Table 1.
Summary of influenza-like adverse events of interest by dose (fasted state)
| Participants, n (%) | Placebo n = 101 | 0.3 mg n = 27 |
1 mg n = 136 |
2 mg n = 139 |
4 mg n = 140 |
6 mg n = 24 |
8 mg n = 21 |
10/12 mg n = 12 |
All VES n = 492 |
|---|---|---|---|---|---|---|---|---|---|
| Any flu-like AEI | 8 (8%) | 1 (4%) | 23 (17%) | 21 (15%) | 33 (24%) | 2 (8%) | 9 (43%) | 7 (58%) | 96 (20%) |
| Grade 1 | 3 (3%) | 1 (4%) | 10 (7%) | 11 (8%) | 19 (14%) | 1 (4%) | 7 (33%) | 4 (33%) | 53 (11%) |
| Grade 2 | 5 (5%) | 0 | 11 (8%) | 8 (6%) | 12 (9%) | 1 (4%) | 1 (5%) | 1 (8%) | 34 (7%) |
| Grade 3 | 0 | 0 | 2 (2%) | 2 (1%) | 2 (1%) | 0 | 1 (5%) | 2 (17%) | 9 (2%) |
| Grade 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| CRS (grade 3) | 0 | 0 | 0 | 0 | 0 | 0 | 1 (5%) | 0 | 1 (< 1%) |
| Pyrexia | 3 (3%) | 1 (4%) | 9 (7%) | 8 (6%) | 18 (13%) | 1 (4%) | 3 (14%) | 6 (50%) | 46 (9%) |
| Grade 1 | 3 (3%) | 1 (4%) | 5 (4%) | 6 (4%) | 13 (9%) | 1 (4%) | 3 (14%) | 3 (25%) | 32 (7%) |
| Grade 2 | 0 | 0 | 2 (2%) | 1 (1%) | 3 (2%) | 0 | 0 | 1 (8%) | 7 (1%) |
| Grade 3 | 0 | 0 | 2 (2%) | 1 (1%) | 2 (1%) | 0 | 0 | 2 (17%) | 7 (1%) |
| Myalgia (grade 2)a | 0 | 0 | 1 (1%) | 1 (1%) | 4 (3%) | 1 (4%) | 1 (5%) | 1 (8%) | 9 (2%) |
| Chills | 2 (2%) | 0 | 3 (2%) | 9 (7%) | 13 (9%) | 0 | 4 (19%) | 6 (50%) | 35 (7%) |
| Grade 1 | 2 (2%) | 0 | 3 (2%) | 8 (6%) | 11 (8%) | 0 | 4 (19%) | 5 (42%) | 31 (6%) |
| Grade 2 | 0 | 0 | 0 | 0 | 2 (1%) | 0 | 0 | 1 (8%) | 3 (1%) |
| Grade 3 | 0 | 0 | 0 | 1 (1%) | 0 | 0 | 0 | 0 | 1 (< 1%) |
| Influenza | 0 | 0 | 2 (2%) | 0 | 1 (1%) | 0 | 0 | 0 | 3 (1%) |
| Grade 1 | 0 | 0 | 1 (1%) | 0 | 1 (1%) | 0 | 0 | 0 | 2 (< 1%) |
| Grade 2 | 0 | 0 | 1 (1%) | 0 | 0 | 0 | 0 | 0 | 1 (< 1%) |
| Influenza-like illness | 0 | 0 | 7 (5%) | 1 (1%) | 9 (6%) | 0 | 0 | 0 | 17 (4%) |
| Grade 1 | 0 | 0 | 5 (4%) | 1 (1%) | 7 (5%) | 0 | 0 | 0 | 13 (3%) |
| Grade 2 | 0 | 0 | 2 (2%) | 0 | 2 (1%) | 0 | 0 | 0 | 4 (1%) |
| Malaise (grade 2)a | 1 (1%) | 0 | 0 | 0 | 1 (1%) | 0 | 0 | 0 | 1 (< 1%) |
| Headache | 3 (3%) | 0 | 6 (4%) | 6 (4%) | 6 (4%) | 0 | 1 (5%) | 1 (8%) | 20 (4%) |
| Grade 2 | 3 (3%) | 0 | 6 (4%) | 5 (4%) | 6 (4%) | 0 | 1 (5%) | 1 (8%) | 19 (4%) |
| Grade 3 | 0 | 0 | 0 | 1 (1%) | 0 | 0 | 0 | 0 | 1 (< 1%) |
| Fatigue (grade 2)a | 2 (2%) | 0 | 3 (2%) | 2 (1%) | 4 (3%) | 0 | 0 | 0 | 9 (2%) |
| Joint pain | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Flu-like AEIs included ≥ grade 2 fatigue, headache, malaise, myalgia; ≥ grade 3 joint pain; any grades of chills, cytokine release syndrome, influenza, influenza-like illness and pyrexia
Fasted state excluded participants who received VES with a high-fat meal, moderate-fat meal, or 4 h after a high-fat meal. Six participants received placebo with a meal. Eighteen participants were treated with VES 8 mg immediately after a high-fat or moderate-fat meal, or 4 h after a high-fat meal (n = 6 per group). Among those, five participants crossed over from the fasted group to the high-fat meal group after a 1-month washout. Four participants in GS-US-382-3961 crossed over from VES 4 mg to 6 mg and three participants in GS-US-382-3961 crossed over from VES 6 mg to 8 mg after a washout
Multiple adverse events were counted only once per participant for the highest severity grade for each preferred term
AEI adverse events of interest, CRS cytokine release syndrome, flu-like AEIs influenza-like adverse events of interest, VES vesatolimod
aAll events of myalgia, malaise and fatigue were grade 2 severity