Table 3.
Summary of safety during the randomized treatment period (safety analysis set) and SUBQ treatment period (SUBQ treated safety analysis set)
| Patients with AEs, n (%) | Randomized treatment period (through day 71) | SUBQ treatment period (through SUBQ day 351) | ||||
|---|---|---|---|---|---|---|
| SUBQ ravulizumab (n = 84) | IV ravulizumab (n = 45) | Total (N = 129) | SUBQ/SUBQ ravulizumab (n = 84) | IV/SUBQ ravulizumab (n = 44) | Total (N = 128) | |
| Any AE | 67 (79.8) | 27 (60.0) | 94 (72.9) | 82 (97.6) | 42 (95.5) | 124 (96.9) |
| Any SAE | 5 (6.0) | 1 (2.2) | 6 (4.7) | 17 (20.2) | 10 (22.7) | 27 (21.1) |
| Death | 0 | 0 | 0 | 1 (1.2) | 0 | 1 (0.8) |
| AEs leading to discontinuation of study drug | 0 | 0 | 0 | 0 | 1 (2.3) | 1 (0.8) |
| Any ADEa | 39 (46.4) | NA | 39 (30.2) | 60 (71.4) | 35 (79.5) | 95 (74.2) |
| Any serious ADEa | 0 | NA | 0 | 1 (1.2) | 0 | 1 (0.8) |
| ADEs that were not device issuesa | 22 (26.2) | NA | 22 (17.1) | 22 (26.2) | 7 (15.9) | 29 (22.7) |
| ADEs that were device issuesa | 21 (25.0) | NA | 21 (16.3) | 56 (66.7) | 35 (79.5) | 91 (71.1) |
| AEs not associated with device/device use | 54 (64.3) | 27 (60.0) | 81 (62.8) | 75 (89.3) | 38 (86.4) | 113 (88.3) |
| AEs by severityb | ||||||
| Grade 1 | 64 (76.2) | 21 (46.7) | 85 (65.9) | 78 (92.9) | 39 (88.6) | 117 (91.4) |
| Grade 2 | 20 (23.8) | 14 (31.1) | 34 (26.4) | 43 (51.2) | 23 (52.3) | 66 (51.6) |
| Grade 3 | 3 (3.6) | 2 (4.4) | 5 (3.9) | 12 (14.3) | 8 (18.2) | 20 (15.6) |
| Grade 4 | 1 (1.2) | 0 | 1 (0.8) | 5 (6.0) | 3 (6.8) | 8 (6.3) |
| Grade 5 | 0 | 0 | 0 | 1 (1.2) | 0 | 1 (0.8) |
| Most common AEs (in ≥ 5% of patients)c | ||||||
| Headache | 11 (13.1) | 4 (8.9) | 15 (11.6) | 12 (14.3) | 6 (13.6) | 18 (14.1) |
| Diarrhea | 11 (13.1) | 2 (4.4) | 13 (10.1) | 11 (13.1) | 1 (2.3) | 12 (9.4) |
| Abdominal pain | 5 (6.0) | 3 (6.7) | 8 (6.2) | 7 (8.3) | 2 (4.5) | 9 (7.0) |
| Nausea | 5 (6.0) | 3 (6.7) | 8 (6.2) | 5 (6.0) | 1 (2.3) | 6 (4.7) |
| Nasopharyngitis | 5 (6.0) | 2 (4.4) | 7 (5.4) | 8 (9.5) | 4 (9.1) | 12 (9.4) |
| Pyrexia | 5 (6.0) | 0 | 5 (3.9) | 10 (11.9) | 4 (9.1) | 14 (10.9) |
| Back pain | 4 (4.8) | 2 (4.4) | 6 (4.7) | 7 (8.3) | 1 (2.3) | 8 (6.3) |
| Asthenia | 3 (3.6) | 0 | 3 (2.3) | 10 (11.9) | 2 (4.5) | 12 (9.4) |
| Anemia | 2 (2.4) | 0 | 2 (1.6) | 8 (9.5) | 2 (4.5) | 10 (7.8) |
| Hemolysis | 1 (1.2) | 1 (2.2) | 2 (1.6) | 5 (6.0) | 3 (6.8) | 8 (6.3) |
| Arthralgia | 1 (1.2) | 1 (2.2) | 2 (1.6) | 5 (6.0) | 2 (4.5) | 7 (5.5) |
| COVID-19 | NR | NR | NR | 11 (13.1) | 7 (15.9) | 18 (14.1) |
| AEs related to study treatment | 31 (36.9) | 7 (15.6) | 38 (29.5) | 31 (36.9) | 10 (22.7) | 41 (32.0) |
| AEs not related to study treatment | 52 (61.9) | 23 (51.1) | 75 (58.1) | 82 (97.6) | 42 (95.5) | 124 (96.9) |
| SAEs related to study treatment | 0 | 0 | 0 | 1 (1.2) | 0 | 1 (0.8) |
| SAEs not related to study treatment | 5 (6.0) | 1 (2.2) | 6 (4.7) | 16 (19.0) | 10 (22.7) | 26 (20.3) |
| Infusion reactionsd | 38 (45.2) | 8 (17.8) | 46 (35.7) | 46 (54.8) | 16 (36.4) | 62 (48.4) |
| Other serious infectionse | 1 (1.2) | 0 | 1 (0.8) | 9 (10.7) | 5 (11.4) | 14 (10.9) |
AEs were coded using MedDRA Version 23.1. Patients are counted in each event by relationship to study treatment and severity category in case of multiple events
ADE adverse device effect, AE adverse event, CTCAE Common Terminology Criteria for Adverse Events, IV intravenous, NA not applicable, NR not reported, OBDS on-body delivery system, SAE serious adverse event, SUBQ subcutaneous
aADEs are noted as “not applicable” because patients in the IV group did not use the ravulizumab OBDS for SUBQ administration device during the randomized treatment period
bSeverity of AEs was graded using CTCAE Version 4.03. Grade 1 = mild; grade 2 = moderate; grade 3 = severe; grade 4 = life-threatening; grade 5 = fatal
cReported in ≥ 5% of all patients during randomized treatment period or SUBQ treatment period; does not include ADEs
dLocal (infusion site or injection site reactions), systemic (infusion-associated/infusion-related reactions), and immune-mediated (hypersensitivity) reactions
eIncludes COVID-19, bacterial infections, bacterial sepsis, COVID-19 pneumonia, gastroenteritis, hepatitis viral, salmonellosis, sinusitis, suspected COVID-19, tubo-ovarian abscess