 (10%) | 2 (7%) | .. | 70 (21%) | 12 (11%) | .. | |
| Grade 2 | 2 (2%) | 0 | .. | 0 | 2 (7%) | .. | 2 (2%) | 0 | .. | 2 (2%) | 4 (14%) | .. | 6 (2%) | 6 (5%) | .. | |
| Grade 3 | 0 | 0 | .. | 0 | 0 | .. | 0 | 1 (4%) | .. | 0 | 0 | .. | 0 | 1 (1%) | .. | |
| Injection site adverse reactions within 0–7 days | ||||||||||||||||
| Pain | 25 (30%) | 2 (7%) | 0·02 | 12 (14%) | 0 | 0·035 | 10 (12%) | 1 (4%) | 0·29 | 6 (7%) | 1 (4%) | 0·68 | 53 (16%) | 4 (4%) | 0·0008 | |
| Grade 1 | 25 (30%) | 2 (7%) | .. | 12 (14%) | 0 | .. | 10 (12%) | 1 (4%) | .. | 6 (7%) | 1 (4%) | .. | 53 (16%) | 4 (4%) | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | |
| Swelling | 2 (2%) | 0 | >0·99 | 0 | 0 | .. | 3 (4%) | 0 | 0·57 | 1 (1%) | 0 | >0·99 | 6 (2%) | 0 | 0·15 | |
| Grade 1 | 2 (2%) | 0 | .. | 0 | 0 | .. | 3 (4%) | 0 | .. | 1 (1%) | 0 | .. | 6 (2%) | 0 | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | |
| Itch | 2 (2%) | 0 | >0·99 | 1 (1%) | 1 (4%) | 0·44 | 0 | 0 | .. | 1 (1%) | 0 | >0·99 | 4 (1%) | 1 (1%) | 0·80 | |
| Grade 1 | 2 (2%) | 0 | .. | 1 (1%) | 1 (4%) | .. | 0 | 0 | .. | 1 (1%) | 0 | .. | 4 (1%) | 1 (1%) | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | |
| Redness | 1 (1%) | 0 | >0·99 | 0 | 0 | .. | 1 (1%) | 0 | >0·99 | 1 (1%) | 0 | >0·99 | 3 (1%) | 0 | 0·32 | |
| Grade 1 | 1 (1%) | 0 | .. | 0 | 0 | .. | 1 (1%) | 0 | .. | 1 (1%) | 0 | .. | 3 (1%) | 0 | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | |
| Rash | 1 (1%) | 0 | >0·99 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 1 (<1%) | 0 | 0·58 | |
| Grade 1 | 1 (1%) | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 1 (<1%) | 0 | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | |
| Systemic adverse reactions within 0–7 days | ||||||||||||||||
| Fever | 1 (1%) | 1 (4%) | 0·44 | 1 (1%) | 0 | >0·99 | 3 (4%) | 1 (4%) | >0·99 | 2 (2%) | 3 (11%) | 0·099 | 7 (2%) | 5 (4%) | 0·18 | |
| Grade 1 | 1 (1%) | 1 (4%) | .. | 1 (1%) | 0 | .. | 2 (2%) | 0 | .. | 1 (1%) | 2 (7%) | .. | 5 (1%) | 3 (3%) | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 1 (1%) | 0 | .. | 1 (1%) | 1 (4%) | .. | 2 (1%) | 1 (1%) | .. | |
| Grade 3 | 0 | 0 | .. | 0 | 0 | .. | 0 | 1 (4%) | .. | 0 | 0 | .. | 0 | 1 (1%) | .. | |
| Fatigue | 5 (6%) | 0 | 0·33 | 2 (2%) | 1 (4%) | >0·99 | 1 (1%) | 3 (11%) | 0·048 | 1 (1%) | 1 (4%) | 0·44 | 9 (3%) | 5 (4%) | 0·35 | |
| Grade 1 | 5 (6%) | 0 | .. | 2 (2%) | 1 (4%) | .. | 1 (1%) | 2 (7%) | .. | 1 (1%) | 0 | 9 (3%) | 5 (4%) | .. | ||
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 0 | 1 (4%) | .. | 0 | 1 (4%) | 0·25 | 0 | 0 | .. | |
| Nausea | 0 | 1 (4%) | 0·25 | 0 | 0 | .. | 2 (2%) | 1 (4%) | >0·99 | 0 | 1 (4%) | 0·25 | 2 (1%) | 3 (3%) | 0·07 | |
| Grade 1 | 0 | 1 (4%) | .. | 0 | 0 | .. | 1 (1%) | 1 (4%) | .. | 0 | 0 | .. | 1 (<1%) | 3 (3%) | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 1 (1%) | 0 | .. | 0 | 1 (4%) | .. | 1 (<1%) | 0 | .. | |
| Headache | 1 (1%) | 0 | >0·99 | 2 (2%) | 0 | >0·99 | 1 (1%) | 2 (7%) | 0·15 | 0 | 1 (4%) | 0·25 | 4 (1%) | 3 (3%) | 0·27 | |
