TABLE 3.
Treatment‐emergent adverse events (safety population)
| Participants with TEAEs, n | Cohort 1 (100 mg) (n = 8) | Cohort 2 (225 mg) (n = 8) | Cohort 3 (400 mg) (n = 8) | Total (N = 24) |
|---|---|---|---|---|
| Any TEAE | 7 (87.5) | 8 (100.0) | 6 (75.0) | 21 (87.5) |
| Any study drug‐related TEAE (≥1) | 1 (12.5) | 4 (50.0) | 5 (62.5) | 10 (41.7) |
| Grade 1 | 1 (12.5) | 2 (25.0) | 0 | 3 (12.5) |
| Grade 2 | 0 | 1 (12.5) | 4(50.0) | 5 (20.8) |
| Grade 3 | 0 | 0 | 1 (12.5) | 1 (4.2) |
| Grade 4 | 0 | 1 (12.5) | 0 | 1 (4.2) |
| Study drug‐related TEAE by system organ class a | ||||
| Blood and lymphatic system disorders | 0 | 0 | 1 (12.5) | 1 (4.2) |
| Hypofibrinogenaemia | 0 | 0 | 1 (12.5) | 1 (4.2) |
| Eye disorders | 0 | 0 | 1 (12.5) | 1 (4.2) |
| Retinal artery thrombosis | 0 | 0 | 1 (12.5) | 1 (4.2) |
| Gastrointestinal disorders | 0 | 1 (12.5) | 0 | 1 (4.2) |
| Nausea | 0 | 1 (12.5) | 0 | 1 (4.2) |
| General disorders and administration site conditions | 0 | 1 (12.5) | 2 (25.0) | 3 (12.5) |
| Injection site erythema | 0 | 0 | 2 (25.0) | 2 (8.3) |
| Injection site inflammation | 0 | 1 (12.5) | 0 | 1 (4.2) |
| Injection site pruritus | 0 | 0 | 2 (25.0) | 2 (8.3) |
| Injection site reaction | 0 | 1 (12.5) | 0 | 1 (4.2) |
| Injection site swelling | 0 | 0 | 1 (12.5) | 1 (4.2) |
| Laboratory investigations b | 1 (12.5) | 0 | 0 | 1 (4.2) |
| Fibrin D‐dimer increased | 1 (12.5) | 0 | 0 | 1 (4.2) |
| Nervous system disorders | 0 | 3 (37.50) | 0 | 3 (12.5) |
| Dizziness | 0 | 1 (12.5) | 0 | 1 (4.2) |
| Headache | 0 | 1 (12.5) | 0 | 1 (4.2) |
| Ischaemic stroke | 0 | 1 (12.5) | 0 | 1 (4.2) |
| Transverse sinus thrombosis | 0 | 1 (12.5) | 0 | 1 (4.2) |
| Skin and subcutaneous tissue disorders | 0 | 0 | 1 (12.5) | 1 (4.2) |
| Erythema | 0 | 0 | 1 (12.5) | 1 (4.2) |
| AESI | 0 | 2 (25.0) | 1 (12.5) | 3 (12.5) |
| Ischemic stroke | 0 | 1 (12.5) | 0 | 1 (4.2) |
| Retinal artery thrombosis | 0 | 0 | 1 (12.5) | 1 (4.2) |
| Transverse sinus thrombosis | 0 | 1 (12.5) | 0 | 1 (4.2) |
| Any TEAE leading to discontinuation | 1 (12.5) | 2 (25.0) | 0 | 3 (12.5) |
| Any serious TEAE | 1 (12.5) | 2 (25.0) | 1 (12.5) | 4 (16.7) |
| Any study drug‐related serious TEAE | 0 | 2 (25.0) | 1 (12.5) | 3 (12.5) |
| Any serious TEAE leading to discontinuation | 1 (12.5) c | 2 (25.0) | 1 (12.5) d | 3 (12.5) |
Data are shown for each participant based on their initial dose cohort.
Some participants experienced ≥1 TEAE;
Increased levels of fibrin D‐dimer.
Serious TEAE of nasal bleeding and paranasal sinus tumour, considered unrelated to study drug.
Study drug was reported to be interrupted for serious TEAE of retinal artery thrombosis; however, the study drug was subsequently discontinued in all subjects and the study was terminated.
AESI, adverse event of special interest; TEAE, treatment‐emergent adverse event. TEAE grades are listed according to the Common Terminology Criteria for Adverse Events, version 5.0 : 36
Grade 1, Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2, Moderate; minimal, local, or non‐invasive intervention indicated; limiting age‐appropriate instrumental activities of daily living (ADL). Grade 3, Severe or medically significant but not immediately life‐threatening; hospitalisation or prolongation of hospitalisation indicated; disabling; limiting self‐care ADL. Grade 4, Life‐threatening consequences; urgent intervention indicated. Grade 5, Death related to AE.