Treatment-emergent AEs according to hemophilia subtype during the main + extension parts of explorer4 (HAwI, HBwI) and explorer5 (HA); safety analysis set
| Hemophilia subtype . | HA (n = 36) . | HAwI (n = 15) . | HBwI (n = 10) . | |||
|---|---|---|---|---|---|---|
| Cumulative concizumab exposure time, including follow-up, y | 71.9 | 27.0 | 18.3 | |||
| Hemophilia subtype . | HA (n = 36) . | HAwI (n = 15) . | HBwI (n = 10) . | |||
|---|---|---|---|---|---|---|
| Cumulative concizumab exposure time, including follow-up, y | 71.9 | 27.0 | 18.3 | |||
| . | n (%) . | E [R] . | n (%) . | E [R] . | n (%) . | E [R] . |
|---|---|---|---|---|---|---|
| All AEs | 33 (91.7) | 298 [4.1] | 13 (86.7) | 67 [2.5] | 9 (90.0) | 64 [3.5] |
| Serious AEs | 5 (13.9) | 5 [0.1] | 0 | 5 (50.0) | 9 [0.5] | |
| Severe | 4 (11.1) | 4 [0.1] | 0 | 2 (20.0) | 4 [0.2] | |
| Fatal | 0 | 0 | 0 | |||
| AEs leading to withdrawal | 0 | 0 | 0 | |||
| AESI (thromboembolic events) | 0 | 0 | 0 | |||
| Most frequent AEs by PT and SOC, ≥5% | ||||||
| Gastrointestinal disorders | ||||||
| Dental caries | 3 (8.3) | 6 [0.1] | 0 | 1 (10.0) | 2 [0.1] | |
| Diarrhea | 1 (2.8) | 1 [0.0] | 3 (20.0) | 3 [0.1] | 1 (10.0) | 2 [0.1] |
| General disorders and administration site conditions | ||||||
| Injection site reactions* | 14 (38.9) | 25 [0.3] | 2 (13.3) | 3 [0.1] | 4 (40.0) | 15 [0.8] |
| Pyrexia | 3 (8.3) | 4 [0.1] | 2 (13.3) | 2 [0.1] | 0 | |
| Infections and infestations | ||||||
| Gastrointestinal infection | 3 (8.3) | 3 [0.0] | 1 (6.7) | 1 [0.0] | 0 | |
| Influenza | 4 (11.1) | 4 [0.1] | 1 (6.7) | 1 [0.0] | 0 | |
| Nasopharyngitis | 12 (33.3) | 22 [0.3] | 0 | 3 (30.0) | 6 [0.3] | |
| Pharyngitis | 3 (8.3) | 3 [0.0] | 1 (6.7) | 2 [0.1] | 0 | |
| Rhinitis | 2 (5.6) | 2 [0.0] | 2 (13.3) | 2 [0.1] | 0 | |
| Upper respiratory tract infection | 5 (13.9) | 7 [0.1] | 2 (13.3) | 4 [0.1] | 2 (20.0) | 4 [0.2] |
| Investigations | ||||||
| D-dimer level increased | 9 (25.0) | 12 [0.2] | 1 (6.7) | 1 [0.0] | 1 (10.0) | 1 [0.1] |
| Prothrombin fragments 1 + 2 increased | 7 (19.4) | 12 [0.2] | 2 (13.3) | 2 [0.1] | 0 | |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 4 (11.1) | 6 [0.1] | 3 (20.0) | 3 [0.1] | 0 | |
| Back pain | 5 (13.9) | 7 [0.1] | 0 | 0 | ||
| Nervous system disorders | ||||||
| Headache | 8 (22.2) | 12 [0.2] | 1 (6.7) | 1 [0.0] | 1 (10.0) | 1 [0.1] |
| Respiratory, thoracic, and mediastinal disorders | ||||||
| Cough | 4 (11.1) | 4 [0.1] | 0 | 0 | ||
| . | n (%) . | E [R] . | n (%) . | E [R] . | n (%) . | E [R] . |
|---|---|---|---|---|---|---|
| All AEs | 33 (91.7) | 298 [4.1] | 13 (86.7) | 67 [2.5] | 9 (90.0) | 64 [3.5] |
| Serious AEs | 5 (13.9) | 5 [0.1] | 0 | 5 (50.0) | 9 [0.5] | |
| Severe | 4 (11.1) | 4 [0.1] | 0 | 2 (20.0) | 4 [0.2] | |
| Fatal | 0 | 0 | 0 | |||
| AEs leading to withdrawal | 0 | 0 | 0 | |||
| AESI (thromboembolic events) | 0 | 0 | 0 | |||
| Most frequent AEs by PT and SOC, ≥5% | ||||||
| Gastrointestinal disorders | ||||||
| Dental caries | 3 (8.3) | 6 [0.1] | 0 | 1 (10.0) | 2 [0.1] | |
| Diarrhea | 1 (2.8) | 1 [0.0] | 3 (20.0) | 3 [0.1] | 1 (10.0) | 2 [0.1] |
| General disorders and administration site conditions | ||||||
| Injection site reactions* | 14 (38.9) | 25 [0.3] | 2 (13.3) | 3 [0.1] | 4 (40.0) | 15 [0.8] |
| Pyrexia | 3 (8.3) | 4 [0.1] | 2 (13.3) | 2 [0.1] | 0 | |
| Infections and infestations | ||||||
| Gastrointestinal infection | 3 (8.3) | 3 [0.0] | 1 (6.7) | 1 [0.0] | 0 | |
| Influenza | 4 (11.1) | 4 [0.1] | 1 (6.7) | 1 [0.0] | 0 | |
| Nasopharyngitis | 12 (33.3) | 22 [0.3] | 0 | 3 (30.0) | 6 [0.3] | |
| Pharyngitis | 3 (8.3) | 3 [0.0] | 1 (6.7) | 2 [0.1] | 0 | |
| Rhinitis | 2 (5.6) | 2 [0.0] | 2 (13.3) | 2 [0.1] | 0 | |
| Upper respiratory tract infection | 5 (13.9) | 7 [0.1] | 2 (13.3) | 4 [0.1] | 2 (20.0) | 4 [0.2] |
| Investigations | ||||||
| D-dimer level increased | 9 (25.0) | 12 [0.2] | 1 (6.7) | 1 [0.0] | 1 (10.0) | 1 [0.1] |
| Prothrombin fragments 1 + 2 increased | 7 (19.4) | 12 [0.2] | 2 (13.3) | 2 [0.1] | 0 | |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 4 (11.1) | 6 [0.1] | 3 (20.0) | 3 [0.1] | 0 | |
| Back pain | 5 (13.9) | 7 [0.1] | 0 | 0 | ||
| Nervous system disorders | ||||||
| Headache | 8 (22.2) | 12 [0.2] | 1 (6.7) | 1 [0.0] | 1 (10.0) | 1 [0.1] |
| Respiratory, thoracic, and mediastinal disorders | ||||||
| Cough | 4 (11.1) | 4 [0.1] | 0 | 0 | ||
%, percentage of patients with adverse event. AESI, AE of special interest; E, number of AEs; PT, preferred term; R, rate calculated as the number of AEs per patient-years of exposure; SOC, system organ class.
Injection site reactions included injection site bruising, injection site hematoma and injection site hemorrhage.