Table 2.
Summary of deaths, serious adverse events, discontinuations due to serious adverse events, and adverse events, regardless of study drug relationship (core and extension studies; pooled safety analysis set)
| Core studies | Extension studies | |||||
|---|---|---|---|---|---|---|
| CAD106 (2201) | CAD106 (2202) | CAD106 (pooled) | Placebo (pooled) | CAD106 total (pooled) | ||
| N = 22 (all s.c.) | N = 25 (n = 9 s.c.; n = 16 i.m.) | N = 47 | N = 11 | N = 45 | ||
| Deaths | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (2.2) | |
| SAEs | 4 (18.2) | 5 (20.0) | 9 (19.1) | 4 (36.4) | 6 (13.3) | |
| Intracerebral hemorrhage | 1 (4.5)** | 0 (0.0) | 1 (2.1) | 0 (0.0) | 0 (0.0) | |
| Discontinuations due to (S)AEs | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 2 (4.4) | |
| Amyloid-related imaging abnormalities* | 1 (4.5) | 0 (0.0) | 1 (2.1) | 1 (9.1) | 2 (4.4) | |
| With hemorrhage | 1 (4.5)** | 0 (0.0) | 1 (2.1) | 1 (9.1) | 2 (4.4) | |
| Any primary system organ class, n (%) | 15 (68.2) | 20 (80.0) | 35 (74.5) | 7 (63.6) | 37 (82.2) | |
| Cardiac disorders | 3 (13.6) | 3 (12.0) | 6 (12.8) | 0 (0.0) | 7 (15.6) | |
| Gastrointestinal disorders | 6 (27.3) | 2 (8.0) | 8 (17.0) | 2 (18.2) | 15 (33.3) | |
| Diarrhea | 3 (13.6) | 0 (0.0) | 3 (6.4) | 0 (0.0) | 6 (13.3) | |
| General disorders and administration site conditions | 6 (27.3) | 8 (32.0) | 14 (29.8) | 2 (18.2) | 9 (20.0) | |
| Pyrexia | 1 (4.5) | 3 (12.0) | 4 (8.5) | 1 (9.1) | 0 (0.0) | |
| Fatigue | 1 (4.5) | 2 (8.0) | 3 (6.4) | 1 (9.1) | 6 (13.3) | |
| Infections and infestations | 8 (36.4) | 3 (12.0) | 11 (23.4) | 3 (27.3) | 16 (35.6) | |
| Nasopharyngitis | 2 (9.1) | 0 (0.0) | 2 (4.3) | 0 (0.0) | 6 (13.3) | |
| Injury, poisoning and procedural complications | 0 (0.0) | 5 (20.0) | 5 (10.6) | 2 (18.2) | 9 (20.0) | |
| Fall | 0 (0.0) | 3 (12.0) | 3 (6.4) | 1 (9.1) | 3 (6.7) | |
| Investigations | 4 (18.2) | 2 (8.0) | 6 (12.8) | 2 (18.2) | 4 (8.9) | |
| Musculoskeletal and connective tissue disorders | 6 (27.3) | 3 (12.0) | 9 (19.1) | 1 (9.1) | 9 (20.0) | |
| Back pain | 1 (4.5) | 3 (12.0) | 4 (8.5) | 0 (0.0) | 3 (6.7) | |
| Nervous system disorders | 4 (18.2) | 6 (24.0) | 10 (21.3) | 2 (18.2) | 11 (24.4) | |
| Headache | 2 (9.1) | 4 (16.0) | 6 (12.8) | 0 (0.0) | 6 (13.3) | |
| Psychiatric disorders | 2 (9.1) | 6 (24.0) | 8 (17.0) | 4 (36.4) | 15 (33.3) | |
| Confusional state | 0 (0.0) | 3 (12.0) | 3 (6.4) | 0 (0.0) | 3 (6.7) | |
| Depression | 1 (4.5) | 2 (8.0) | 3 (6.4) | 0 (0.0) | 6 (13.3) | |
| Renal and urinary disorders | 2 (9.1) | 4 (16.0) | 6 (12.8) | 1 (9.1) | 4 (8.9) | |
| Skin and subcutaneous tissue disorders | 0 (0.0) | 6 (24.0) | 6 (12.8) | 1 (9.1) | 7 (15.6) | |
AE, Adverse event; ARIA-E, Amyloid-related imaging abnormalities corresponding to vasogenic edema; ARIA-H, Amyloid-related imaging abnormalities corresponding to microhemorrhage; FLAIR, Fluid-attenuated inversion recovery; ICH, Intracerebral hemorrhage; i.m., Intramuscular; N, Number of patients in treatment group; n, Number of patients reporting event; SAE, Serious adverse event; s.c., Subcutaneous; SOC, System organ class. *ARIA-H include two or more new microhemorrhages, subarachnoid hemorrhages or hemosiderosis. No ARIA-E findings were reported. One patient with T2-weighted FLAIR at Week 52 was confirmed as ischemic stroke at an unscheduled scan (Week 56 extension baseline), ruling out the likelihood of vasogenic edema. **The same patient experienced subarachnoid hemorrhage at Week 20 and ICH at Week 36. SOCs are presented in alphabetical order for incidences >10% in any CAD106 treatment group. Within each SOC, preferred terms for AEs with an incidence >10% in any CAD106 treatment group are shown. A subject with multiple occurrences of an AE under one treatment is counted only once in each AE category for that treatment. A subject with multiple AEs within a SOC or preferred term is counted only once in the total row for the core and extension studies. Ongoing events at the end of the core study are counted again in the extension studies; therefore, patients may be counted twice in the total columns for the core and extension studies.