| Grade 1 | 1 (1%) | 0 | .. | 2 (2%) | 0 | .. | 1 (1%) | 2 (7%) | .. | 0 | 0 | .. | 4 (1%) | 2 (2%) | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 1 (4%) | .. | 0 | 1 (1%) | .. | |
| Itch (non-injection site) | 0 | 0 | .. | 2 (2%) | 0 | >0·99 | 0 | 1 (4%) | 0·25 | 1 (1%) | 0 | >0·99 | 3 (1%) | 1 (1%) | >0·99 | |
| Grade 1 | 0 | 0 | .. | 2 (2%) | 0 | .. | 0 | 1 (4%) | .. | 1 (1%) | 0 | .. | 3 (1%) | 1 (1%) | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | |
| Cough | 0 | 0 | .. | 0 | 1 (4%) | 0·25 | 0 | 0 | .. | 1 (1%) | 0 | >0·99 | 1 (<1%) | 1 (1%) | 0·41 | |
| Grade 1 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 1 (4%) | .. | 0 | 0 | .. | 1 (1%) | 0 | .. | 1 (<1%) | 1 (1%) | .. | |
| Diarrhoea | 2 (2%) | 0 | >0·99 | 2 (2%) | 1 (4%) | >0·99 | 0 | 2 (7%) | 0·061 | 0 | 0 | .. | 4 (1%) | 3 (3%) | 0·27 | |
| Grade 1 | 2 (2%) | 0 | .. | 2 (2%) | 1 (4%) | .. | 0 | 2 (7%) | .. | 0 | 0 | .. | 0 | 0 | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | |
| Muscle pain | 1 (1%) | 0 | >0·99 | 1 (1%) | 0 | >0·99 | 0 | 0 | .. | 0 | 0 | .. | 1 (<1%) | 1 (1%) | 0·41 | |
| Grade 1 | 1 (1%) | 0 | .. | 1 (1%) | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 1 (<1%) | 1 (1%) | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | |
| Anaphylaxis | 1 (1%) | 0 | >0·99 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 1 (<1%) | 0 | 0·58 | |
| Grade 1 | 1 (1%) | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 1 (<1%) | 0 | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | |
| Other adverse reactions within 0–7 days | ||||||||||||||||
| Drowsiness | 0 | 0 | .. | 0 | 0 | .. | 1 (1%) | 0 | >0·99 | 0 | 0 | 1 (<1%) | 0 | 0·58 | ||
| Grade 1 | 0 | 0 | .. | 0 | 0 | .. | 1 (1%) | 0 | .. | 0 | 0 | .. | 1 (<1%) | 0 | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | |
| Dizziness | 1 (1%) | 0 | >0·99 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 1 (<1%) | 0 | 0·58 | |
| Grade 1 | 1 (1%) | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 1 (<1%) | 0 | .. | |
| Grade 2 | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | 0 | 0 | .. | |
| Overall adverse events within 0–30 days | ||||||||||||||||
| Any | 33 (39%) | 3 (11%) | 0·015 | 19 (23%) | 6 (21%) | >0·99 | 15 (18%) | 6 (21%) | 0·78 | 11 (13%) | 6 (21%) | 0·36 | 78 (23%) | 21 (19%) | 0·32 | |
| Grade 1 | 30 (36%) | 3 (11%) | .. | 17 (20%) | 3 (11%) | .. | 13 (15%) | 4 (14%) | .. | 5 (6%) | 2 (7%) | .. | 65 (19%) | 12 (11%) | .. | |
| Grade 2 | 2 (2%) | 0 | .. | 2 (2%) | 3 (11%) | .. | 2 (2%) | 1 (4%) | .. | 6 (7%) | 4 (14%) | .. | 12 (4%) | 8 (7%) | .. | |
| Grade 3 | 1 (1%) | 0 | .. | 0 | 0 | .. | 0 | 1 (4%) | .. | 0 | 0 | .. | 1 (<1%) | 5 (1%) | .. | |
Data are n (%). Any refers to all the participants with any grade adverse reactions or events. Adverse reactions and events were graded according to the scale issued by the China State Food and Drug Administration. One placebo recipient in the days 0 and 21 schedule reported grade 3 fever (38·5°C), but was self-limited and recovered. Grade 3=severe.